HPN May 2016
HOSPITAL PROFESSIONAL NEWS IRELAND Ireland’s Dedicated Hospital Professional Publication
IN THIS ISSUE: IN DMARD-IR AND TNF-IR RA PATIENTS, WHEN COMBINATION WITH MTX IS NOT AN OPTION...
NOW AVAILABLE IN SUBCUTANEOUS (SC) ABRIDGED PRESCRIBING INFORMATION (For full prescribing information, refer to the Summary of Product Characteristics [SmPC]). RoActemra (tocilizumab) 20mg/ml Concentrate for Solution for Infusion (RoActemra IV) and RoActemra® 162mg solution for injection in pre-filled syringe (RoActemra SC). Indications: ABRIDGED PRESCRIBING INFORMATION (For full prescribing information, refer to the Summary of Product Characteristics [SmPC]). RoActemra® (tocilizumab) 20mg/ml Concentrate for Solution for Infusion (RoActemra IV) and RoActemra® 162mg solution for injection in pre-filled syringe (RoActemra SC). Indications: RoActemra SC: In combination with methotrexate (MTX), for the treatment of adult patients with moderate to severe active rheumatoid arthritis (RA) who have had an inadequate response or intolerance to one or more disease-modifying antirheumatic drugs (DMARDs) or tumour necrosis factor (TNF) antagonists. RoActemra IV: In combination with MTX for the treatment of (i) severe, active and progressive RA in adults not previously treated with MTX, (ii) adult patients with moderate to severe active RA who have had an inadequate response or intolerance to one or more DMARDs or TNF antagonists, (ii) active systemic juvenile idiopathic arthritis (sJIA) in patients ≥ 2 years of age, who responded inadequately to previous therapy with NSAIDs and systemic corticosteroids, (iii) juvenile idiopathic polyarthritis (pJIA) (rheumatoid factor positive or negative and extended oligoarthritis) in patients ≥ 2 years of age, who responded inadequately to previous therapy with MTX, RoActemra IV/SC can be given as monotherapy in case of intolerance to MTX or where continued treatment with MTX is inappropriate for all indications. RoActemra IV/ SC has been shown to reduce the rate of progression of joint damage as measured by X-ray and to improve physical function when given in combination with MTX for the treatment of adult RA patients. Dosage & Administration: Treatment should be initiated by HCPs experienced in the diagnosis and treatment of RA, sJIA or pJIA and all patients should be given the Patient Alert Card. RA: RoActemra IV: 8mg/kg diluted to a final volume of 100ml, given once every 4 weeks by IV infusion over 1 hour. For patients >100kg, doses >800mg per infusion are not recommended. No data on doses above 1.2g. RoActemra SC: 162mg once every week, irrespective of weight. Patients may self-inject after training. Rotate injection site frequently. sJIA (RoActemra IV only): Patients <2 years of age – no data. Patients >2 years, 8mg/kg diluted to final volume of 100ml for patients ≥ 30kg or 12mg/kg diluted to final volume of 50ml for patients < 30kg once every 2 weeks by IV infusion over 1 hour. Clinical improvement generally seen within 6 weeks of starting RoActemra; reconsider continued therapy if no improvement. pJIA (RoActemra IV only): Patients <2 years of age - no data. Patients >2 years of age, 8mg/kg diluted to final volume of 100ml for patients ≥ 30 kg or 10 mg/kg diluted to final volume of 50ml for patients <30kg once every 4 weeks by IV infusion over 1 hour. Clinical improvement generally seen within 12 weeks of starting RoActemra; reconsider continued therapy if no improvement. For pJIA/sJIA: check patient’s weight at each visit. Dose adjustments: For raised liver enzymes, modify concomitant DMARDs if appropriate, reduce or interrupt dose of RoActemra; for low absolute neutrophil count (ANC) or low platelet count reduce or interrupt RoActemra. In some instances discontinue RoActemra (see SmPC). Special Populations: No data available for RoActemra SC in patients <18 years of age. Closely monitor renal function in patients with moderate to severe renal impairment. No data in patients with hepatic impairment. No dose adjustments in patients >65 years. Contraindications: Hypersensitivity to any component of the product; active, severe infections. Warnings & Precautions: Cases of serious infections (sometimes fatal) have been reported; interrupt therapy until controlled. Caution in patients with recurring/chronic infections, or other underlying conditions (e.g. diverticulitis, diabetes and interstitial lung disease) which predisposes to infection. Patients and parents/guardians of sJIA and pJIA patients should contact their HCP when symptoms suggestive of infection appear. Screen for latent TB and treat if required prior to starting therapy. Patients to seek medical attention if sign/symptoms suggestive of TB occur during or after treatment. Viral reactivation (e.g. hepatitis B) reported with biologic therapies. Caution in patients with a history of intestinal ulceration or diverticulitis. Serious hypersensitivity reactions, including anaphylaxis, reported and may be more severe and potentially fatal in patients who have experienced hypersensitivity reactions during previous treatment even if they have received premedication with steroids and anti-histamines. If an anaphylactic reaction or other serious hypersensitivity/serious infusion related reaction occurs, permanently discontinue RoActemra. Use with caution in patients with active hepatic disease/impairment. Not recommended in patients with baseline ALT or AST > 5 x ULN; caution in patients with ALT or AST > 1.5 x ULN (see SmPC). Risk of neutropenia may increase in patients previously treated with TNF antagonist. Continued therapy not recommended in patients with ANC < 0.5 x 109/l or platelet count < 50 x 103/μl. Do not initiate RoActemra treatment were ANC is below 2 x 109/l. Caution in patients with low platelet count; monitor neutrophils and platelets in RA, sJIA and pJIA patients according to SmPC. Elevations in lipid parameters seen; if elevated, follow local guidelines. Be vigilant for symptoms of new-onset central demyelinating disorders. Immunomodulatory medicines may increase malignancy risk in RA patients. Live and live attenuated vaccines should not be given concurrently (see SmPC). Not recommended for use with other biological agents. Macrophage activation syndrome (MAS), a serious life-threatening disorder, may develop in sJIA patients – RoActemra not studied in patients during an active MAS episode. Trade name should be clearly recorded in patient file to improve traceability of biological medicines. Drug Interactions: Studies only performed in adults. Monitor patients taking medicines individually adjusted and metabolised via CYP450 3A4, 1A2 or 2C9 when starting/stopping RoActemra, as doses may need to be increased to maintain therapeutic effect. Effects of tocilizumab on CYP450 enzyme activity may persist for several weeks after stopping therapy (refer to SmPC for further details on cytochrome CYP450 and other drug interactions). Fertility, Pregnancy & Lactation: Women should use contraception during and up to 3 months after treatment. No adequate data from use in pregnant women. Animal study showed increased risk of spontaneous abortion/embryo-foetal death at high dose. RoActemra should not be used during pregnancy unless clearly necessary. No lactation data in humans. A decision on whether to continue/discontinue breastfeeding or RoActemra therapy should be made taking into account the relative benefits to the child and mother. Refer to SmPC. Effects on ability to drive and use machines: RoActemra has minor influence on the ability to drive and use machines (dizziness). Undesirable Effects: Prescribers should consult SmPC for full details of ADRs. RoActemra IV: RA: ADRs occurring in RoActemra trials: Very Common (> 1/10): upper respiratory tract infections, hypercholesterolaemia. Common (>1/100 - <1/10): cellulitis, pneumonia, oral herpes simplex, herpes zoster, abdominal pain, mouth ulceration, gastritis, rash, pruritus, urticaria, headache, dizziness, hepatic transaminases increased, weight increased, total bilirubin increased, hypertension, leucopenia, neutropenia, peripheral oedema, hypersensitivity reactions, conjunctivitis, cough and dyspnoea. sJIA: ADRs were similar to those seen in RA patients. Serious infections of varicella and otitis media reported (in addition to infections for RA). Hypersensitivity reactions requiring treatment discontinuation occurred in <1% of patients. Other events occurring within 24 hours of infusion (16% of patients) included rash, urticaria (considered serious), diarrhoea, epigastric discomfort, arthralgia and headache. Decreased IgG levels during therapy. pJIA: ADRs were similar to those seen in RA and sJIA patients. Nasopharyngitis, headache, nausea, and decreased neutrophil count more frequently reported in the pJIA population. The incidence of infections leading to dose interruptions was numerically higher in patients weighing <30 kg, the rate of serious infections was also higher in these patients. 20.2% experienced an infusion reaction within 24 hours of infusion. RoActemra SC: The safety and immunogenicity was consistent with the known safety profile of IV. Injection site reactions (including erythema, pruritus, pain and haematoma) were mild to moderate in severity. Serious or Potentially Serious: serious infections, active tuberculosis, invasive pulmonary infections, interstitial lung disease (including pneumonitis and pulmonary fibrosis), GI perforations (as complications of diverticulitis), serious hypersensitivity reactions, Stevens-Johnson syndrome. See SmPC section 4.8 for instructions on the reporting of Suspected Adverse Reactions. Legal Category: Subject to medical prescription which may not be renewed (A). Presentations & Marketing Authorisation Numbers: 80mg of tocilizumab in 4ml (20mg/ml) pack of 1 (EU/1/08/492/001); 200mg of tocilizumab in 10ml (20mg/ml) pack of 1 (EU/1/08/492/003); 400mg of tocilizumab in 20ml (20mg/ml) pack of 1 (EU/1/08/492/005); 162mg tocilizumab solution for injection (in 0.9ml) in pre-filled syringe (EU/1/08/492/007). Marketing Authorisation Holder: Roche Registration Limited, 6 Falcon Way, Shire Park, Welwyn Garden City, AL7 1TW, United Kingdom. RoActemra is a registered trade mark. Further information is available from Roche Products (Ireland) Limited, 3004 Lake Drive, Citywest, Naas Road, Dublin 24. Telephone: (01) 4690700. Fax: (01) 4690791. Date of Preparation: March 2015. Reference: 1. Nisar MK et al. The role of tocilizumab monotherapy in the management of rheumatoid arthritis: a review. Int. J. Clin. Rheumatol. (2012) 7(1): 9-19. Date of item: February 2016. IE/RACTE/0216/0001 ®
NEWS: PHA 6-point plan for health Page 5 PROFILE: Professor John Crown on health and politics Page 9 CONFERENCE: Calls for IT funding from HPAI Page 11 CPD: Melanoma Management Page 27 AWARDS: 2016 Hospital Professional Awards Page 32 CLINICAL: Updates on COPD in Ireland Page 48
Expanding Treatment Extending Survival... ...in mCRC and unresectable or metastatic GIST Proven efficacy as a single-agent1,2,3 Convenient, once-daily, oral monotherapy1,2,3 Generally manageable and reversible adverse event profile1,2,3 A New Hope is Within Reach Now available on High-Tech Drug Scheme (code 88493) Stivarga® isis subject thetofirst multi-kinase inhibitor to offer ▼This medicinal product additionaloral monitoring. This will allow quick identification of new safety information. Healthcare professionals are asked to report any suspected adverse reactions. See section 4.8 of
References: 1. Grothey A, et al. Lancet. 2013;381(9863):303-12. 2. Demetri et al. GRID. Lancet 2012;381 (9863). 3. STIVARGA Summary of Product Characteristics, available at www.medicines.ie
the SPC for how to report adverse reactions. advanced mCRC patients improved overall survival after other Stivarga 40mg film-coated tablets (Regorafenib). failed, regardless of containing K-RAS status Please refertherapies to full SmPC beforehave prescribing. Presentation: Film-coated tablet 40mg of regorafenib. Indication: Treatment of adult patients with 1. metastatic colorectal cancer (CRC) who have been previously treated with, or are not considered candidates for, availablein therapies. These include fluoropyrimidine based chemotherapy, an anti VEGF therapy and an anti EGFR therapy; 2. unresectable or metastatic gastrointestinal progression free survival unresectable GIST patients stromal tumors (GIST) who progressed on or are intolerant to prior treatment with imatinib and sunitinib. Dosage and Administration: Adults: Treatment should be prescribed by physicians experienced in the administration after progression on two prior TKI’s of anticancer therapy. The recommended dose is 160 mg (4 tablets of 40 mg) taken once daily with water after a light meal that contains less than 30% fat for 3 weeks followed by 1 week off therapy. This 4 week period is tolerable adverse event profile was shown to maintain considered aatreatment cycle. Treatment should continue as long as clinical and benefit is observed or until unacceptable toxicity occurs. Dose interruptions and/or dose reductions may be required based on individual safety and tolerability. Dose modifications are to be applied in 40compared mg (one tablet) steps. The lowest recommended daily dose is 80 mg. The maximum daily dose is 160 mg. Hepatic impairment: No dose adjustment is required in patients patient quality of life with best supportive care with mild hepatic impairment. Close monitoring of overall safety is recommended in patients with hepatic impairment. Renal impairment: No dose adjustment is required in patients with mild or moderate renal impairment. a convenient oral, single agent, once daily dosing Contraindications: Hypersensitivity to the active substance or any of the excipients. Warnings and Precautions: It is recommended to perform liver function tests before initiation of treatment and monitor closely (at least every 2 weeks) during the first 2 months of treatment. Thereafter, periodic monitoring should be continued at least monthly and as clinically indicated. Mild, indirect (unconjugated) hyperbilirubinaemia may occur in patients with Gilbert’s syndrome. Stivarga is not recommended for use in patients with severe hepatic impairment (Child-Pugh C). Blood counts and coagulation parameters should be monitored in patients with conditions predisposing bleeding, and in those with anticoagulants or other facculpa concomitantque medicinal products that increase the riskdolorem of bleeding.quam Permanent discontinuation should be considered the event of is severe odi venimintur sandi doles ipsam, in accate ea modit ped m Magnatus eos sintonum esequas qui treated similit harciet voluptiassit venecep udamus preptaInipsam, solore, imi, vendemo digendu ciaest, ut veleseq uiatio mo rem remoloria voluptaquam etmonitored laut aboritat. et is ex evel bleeding. eatur Patientssitatenis with a historyet of ommodit ischaemic heart disease should be for clinicalXerum signs andas symptoms of myocardial ischaemia. patients who develop cardiac ischaemia and/or infarction, interruption of Stivarga pelecer feruntem quias alitem ut explaut mos vel est, nam int iusa dolorum molorro quo te pliquissi aut demolupta dolo occupta incti ut eveliquation rehenec totaquiam is recommended until resolution. Thequid decision to restart Stivarga therapyesequo should be coriasp based on careful consideration of the potential benefits/risks of treatment for the individual patient. Stivarga should be permanently nonsendi offictur am nimpores postia doluptatio everum quae non recep hil eicipide pra sitis asimagnia ped que ex esequissecus ercium nus et que aspernam sam venet ent occus and autsupportive volor asmedical perspidunt magnat et eat quatatem ressiminci nonsed ut utent ea des sit labo. Ni tem ut aut et inusamsyndrome ide et (PRES), velluptas discontinued if there is no resolution. In patients developing posterior reversible encephalopathy discontinuation of Stivarga, alonghicilit with control of hypertension management of rem volenecuptas audipis ad mo cus remporecae la et mint. Adis event liqu enducil liscideste cus, to debist molo dolores eos dolorio. Nequis aliti toribus quam simaxim other symptoms is recommended. Discontinuation Stivarga is recommended in patients developing perforationpereiumquo or fistulae. Bloodeveliqu pressure should be controlled prioraut to initiation and during treatment andpla corum asitaquos eos mi, quo debit volorporeste quam dolest, sundigenim iducium doluptatofeum restes ducidestist, sam quat.gastrointestinal Iquo explign rat idiciet inctas ut offictem. Itasperi voluptatat aut fuga. Eleniet itatem resequis erferi to ad utat ulpa perferu mquatec ad ea qui ut alibus, quodi andant. it is recommended treat hypertension. In cases of severe ortatisqui persistentni hypertension despite adequate medical management, treatment should be temporarily interrupted and/or the dose reduced.ipsandis In case of hypertensive culluptistia iducimus et di doluptaturia est acesti corrovitas sunt lacepedis Iqui sum, eturibus ene reperia eaquos asimaio. Volupta ad quis explis accum quatem repra sitas Stivarga should be discontinued. For patients undergoing major surgical procedures it is recommended to interrupt treatment temporarily for precautionary reasons, and to resume apit, treatment based onmo clinical latenimpos es eius ipsuntia vel is reicatiamus sunturest esene prer reriaes acrisis, simaion sequos simincte et eum imporum re lauda que sime officium ium experum as moluptate num autrelief. voluptatest reped eum inciam con coriandel m rerum intur, soloreh enderib nihil of magnam, volum suntem voluptus et aut judgment of adequate woundeatempore healing. Management hand-foot skin reaction (HFSR) may include thevidignis use of keratolytic creams and moisturizingexperepe creams for symptomatic Dose reduction and/or temporary interruption, eum utassi bea sumet.Occaepera velis etus verferiae. Itasimpora conet an aceatem volut asimus. At hicae. Ita dolupicat. Aximusc illupid modipsum vel ipsam fuga. Lorepta or, in severe or persistent cases, permanent discontinuation of Stivarga should be considered. It is recommended to monitor biochemical and metabolic parameters during treatment and to institute replacement therapy if net, comnistio blaccum sunt ma prate volum quiatet, si consecabo. Ga. Ro tquodis aceruptam qui accum inis minus sunderum as venda pratem alist, volut aut ventem required. Dose interruptions or reduction, velia or permanent discontinuation be considered in case of vel persistent or recurrent significant abnormalities. In clinical trials, a higher est incidence of HFSR, liver function test doluptatist, omnis veliqui beriam es ut quesevere eresto dolupti ut excepre audae. Nam, que volum laut magnam nis aut labore et should id quam seruntur? Qui maximus ut aut aut EtEach laborum ndebitat.Solest ipsam soloreic to apis ut eaquis dem Minctius sim rehenia ea Japanese) verspiepatients ndictus magni abnormalities andsectiatur? hepatic dysfunction was observed in Asian (incum particular treated with Stivarga compared withautem. Caucasians. daily doseenitate of 160 mg contains 2.427 mmol (orqui 55.8dolupisi mg) of sodium and 1.68 dolorerita sundictore, cus, ut qui sit rehende llautem expellectum fugiae dicium accustin provit Iliquiae natiistrum reperat ustemod quuntur atius volenis exeriae neceptu mg of lecithin from soya). Very common: anaemia, and food intake, headache, haemorrhage*, hypertension, dysphonia, diarrhoea, stomatitis, aut etu labo. Ulparum rem(derived aut eum fuga.Undesirable Ut aliteseffects: aria volorem nosinfection, autet thrombocytopenia, volorib usandistio ea decreased sundae appetite quibusdam fugitati velit omnihilla cus esciaerum none vel magnimet vomiting, nausea, hyperbilirubinaemia, HFSR, rash, alopecia, asthenia/fatigue, pain, fever, mucosal inflammation, weight loss. Common: leucopenia, hypothyroidism, hypokalaemia, hypophosphataemia, hypocalcaemia, hyponatraemia, hypomagnesaemia, hyperuricaemia, tremor, taste disorders, dry mouth, gastro-oesophageal reflux, gastroenteritis, increase in transaminases, dry skin, exfoliative rash, musculoskeletal stiffness, proteinuria, increase in amylase, increase in lipase, abnormal INR. Uncommon: hypersensitivity reaction, myocardial infarction, myocardial ischaemia, hypertensive crisis, gastrointestinal perforation*, gastrointestinal fistula, severe liver injury*, nail disorder, erythema multiforme. Rare: keratoacanthoma/squamous cell carcinoma of the skin, PRES, Stevens-Johnson syndrome, toxic epidermal necrolysis.*fatal cases have been reported. Prescription only. Marketing Authorisation Holder: Bayer Pharma AG, D-13342 Berlin, Germany. MA number(s): EU/1/13/858/002. Further information available from: Bayer Ltd., The Atrium, Blackthorn Road, Dublin 18. Tel: 01 2999313. Date of Preparation: October 2015.
HPN May 2016 Issue 27
Research highlights role of polypharmacy in older adults P4
Colonscopy wait times not acceptable P8
Ireland’s new Minister for Health has a large schedule of priorities on his plate as he begins his tenure, not least of which the Irish Medical Organisation says is substantial proposals for the health services.
Kelly Jo Eastwood
HPAI Annual Conference calls for additional funding P11 Patient blood management symposia clinical round-up P16 Self-harm presentations in Emergency Departments P24
Dr Duddy said, “Minister Varadkar shouldn’t wait for Fianna Fail to force his hand on investment in health services. If he believes this investment is necessary, and it clearly is, then he can prioritise it himself and ensure that it forms a key part of any Programme for Government.”
In other news, Ireland has a critical shortage of consultant dermatologists at a time when cases of skin cancer are increasing and early detection can be key to saving lives, according to the Irish Skin Foundation.
Hospital Professional Awards 2016 P32 Regulars CPD: Melanoma P27
Event Gallery P52 24
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imi, corionserit que m, int labore isquam pelis dolorer uptatat tur reruntiatio ipsam ue nis nihita ditaece m faccum, simagnim t explaudit, commolo s pe excest qui quam rum idus, ni bera quo minciusciet re con no ndis quas evenia pa ovitat vent aditatusa e icaborro optios ut otat hil idundebitio. us, ne officiam et aut ur.
MANAGING DIRECTOR Natalie Maginnis firstname.lastname@example.org EDITOR Kelly Jo Eastwood email@example.com 00447876548989 ACCOUNTS Jennifer Dunseath firstname.lastname@example.org
On its own, the increasing instance of skin cancer threatens to overwhelm dermatology services. However, the systemic shortage also affects thousands of people with psoriasis, eczema and other difficult skin conditions requiring hospital care. In recent years demand has outstripped capacity in hospital dermatology clinics. At the same time, the HSE has not provided sustained resources for additional posts or investment in clinic infrastructure and development. With small numbers of specialist registrars in training and challenging working conditions, locum and permanent posts in dermatology services are not easily filled.
Feature: Chronic Obstructive Pulmonary Disease P48
Clinical R&D P54
Dr John Duddy was responding to comments by the Minister for Health, Leo Varadkar at the end of last month (April) in which he expressed surprise that Fianna Fail had prioritised the issue of water over demands for a multi-billion investment programme for the health services.
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“We need at least one dermatologist per 62,500 people to provide an effective service” says David McMahon, Head of Advocacy with the Irish Skin Foundation. “Dermatology clinics lack spare capacity; there is little or no room to cope with predictable eventualities such as illness and maternity leave.” Elsewhere this issue also sees the continuation in our launch of the Hospital Professional Awards for 2016. On page 32 onwards, you can read about the exciting 12 Award Categories that are up for grabs this year, the entry criteria and how to submit your entry form. The annual Hospital Pharmacy Awards will be held in the Hilton DoubleTree Hotel, Dublin on the 17th of September 2016 and we are expecting more than 400 of the country’s leading hospital professionals, including pharmacists and consultants alongside industry representatives who will gather to recognise those demonstrating dedication to their profession. Turn to page 32 for all the details or visit our website at www.pharmacynewsireland.com
HOSPITAL PROFESSIONAL NEWS IRELAND Ireland’s Dedicated Hospital Professional Publication HPN • May 2016
Has the HSE plundered mental health budget? During Dáil statements on mental health services, Fianna Fáil's health spokesperson Billy Kelleher has said that mental health funding would be "raided" again this year, as they have been raided in previous years. Mr Kelleher said the HSE plan for the mental health service was short on detail and resourcing and stressed the urgency regarding mental health services for adolescents. He added that people were suffering in silence or in some cases, in "a public way".
Minister for Health Leo Varadkar said that since 2012 the Government has provided additional funding for mental health. He said the spend in this area in 2012 was ¤711m and today it is ¤827m and that since last year it was increased by 6.7%. Meanwhile, the Department of Health has not yet released any of the ¤35 million in development funding for mental health to the HSE which was supposed to be ring-fenced in Budget 2016, it has emerged.
Speaking on the Claire Byrne Live Show on RTE, the National Director for Mental Health Services in the HSE, Ms Anne O’ Connor explained that the ¤35 million in additional development funding was to recruit staff and develop new services. However she stated “that funding actually sits with the Department of Health at the moment. So it hasn’t come to me, or come to the HSE.”
the delay in releasing these funds as “extremely worrying”. “Not only has mental health funding had its budget reduced in 2016 by ¤12 million, it has not even received the reduced pot of funding after almost four months into the year. This completely avoidable delay in releasing funds means that the development of new services will also be delayed,” Dr McDaid said.
The Director of Mental Health Reform Dr Shari McDaid described
Polypharmacy commonplace says latest research Professor Mary McCarron,TCD
New findings from Trinity College Dublin’s IDS-TILDA study highlights that polypharmacy is commonplace among older adults with intellectual disabilities. The team’s research discovered that people with intellectual disabilities are likely to be exposed to multiple medicines (polypharmacy) to treat a multiple chronic conditions – 20% of participants used 10 or
more medicines; over 30% used between five and nine. The research also showed that while polypharmacy, when used appropriately, plays a critical role in maintaining health, there is clear evidence that it is also associated with increased prescribing errors, and a higher prevalence of drug related adverse effects as more drugs are prescribed
These latest findings are drawn from Wave 1 of IDS-TILDA, a nationally representative longitudinal study of older adults with intellectual disability by researchers from Trinity College Dublin. Professor Mary McCarron, the Principal Investigator for IDSTILDA and Dean of the Faculty of Health Sciences noted, “This
is the first time there has been a comprehensive review of medicines use in people with intellectual disabilities, and particularly older people with intellectual disabilities in Ireland.” Lead author and Assistant Professor in the School of Pharmacy and Pharmaceutical Sciences Dr Máire O’Dwyer commented, “Our findings highlight that polypharmacy is commonplace for older adults with intellectual disabilities in Ireland, reflecting the high prevalence of multiple chronic conditions experienced by people with intellectual disabilities. Comprehensive, regular reviews of medicines use are essential, given that polypharmacy may place older adults with intellectual disabilities at risk of side effects.” Initiatives to address these polypharmacy concerns will also likely benefit all older people especially those with cognitive impairment.
Welcome news on New Children’s Hospital The Dublin Midlands Hospital Group has welcomed the granting of planning permission for the New Children’s Hospital on the campus of St James Hospital. Dr Susan O’Reilly, CEO of the Hospital Group said the news marks a significant step for the Children’s Hospital and for management and staff. “We are delighted for all those who championed the development of the new children’s hospital on the campus of St James, including our chairman Mr Frank Dolphin. The future is most definitely bright for the children of Ireland. “The group fully endorses this development and looks forward to continuing our work with Eilish Hardiman, CEO of Children’s Hospital Group to support the development of effective clinical care pathways so our children can be treated in the most appropriate setting at the right time and by the right people. “In addition, we welcome the Ministers commitment to develop the new Coombe Women and Infants University Hospital on the campus which will provide for the provision of tri-located adult, maternity and paediatric services. This development will strengthen the model of care we can provide for women and children in our Hospital Group.”
May 2016 • HPN
Latest proposals to ease health pressure The Private Hospitals Association (PHA),formerly the Independent Hospitals Association of Ireland, has published 6 proposals which it believes will bring significant, positive, outcomes for patients, support the public health system and ease some of the pressures it is facing in the coming years. Every year, the association of 19 hospitals providing acute medical and mental health services, makes over 1 million bed nights available, treats 400,000 patients, carries out over 250,000 procedures and completes 3 million diagnostic tests. PHA members undertake around 50% of all heart surgeries and 65% of all spinal surgeries carried out every year and provide one in ten inpatient psychiatric beds in Ireland. The Association’s steps which they say the incoming Minister for Health must address are:
1. Design a joint public and private sector initiative to tackle waiting lists for both inpatient and outpatient treatments including a focus on diagnostics; 2. Move patients more quickly through Emergency Departments by using all available beds in both the public and private sectors; 3. Address the gaps delaying patient treatment by launching a coordinated approach to attracting consultants and other health professionals to work in Ireland; 4. Introduce a new competitive system for commissioning hospital care by 2018; 5. Co-ordinate planned investment in medical facilities and equipment to avoid duplication, get value and create efficiencies;
6. Establish a task force to boost co-operation between public and private healthcare systems. Recently appointed PHA CEO, Simon Nugent said, “We must focus on three things: Patients, Planning and Partnership. If we all plan together, there is great scope for private hospitals to help the Minister for Health and the HSE tackle the challenges they are facing. Our members can help in the treatment of many waiting-list patients but we can only make a significant impact if we work in close partnership with the public hospitals system.” Taking, as a case study, recent media coverage about patients facing long delays for diagnostic tests he added, “No patient should need to wait longer than three months for an MRI or an endoscopy. We have the equipment. We have the skilled
staff. We should just make a plan and clear that backlog.” The PHA’s proposals have a twin focus – to help tackle the increasing waiting lists in the short term and to address some of the underlying longer term challenges in the health system. “The new Government will want to deliver effective, good quality services for all patients. While the quality of care delivered is relevant, the location or provider should not be. The PHA’s suggested approach will deliver better patient outcomes, and these should be the incoming Minister’s priority,” Nugent concluded.
Health non priority status a disgrace, says IMO The President of the Irish Medical Organisation (IMO) has called on the parties negotiating a new Programme for Government to develop meaningful, substantial proposals for the health services before any agreement is reached on the formation of a new Government. Dr John Duddy was responding to comments by the Minister for Health, Leo Varadkar at the end of last month (April) in which he expressed surprise that Fianna Fail had prioritised the issue of water
over demands for a multi-billion investment programme for the health services. Dr Duddy said, “Minister Varadkar shouldn’t wait for Fianna Fail to force his hand on investment in health services. If he believes this investment is necessary, and it clearly is, then he can prioritise it himself and ensure that it forms a key part of any Programme for Government.” He added that the mantra for the new Government on health should be:
Invest Increase Improve Dr Duddy said it is nothing short of a national disgrace that our public health services were not the priority issue for talks on a new Government and instead, true to form, politicians focused on their own self-interest. He said that the new Government will have to find significant additional money for the health services or face further
deterioration in the form of reduced services, increased waiting lists and inadequate GP services. “The current budget is simply insufficient even to maintain services at current levels. We need a commitment to provide significant additional funds for the health services. We need to commit now to urgent action to improve patient experiences and health outcomes,” he added.
Biobank established in RCSI Brain Tumour Ireland is supported RCSI (Royal College of Surgeons in Ireland) in the establishment of its brain tumour biobank, which will encourage research aimed at individualised treatments and increasing survival rates for brain tumour patients. Facilitated by the Departments of Neurosurgery and Neuropathology in Beaumont Hospital, every patient undergoing brain tumour surgery will be given the opportunity to consent to have their tissue included in the biobank.
By collecting brain tumour cells from patients, the biobank will enable new and targeted therapies for brain tumours to be examined in the lab using these cells. Only patients who consent, can have their tissue used in the biobank, and only tissue surplus to diagnostic requirements can be biobanked. Speaking on behalf of Brain Tumour Ireland, Chairperson Natasha Roche said, “Brain Tumour Ireland is extremely pleased to be supporting this important biobank with such
a prestigious educational and research institution as RCSI.
for those diagnosed with a brain tumour.”
“This achievement is only made possible by the many kind donors who have raised money for us over the first three years of our existence, and we thank them most gratefully.
Professor Jochen Prehn, Director of the RCSI Centre for Systems Medicine and Science Foundation Ireland Investigator, added, “We are very excited about this instrumental support provided by Brain Tumour Ireland. The biobank will enable us to analyse the molecular composition (or ‘building stones’) of brain tumours, and to use this knowledge to develop much needed, novel therapies for the treatment of brain tumours.”
“It is our hope that the research supported by this biobank will lead the way for new and targeted therapies for brain tumours, and individualised treatments for patients. This is crucial in achieving increased survival rates
HPN • May 2016
Facing the demand with allergic rhinitis when they eat certain foods, especially fruit and vegetables, during the pollen season. This is due to cross sensitivity of food proteins and some pollens.
Pollen driven allergic rhinitis (hay fever) will affect close to 21 million in Ireland and the UK this summer (24% of that population). That’s a significant demand on pharmacy and allied healthcare professionals’ time. 85% of hay fever sufferers self-medicate leaving 15% so blighted they’ll seek more insightful advice. Unfortunately many GPs and allied doctors consider allergic rhinitis no more than a poorly understand nuisance. Offering advice that’s a variation of what’s already been tried is less than helpful.
If even 50% of these symptoms occur hay-fever sufferers feel exhausted and drained of all energy.
Here are the main symptoms of allergic rhinitis (AR).
• Allergic rhinitis may cause nose/ sinus symptoms only.
Blocked nose: from nasal turbinate swelling.
• Allergic rhinitis may provoke asthma.
Sneezing: from nasal mucosal irritability.
• Allergic rhinitis in children with asthma causes more asthmarelated hospital admissions and greater total days spent in hospital
Runny nose: the irritable nasal lining secretes mucus. Sinus pain/congestion: from sinus ostia obstruction related to swollen nasal mucosa. Cough, wheeze and shortness of breath: nose/ sinus inflammation also irritates the lungs. Eyes redden, itch, water and swell: pollen conjunctivitis is a real irritant but in severe hayfever, especially with children, the inner surface of the upper lids distort with what look like ‘cobble-stone’ bumps. Itchy mouth and throat or oral-allergy syndrome. Some hay fever sufferers experience itch and swelling along the inside of the mouth, lips and tongue
Hay fever and asthma Aggressive hay-fever causes both upper and lower airway inflammation with a pathway as illustrated:
Treatments There are five medical compounds which, when used correctly, give relief from AR. (1) Anti-histamines ‘mop-up’ excess histamine circulating in the blood stream during allergy attacks. (2) Leukotrienes cause long term swelling within the nose and sinuses. Anti-leukotrienes reverse this. (3) Steroid or cortisone compounds (eye and nose drops, nasal sprays, and tablets) reverse allergic swelling and irritation that occur in the nose, sinuses, eyes and lungs.
(4) Sodium cromoglycate eye drops. (5) Fast acting nasal decongestants. My advice: Never underestimate the misery hay fever sufferers’ experience. Assume the patient/customer has an array of self-help products so ask: “have you tried anything before you came in here?” Assume your patient/customer’s nose is so blocked that any OTC spray will not reach its target. Advise using short term nasal decongestant (Otrivine) before using any steroid nasal spray. Warn about overuse/prolonged use of Otrivine.
Push the dose of antihistamine to maximum allowed during high pollen days. Ask about reduced sense of taste and smell and exhaustion: if your customer sniffs a wet ‘yes’ to these queries they need an antileukotriene as well as steroid nasal drops. Better involve their GP. Dr Paul Carson has been dealing with allergy problems for 30+ years. He’s the author of seven popular health books including Hay Fever, how to beat it (Sheldon Press UK). He’s the medical advisor on the Hay Fever Relief app (www.hayfever-relief.com), available to download free from April 5th.
Critical shortage of Dermatologists Ireland has a critical shortage of consultant dermatologists at a time when cases of skin cancer are increasing and early detection can be key to saving lives, according to the Irish Skin Foundation. On its own, the increasing instance of skin cancer threatens to overwhelm dermatology services. However, the systemic shortage also affects thousands of people with psoriasis, eczema and other difficult skin conditions requiring hospital care. In recent years demand has
May 2016 • HPN
outstripped capacity in hospital dermatology clinics. At the same time, the HSE has not provided sustained resources for additional posts or investment in clinic infrastructure and development. With small numbers of specialist registrars in training and challenging working conditions, locum and permanent posts in dermatology services are not easily filled. “We need at least one dermatologist per 62,500 people to provide an effective service” says David McMahon, Head of
Advocacy with the Irish Skin Foundation. “Dermatology clinics lack spare capacity; there is little or no room to cope with predictable eventualities such as illness and maternity leave.”
primarily by rising occurrence of skin cancer, increased diagnosis of other major skin diseases like psoriasis, greater complexity in treatment and the aging of our population.
“With year-on-year increases in referrals, policy makers must do more to address the issues affecting services or patients will experience even longer waiting times, delayed diagnosis and treatment.”
The ISF says that this is most worrying in situations where a patient has a suspected melanoma. “However, people with psoriasis, eczema, hidradenitis suppurativa (HS) and other skin diseases experience life-limiting effects, serious co-morbidities and also deserve timely access to dermatology services.”
Increasing demand for dermatology services is driven
fluticasone furoate Allergic rhinitis relief
Relieving the symptoms of allergic rhinitis1
The incidence of epistaxis during long term treatment was higher than 10% but was generally mild to moderate in intensity1
Prescribing Information (Please refer to the full Summary of Product Characteristics before prescribing) Avamys® Nasal Spray Suspension (ﬂuticasone furoate 27.5 micrograms/metered spray). Uses: Treatment of symptoms of allergic rhinitis in adults and children aged 6 years and over. Dosage and Administration: For intranasal use only. Adults and adolescents (12 years and older): Two sprays per nostril once daily (total daily dose, 110 micrograms). Once symptoms controlled, use maintenance dose of one spray per nostril once daily (total daily dose, 55 micrograms). Reduce to lowest dose at which effective control of symptoms is maintained. Children aged 6 to 11 years: One spray per nostril once daily (total daily dose, 55 micrograms). If patient is not adequately responding, increase daily dose to 110 micrograms (two sprays per nostril, once daily) and reduce back down to 55 micrograms daily dose once control is achieved. Contraindication: Hypersensitivity to active substance or excipients. Special warnings and precautions: Systemic effects of nasal corticosteroids may occur, particularly when prescribed at high doses for prolonged periods. These effects are much less likely to occur than with oral corticosteroids and may vary in individual patients and between different corticosteroid preparations. Potential systemic effects may include Cushing’s syndrome, Cushingoid features, adrenal suppression, growth retardation in children and adolescents, cataract, glaucoma and more rarely, a range of psychological or behavioural effects including psychomotor hyperactivity, sleep disorders, anxiety, depression or aggression (particularly in children). Treatment with higher than recommended doses of nasal corticosteroids may result in clinically signiﬁcant adrenal suppression. Consider additional systemic corticosteroid cover during periods of stress or elective surgery. Caution when prescribing concurrently with other corticosteroids. A reduction in growth velocity has been observed in children treated with ﬂuticasone
furoate 110 micrograms daily for one year. Therefore, children should be maintained on the lowest possible efﬁcacious dose which delivers adequate symptom control. It is recommended that growth of children receiving prolonged treatment with nasal corticosteroids is regularly monitored. Consider referring to a paediatric specialist. May cause irritation of the nasal mucosa. Nasal and inhaled corticosteroids may result in the development of glaucoma and/or cataracts. Close monitoring is warranted in patients with a change in vision or with a history of increased intraocular pressure, glaucoma and/or cataracts. Drug interactions: Caution is recommended when co-administering with potent CYP3A4 inhibitors e.g. ketoconazole and co-administration with ritonavir is not recommended because of the risk of increased systemic exposure of ﬂuticasone furoate. Pregnancy and Lactation: No adequate data available. Recommended nasal doses result in minimal systemic exposure. It is unknown if ﬂuticasone furoate nasal spray is excreted in breast milk. Only use if the expected beneﬁts to the mother outweigh the possible risks to the foetus or child. Side effects: Very common (≥1/10): epistaxis. Epistaxis was generally mild to moderate, with incidences in adults and adolescents higher in longerterm use (more than 6 weeks). Common (≥1/100 and <1/10): headache, nasal ulceration. Uncommon (≥1/1000 and <1/100): rhinalgia, nasal discomfort (including nasal burning, nasal irritation, and nasal soreness), nasal dryness. Rare (≥1/10,000 and <1/1000): hypersensitivity reactions including anaphylaxis, angioedema, rash, and urticaria. Not known: transient ocular changes, growth retardation. Very rare (<1/10,000): Nasal septum perforation. Marketing Authorisation (MA) Holder: Glaxo Group Ltd, 980 Great West Road, Brentford, Middlesex, UK TW8 9GS. MA Number: EU/1/07/434/003. Legal category: POM S1B. Last date of revision: January 2016 Job Ref: IE/FF/0002/16. Further information available on request from GlaxoSmithKline, 12 Riverwalk, Citywest Business Camp, Dublin 24. Tel: 01-4955000.
Avamys® is a registered trademark of the GlaxoSmithKline group of companies. © GlaxoSmithKline group of companies 2015.
Adverse events should be reported to the Health Products Regulatory Authority (HPRA) using an Adverse Reaction Report Form obtained either from the HPRA or electronically via the website at www.hpra.ie. Adverse reactions can also be reported to the HPRA by calling (01) 6764971. Adverse events should also be reported to GlaxoSmithKline on 1800 244 255. Reference: 1. Avamys Summary of Product Characteristics, available on www.medicines.ie, accessed 30 March 2016. IE/FF/0001/14a(1)a Date of preparation: March 2016
Not actual size
Colonscopy wait times at an all - time high The number of public patients waiting over three months for a colonoscopy - a procedure that is often used to detect bowel cancer - reached an all-time high at the end of March, the Irish Cancer Society (ICS) has highlighted. It is calling on political parties to commit to tackling this serious issue. The call comes as an immediate priority, after the number of public patients waiting over three months for the test, which is used to detect cancers, reached an all-time high of 4,343 at the end of March. Since the turn of the year, the number of public patients waiting more than three months for a colonoscopy has risen by almost 1,000 people. Private patients can get the test done within 12 days. The Irish Cancer Society says these figures highlight the health gap between those who can pay and those who cannot. Donal Buggy, Head of Services and Advocacy at the Irish Cancer Society says, “Colonoscopy waiting times have reached a critical point. This issue requires political intervention before it worsens.” Currently, 44% of patients are waiting longer than three months for the cancer test. At two hospitals, over 75% have been
waiting for longer than three months, and at a further two hospitals, this figure exceeds 60%. The Irish Cancer Society estimates that if waiting times continue to rise at the rate they have since the end of December, 7,187 people could be waiting more than three months for a colonoscopy by the end of this year. Mr Buggy added, “We acknowledge the efforts of the HSE in tackling waiting times, through external appointments at private facilities, but this only appears to have a short-term impact. An ambitious, long-term approach is needed to resolve the current situation, and we believe that political input is required to do so.” Towards the end of 2015, the HSE, through National Treatment Purchase Fund (NTPF), arranged appointments in private hospitals, for public patients listed as waiting over 12 months for colonoscopy procedures. This helped reduce waiting times over 12 months to 114 at the end of December. However, since then this number has almost quadrupled to 544. HSE Interventions Up until 2016, the HSE’s own target was that 100% of patients should have a colonoscopy performed within 13 weeks of referral by their GP. In their National Service Plan for
2016, this was revised downwards to 70%. Mr Buggy says, “No one should be waiting longer than three months for a colonoscopy. The stark reality is that we can expect some colorectal (bowel) cancers to be diagnosed when patients on waiting lists eventually receive their colonoscopy.” Additionally, the HSE has yet to implement HIQA guidelines on referral thresholds for patients with gastrointestinal symptoms, published in late 2014, which, according to Mr. Buggy, would “help ensure that the right patients receive referral and treatment at the right time”. “While we welcome actions such as the move to appoint a Clinical Lead to the National Endoscope Working Group, and we have seen some progress in the closer coordination of colonoscopy workloads within hospital groups, it is clear that colonoscopy waiting lists require a handson approach and we believe it is the responsibility of the next Government to co-ordinate this,” he added. “We realise that there is no onesize fits all solution to a problem that has been with us for years. Creative thinking is now needed to address it and we are willing to contribute to this discussion in whatever way possible”.
The Irish Cancer Society wants: Adequate investment so there are enough radiographers and gastroenterologists working in Irish hospitals; Investment in, and training of, additional Advanced Nurse Practitioners (ANPs) to enable them to perform colonoscopies safely and effectively; Continued and closer coordination of colonoscopy lists between hospitals working within the same hospital group, so that a situation where endoscopy suites in one hospital are under-utilised while a hospital in the same group is overburdened, is avoided;
GPs to have clear guidelines for when they should refer a patient for a colonoscopy and when another investigation is better suited.
No one should be waiting longer than three months for a colonscopy. The stark reality is that we can expect some colorectal cancers to be diagnosed when patients on waiting lists eventually receive their colonscopy
Practical Guide to Medical Negligence published negligence actions including many of the leading Irish medical negligence cases including the leading landmark case of Dunne v National Maternity Hospital (where he acted for the plaintiff). He has lectured extensively and has written numerous articles and book chapters.
A new book entitled A Practical Guide to Medical Negligence Litigation by Mr Michael Boylan has been officially launched. The publication provides a practical legal focus on the topic of medical negligence. The law relating to medical negligence has developed significantly over the past 30 years with in excess of 900 High Court actions commenced annually seeking damages for medical or clinical negligence. However, this significantly underrepresents the level of clinical/medical accidents and errors which occur annually. Over the past 30 years Mr Boylan has specialised in the area of medical negligence and has been involved in hundreds of medical May 2016 • HPN
Mr Michael Boylan, Author
The Hon Mr Justice Liam McKechnie, Judge of the Supreme Court, described the new book as a “dynamic mix of the practical and the substantive, with the discursive treatment of the legal principles being at the highest insightful level. The author engages with the big issues reflecting current law and practice, but challenges in the process a number of the underlying principles.”
A Practical Guide to Medical Negligence Litigation covers the lifetime of a High Court medical negligence action from first contact with a client through to plenary hearing, settlement and mediation including inquests. This practical guide to procedural steps that must be taken cites all relevant case law and statutes including the Rules of the Superior Courts, the Civil Liability and Courts Acts 2004, the various statutory instruments and Coroners Act.
Wearing Two Crowns – in Medicine and Politics Professor John Crown
Known throughout Ireland as an outspoken Senator and a renowned Consultant Oncologist, Professor John Crown doesn’t hold back when it comes to criticising pillars of establishment or fighting fires for patient rights. From the Healthcare Products Regulatory Authority to former Health Minister, no one ior body has been left untouched. “I’ve made no secret of the fact that I think we have very bad oncology services in this country,” he says. “It is a shame that the Department of Health have had to be cajoled, humiliated and bullied in public into doing something about it. The disastrous health service we’ve had over the past ten to twenty years reflected a complete lack of planning on the part of the Department. It wasn’t until certain people started to make very public criticisms of the state of the cancer service that they were shamed into doing something about it. I think it’s an awful pity
that that’s the way the public discourse has to work in a democracy.” Dr John Crown eschews the popular opinion in favour of the truth, however unpalatable it might be. To the undoubted chagrin of those who manage it, he’s forever shaking things up, rattling cages, exposing the chinks and cracks in our health system. It’s a wonder, though, that he finds the time to be anything other than exhausted. In addition to his responsibilities at St. Vincent’s and DCU, he’s a founding member and leader of the Irish Clinical Oncology Research Group (ICOR); the Anglo-Celtic Oncology Group; the European Breast Cancer Dose Intensity Study; and the Irish Society of Medical Oncology. He’s also a member of the American Society of Clinical Oncology; the American Association for Cancer Research; the New York Metropolitan Breast Cancer Group; and the European Society of Medical Oncology
(ESMO). He is chair of the Breast Committee of the Irish Clinical Oncology Research Group (ICORG), and several years ago became the first Irish oncologist to be awarded a merit award from ESMO for his work in breast cancer research.
more than 14,200 cancer patients. With continued support and perseverance these figures are increasing all the time.
ICORG was set up in 1996 by Professor Crown and a group of cancer Consultants. The aim was to create more research opportunities for patients by putting a formal structure in place to make Ireland more attractive as a location to international cancer research groups and the pharmaceutical industry.
ICORG has also developed strong links with many leading international cancer research groups such as the ECOG-ACRIN, NRG, TRIO, UNC Cancer Network and CRUK and those in industry developing the most promising new cancer treatments. As a result of these positive relationships Irish patients are now being offered cutting edge research options that previously would only have been available in the United States and Europe.
In 2000 the group expanded its membership to include Northern Ireland. Today it counts more than 95% of the Islands cancer treating consultants among its membership ensuring that research into cancer develops at a national level across all localities. Since its incorporation, ICORG has opened 340 research protocols and this has allowed access to research treatments for
Turning back to the war on cancer, Professor Crown comments, “I think we have a different understanding of the nature of the war against cancer. Throughout the 1950s and 1960s, and even up until the 1970s, there was an expectation that we would have a Eureka! moment when we cured cancer on the basis of some magic bullet treatment. If we could put a man on the moon, there was HPN • May 2016
10 Profile Ireland had about one quarter the number of medial oncologists that it should have per head of population, and this was not unusual for specialties in Ireland. Twenty-five of the 35 Irish medical oncologists trained in the top five American cancer centres, there is no county in the world can say that a feeling that if we set a single task to science – any task – it could be done within a certain amount of time. We probably exercised a certain amount of hubris in the face of nature in terms of the task we were setting out to do. Cancer is a very complex illness, and the focus of the war on cancer has changed. “I think now there’s an appreciation that what is going to happen with some cancers is that they may be transformed into chronic illnesses. This means that people will live with them for a long – and hopefully an increasingly long period of time – without necessarily being cured. It may be a pipe-dream, but I believe we will see that happening more and more with cancer.” Professor Crown received his medical training at the University College Dublin and the State University of New York. After his internship and internal medicine training, he completed postdoctoral training on both sides of the Atlantic, including registrars in Gastroenterology and General Medicine at Guy's Hospital in London and in haematology at St James's Hospital in Dublin. He completed his fellowship training in oncology at Mount Sinai Medical Center and in haematology/oncology at Memorial Sloan Kettering Cancer Center, both in New York. Professor Crown also served as assistant professor at Cornell University Medical College before joining St Vincent's in 1993. In November 2003 he was awarded the Thomas Baldwin Research Chair in Translational Cancer Research from Dublin City University. He continues, “When I came home to Ireland, I was the fourth oncologist in the country. I was often in the elevator at Memorial Sloan Kettering in New York with May 2016 • HPN
more Irish oncologists than there were in Ireland. “Ireland had about one-quarter the number of medical oncologists that it should have per head of population, and this was not unusual for specialties in Ireland. Twenty-five of the 35 Irish medical oncologists trained in the top five American cancer centres,” he adds. “There is no country in the world — including America — that can say that. “For many years nearly all of Ireland’s senior specialists had trained in top centres abroad. It is a uniquely Irish phenomenon.” The defining reality when Professor Crown qualified was an absolute shortage of jobs. When he returned to Ireland in 1993, he was the first appointment for 10 years in his specialty. He also founded the Clinical Trials Unit at St Vincent’s University Hospital, which has developed an international leadership role in oncology trials, and 11,000 women around the world have now been enrolled on six randomised trials which were Chaired or Co-Chaired by Professor Crown.
from clinical observations and also designs and implements clinical research based on laboratoryderived hypotheses.
speech five years ago, I said I would not run again — unless they reformed the Seanad. They did not do that,” he says.
As previously mentioned, Professor Crown is also an outspoken senator with a passion for health service reform. He became a vocal critic of the health policy of the Irish Government led by Bertie Ahern and his successor Brian Cowen, and of the Minister for Health Mary Harney.
“I have stated very plainly that the way the Seanad is elected is an affront to democracy. Perhaps unusually — for a politician — I said I would do something and I am doing it. Thus, I will not run in 2016.”
In November 2007 he was involved in a controversy with the state broadcaster RTÉ when he was unexpectedly dropped from a discussion panel on The Late Late Show. The broadcaster denied that pressure had been applied by the government, but the decision was attacked by opposition politicians as "censorship and a denial of free speech". In March 2011 Crown announced that he would be standing for election to Seanad Éireann on the National University of Ireland (NUI) Panel. He stood as a non-party candidate, and if elected pledged to give his senator's salary to cancer research. In his regular column in the Sunday Independent, Crown expressed hope that James Reilly, Health Minister in the new government elected in February 2011 would reform the health services. Offering the electorate what he called "fresh thinking, new abilities, and a different perspective" he was elected on the 24th and final count of the NUI Panel. Since election to the Seanad Professor Crown has brought three bills before the house, The Reporting of Lobbying in Criminal Legal Cases Bill 2011, the Protection of Children's Health from Tobacco Smoke Bill 2012, and the Seanad Electoral Reform Bill 2013.
In recent years, he has developed an inter-institutional programme of bi-directional translational breast cancer research in collaboration with Professor Martin Clynes (NICB), Professor Joe Duffy and Dr Susan Kennedy (SVUH/UCD), and Professor Dennis Slamon, (UCLA).
The Reporting of Lobbying in Criminal Legal Cases Bill in legal cases was rejected by the government.
He was awarded a Health Research Board (HRB) Clinician Scientist Award in 2007, which provides protected time for research.
According to Crown, the Opus Dei prelature is mobilising within the Irish professions to influence efforts at Irish abortion law legalisation.
As a result Professor Crown now has an increasing involvement at the clinical-laboratory research interface, where he provides direction for laboratory research which addresses questions arising
He announced this year that is not seeking re-election to the Seanad due to the lack of reform of the upper House of the Oireachtas.
The protection of Children's Health from tobacco smoke Bill 2012 was accepted by the government.
“When I made my acceptance
More recently he has stated that Ireland’s health service needs to critically move forward. “Ireland’s health service has, unfortunately over the last 30 years not moved on enough, preferring rather to stand still,” he says. “Figures have recently emerged that show we have an 11,000% increase in the number of people on waiting lists for inpatient or day-care treatment for more than 18 months and some 13,000 individuals have been waiting more than 18 months for an outpatient appointment. I was in the Accident and Emergency Department in St. Vincent’s University Hospital on several occasions recently. It was jam packed with trolleys throughout all the corridors. We have had an increasing focus in the past few days on the emigration of medical personnel. “I emigrated in 1985. Thankfully, I came back. Two thirds of my classmates in medical school emigrated and most of them did not come back. Figures released also show that, in addition to being the largest exporter of doctors in the world, Ireland is also the largest importer of doctors. At the same time, we have the highest number of medical schools per head of population. “What I can say is we need to have either a debate in the House or perhaps a public consultation forum on the issue of medical manpower and the structure of medical careers. The only way we can get to grips with this 30 or 50-year festering problem is to recognise that we churn out large numbers of Irish doctors who then expect to find an adequate number of training positions as junior doctors, but, in many cases, as they are not available, they leave. On the other hand, we have a health bureaucracy that wants them to stay here, not because it wants to train them but because it wants them to continue as cheap labour as opposed to appointing them to appropriate career level positions. There is an urgent need for us to tackle these issues.”
HPAI Conference 11
Additional funding for hospital pharmacy IT systems needs to be made available – Hospital Pharmacists Association of Ireland Conference hears about promising IT developments in hospital pharmacies, but more investment required
Moninne Howlett, Our Lady's Hospital for sick children, crumlin
Hospital pharmacists are calling for urgent investment to be made into the State’s healthcare IT infrastructure, stating that the current pharmacy systems are not fit for purpose. The Hospital Pharmacists Association of Ireland (HPAI) Annual Conference, which was held in the Crowne Plaza Hotel, Santry, Dublin from April 8 to 10, heard presentations on a number of exciting and pioneering IT projects established in hospital pharmacies across the country. These included: the introduction of robots used for the storage and retrieval of medicines; the impact of electronic prescribing on the quality and safety of chemotherapy prescribing in oncology and a national solution for paediatric standardised concentration infusions. HPAI President and Chief Pharmacist in Cork University Hospital Ms Deirdre Lynch said that although there are many examples of high quality IT initiatives in hospital pharmacies by pharmacists, overall the sector
requires a major automation and technology upgrade due to years of under-investment. “We welcome the innovations that have occurred in recent years,” according to Ms Lynch. “But the hospital pharmacy IT sector has suffered years of under-investment. We are calling for investment to be made into hospital pharmacy IT and robotics as the current structure lags far behind even the most basic pharmacy systems in other countries. Additional funding is extremely important in order to improve the quality of patient care in our hospitals and we urge healthcare leaders and managers to make Hospital Pharmacy IT infrastructure a priority in IT strategy” A 2012 Pharmaceutical Society of Ireland hospital pharmacy baseline report highlighted the poor standard of IT systems in hospital pharmacies, and a recent survey conducted by the European Association of Hospital Pharmacists found no improvement from the PSI 2012
findings and that the technological infrastructure in hospital pharmacies in Ireland lags behind European counterparts such as the UK and the Netherlands. In spite of the present IT systemic problems, Ms Lynch said that the HSE’s IT strategy, eHealth Ireland, which is spearheaded by the Executive’s Chief Information Officer, Mr Richard Corbridge, offers hope for the future. Mr Corbridge delivered the conference’s keynote address on the progress of the implementation of the strategy to date, including the establishment of a national electronic health record. “An electronic health record across the hospital sector is essential,” according to Mr Corbridge. “We are trying to deliver integrated care across the hospital system. At this moment in time we have silos of paper and silos of older systems that don’t communicate with each other. We need to get to the point where the information is held in a single place and we can link medication
records to that and communicate the information to GPs. That is what we are trying to do. If we are successful, we will save money and we will save lives. Additional investment in technology in health is required in all areas. Capital and revenue extensions will be required to modernise the healthcare system and the eHealth Ireland team are working closely with the Department of Health to ensure that the right funding models can be put in place for this in the future.” Mr Corbridge said he was impressed by the quality of presentations delivered during the conference, which showed that innovative IT projects were taking place in hospital pharmacies across the country. E-pharmacy forms a central component of the overall health IT strategy. One presentation focused on the introduction of two robots to the pharmacy department of the Mater Misericordiae University Hospital (MMUH) to help with the storage and retrieval of medicines. HPN • May 2016
12 HPAI Conference
Dearbhla Murphy, Mater Hospital
The introduction of the robots has not only led to process improvements in the dispensary, but also to a much more efficient daily workflow system, while improving stock control and optimising the space required to store medications.
Conference delegates also heard about how a national neonatal standardised concentration infusion drug library has been developed with a phased roll out across neonatal intensive care units and the National Neonatal Transport Team planned to commence in 2016.
Another presentation showed how the introduction of the electronic software system CATOÂŽ in the Mater Hospital for chemotherapy prescribing, compounding and administration has significantly reduced prescribing errors and omissions.
The move is a positive development given implementation of paediatric standardised concentration infusions, however the use of smart-pump technology has been slow despite international safety agency recommendations.
Fionnuala Nevin, St James's Hospital
Brian Rattigan, Sligo Hospital at podium
Fionnuala Kennedy, Mater Private Hospital
Moninne Howlett, Our Lady's Hospital for sick children, crumlin
Joan Peppard, President, European Association of Hospital Pharmacists
HPAI Educational Committee
May 2016 â€˘ HPN
ONE WHO CAN CHANGE WHAT’S POSSIBLE FOR HCV GT1 ADULT PATIENTS1
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94–97% of treatment-naïve, non-cirrhotic patients with 8 wks*4
99% of treatment-naïve patients with 12 wks2
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• 8 weeks may be considered for treatment-naïve, non-cirrhotic patients1 •
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Albert Einstein used with permission of the HUJ/GreenLight.
*97% relates to the SVR for patients with a viral load of less than 6 million IU/ml
HARVONI is indicated for the treatment of chronic hepatitis C infection in adults1 ®
PRESCRIBING INFORMATION Consult the Summary of Product Characteristics before prescribing. HARVONI® 90mg ledipasvir/400mg sofosbuvir film coated tablets. Indications: For the treatment of chronic hepatitis C (CHC) in adults. Dosage & Administration: Adults: One tablet, taken orally, once daily with or without food. Genotype 1, 4, 5 or 6; without cirrhosis: 12 weeks of treatment with Harvoni is recommended. 8 weeks may be considered in previously untreated genotype 1-infected patients. Harvoni + ribavirin for 12 weeks or Harvoni (without ribavirin) for 24 weeks should be considered for previously treated patients with uncertain subsequent retreatment options. Genotype 1, 4, 5 or 6; with compensated cirrhosis: Harvoni + ribavirin for 12 weeks or Harvoni (without ribavirin) for 24 weeks of treatment with is recommended. Harvoni (without ribavirin) for 12 weeks may be considered for patients deemed at low risk for clinical disease progression and who have subsequent retreatment options. Genotype 1, 4, 5 or 6; post liver transplant without cirrhosis or with compensated cirrhosis: Harvoni + ribavirin for 12 weeks. Harvoni (without ribavirin) for 12 weeks (in patients without cirrhosis) or 24 weeks (in patients with cirrhosis) may be considered for patients who are ineligible for or intolerant to ribavirin. Genotype 1, 4, 5 or 6; with decompensated cirrhosis: Harvoni + ribavirin for 12 weeks. Harvoni (without ribavirin) for 24 weeks may be considered in patients who are ineligible for or intolerant to ribavirin. Genotype 3 with compensated cirrhosis and/or prior treatment failure: 24 weeks treatment with Harvoni in combination with ribavirin is recommended. Please refer to the SmPC for recommended dose & treatment duration for combination therapy. When used in combination with ribavirin, refer also to the SmPC of ribavirin. Refer to the individual SmPCs for additional information regarding dose modifications & discontinuations. Renal impairment: Mild or moderate renal impairment: no dose adjustment required. Severe renal impairment or end stage renal disease (ESRD) requiring haemodialysis: not recommended. Refer to the SmPC for ribavirin for patients with creatinine clearance (CrCl) < 50 mL/min. Hepatic impairment: Mild, moderate or severe hepatic impairment: no dose adjustment required. Safety and efficacy of Harvoni have been established in patients with decompensated cirrhosis. Children and adolescents: The safety and efficacy of Harvoni in children & adolescents aged <18 years have not yet been established. Elderly: No dose adjustment is warranted for elderly patients. Contraindications: Hypersensitivity to the active substance or to any of the excipients, and co-administration with rosuvastatin or St. John’s wort (Hypericum perforatum). When Harvoni is used in combination with ribavirin, the contraindications applicable to that agent is applicable to combination therapies. Refer to the ribavirin SmPC for a list of contraindications. Warnings and Precautions: Harvoni should not be administered concomitantly with other medicinal products containing sofosbuvir. The clinical data to support the use of Harvoni in HCV genotype 2, 3 and 6 patients are limited. A conservative 24 weeks of therapy is advised in all treatment-experienced genotype 3 patients and those treatmentnaïve genotype 3 patients with cirrhosis. Severe bradycardia and heart block: Cases of severe bradycardia and heart block have been observed when Harvoni is used with concomitant amiodarone with or without other drugs that lower heart rate. The mechanism is not established. Should concomitant use of amiodarone be considered necessary, it is recommended that patients are closely monitored when initiating Harvoni. All patients receiving Harvoni in combination with amiodarone with or without other drugs that lower heart rate should be warned of the symptoms of bradycardia and heart block and should be advised to seek medical advice urgently should they experience them. Patients who are identified as being high risk of bradyarrhythmia should be continuously
Cure defined as SVR12
1. HARVONI® SmPC available at https://www.medicines.org.uk/emc/medicine/29471 (Accessed March 2016) 2. Afdhal N et al. N Engl J Med 2014;370:1889–1898. 3. Afdhal N et al. N Engl J Med 2014;370:1483–1493. 4. Kowdley KV et al. N Engl J Med 2014;370:1879– 1888. 5. Gilead Data On File – SOFUK1601 (February 2016)
monitored for 48 hours in an appropriate clinical setting. Due to the long half-life of amiodarone, appropriate monitoring should also be carried out for patients who have discontinued amiodarone within the past few months and are to be initiated with Harvoni. Treatment of patients with prior exposure to HCV direct-acting antivirals: There are no data to support the effectiveness of retreatment of patients who have failed Harvoni with a subsequent regimen that contains an NS5A inhibitor. Consideration should be given to longer treatment for patients with uncertain subsequent retreatment options. Patients with decompensated cirrhosis and/or who are awaiting liver transplant or post-liver transplant: The efficacy of Harvoni in genotype 5 and 6 with decompensated cirrhosis and/or who are awaiting liver transplant or post-liver transplant has not been investigated. Treatment with Harvoni should be guided by an assessment of the potential benefits and risks for the individual patient. Use with potent P-gp inducers: Medicinal products that are potent P-glycoprotein (P-gp) inducers (e.g. rifampicin, carbamazepine and phenytoin) may significantly decrease ledipasvir and sofosbuvir plasma concentration which may lead to reduced therapeutic effect of Harvoni. Such medicinal products should not be used with Harvoni. Use with certain HIV antiretroviral regimens: Harvoni has been shown to increase tenofovir exposure, especially when used together with an HIV regimen containing tenofovir disoproxil fumarate and a pharmacokinetic enhancer (ritonavir or cobicistat). The safety of tenofovir disoproxil fumarate in this setting has not been established. The potential risks and benefits associated with co-administration of Harvoni with the fixed-dose combination tablet containing elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil fumarate or tenofovir disoproxil fumarate given in conjunction with a boosted HIV protease inhibitor (e.g. atazanavir or darunavir) should be considered, particularly in patients at increased risk of renal dysfunction. Patients receiving Harvoni concomitantly with elvitegravir/cobicistat/ emtricitabine/tenofovir disoproxil fumarate or with tenofovir disoproxil fumarate and a boosted HIV protease inhibitor should be monitored for tenofovir-associated adverse reactions. Refer to the SmPCs of the aforementioned agents for recommendations on renal monitoring. Use with HMG-CoA reductase inhibitors: Co-administration of Harvoni and HMG-CoA reductase inhibitors (statins) can significantly increase the concentration of the statin, which increases the risk of myopathy and rhabdomyolysis. HCV/HBV co-infection: There are no data available. Excipients: Harvoni contains sunset yellow FCF aluminium lake (E110), which may cause allergic reactions. It also contains lactose. Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency, or glucose-galactose malabsorption should not take Harvoni. Interactions: Harvoni should not be administered concomitantly with other medicinal products containing sofosbuvir. Ledipasvir is an in vitro inhibitor of drug transporter P-gp and breast cancer resistance protein (BCRP) and may increase intestinal absorption of co-administered substrates for these transporters. Ledipasvir may be a weak inducer of metabolising enzymes such as CYP3A4, CYP2C and UGT1A1. Compounds that are substrates of these enzymes may have decreased plasma concentrations when co-administered with Harvoni. In vitro ledipasvir inhibits intestinal CYP3A4 and UGT1A1. Medicinal products that have a narrow therapeutic range and which are metabolised by these isoenzymes should be used with caution and carefully monitored. Ledipasvir and sofosbuvir are substrates of drug transporter P-gp and BCRP while GS-331007 is not. Medicinal products that are potent P-gp inducers (e.g. rifampicin, St. John’s wort, carbamazepine and phenytoin) may decrease ledipasvir and sofosbuvir plasma concentrations leading to reduced therapeutic effect of Harvoni and should not be used with Harvoni. Co-administration with medicinal products that inhibit
P-gp and/or BCRP may increase ledipasvir and sofosbuvir plasma concentrations without increasing GS-331007 plasma concentration; Harvoni may be co-administered with P-gp and/or BCRP inhibitors. Refer to SPC for full information regarding interactions. Use in pregnancy and lactation: When Harvoni is used in combination with ribavirin; extreme care must be taken to avoid pregnancy in female patients and in female partners of male patients. Significant teratogenic and/or embryocidal effects have been demonstrated in all animal species exposed to ribavirin. Women of childbearing potential or their male partners must use an effective form of contraception during treatment and for a period of time after the treatment has concluded as recommended in the SmPC for ribavirin. Refer to the SmPC for ribavirin for additional information. There are no or limited amount of data (<300 pregnancy outcomes) from the use of ledipasvir, sofosbuvir or Harvoni in pregnant women. As a precautionary measure, it is preferable to avoid the use of Harvoni during pregnancy. Harvoni should not be used during breast-feeding. See also the SmPC for ribavirin for pregnancy and breast-feeding. Side effects: When Harvoni was studied with ribavirin, the most frequent adverse drug reactions to Harvoni in combination with ribavirin were consistent with the known safety profile of ribavirin, without increasing the frequency or severity of the expected adverse drug reactions. The following adverse drug reactions have been identified with Harvoni. Frequencies are defined as follows: Very commonly reported adverse events (≥1/10): headache and fatigue. Description of selected adverse reactions; Cardiac arrhythmias: Cases of severe bradycardia and heart block have been observed when Harvoni is used with concomitant amiodarone and/or other drugs that lower heart rate. Legal Category: POM. Package Quantities: Bottle of 28 film-coated tablets. Price: UK NHS Price - £12,993.33; Eire Price - €TBA Marketing Authorisation Number: EU/1/14/958/001 Further information is available from the local representative of the marketing authorisation holder: Gilead Sciences Ltd, 280 High Holborn, London, WC1V 7EE, UK. Telephone: +44 (0) 8000 113700, For Ireland: +353 214 825 999. E-mail: email@example.com. Harvoni is a trademark. Date of PI preparation: January 2016: HAR/UK/15-11/MM/1992(1) This medicinal product is currently subject to additional monitoring. Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Any suspected adverse reactions to Harvoni should be reported to Gilead via email to safety_FC@gilead.com or by telephone +44 (0) 1223 897500. Adverse events should be reported. Reporting forms and information can be found at www.mhra.gov.uk/yellowcard. Suspected adverse reactions should be reported to the HPRA Pharmacovigilance using a Yellow Card obtained either from the HPRA, or electronically via the website at www.hpra.ie. Adverse reactions can also be reported to the HPRA by calling +353 1 6764971. © 2016 Gilead Sciences, Inc. All rights reserved. Date of preparation: March 2016 HAR/UK/14-11/MI/1033(5)
Heart attack protocols saving lives Up to 30 lives a year will be saved through the introduction of a new standardised treatment for heart attack patients, according to the HSE. Speaking at the launch of a report entitled “Heart Attack Care in Ireland 2014” HSE Director General Mr Tony O’Brien noted how the report demonstrated that “in 2014, 92% of appropriate patients received angioplasty compared with 55% in 2011. For our patients, this means a better service and more life-saving opportunities.” Congratulating all those involved, Mr O’Brien said, “This very significant change is a tribute to the co-operation and commitment between dedicated hospital teams and the National Ambulance Service. This modernised approach puts Ireland on a par with our European neighbours.” The gold standard treatment for a major heart attack (described as a ‘ST Elevation Myocardial Infarction (STEMI) heart attack) is internationally agreed to be Primary Percutaneous Coronary Intervention (also known as angioplasty) as early as possible after the patient first experiences symptoms. PPCI (angioplasty) is a medical procedure in which a balloon is used to open a blockage in a coronary artery. This procedure usually involves the placement of stents to improve blood flow to the heart. The HSE, through the Acute Coronary Syndrome (ACS) clinical programme has designated a
Professor Kieran Daly, Clinical Lead Programme for ACS range of centres across the country to deliver PPCI (angioplasty). According to Prof Kieran Daly, Clinical Lead Programme for ACS, “International evidence has shown that PPCI (angioplasty) intervention is most effective if the dedicated centre can be reached within 90 minutes of diagnosis. The aim of our programme, established over two years ago, was to save lives by standardising the care of these patients across the country. And at 92%, our high level of PPCI (angioplasty) access compares favourably with other countries such as Wales at 72% and England at 97%.” The establishment of dedicated cardiology teams in the PPCI centres allowing for the maintenance of a 24/7 service with direct access Catheter Laboratories has been an essential development. Equally important have been developments within the National Ambulance Service. Their vehicles are now equipped with specific ECG machines and paramedics are all trained in their use and interpretation. Paramedics are also trained in STEMI heart attack recognition. Ambulance crews can speak directly with the PPCI centre through a dedicated freephone. A defined protocol has been agreed and implemented which ensures that patients are brought to the most appropriate medical setting. If a STEMI heart attack patient
cannot be transferred to a PPCI centre within 90 minutes, they will be transferred to the nearest Hospital Emergency Department to allow for thrombolysis (clot busting drugs) to be administered. Helicopter transfer for STEMI heart attack patients to the PPCI centre is also an option in certain areas. According to Prof Daly, once a new cross border service is in place in the coming weeks 90% of the population nationally will have access to a PPCI centre within 90 minutes. “We have been building this service over the last three years and this is a significant development. The small proportion of patients outside this 90 minute transfer time are also dealt with according to national protocols through thrombolysis and then transferred on an urgent basis to a PPCI centre. All international
programmes face similar challenges but we feel we are succeeding in reaching a very high percentage of our population at present.” The designated 24/7 centres are: St James’s Hospital, Dublin; Cork University Hospital; Galway University Hospital; Mater Misericordiae University Hospital Dublin; University Hospital Limerick. University Hospital Waterford operates as a PPCI centre on a nine to five, Monday to Friday basis supplemented by a thrombolysis service out of hours. A new service in the North West will commence shortly featuring an innovative cross border service that will give Donegal patients suffering from a STEMI heart attack direct access to services in Altnagelvin Hospital, Derry. It is anticipated that up to 60 patients a year will be treated in the Derry hospital.
Disappointment at NCPE decision Muscular Dystrophy Ireland has expressed its disappointment at the decision by the National Centre for Pharmacoeconomics (NCPE) not to recommend Translarna for reimbursement.
a number of occasions in recent months, including on World Duchenne Awareness Day, and in various meetings with public representatives and other stakeholders.
Translarna is a new treatment for people with a particular type of Duchenne Muscular Dystrophy - specifically those patients who condition is caused by a particular genetic defect, called a nonsense mutation in the dystrophin gene, and who are aged 5 years and older and able to walk. It is the first to address the underlying genetic cause of Duchenne muscular dystrophy.
Translarna has already been approved for use in England under a managed access agreement wherein it is being made available for a period of time to allow further evidence to be gathered on its use whilst also ensuring that patients receive access to the drug. Translarna has become the first Duchenne Muscular Dystrophy targeting therapy to receive conditional marketing approval by the European Medicines Agency (EMA). The drug is currently available and being prescribed to
Muscular Dystrophy Ireland has raised access to this therapy on May 2016 • HPN
boys in over 20 countries within the European Union with some children receiving the drug since late 2014. John Bennett, MDI Commented, “It is only fair and reasonable to expect Irish children to have the same opportunities as the children in other European Countries who have access to this medication. “It is our information that this new treatment would only apply in Ireland to a very small number of patients - in the low single digits. “However, for those young people it would make a huge difference in slowing progression of the condition and in keeping them on their feet for longer. It means
that they may experience more of what life has to offer and delay the requirement for other medical and social care supports. For young people and their families whose quality of life and life expectancy is significantly impacted by this condition, this is of immense value. “While this recommendation has been made by the NCPE, the final decision on reimbursement rests with the Health Service Executive (HSE). We are now calling on the HSE to enter into discussions with the manufacturer and to come to an arrangement which would make the therapy available here and to do so in as timely a manner as possible.”
Improved outcomes start here
Make it part of your ACS Treatment Plan
BRILIQUE® 60MG & 90MG FILM-COATED TABLETS (ticagrelor) PRESCRIBING INFORMATION. Consult Summary of Product Characteristics (SmPC) before prescribing. Use: Adults aged 18 years and older, co-administered with 75-150mg acetylsalicylic acid (ASA) daily unless specifically contraindicated: for the prevention of atherothrombotic events in patients with acute coronary syndromes (ACS); or a history of a myocardial infarction (MI) and a high risk of developing an atherothrombotic event. Presentation: 60mg or 90mg ticagrelor film-coated tablets. Dosage and administration: ACS: Treatment should be initiated with a single 180mg loading dose (two tablets of 90mg) and then continued at 90mg twice daily. Treatment with Brilique 90mg is recommended for 12 months in ACS patients unless discontinuation is clinically indicated. History of MI: 60mg twice daily for extended treatment in patients with a history of MI of at least one year and a high risk of an atherothrombotic event. Treatment may be started without interruption as continuation therapy after the initial one year treatment with Brilique 90mg or other adenosine diphosphate (ADP) receptor inhibitor therapy in ACS patients with high risk of an atherothrombotic event. Treatment can also be initiated up to 2 years from the MI, or within one year after stopping previous ADP receptor inhibitor treatment. Limited data on efficacy and safety of Brilique beyond 3 years of extended treatment. If a switch is needed, the first dose of Brilique should be administered 24 hours following the last dose of the other antiplatelet medication. Lapses in therapy should be avoided. For oral use. Brilique can also be crushed, mixed with water and either drunk or administered via a nasogastric tube. Contraindications: Hypersensitivity to the active substance or to any of the excipients. Active pathological bleeding. History of intracranial haemorrhage. Severe hepatic impairment. Co-administration with strong CYP3A4 inhibitors (e.g. ketoconazole). Precautions: Use with caution in patients at an increased risk for bleeding (e.g. recent trauma or surgery, coagulation disorders or recent gastrointestinal bleeding) or those on concomitant medication that may increase bleeding risk (e.g. NSAIDs, oral anticoagulants and/or fibrinolytics) within 24 hours of taking Brilique. Brilique should be stopped 7 days prior to elective surgery if the antiplatelet effect is not desired. In patients with a history of MI with prior ischemic stroke, treatment beyond 1 year is not recommended. Not recommended in patients on renal dialysis. Use with caution in patients with moderate hepatic impairment. Use with caution in patients with an increased risk of bradycardic events or when administered concomitantly with medicinal products known to induce bradycardia. Use with caution in patients with a history of asthma and/or COPD or a history of hyperuricaemia or gouty arthritis. Use in patients with uric acid nephropathy is discouraged. Creatinine levels may increase during treatment with Brilique, renal function should be checked according to routine medical practice and in ACS patients, one month after starting Brilique, paying special attention to patients ≥ 75 years, patients with moderate-
to-severe renal impairment and those receiving concomitant treatment with an ARB. Premature discontinuation with antiplatelet therapy including Brilique could result in an increased risk of CV death or MI due to the patient’s underlying disease and should therefore, be avoided. Co administration of Brilique is not recommended with a high maintenance dose of ASA (> 300mg) or with doses of simvastatin > 40mg. Co administration of ticagrelor with strong CYP3A inducers is discouraged, as this may lead to a decrease in exposure and efficacy of ticagrelor. No data are available on concomitant use of Brilique with other drugs that also are potent P-glycoprotein (P-gp) inhibitors and moderate CYP3A4 inhibitors (e.g. verapamil, quinidine) that may increase ticagrelor exposure. If the association cannot be avoided, their concomitant use should be made with caution. Caution is advised in co-administration with medicinal products that alter haemostasis or with SSRIs. Brilique is not recommended during pregnancy and breastfeeding. Patients who experience dizziness and confusion during treatment should be cautious when driving or using machines. Undesirable events: Very Common: blood disorder bleedings, hyperuricaemia, dyspnoea Common: gout/gouty arthritis, dizziness, syncope, headache, vertigo, hypotension, respiratory system bleedings, gastrointestinal haemorrhage, diarrhoea, nausea, dyspepsia, constipation, subcutaneous or dermal bleeding, rash, pruritus, urinary tract bleeding, blood creatinine increased, post procedural haemorrhage and traumatic bleedings. Uncommon: tumour bleedings, hypersensitivity including angioedema, confusion, intracranial haemorrhage, eye haemorrhage, ear haemorrhage, retroperitoneal haemorrhage, muscular bleedings and reproductive system bleedings. Consult SmPC for a full list of adverse events.Legal category: POM. Marketing authorisation number: 60mg – EU/1/10/655/011 and 90mg – EU/1/10/655/004. Further product information available on request from: Freephone 1800 800 899 or contact AstraZeneca UK Limited, Horizon Place, 600 Capability Green, Luton, Bedfordshire, LU1 3LU, United Kingdom. BRILIQUE is a trade mark of the AstraZeneca group of companies. Date of API preparation: 03/2016. Adverse events should be reported directly to: HPRA Pharmacovigilance, Earlsfort Terrace, Dublin 2. Tel: +353 1 6764971 Fax: +353 1 6762517 Website: www.hpra.ie e-mail: firstname.lastname@example.org. Adverse events should also be reported to AstraZeneca Medical Information on 1800 800 899. Approval ID: 969591.011. Date of preparation: May 2016.
16 Clinical Synopsis
Patient Blood Management Annual Symposia The Network for the Advancement of Patient Blood Management Haemostasis and Thrombosis (NATA) held their 17th annual symposia in Europe since 2000, with its 17th taking place this week at in the Royal Dublin Society Ballsbridge on 14th and 15th April. The annual NATA symposium provides a unique opportunity for Doctors, Nurses and Transfusion Scientists to experience stimulating and constructive exchanges across different specialities involved in Patient Blood Management. Irish experts in Patient Blood Management, Haemostasis and Thrombosis along with experts from Europe, Australia and North America, shared their knowledge with over 500 delegates from approximately 40 countries in attendance. This year’s theme fell under the umbrella of ‘From Theory to Praxis’, and included talks covering subjects such as avoiding the first transfusion, patient blood management before, during and after surgery, haemostasis and thrombosis and patient blood management in obstetrics. Abstracts How to avoid the first transfusion? Patient Blood Management before, during and after surgery 1. Preoperative measures to avoid the first transfusion Diagnosis and management of anaemia and iron deficiency M. Muñoz and S. Gómez-Ramírez, Perioperative Transfusion Medicine, Department of Surgical Specialties, Biochemistry and Immunology at the School of Medicine, University of Malaga Perioperative anaemia is frequent and, unsurprisingly, independently associated with subsequent transfusion, but also with postoperative morbidity and mortality and longer hospital stay.1–3 Anaemia should be detected before surgery that is likely to cause significant blood loss, preferably at least 30 days before scheduled operations.4–6 The WHO defines anaemia for men and women by haemoglobin (Hb) concentrations <13 g/dL and <12 g/dL, respectively, at sea level. However, a target Hb of at least 13 g/dL should be used for all adult patients until research determines more useful ‘suboptimal’ preoperative Hb.7 Once detected, the cause of anaemia should be identified and treated if possible.4–7 Major surgery may have to be rescheduled, whereas minor procedures without blood loss can proceed in parallel with the evaluation of anaemia.4–7 There are three types of iron-restricted erythropoiesis, the most common cause of anaemia worldwide: absolute iron deficiency; iron sequestration due to inflammation; and functional iron deficiency due to insufficient iron availability during treatment with erythropoiesis-
May 2016 • HPN
stimulating agents (ESA). Serum ferritin concentrations <30 ng/mL indicate absent iron stores, i.e. iron-deficiency anaemia, which is treatable with oral iron.8 Serum ferritin concentrations between 30–100 ng/mL suggest a combination of iron-deficiency anaemia and anaemia of chronic disease, which is treatable with intravenous iron.9 Serum ferritin concentrations >100 ng/mL suggest anaemia of chronic disease due to iron sequestration, which is treatable with ESAs. Transferrin saturation measures iron transport capacity, not the amount of stored iron. Values
drug–drug interactions. In addition, alteration of renal function interferes with most of DOACs. As a result, an unexpected high number of major bleeding events have been reported, especially with dabigatran, focusing the attention on these new anticoagulant agents. Furthermore, as new biological tests become more readily available for monitoring that include the diluted thrombin time for dabigatran (Hemoclot®) and specific anti-Xa assays for rivaroxaban, apixaban, and edoxaban, ranges for optimal anticoagulation and potential thresholds for increased bleeding risks are not well-defined.
<20% indicate anaemia that will respond to a combination of parenteral iron and ESA.8,9 Iron sequestration is identified by >5% red cells being hypochromic or a reticulocyte haemoglobin content <27 pg.9 If these measures are unavailable, the concentration of soluble transferrin receptor, with or without the ferritin assay, and the red blood cell size factor
Several groups and major societies, including the European Society of Cardiology (ESC), have recently issued several sets of recommendations focusing on periprocedural management: when to stop DOACs, whom to bridge and when to restart. The Groupe d’Intérêt en Hémostase Périopératoire (GIHP) has updated its 2011 recommendations which are now in line with the ESC proposals. As a summary, dabigatran should be stopped (last intake) 4 or 5 days before the procedure, depending of the renal function. The “xabans” (anti-Xa agents: apixaban, edoxaban, rivaroxaban) need a shorter interruption with a last oral intake three days before. No more bridging is requested, whatever the level of thrombotic risk. No biological tests are requested, as far as a scheduled procedure is concerned. Immediately after the invasive procedure, a once-daily subcutaneous preventive dose of low-molecular-weight heparin (LMWH) should be injected (enoxaparin 40mg or dalteparin 5000 IU). DOACs should be re-started only when surgical haemostasis is secured, i.e. mainly after 72 hours. These proposals are summarised in the table below.
(<88 fL) may help determine whether anaemia of chronic disease is contributed to by iron deficiency.9,10 When iron-restricted erythropoiesis does not explain anaemia, other investigations including serum B12 (especially for those >60 years), lactate dehydrogenase and serum creatinine may exclude other nutritional deficiencies, haemolysis or renal disease.7,10 Red cell folate may be useful if malabsorption or severe malnutrition is present.7,10 Preoperative iron and vitamin deficiencies, with or without anaemia, should be also corrected.4–7 Patients should be referred to the haematologist for further evaluation when a diagnosis is not reached. The possible benefits of oral and intravenous iron, with or without ESA, depend on the accuracy of diagnosis, the severity of anaemia and the available time frame.6,11 Newer formulations, for instance iron isomaltoside and ferric carboxymaltose, can be given quickly in single large doses of 1g or more, which is more convenient for patients and less expensive.7 Doses of ESA should be adjusted with reference to an individual’s target haemoglobin concentration, whilst ensuring adequate iron supply to the bone marrow and thromboembolic prophylaxis.4–7,11 Blood transfusion should be restricted to patients who are bleeding, with severe anaemia or poor physiological reserve.10,12 Anti-thrombotics: when to stop and whom to bridge? When to re-start? C.-M. Samama, Department of Anaesthesia and Intensive Care Medicine, Cochin and Hôtel-Dieu University Hospitals, Paris, France Direct oral anticoagulants (DOACs) are now recognised as a major step forward for our patients. However, several issues related to DOACs deserve our attention.1,2 Reports on the pharmacokinetics and pharmacodynamics for these agents show a major intra- and interindividual variability and a large number of
Bleeding tendency – how to screen and how to monitor? B. J. Hunt, Professor of Thrombosis and Haemostasis, King’s College; Consultant, Guy’s & St Thomas’ NHS Foundation Trust, London, UK Sadly, little has changed since the British Committee for Standards in Haematology wrote their guidelines in 2008 and unselected coagulation testing is widely practiced in the process of assessing bleeding risk prior to surgery. This may delay surgery and cause unnecessary concern in patients found to have “abnormal” tests. This practice is also associated with significant costs. Old-fashioned assessment with a bleeding history including details of family history, previous excessive post-traumatic bleeding or postsurgical bleeding and use of antithrombotic drugs should be taken in all patients preoperatively. If the bleeding history is negative, no further testing is required. If the bleeding history is positive or there is a clear clinical indication, e.g. renal disease, a comprehensive assessment guided by clinical features is required. Those with a bleeding tendency should ideally have this identified
Single Agent Once Daily Oral Therapy for R/R CLL and R/R MCL*
Discover how far therapy can go * Relapse/Refractory Chronic Lymphocytic Leukemia and Relapse/Refractory Mantle Cell Lymphoma.
IMBRUVICA® is indicated for the treatment of adult patients with: 1 • Relapsed or refractory mantle cell lymphoma • Chronic lymphocytic leukaemia who have received at least one prior therapy, or in ﬁrst line in the presence of 17p deletion or TP53 mutation in patients unsuitable for chemo-immunotherapy • Waldenström’s macroglobulinaemia who have received at least one prior therapy, or in ﬁrst-line treatment for patients unsuitable for chemo-immunotherapy IMBRUVICA® 140 mg Hard Capsules PRESCRIBING INFORMATION ACTIVE INGREDIENT: Ibrutinib. Please refer to Summary of Product Characteristics (SmPC) before prescribing. INDICATIONS: Treatment of adult patients with: relapsed or refractory mantle cell lymphoma (MCL); chronic lymphocytic leukaemia (CLL) who have received ≥ one prior therapy, or first line in presence of 17p deletion/TP53 mutation and are unsuitable for chemo-immunotherapy; Waldenström’s macroglobulinaemia (WM) who have received ≥ one prior therapy, or in first line in patients unsuitable for chemo immunotherapy. DOSAGE & ADMINISTRATION: Adults: Orally, once daily, swallowed whole with water. MCL - 4 capsules. CLL & WM - 3 capsules. Concomitant moderate/ strong CYP3A4 inhibitors – reduce to 1 capsule (or, with strong inhibitors, withhold IMBRUVICA for up to 7 days). Withhold IMBRUVICA therapy for any new onset/worsening grade ≥ 3 non-haematological toxicity, grade ≥ 3 neutropenia with infection/fever, or grade 4 haematological toxicities. Re-initiate when toxicities resolved to grade 1 or baseline. If toxicities recur, reduce dose by 1-2 capsules. Discontinue IMBRUVICA if toxicities persist/recur following two dose reductions. Children: Safety/efficacy not established ≤ 18 years old. Elderly: No dose adjustment required. Renal impairment: Mild/moderate - no dose adjustment. Severe – no data; consider benefit/risk and monitor closely. No data with dialysis. Hepatic impairment: Mild (Child-Pugh class A) – 2 capsules daily; moderate (Child-Pugh class B) – 1 capsule daily; severe (Child-Pugh class C) – not recommended. Monitor for toxicities. Severe cardiac disease: No clinical data. CONTRAINDICATIONS: Hypersensitivity to active substance/excipients. St. John’s Wort preparations. SPECIAL WARNINGS & PRECAUTIONS: Bleeding-related events: Minor and major haemorrhagic events reported; caution with anticoagulant therapy – do not use concomitantly with warfarin or other vitamin K antagonists, avoid fish oil and vitamin E preparations. Withhold IMBRUVICA ≥ 3 to 7 days pre-/post-surgery. Leukostasis: Cases reported; consider temporary withhold of IMBRUVICA; monitor closely, give supportive care. Infections: Infections seen, some resulting in hospitalisation and death; monitor for fever, neutropenia and infections and give anti-infective therapy. Cytopenias: Treatment-emergent grade 3/4 cytopenias reported; monitor complete blood counts monthly. Atrial fibrillation/flutter: reported particularly in patients with cardiac risk factors/acute infections/previous history of atrial fibrillation; periodic clinical monitoring; consider ECG if arrhythmic symptoms or new onset dyspnoea develop; consider alternative to IMBRUVICA when pre-
existing atrial fibrillation requiring anticoagulant therapy or high risk of thromboembolic disease; where no suitable alternatives to IMBRUVICA, consider tightly controlled treatment with anticoagulants. Tumour lysis syndrome: cases reported. Monitor at risk patients closely, take precautions. Effects on the QT interval: mild decrease in QTcF interval seen; use clinical judgment before prescribing for patients at risk from further shortening QTc duration. Drug-drug interactions: Strong/ moderate CYP3A4 inhibitors may increase ibrutinib exposure; CYP3A4 inducers may decrease ibrutinib exposure. Avoid where possible, if not monitor closely for toxicities/lack of efficacy. SIDE EFFECTS: Very common: Pneumonia, upper respiratory tract infection, urinary tract infection, sinusitis, skin infection, neutropenia, thrombocytopenia, anaemia, dizziness, headache, haemorrhage, epistaxis, bruising, petechiae, diarrhoea, vomiting, stomatitis, nausea, constipation, rash, arthralgia, musculoskeletal pain, pyrexia, oedema peripheral. Common: Sepsis, febrile neutropenia, leukocytosis, lymphocytosis, dehydration, hyperuricaemia, vision blurred, atrial fibrillation, subdural haematoma, dry mouth. Other side effects: Leukostasis, tumour lysis syndrome, hepatic failure, angioedema. Refer to SmPC for other side effects. PREGNANCY: Women of child-bearing potential must use highly effective contraceptive measures during and for 3 months after stopping treatment; if using hormonal contraceptives, add barrier method. Not to be used during pregnancy. LACTATION: Discontinue breast-feeding during treatment. INTERACTIONS: CYP3A4 inhibitors: Strong: Avoid where possible or reduce dose (or withhold IMBRUVICA for ≤ 7 days) and monitor closely; e.g. ketoconazole, indinavir, nelfinavir, ritonavir, saquinavir, clarithromycin, telithromycin, itraconazole, nefazadone, cobicistat. Moderate: Avoid where possible or reduce dose and monitor closely; e.g. diltiazem, voriconazole, erythromycin, amprenavir, aprepitant, atazanavir, ciprofloxacin, crizotinib, darunavir/ ritonavir, diltiazem, fluconazole, fosamprenavir, imatinib, verapamil, amiodarone, dronedarone. Avoid grapefruit and Seville oranges. Mild: No dose adjustment required; monitor closely. CYP3A inducers: Strong/moderate: Avoid or monitor closely for lack of efficacy; e.g. carbamazepine, rifampicin, phenytoin. Mild: may be used; monitor for lack of efficacy. Medicines that increase stomach pH (e.g. proton pump inhibitors) may decrease ibrutinib exposure. Potential interactions: Oral narrow therapeutic range P gp or breast cancer resistance protein (BCRP) substrates (e.g. digoxin, methotrexate) should be taken ≥ 6 h before/after IMBRUVICA. Ibrutinib may inhibit BCRP in the liver and
so increase exposure of drugs undergoing BCRP-mediated hepatic efflux (e.g. rosuvastatin). Ibrutinib may inhibit intestinal CYP3A4 and thus increase exposure of some CYP3A4 substrates sensitive to gut CYP3A metabolism; caution with narrow therapeutic range oral CYP3A4 substrates (e.g. dihydroergotamine, ergotamine, fentanyl, cyclosporine, sirolimus, tacrolimus). Ibrutinib is a weak CYP2B6 inducer and may affect expression of other enzymes and transporters regulated via the constitutive androstane receptor (CAR) (e.g. CYP2C9, CYP2C19, UGT1A1, MRP2). Exposure to substrates of CYP2B6 (e.g. efavirenz, bupropion) and co -regulated enzymes may be reduced with ibrutinib. Refer to SmPC for full details of interactions. LEGAL CATEGORY: Prescription only medicine. PRESENTATIONS PACK SIZES Bottles Bottles
90 capsules 120 capsules
MARKETING AUTHORISATION HOLDER: Janssen-Cilag International NV, Turnhoutseweg 30, B-2340 Beerse, Belgium FURTHER INFORMATION IS AVAILABLE FROM: Janssen-Cilag Limited, 50-100 Holmers Farm Way, High Wycombe, Buckinghamshire, HP12 4EG UK. Prescribing information last revised: February 2016. Reference: 1. Imbruvica® Summary of Product Characteristics. Janssen Cilag International Feb. 2016. Date of preparation: March 2016 PHIR/IBR/0316/0010 Adverse events should be reported. This medicinal product is subject to additional monitoring and it is therefore important to report any suspected adverse events related to this medicinal product. Healthcare professionals are asked to report any suspected adverse events via: HPRA Pharmacovigilance, Earlsfort Terrace, IRL - Dublin 2, Tel: +353 1 6764971, Fax: +353 1 6762517, Website: www.hpra.ie, E-mail: email@example.com Adverse events should also be reported to Janssen-Cilag Limited on +44 1494 567447 or at firstname.lastname@example.org
IMBRUVICA® is co-developed with Pharmacyclics. Janssen-Cilag Limited is the marketing authorisation holder and responsible editor of this document.
@JanssenIE © Pharmacyclics LLC 2016
MARKETING AUTHORISATION NUMBER(S) EU/1/14/945/001 EU/1/14/945/002
© Janssen Cilag Limited 2016
18 Clinical Synopsis fully preoperatively so that the appropriate management can be given. How to avoid the first transfusion? Patient Blood Management before, during and after surgery 2. Intraoperative measures to avoid during the first transfusion Restrictive RBC transfusion strategy – but how low? J. L. Carson, Richard C Reynolds Professor of Medicine, Chief, Division of General Internal Medicine, Rutgers Robert Wood Johnson Medical School, New Brunswick, NJ, USA Clinical trials evaluating transfusion thresholds compare liberal transfusion (higher haemoglobin thresholds) to restrictive transfusion (lower haemoglobin thresholds). Most clinical trials have either used a restrictive transfusion threshold of 8 to 9 g/dL (n=4 712) or restrictive threshold of 7 g/dL (n=5 676).The risk ratio for 30-day mortality was similar in the two groups of trials although the clinical settings were different. Most of the trials in the 7 g/dL restrictive group were performed in critical care patients while the clinical settings included surgical and other patient populations.1–10 Surgical techniques and toys T. Richards, Division of Surgery and Interventional Science, University College, London, London, UK Advances and recognition of interventional radiological techniques to prevent or control major bleeding has led to these becoming a more commonly used adjunct in surgery. Transcatheter arterial techniques are commonly used for uterine fibroid and tumour embolisation. This technology has developed for control of emergency bleeding and gained acceptance and practice in the management of gastrointestinal bleeding or post-surgical bleeding. Major trauma units in the USA and conflict zones have proposed the use of resuscitative endovascular balloon occlusion (REBOA). Developed initially to control bleeding in aortic surgery, a soft compliant balloon is placed inside the aorta and inflated to control blood flow. In the trauma setting of major haemorrhage a balloon can be placed over a guide wire from the brachial or preferably femoral artery into the aorta and inflated to prevent exsanguination and allow time for stabilisation and definitive treatment in the operating room. In the elective setting, similar techniques can be employed in elective cases where major haemorrhage is anticipated, such as postpartum haemorrhage or major pelvic tumour resection. Breaking Topics DIC interventions: what have we learnt? M. Levi, Department of Vascular Medicine, Academic Medical Centre, University of Amsterdam, the Netherlands Disseminated intravascular coagulation (DIC) is a syndrome characterised by systemic intravascular activation of coagulation, leading to widespread deposition of fibrin in
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the circulation. In patients with DIC a variety of altered coagulation parameters may be detectable, such as thrombocytopenia, prolonged global coagulation times, reduced levels of coagulation inhibitors, or high levels of fibrin split products. There is not a single test, however, that is sufficiently accurate to establish or reject a diagnosis of DIC. Nevertheless, a combination of widely available tests may be helpful in making the diagnosis of DIC and can also be helpful to guide in the selection of DIC patients that require specific, often expensive, interventions in the coagulation system. Recent knowledge on important pathogenetic mechanisms that may lead to DIC has resulted in novel preventive and therapeutic approaches to patients with DIC. Molecular pathways that contribute to inflammation-induced activation of coagulation have been precisely identified. Pro-inflammatory cytokines and other mediators are capable of activating the coagulation system and downregulating important physiological anticoagulant pathways. Activation of the coagulation system and ensuing thrombin generation is dependent on expression of tissue factor on activated mononuclear cells and endothelial cells and is insufficiently counteracted by tissue factor pathway inhibitor. Simultaneously, endothelial-bound anticoagulant mechanisms, in particular the protein C system, is shut-off by pro-inflammatory cytokines. Cytokine-mediated downregulation of thrombomodulin on endothelial cells appears to be a key phenomenon in this respect. In addition, fibrin removal is severely inhibited, due to inactivation of the fibrinolytic system, caused by an upregulation of its main inhibitor, plasminogen activator inhibitor type 1 (PAI-1). Increased fibrin formation and impaired removal leads to (micro) vascular thrombosis, which may result in tissue ischemia and subsequent organ damage. Transfusion-related acute lung injury in perioperative and intensive care settings A. Vlaar, Laboratory of Experimental Intensive Care and Anaesthesia/Intensive Care, Academic Medical Centre, Amsterdam, the Netherlands Transfusion-related acute lung injury (TRALI) is the leading cause of transfusion-related morbidity and mortality.1 TRALI is defined as the acute onset of pulmonary oedema within 6 hours of a transfusion in the absence of cardiac overload.2 The incidence is reported between 1-3% of the perioperative patients and 5-15% of the critically ill patients.3–7 TRALI is thought to be a “two-hit” event.8 The “first hit” is the underlying condition of the patient which results in priming of the pulmonary endothelium and/or neutrophils. The “second hit” is the transfusion of any blood product which causes activation of the endothelium and neutrophils resulting in capillary leakage and subsequent the onset of pulmonary oedema. Prospective studies have identified patient risk factors (i.e. the “first hit”) for the onset of TRALI in the perioperative and intensive care setting. Risk factors include, for example, liver surgery, spine surgery, time on cardiopulmonary bypass, mechanical ventilation, sepsis and massive transfusion.9 The “second hit” (i.e. transfusion factors) can be divided in antibody- and non-antibody-mediated
TRALI. Antibody-mediated TRALI is caused by the passive infusion of donor antibodies directed against the recipient’s antigens.10 Non-antibody mediated TRALI is thought to be caused by the accumulation of pro-inflammatory mediators during storage and/or the ageing of the cells themselves.11 Currently no treatment options are available for this life-threatening syndrome. However, preventive strategies, such as the introduction of a male-only donor policy for high-volume plasma products, has successfully been implemented and has resulted on average in a two-third reduction of TRALI incidence Anaemia in children: impact and prevention S. M. Goobie, Department of Anaesthesiology, Perioperative and Pain Medicine, Boston Children’s Hospital, Boston, MA, USA Anaemia is a condition in which the concentration of red blood cells, and therefore their oxygen-carrying capacity, is insufficient to meet the body’s physiological needs.1 Anaemia is defined as a haemoglobin concentration less that the 5th percentile for age. At least one in four, or 30%, of preschool age children in industrialised countries are anaemic. The global prevalence of anaemia in children is 42.6% (95% CI: 37–47).2 The incidence of anaemia in hospitalised children has not been reported but up to 37% of neonates in US hospitals are anaemic.3,4 Severe anaemia is associated with substantially worse mortality and cognitive and functional outcomes; its prevalence in children ranges from 0.9% to 1.5%.2 The common aetiologies of preoperative anaemia in children are nutritional, irondeficiency anaemia and iatrogenic blood loss.5 Daily phlebotomy blood loss of up to 5% of an infant’s total blood volume is not uncommon in US hospitals.6 Preoperative anaemia is associated with increased mortality.7 Preoperative anaemia (defined as Hct <40%) is an independent risk factor for postoperative mortality in neonates (the most vulnerable group), the odds ratio being 5.8 (95% CI 3.6-9.1).8 Furthermore, the prevalence of postoperative neonatal mortality is significantly higher (8% [95% CI 6-10%] vs. 1% [95% CI 1-2%]) with a preoperative Hct <40% than with a preoperative Hct ≥40%.8 Prevention is imperative. Reducing blood draws directly correlates with reduced transfusion.9 Treatment includes enteral or intravenous iron therapy. Therapies such as recombinant human erythropoietin may be utilised to further increase RBC production.10 Transfusion of blood may be a therapeutic modality to consider, but may also be associated with risks. Therefore, alternative strategies should be first and foremost utilised. Timely diagnosis, prevention and appropriate treatment of preoperative anaemia in children will improve outcomes and survival.
Real world patients remain on Stelara over the long term versus any other 1st line anti TNF1-3 Newly published PSOLAR data demonstrates greater drug persistency* over 4 years for Stelara compared to any other anti-TNF therapy2 Persistence of Therapy in Biologic-Naïve Patients2
Proportion of patients continuing therapy
0.6 Infliximab† 0.4
Adapted from Menter A et al. 2015
36 48 Time on therapy (months)
• A higher proportion of patients stayed on Stelara® over the
long term versus any other 1st line anti TNF.2
• Fewer patients discontinued Stelara® vs. adalimumab, etanercept and infliximab.2 • Higher drug persistency was observed for Stelara® compared to the other biologics based
on statistically significant differences in time to stop/switch for each biologic vs Stelara®.2
* Drug Persistence Reflects various factors including: Primary or Secondary Drug Effectiveness, Drug Safety, AE Profile, Tolerability.1 Persistency was assessed by Kaplan-Meier analysis for time to therapy stop/switch seperately for Stelara®, infliximab, adalimumab and etanercept Study Limitations: Data in the overall population were adjusted for possible differences amongst groups. Data were not adjusted for variability such as socioeconomic factors (e.g. access to medication), setting of administration (self- versus physician-administered), geographic region, and clinical characteristics.
STELARA® solution for injection PRESCRIBING INFORMATION ACTIVE INGREDIENT(S): Ustekinumab. Please refer to Summary of Product Characteristics (SmPC) before prescribing. INDICATION(S): Plaque psoriasis adults: Treatment of moderate to severe plaque psoriasis in adults who failed to respond to, or who have a contraindication to, or are intolerant to other systemic therapies including ciclosporin, methotrexate or PUVA. Plaque psoriasis paediatrics: Moderate to severe plaque psoriasis in adolescent patients from the age of 12 years and older, who are inadequaely controlled by, or are intolerant to, other systemic therapies or phototherapies. Psoriatic arthritis: Alone or in combination with methotrexate for the treatment of active psoriatic arthritis in adult patients when the response to previous non-biological diseasemodifying anti-rheumatic drug (DMARD) therapy has been inadequate. DOSAGE & ADMINISTRATION: Under the guidance and supervision of a physician experienced in diagnosis and treatment of psoriasis or psoriatic arthritis. Subcutaneous injection. Avoid areas with psoriasis. Self-injecting patients or caregivers ensure appropriate training Physicians are required to follow-up and monitor patients. Plaque psoriasis, adults & elderly: Patients <100kg, 45 mg at week 0 followed by a 45 mg dose at week 4, then every 12 weeks. Patients >100 kg, 90 mg at week 0 followed by a 90 mg dose at week 4, then every 12 weeks (45 mg was less effective in these patients). Plaque psoriasis paediatrics (12 years and older): Patients <60 kg, 0.75 mg/kg at week 0, followed by 0.75 mg/kg at week 4 then every 12 weeks thereafter. Patients ≥60-<100kg, 45 mg at week 0 followed by 45 mg at week 4, then every 12 weeks. Patients >100 kg, 90mg at week 0, followed by 90mg at week 4, then every 12 weeks. Psoriatic arthritis, adults & elderly: 45 mg at week 0 followed by a 45 mg dose at week 4, then every 12 weeks. Alternatively, 90 mg may be used in patients with a body weight >100 kg. Consider discontinuation if no response after 28 weeks. Children <12 years: Not recommended. Renal & Hepatic impairment: Not studied. CONTRAINDICATIONS: Hypersensitivity to product; clinically important, active infection. SPECIAL WARNINGS & PRECAUTIONS: Infections: Potential to increase risk of infections and reactivate latent infections. Caution in patients with a chronic infection or history of recurrent infection, particularly TB. Patients should be evaluated for tuberculosis prior to initiation of STELARA. Consider anti-tuberculosis therapy prior
to initiation of STELARA in patients with past history of latent or active tuberculosis. Patients should seek medical advice if signs or symptoms suggestive of an infection occur. If a serious infection develops, they should be closely monitored and STELARA should not be administered until infection resolves. Malignancies: Potential to increase the risk of malignancy. No studies in patients with a history of malignancy or in patients who develop malignancy while receiving STELARA. Monitor all patients, in particular those older than 60, patients with a medical history of prolonged immunosuppressant therapy or those with a history of PUVA treatment for non-melanoma skin cancer. Concomitant immunosuppressive therapy: Caution, including when changing immunosuppressive biologic agents. Hypersensitivity reactions: Serious hypersensitivity reactions (anaphylaxis and angioedema) reported, in some cases several days after treatment. If these occur appropriate therapy should be instituted and, STELARA discontinued immediately. Latex sensitivity: Needle cover contains natural rubber (latex), may cause allergic reactions. Immunotherapy: Not known whether STELARA affects allergy immunotherapy. Serious skin conditions: Exfoliative dermatitis has been reported following treatment. Discontinue STELARA if a drug reaction is suspected. SIDE EFFECTS: Common: dental infections, upper respiratory tract infection, nasopharyngitis, dizziness, headache, oropharyngeal pain, diarrhoea, nausea, pruritus, back pain, myalgia, arthralgia, fatigue, injection site erythema, injection site pain, antibodies to ustekinumab. Other side effects include: cellulitis, serious hypersensitivity reactions (including anaphylaxis, angioedema), skin exfoliation, exfoliative dermatitis. Studies show adverse events reported in ≥12 year olds with plaque psoriasis were similar to those seen in previous studies in adults with plaque psoriasis. Refer to SmPC for other side effects. FERTILITY: The effect of ustekinumab has not been evaluated. PREGNANCY: Should be avoided. Women of childbearing potential: Use effective contraception during treatment and for at least 15 weeks posttreatment. LACTATION: Limited data in humans. INTERACTIONS: In vitro, STELARA had no effect on CYP450 activities. Vaccinations: Live vaccines should not be given concurrently with STELARA, and should be witheld for at least 15 weeks after last dose of STELARA. STELARA can resume at least 2 weeks after such vaccinations. No data on secondary transmission of infection by live vaccines
in patients receiving STELARA. Concomitant immunosuppressive therapy: Psoriasis: The safety and efficacy of STELARA in combination with other immunosuppressants, including biologics, or phototherapy have not been evaluated. Refer to SmPC for full details of interactions. LEGAL CATEGORY: Prescription Only Medicine. PRESENTATIONS, PACK SIZES, MARKETING AUTHORISATION NUMBER: 45 mg: 1 x vial. EU/1/08/494/001, 45mg: 1 x 0.5ml prefilled syringe. EU/1/08/494/003. 90mg: 1 x 1.0ml pre-filled syringe. EU/1/08/494/004. MARKETING AUTHORISATION HOLDER: JANSSEN-CILAG INTERNATIONAL NV, Turnhoutseweg 30, B-2340 Beerse, Belgium. FURTHER INFORMATION IS AVAILABLE FROM: Janssen-Cilag Ltd, 50 – 100 Holmers Farm Way, High Wycombe, Buckinghamshire, HP12 4EG UK. © Janssen-Cilag Ltd 2015 Adverse events should be reported. Healthcare professionals are asked to report any suspected adverse events via: HPRA Pharmacovigilance, Earlsfort Terrace, IRL - Dublin 2, Tel: +353 1 6764971, Fax: +353 1 6762517, Website: www.hpra. ie, E-mail: email@example.com. Adverse events should also be reported to Janssen-Cilag Ltd on +44 1494 567447. Prescribing information last revised: 06/2015 References: 1. Warren RB et al. J Inv Dermatol. Accepted article: June 2015; doi: 10.1038/jid.2015.208. 2. Menter et al. P1705: Presented at the AAD annual meeting 2015. 3. Gniadecki R et al. Br J Dermatol. 2015 Jan; 172(1): 244-252. 4. Kimball AB et al. JEADV 2013; 37: 1535-1545. Date of preparation: April 2016 | PHIR/STE/0416/0002
Five new breast cancer genes discovered The largest-ever study to sequence the whole genomes of breast cancers has uncovered five new genes associated with the disease and 13 new mutational signatures that influence tumour development. The results of two papers published in Nature and Nature Communications also reveal what genetic variations exist in breast cancers and where they occur in the genome. Dr Serena Nik-Zainal of the Wellcome Trust Sanger Institute led analysis of 560 breast cancer genomes; 556 from women and four from men. This international collaboration included breast cancer patients from around the world, including the USA, Europe and Asia. The results reveal more about the causes of breast tumours and provide evidence that breast cancer genomes are highly individual. Dr Nik-Zainal’s team hunted for mutations that encourage cancers
to grow and looked for mutational signatures in each patient’s tumour. They found that women who carry the BRCA1 or BRCA2 gene, and so have increased risk of developing breast and ovarian cancer, had whole cancer genome profiles that were highly distinctive from each other and were also very different to other breast cancers. This discovery could be used to classify patients more accurately for treatment. Exactly where mutations occur in breast cancer genomes is important too. Collaborator Dr Ewan Birney, from the European Bioinformatics Institute, used computational techniques to analyse the sequence of genetic information held in each of the sample genomes. The uncovering of genes that are likely to lead to the growth of breast cancer cells by the Wellcome Trust Sanger Institute could lead to new cancer trials in Ireland to test new treatments, says ICORG.
Commenting on the study, Professor Bryan Hennessy, Clinical Lead at ICORG, said that while ICORG has already conducted or will conduct trials with drugs such as palbociclib and copanlisib which target cancer genes such as CDK and PI3K he expects a lot more in the future. “Our understanding of the role of abnormal genes in generating breast cancer cells has been growing. The significance of the Wellcome Trust Sanger Institute study is its size, the huge volume of data it generated and the identification of new genes associated with the disease,” he said. “Our molecular level research shows us that breast cancer cells may look the same under the microscope. But when we look at their genetic building blocks we can see important differences between them”, he said.
differences in cancer cells, the next steps are to develop and test treatments that intervene and stop the genes generating the individualised cancer cells.” “There is great potential, and it is an area attracting much interest, to develop treatments that are more targeted to individual patients based on the abnormal genes that are driving their cancers.” “This will involve cancer trials similar to those that ICORG has been conducting. Our network of cancer trials centres in hospitals across the country, highly experienced researchers and history of international collaborations means we are well placed to ensure patients in Ireland get early access to these treatments as they emerge for testing over the next decade,” Professor Bryan Hennessy said.
“Having identified at a molecular level what can cause the
Out the Other Side: Stories of Breast Cancer Survival’ exhibition The Mater Misericordiae University Hospital, Dublin, was the second hospital to host an inspiring exhibition recently, that will continue to tour Ireland over the coming months, having received national attention last year. ‘Out the Other Side: Stories of Breast Cancer Survival’ is a collection of individual stories and photographs of Irish women who have survived breast cancer. The exhibition was developed to offer encouragement to other breast cancer survivors and women living with the disease in Ireland. The tour of the installation, which has been developed by Roche in partnership with the Marie Keating Foundation, began in March in University Hospital Galway. As
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the second stop of the tour, it was hosted in the Atrium area of The Whitty Building, in the Mater Misericordiae University Hospital. The exhibition features the stories of ten women, with each comprising three elements: a shared personal experience of surviving breast cancer; a photograph of each survivor as they are today; and a photograph which each of these women feels represents their ‘survivorship milestone’, essentially, what surviving breast cancer has meant for each of them. The exhibition was first installed in St Stephen’s Green Park in Dublin for the duration of October last year, which is breast cancer awareness month.
“Due to advances in research, the treatment of breast cancer today is very different to what it was fifteen years ago. Our understanding of the several diseases that are breast cancer has enabled us to treat it more appropriately and effectively, leading to better outcomes for patients. I’m really pleased to see the exhibition coming to the Mater Misericordiae University Hospital. It is a perfect platform to shed light on these important stories of survivorship,” said Dr Catherine Kelly, Consultant Medical Oncologist, the Mater Misericordiae University Hospital, Dublin. According to the Marie Keating Foundation, there are currently over 28,000 women in Ireland who
have survived breast cancer. But surviving breast cancer doesn’t mean the end of the journey and for many women what happens after breast cancer is a challenge in itself. General Manager, Roche Products (Ireland) Limited, Sheri Morin said, “As a leading developer of medicines and diagnostics to improve cancer care, we are proud to be part of this celebration of survivorship. Our hope is that as this campaign travels throughout Ireland, that it will be a source of comfort and hope to women at various stages of their cancer journey.”
Less waiting time More free time 1
ABRIDGED PRESCRIBING INFORMATION (For full prescribing information, refer to the Summary of Product Characteristics [SmPC]) HERCEPTIN® (trastuzumab) 600mg solution for injection in vial Indications: Metastatic Breast Cancer (MBC): Treatment of adult patients with HER2 positive MBC: (i) as monotherapy following at least 2 chemotherapy regimens for MBC. Prior chemotherapy to include at least an anthracycline and a taxane, unless unsuitable for treatments. Hormone receptor positive patients must also have failed hormonal therapy, unless unsuitable for treatments. (ii) in combination with paclitaxel for patients who have not received chemotherapy for MBC and where anthracyclines not suitable. (iii) in combination with docetaxel for patients who have not received chemotherapy for MBC. (iv) in combination with an aromatase inhibitor for the treatment of postmenopausal patients with hormone-receptor positive MBC, not previously treated with Herceptin. Early Breast Cancer (EBC): Treatment of adult patients with HER2 positive EBC (i) following surgery, chemotherapy (neoadjuvant or adjuvant) and radiotherapy (if applicable) (ii) following adjuvant chemotherapy with doxorubicin and cyclophosphamide, in combination with paclitaxel or docetaxel. (iii) in combination with adjuvant chemotherapy consisting of docetaxel and carboplatin. (iv) in combination with neoadjuvant chemotherapy followed by adjuvant Herceptin therapy for locally advanced (including inflammatory) disease or tumours >2cm diameter. Herceptin should only be used in MBC or EBC patients whose tumours have either HER2 overexpression or HER2 gene amplification as determined by an accurate and validated assay. Dosage and Administration: HER2 testing is mandatory prior to Herceptin therapy. Only physicians experienced in cytotoxic chemotherapy should initiate Herceptin: The injection should be administered by a healthcare professional only. Herceptin subcutaneous (SC) formulation is not intended for intravenous (IV) administration and should be administered via a SC injection only. Check product labels to ensure correct formulation is being administered, as prescribed. In order to prevent medication error it is important to the check the vial labels to ensure that the drug been prepared and administered is Herceptin (trastuzumab) and not Kadcyla (trastuzumab emtansine). Not recommended in patients <18 years of age. Dedicated PK studies in older people and those with renal or hepatic impairment have not been carried out. Refer to SmPC for dose reduction and missed doses. Treat MBC patients until disease progression. Treat EBC patients for 1 year or until disease recurrence; whichever occurs first, extending treatment beyond one year in EBC is not recommended. Recommended dose is 600mg irrespective of the patient’s body weight. No loading dose is required. This dose should be administered subcutaneously over 2-5 minutes every three weeks, refer to SmPC for further information regarding administration. Patients should be observed for six hours after the first injection and for two hours after subsequent injections for signs or symptoms of administration-related reactions. Refer to SmPC for chemotherapy combination dosing and information on switching from Herceptin IV to Herceptin SC and vice versa. Contraindications: Hypersensitivity to trastuzumab, murine proteins, hyaluronidase or any excipients. Severe dyspnoea at rest due to complications of advanced malignancy or requiring supplementary oxygen therapy. Warnings and Precautions: In order to improve traceability, the trade name and batch number of the administered product should be clearly recorded (or stated) in the patient file. HER2 testing in a specialised laboratory is mandatory to ensure adequate validation of test. No trial data available on re-treatment of patients with previous exposure to Herceptin in the adjuvant setting. Cardiac dysfunction: Congestive heart failure or asymptomatic cardiac dysfunction observed in patients receiving monotherapy or in combination with paclitaxel or docetaxel, particularly following anthracycline-containing regimens: may be moderate to severe, has been fatal. Caution should be exercised in treating patients with increased cardiac risk, refer to SmPC. All candidates for treatment (especially those with prior anthracycline and cyclophosamide exposure) should undergo baseline cardiac assessment including history and physical examination, ECG, echocardiogram, and/or MUGA scan or magnetic resonance imaging. Monitor for identification of cardiac dysfunction. In all patients cardiac assessments should be repeated every 3 months during treatment and every 6 months following discontinuation until 24 months from the last dose. A careful risk-benefit assessment should be made before deciding to treat with Herceptin. Anthracycline therapy should be avoided for up to 7 months after stopping Herceptin, refer to SmPC. Formal cardiological assessment should be considered in patients with cardiovascular concerns following baseline screening. In all patients, monitor cardiac function e.g. every 12 weeks. Monitor patients who develop asymptomatic cardiac dysfunction more frequently (e.g. every 6-8 weeks). Consider discontinuing treatment in patients with asymptomatic decreased LVEF function if no clinical benefit seen. The safety of continuing or resumption of Herceptin in patients who experience cardiac dysfunction has not been studied. Caution in treating patients with symptomatic heart failure, history of hypertension, Coronary artery disease, and in EBC patients with LVEF of 55% or less. If LVEF % drops ≥ 10 points from baseline AND to below 50%, suspend treatment, repeat LVEF assessment within 3 weeks. If LVEF does not improve or further declines, or symptomatic CHF develops strongly consider discontinuation, refer to SmPC. All such patients should be reviewed by cardiologist and followed up. If symptomatic cardiac failure develops during therapy, treat with standard medications. Most patients in the pivotal trials who developed CHF or asymptomatic cardiac dysfunction improved with standard medication, refer to SmPC. MBC: Herceptin and anthracyclines should not be given concurrently in the MBC setting. Increased risk of cardiac dysfunction in patients who previously received anthracycline therapy. EBC: For EBC patients, cardiac assessment, as performed at baseline, should be repeated every 3 months during treatment and every 6 months following discontinuation of treatment for duration of 24 months from the last dose. Further monitoring is recommended for patients receiving anthracycline containing chemotherapy and should occur yearly up to 5 years from the last dose or longer if a continuous decrease of LVEF is observed. In EBC, no data on patients with history of MI, angina pectoris requiring medical treatment, existing or a history of documented CHF (NYHA Class II-IV), LVEF of <55%, other cardiomyopathy, cardiac arrhythmia requiring medical treatment, clinically significant cardiac valvular disease, poorly controlled hypertension and hemodynamic effective pericardial effusion therefore treatment not recommended in such patients. Herceptin and anthracyclines should not be given concurrently in the adjuvant treatment setting. In EBC adjuvant patients, the incidence of symptomatic and asymptomatic cardiac events increased when Herceptin (IV formulation) was administered after anthracycline-containing chemotherapy compared to administration with a non-anthracycline regimen of docetaxel and carboplatin and was more marked when Herceptin (IV formulation) was administered concurrently with taxanes than when administered sequentially to taxanes. Most symptomatic cardiac events occurred within the first 18 months, regardless of the regimen used, refer to SmPC for further details. Risk factors for cardiac event include age >50 yrs, LVEF< 55% at baseline declining by 10-15 points prior to or following initiation of paclitaxel treatment and prior or concurrent use of anti-hypertensive medicinal products. In patients receiving Herceptin after completion of adjuvant chemotherapy, risk of cardiac dysfunction was associated with a BMI > 25 kg/m2 and a higher cumulative dose of anthracycline therapy given prior to initiation of Herceptin. In EBC patients eligible for neoadjuvant-adjuvant treatment, low dose anthracycline regimens (maximum cumulative doses: doxorubicin 180 mg/m2 or epirubicin 360 mg/m2) can be administered concurrently with chemotherapy naïve Herceptin patients. If patients have been treated concurrently with low dose anthracyclines and Herceptin in the neoadjuvant setting, no additional cytotoxic chemotherapy should be given after surgery. Experience of concurrent administration with low dose anthracycline regimens is currently limited to two trials, MO16432 and BO22227, refer to SmPC for details. Clinical experience is limited in neoadjuvant-adjuvant patients above 65 years of age. Administration-related reactions (ARRs) and Pulmonary events: ARRs are known to occur with Herceptin SC formulation. Pre-medication may reduce risk, refer to SmPC. Serious ARRs were not reported in the clinical trial however ARRs have been associated with the IV formulation; exercise caution.
References 1. 2. 3. 4. 5.
Pivot X, Semiglazov V, Chen S, et al. Subcutaneous injection of trastuzumab – analysis of administration time and injection site reactions. Poster presentation at the 37th European Society for Medical Oncology conference, Vienna, Austria, 28 September – 2 October 2012 (Abstract 272P). Herceptin SC Summary of Product Characteristics, 18th February 2016. Herceptin IV Summary of Product Characteristics, 18th February 2016. Ismael G, Hegg R, Muehlbauer S, et al. Subcutaneous versus intravenous administration of trastuzumab in patients with HER2positive, clinical stage I–III breast cancer: phase 3, randomised, open-label, multicentre (neo)adjuvant HannaH study. Lancet Oncol 2012; 13:869–878. Jackisch C, Stroyakovskiy D, Muehlbauer S, et al. Subcutaneous administration of trastuzumab in patients with HER2-positive early breast cancer: Results from the Phase III randomised, open-label, multi-centre (neo)adjuvant HannaH study. Oral presentation at the 8th European Breast Cancer Conference, Vienna, Austria (Abstract 1BA). 21 – 24 March 2012.
Observe patients for 6 hours after first injection and for 2 hours after subsequent injections. ARRs can be treated with an analgesic/antipyretic, or antihistamine. In rare cases, ARRs have resulted in fatal outcome. Patients experiencing dyspnoea at rest due to complications of advanced malignancy and co-morbidities may be at increased risk of fatal ARR and pulmonary events, therefore these patients should not be treated with Herceptin. Refer to SmPC for delayed (including fatal) ARR and pulmonary events. Severe pulmonary events have been reported with use of the IV formulation, occasionally fatal therefore exercise caution with the SC formulation. Cases of interstitial lung disease reported: risk factors include prior or concomitant therapy with other anti-neoplastic therapies known to be associated with it such as taxanes, gemcitabine, vinorelbine and radiation therapy. Patients experiencing dyspnoea at rest due to complications of advanced malignancy and comorbidities may be at increased risk of pulmonary events – do not treat these patients with Herceptin. Exercise caution for pneumonitis, especially in patients treated concomitantly with taxanes. Drug Interactions: No formal drug interaction studies have been performed. Effect of Herceptin on the pharmacokinetics of other antineoplastic agents: Pharmacokinetic data (PK) from studies BO15935 and M77004 in women with HER2 positive MBC suggest that exposure to paclitaxel and doxorubicin (and their major metabolites 6-α hydroxylpaclitaxel, POH, and doxorubicinol, DOL) is not altered by Herceptin IV loading or maintenance dose, refer to SmPC. However Herceptin may elevate the overall exposure of one doxorubicin metabolite (7-deoxy-13 dihydro-doxorubicinone, D7D). The bioactivity of D7D and the clinical impact of the elevation of this metabolite is unclear. Study JP16003 in HER2 positive Japanese MBC patients suggest administration of Herceptin has no effect on the single dose PK of docetaxel. Study JP19959, a substudy of BO18255 performed in male and female Japanese patients with advanced gastric cancer studied the PK of capecitabine and cisplatin administered with or without Herceptin. Exposure to the bioactive metabolite 5 –FU of capecitabine was not affected by the concurrent use of cisplatin plus Herceptin. However, higher concentrations and a longer half-life of capecitabine were demonstrated when combined with Herceptin. The PK of cisplatin was not affected by concurrent use of capecitabine or by concurrent use of capecitabine plus Herceptin, refer to SmPC. Effect of antineoplastic agents on Herceptin pharmacokinetics: Study JPI6003 in Japanese HER2 positive MBC patients found no evidence of a PK effect on Herceptin with concurrent administration of docetaxel. Comparison of PK results from phase II & III clinical trials in HER2 positive MBC patients indicate that individual and mean Herceptin trough serum concentrations varied within and across studies however no clear effect of the concomitant administration of paclitaxel on the pharmacokinetics of Herceptin, refer to SmPC for further details. The administration of anastrozole did not appear to influence the pharmacokinetics of trastuzumab. Fertility, Pregnancy and Lactation: Avoid during pregnancy unless potential benefit for mother outweighs risk to foetus. Do not breast-feed during and for 7 months after last treatment. Cases of foetal renal growth and and/or function impairment in association with oligohydramnios (some associated with fatal pulmonary hypoplasia of the foetus) reported in pregnant women in the post-marketing setting. Use effective contraception during and for at least 7 months after treatment has concluded. Advise women who become pregnant of potential foetal harm and manage with a multidisciplinary team. Effects on ability to drive and use machines: Patients experiencing administration-related symptoms (see section 4.4) should be advised not to drive and use machines until symptoms abate. Side Effects and Adverse Reactions: Most serious and/or common adverse reactions (reported for IV and SC formulations) are cardiac dysfunction, ARRs, haematotoxicity (especially neutropenia), infections and pulmonary events. The safety profile of Herceptin SC formulation from the pivotal trial in EBC was overall similar to the known safety profile of the IV formulation. Adverse events reported more frequently for the SC formulation: serious adverse events which included post-operative wounds infections, ARRs (during treatment phase), hypertension. The following adverse reactions have been reported with Herceptin IV monotherapy or in combination with chemotherapy in trials and in the post marketing setting: Very Common (≥1/10): infection, nasopharyngitis, febrile neutropenia, anaemia, neutropenia, decreased WBC count/leukopenia, thrombocytopenia, weight decreased/weight loss, anorexia, insomnia, tremor, dizziness, headache, paraesthesia, dysgeusia, conjunctivitis, increased lacrimation, increased/ decreased BP, irregular heart beat, palpitation, cardiac flutter, decreased ejection fraction, hot flush, wheezing*, dyspnoea*, cough, epistaxis, rhinorrhoea, diarrhoea, vomiting, nausea, lip swelling, abdominal pain, dyspepsia, constipation, stomatitis, erythema, rash, face swelling, alopecia, nail disorder, palmar-plantar erythrodysaesthesia syndrome, arthralgia, muscle tightness, myalgia, asthenia, chest pain, chills, fatigue, influenza-like symptoms, IRR, pain, mucosal inflammation, peripheral oedema and pyrexia. Common (≥1/100 - <1/10): neutropenic sepsis, cystitis, herpes zoster, influenza, sinusitis, skin infection, rhinitis, upper respiratory tract infection, urinary tract infection, erysipelas, cellulitis, pharyngitis, hypersensitivity, anxiety, depression, abnormal thinking, peripheral neuropathy, hypertonia, somnolence, ataxia, dry eye, congestive cardiac failure*, supraventricular tachyarrhythmia*, cardiomyopathy, hypotension*, vasodilation, asthma, pneumonia*, lung disorder, pleural effusion*, pancreatitis, haemorrhoids, dry mouth, hepatocellular injury, hepatitis, liver tenderness, acne, dry skin, ecchymosis, hyperhydrosis, maculopapular rash, pruritus, onychoclasis, dermatitis, arthritis, back pain, bone pain, muscle spasms, neck pain, pain in extremity, renal disorder, breast inflammation/mastitis, malaise, oedema and contusion. Immunogenicity: Neutralizing anti-trastuzumab antibodies were detected in post-baseline samples in Herceptin intravenous and Herceptin subcutaneous patients. 20.0% of patients treated with Herceptin subcutaneous formulation developed antibodies against the excipient hyaluronidase (rHuPH20). The clinical relevance of these antibodies is not known; nevertheless the pharmacokinetics, efficacy and safety determined by occurrence of ARRs of Herceptin IV and SC do not appear to be adversely affected by these antibodies. Adverse reactions of lesser frequency: anaphylactic reaction*, anaphylactic shock*, pulmonary fibrosis*, respiratory distress*, lung infiltration*, acute respiratory distress syndrome*, bronchospasm*, hypoxia*, oxygen saturation decreased*, respiratory failure* and acute pulmonary oedema*. *Denotes adverse reactions that have been reported in association with a fatal outcome. Refer to SmPC for full listings of adverse events. See SmPC section 4.8 for instructions on reporting adverse events. Legal Category: Product subject to medical prescription which may not be renewed (A). Presentation and Marketing Authorisation Number: EU/1/00/145/002 - Pack of one 6mL vial containing 5mL of solution. Marketing Authorisation Holder: Roche Registration Limited, 6 Falcon Way, Shire Park, Welwyn Garden City, AL7 1TW, United Kingdom. Herceptin is a registered trade mark. Further information is available from Roche Products (Ireland) Limited, 3004 Lake Drive, Citywest, Naas Road, Dublin 24. Telephone: (01) 4690700. Fax: (01) 4690791. Date of Preparation: January 2016
If a pregnancy occurs while using Herceptin or within 7 months following the last dose of Herceptin, please immediately report pregnancy to the Roche Adverse Event Line at Tel: (01) 4690700, Fax: (01) 4690793, Email: firstname.lastname@example.org, Out of Hours: (01) 2910943. Additional information will be requested during a Herceptin-exposed pregnancy and the first year of the infant’s life. This will enable Roche to better understand the safety of Herceptin and to provide appropriate information to Health Authorities, Healthcare Providers and patients. IE/HERS/0915/0009(1)
Date of item: April 2016
All the benefits of Herceptin, now in a faster format1-5
22 Meeting Report
Steep increase in working age Stroke Dr Paul McElwaine, Stroke Research Fellow with the HSE National Stroke programme
figures show that men account for almost three-quarters of strokes across the younger age categories. The increase is in stark contrast to audit results showing a reduction in overall stroke mortality of over a quarter and of almost 50% in the rate of severe disability. The proportion of strokes among people of working age in Ireland has soared by over a quarter in just the last seven years it was revealed at a recent two day National Stroke Conference – prompting calls for significant new investment in prevention programmes, along with health and community care services to cater for younger stroke survivors.
The research shows that 40% of the younger stroke sufferers are smokers – more than twice our national smoking rate – whilst the rate of people already diagnosed with high blood pressure was also worryingly high. Similar results in the UK have largely been ascribed to increasing sedentary and unhealthy lifestyles.
Statistics from the National Stroke Audit published jointly by the Irish Heart Foundation and the HSE’s National Stroke Programme, revealed a 26% increase in the proportion of strokes among under 65s – the equivalent of over 300 extra strokes among people of working age in Ireland every year.
“Whilst the reasons behind this increase have not yet been fully established and may be complex, it is clear that preventable risk factors such as smoking and high blood pressure are significant contributors,” said Dr Paul McElwaine, Stroke Research Fellow with the HSE National Stroke programme which led the audit research.
Although more women die from stroke across all age groups, the
“This raises the distinct possibility that whilst people in older age
groups are acting on advice and information campaigns to minimise their risk of stroke and cardiovascular disease generally, middle aged men are not, perhaps because they do not understand their level of risk.” Irish Heart Foundation head of advocacy, Chris Macey said the statistics show that stroke can no longer be seen as only a disease of older people. “People of working age are now accounting for one in four of all strokes and the rate is growing rapidly in spite of Ireland’s ageing population. It appears that middle aged men in particular are not heeding the health messages around prevention of stroke and we must remedy this starting with prevention awareness campaigns specifically targeted at them.” With more people than ever surviving stroke and returning home, there was also a need to develop community health and social care services for younger stroke sufferers who may have to cope for decades with the disabilities caused by stroke. This includes an overhaul of programmes to help working age stroke survivors return to work in response to separate research carried out by the RCSI and the Irish Heart Foundation showing that only 32% of those who returned to employment were working full-time one year after their stroke.
“Having a stroke is a devastating experience, the impact of which could be significantly reduced by the development of better community health, social care and vocational services that can provide enormous help on the road to recovery, whilst also benefiting society as a whole both socially and economically,” added Mr Macey. Dr McElwaine said the national stroke audit showed major reductions in death and permanent severe disability from stroke and a sharp increase in the proportion of milder strokes hitting younger people. One specific and cost effective service improvement benefiting this group would be to extend Early Supported Discharge (ESD) programmes that enable stroke survivors to be discharged quicker after stroke and receive intensive therapy services in their own homes. Only 10% of Irish stroke survivors were able to avail of ESD, compared to 30% in the UK despite conclusive international and Irish evidence on their effectiveness in improving outcomes and reducing overall health service costs. The ESRI has estimated that over half of all stroke survivors could avail of ESD – more than 3,000 people annually – delivering a saving of 24,000 bed days a year in Irish hospitals, along with significant quality of life improvements for patients.
First Charter of Rights for Dementia The Alzheimer Society of Ireland (ASI) and the Irish Dementia Working Group have published a charter highlighting the rights of people with dementia, influenced by the Scottish Charter of Human Rights developed by the CrossParty Group in the Scottish Parliament on Alzheimer’s. The Charter of Rights for People with Dementia stresses the need for a parity of rights for the 48,000 people estimated to have the condition in Ireland. The Charter of Rights for People with Dementia calls for greater participation, accountability,
May 2016 • HPN
equality, empowerment, and legal recognition for the rights of people with dementia. Specifically, it highlights policy gaps in the areas of stigma and the “inadequate and inappropriate” nature of services. People with dementia can face discrimination and treatment that contravenes their human rights for three key reasons: Ageism The stigma and discrimination associated with the condition Lack of capacity to challenge and report incidents that occur.
The ASI believes people with dementia need a charter that explicitly states their rights to counter the prevailing stigma and unmet needs of people with dementia; the inadequate and inappropriate services available and the nature of the condition. These policy gaps are not about simply the needs of people with dementia; they are about their rights. Helen Rochford-Brennan, Chairperson of The ASI’s, Irish Dementia Working Group said, “As a person living with dementia this is a momentous day for those of us who are dedicated to
fighting for equal rights as citizens. “Dementia has long been shrouded by stigma and there is still a very low level of awareness of the full demographic of those with the condition. There are people with young families living with it, there are children caring for parents with the condition and there are older people in long term care who are not receiving the supports they need. We are fighting for the rights of every single one of these people and their families who are everyday fighting to stay in their homes, access services and be treated with the dignity they deserve.”
Trinity Forms Academic Link with Our Lady’s Hospice & Care Services Trinity and Our Lady’s Hospice & Care Services signed a Memorandum of Understanding (MOU) formalising an academic link between the two on 18 May. This MOU complements agreements the School of Pharmacy and Pharmaceutical Sciences already has in place with St James’s and Tallaght Hospitals. Explaining the meaning of this relationship for Trinity, Head of School of Pharmacy and Pharmaceutical Sciences, Professor Anne Marie Healy said, “Palliative care impacts upon us all and it is growing in importance. Palliative care will continue to evolve as a discipline and as a service and the School is excited to be entering this partnership with Our Lady’s and is concerned to ensure that all of our students, undergraduate and postgraduate, have the opportunity to learn with and from the best and that we, as a School, can contribute in some way to improving patients’ quality of life through palliative care.” Chief Pharmacist at Our Lady’s Hospice & Care Services, Eimear O’Dwyer said, “In
return for our clinical support, this link with Trinity will support our staff to participate in regular audits, research and Continuing Professional Development (CPD). We will also be in a position to engage in wider reaching internal and external research in the disciplines of Palliative Medicine, Rheumatology and Gerontology. As well as playing a role as an educator, our pharmacy department has a longstanding record of being progressive and innovative with its history of a fruitful affiliation with St James’s Hospital for many years. This has led to our current standalone service with a strong patient-centred focus. Our ‘Palliative Meds Info’ service is now a well-established and widely used resource for health professionals on all aspects of drug therapy that are used in palliative care. For the future, we are interested in further developing our clinical services across the organisation. We are constantly exploring opportunities to develop practices in line with the evidence base, including improved systems facilitating self-administration by patients.”
Prof Linda Hogan, Vice-Provost and Chief Academic Officer of Trinity; Audrey Houlihan, Chief Executive of Our Lady’s Hospice & Care Services; Back row: Eimear O’Dwyer, Chief Pharmacist at Our Lady’s Hospice & Care Services; Prof Anne Marie Healy, Head of Trinity's School of Pharmacy and Pharmaceutical Sciences
Chief Executive of Our Lady’s Hospice & Care Services, Ms Audrey Houlihan said, “We are delighted to be a recognised education partner of Trinity. This formalises a relationship that has existed for over a decade with the School of Pharmacy and Pharmaceutical Sciences. We believe this formal commitment to teaching, research and clinical links provides a wonderful opportunity for our staff and Trinity students and promotes excellence in patient care. We hope that future
multidisciplinary education programmes at Our Lady’s Hospice & Care Services will also benefit from this affiliation. It will encourage greater opportunity for research projects across the organisations and will provide additional opportunities for the education of pharmacists in the care specialties offered at Our Lady’s Hospice & Care Services and for the professional development of pharmacy staff.”
Leading researcher joins local team UCC and Tyndall National Institute have appointed Professor Stefan Andersson-Engels to lead a new ¤6m SFI funded biophotonics research programme to develop further Ireland’s medical device and diagnostics research capability. Professor Andersson-Engels has been appointed Professor of Biophotonics in the Department of Physics, UCC and Head of the newly-established Biophotonics Group at the Science Foundation Ireland Irish Photonic Integration Research Centre (IPIC). He will lead the new research programme under the Science Foundation Ireland Research Professorship Programme. Biophotonics is an emerging area
of scientific research that uses light to understand the inner workings of cells and tissues in living organisms, allowing researchers to see, measure and analyse living tissues in ways that have not been possible before. Commenting on his appointment, Professor Andersson-Engels said, “I am delighted to be joining the talented team in Cork and look forward to working with colleagues across Tyndall, UCC and IPIC. With the medical devices sector in Ireland recognised as one of the five emerging global hubs, it is an exciting time for the Biophotonics Group to forge close collaborations with companies, clinicians and research centres for the faster development and deployment
of more accurate, less invasive diagnostic treatment methods for cancer and other diseases.” Professor Andersson-Engels has received several prizes for his research achievements. His impressive track record in the development and commercialisation of technology has been critical to ensuring that patients will benefit from results of scientific research. His pioneering work in the area of ALA-PDT (Photodynamic therapy (PDT) using the topical application of aminolevulinic acid (ALA), a photosensitizing agent) for the treatment of non–melanoma skin cancer is currently one of the first lines of treatment at most skin cancer clinics around the world.
Previously, Professor AnderssonEngels was Deputy Head of the Atomic Physics Division and Head of the Medical Laser Centre at Lund University, Sweden. He is co-founder of the renowned international summer school ‘Biophotonics’. Professor Andersson-Engels received the “Lindbomska belöningen” from the Swedish Royal Academy of Sciences in Stockholm in recognition of his outstanding achievements in teaching. His contribution to business has also been acknowledged through the SKAPA award, the most prestigious entrepreneurship award in Sweden.
HPN • May 2016
Self-Harm Presentations in Emergency Departments Dr Ruth Loane, President, The College of Psychiatrists of Ireland
The Clinical Programme for Management of Self Harm Presentations in Emergency Departments was launched by the HSE in March of this year, presenting a timely and practical programme which puts into operation a practical expert response to a growing and concerning problem in our communities nationally. The programme provides a standardised process for the assessment and management of people of all age ranges who self-harm. The process guarantees people in distress a timely assessment leading to triage and on to needs based follow up by skilled clinicians. The Clinical Programmes bring clinical leadership to the heart of the clinical decision-making process with the ultimate aim of improving quality, access and value of healthcare in the country using evidence-based approaches to system reform. The HSE clinical care programmes in mental health are collaboratively developed with the us at the College of Psychiatrists. The College’s role is to ensure that all clinical care programmes in mental health use internationally recognised best practice in supporting people with mental health problems. Suicide is well recognised as a serious public health issue with 11,126 self-harm presentations to Emergency Departments (ED) in Ireland and 459 deaths in 2014. It requires a diversity of responses: social, educational, occupational and health related. This Clinical Programme is a part of an overall strategy and specifically addresses the care and treatment required by people who present to the Emergency Departments (ED) of acute hospitals following an episode of self-harm or with prominent suicidal ideation. It aims to provide a standardised specialist response to all such people and, by so doing, reduce the numbers leaving Emergency Departments without an assessment, link people into appropriate care, involve families and friends as appropriate with an overall aim of reducing
May 2016 • HPN
Dr Kevin Carson, President, College of Anaesthetists, Dr Ruth Loane, President, College of psychiatrists Ireland, Mr Fintan Foy, CEO, College of Anaesthetists
repetition which is known to be associated with an increased risk of completed suicide. 35.5 clinical nurse specialist nurses have been allocated to emergency departments across the country to deliver the programme in addition to the teams and staff already in place. In tandem with the programme a training plan has been developed to ensure that staff are skilled and have on-going opportunities to develop competencies and have access to supervision in this clinical area. Training will also be provided to emergency health care staff in working with self-harm or suicidal patients to foster improved knowledge of self-harm, more positive attitudes and increased confidence in assessing and managing people in the ED. Multidisciplinary community mental health teams for all age groups have developed and expanded in recent years and so are able to respond to acute mental health problems on the same day. However, there will always be people who directly access Emergency Departments either by choice or necessity and hence it is essential to ensure that staff with the requisite skills are available to meet their needs in a timely fashion. Self-harm is the single biggest risk factor for completed suicide, increasing the risk of suicide 40fold, as compared to the general population (Owen et al, 2002;
Carroll et al, 2014). Suicide is now the commonest cause of death for young men (aged 15-24 years) and middle aged men (45-54 years). Alcohol consumption is implicated in more than 37% of cases of selfharm (Griffin et al, 2015) and half of those who die by suicide have had a history of alcohol abuse in the final year of their lives (Arensman et al, 2013). Diversity with regard to assessment procedures and management in health settings, as well as feedback from families bereaved by suicide, have led to repeated calls for the development and resourcing of an effective response for people who present to health services having engaged in self-harm.
Training offered by this programme will ensure that patients and their families have access to clinicians with sufficient expertise to provide high-quality, evidence-based care and treatment. Critical to the success of this clinical programme will be the consolidation and further development of (and, in some areas, formation of) close working relationships between the ED clinical team, mental health liaison staff and community mental health teams (CMHTs) and General Practitioner (GP) services. The objectives are to: Improve the assessment and management of all individuals who present to ED with self-harm
This National Clinical Care Programme (NCP) refers to the mental health/bio-psychosocial assessment and initial management of both risk and need following self-harm, in the acute hospital Emergency Department, from time of presentation to discharge.
Reduce rates of repeated self-harm
This requires that all patients presenting to ED with self-harm (including suicidal ideation and intent) will receive standardised triage, bio-psycho-social assessment and assertive follow up by skilled clinicians.
Optimise the experience of families and carers in trying to support those who present with self-harm.
Family/carers will be included in the assessment and follow up process. The quality of the programme will be monitored through a set of key metrics.
Improve access to appropriate interventions at times of personal crisis Ensure rapid and timely linkage to appropriate follow-up care
I would like to specifically thank two College members, Dr Siobhán MacHale, Chair of the Programme subgroup, and Dr Eugene Cassidy for their time and commitment to the development of this programme.
Plans to bridge the ‘digital gap’ HSE Director General, Mr Tony O Brien has announced plans to have all HSE staff digitally connected by the end of the year. This ambitious project will provide e-mail and online connectivity to over 30,000 staff in the health services who currently do not currently have access to digital tools to support them in their roles. According to Mr. O Brien, “I want the HSE to have a more digitally connected workforce. The modern healthcare system must value connectivity highly and we need to embrace this in every way we can. In investing in our staff, and supporting them with the tools they need, we in turn are better able to provide a safer, more efficient and ultimately better service to our patients and to the public.” At present, 30,000 HSE staff have no digital identity but by the end of 2016, all these individuals will have been provided with access to e-mail to enable them to have a healthcare digital identity. A further 10,000 staff members working in primary care in community settings have no IT
Tony O'Brien, HSE Director General
tools to support them in their roles. This project will provide all of these staff with a digital device and the tools and support to use them in their work by the end of the year. The project is being led out by the HSE’s Chief Information Officer, Mr Richard Corbridge and eHealth Ireland. According to Mr Corbridge, “This is a great opportunity to get all of our staff digitally connected. We are committed to delivering on our
Knowledge and Information Plan to provide a secure information structure. We are all aware of the significant contribution that IT is making in providing innovative solutions within healthcare. Equally we know that the pace of advance and development is accelerating. We want all our staff to be connected and to be facilitated and empowered to participate, belong and ensure our patients and our public are the ultimate benefactors.”
In 2015 the HSE began to address its “digital gap” with the appointment of a Chief Information Officer and a Head of Digital Communications, which signalled a change in approach to digital in the health services. Building a better health service requires greater digitally connectivity within the HSE so that health service staff can communicate more effectively, with each other and with patients and the public.
IAEM express concern on lack of focus The Irish Association for Emergency Medicine says it is seriously concerned about the misplaced focus of the Fine Gael and Fianna Fail parties in their almost comical attempts to form a government.
taken by the two largest political parties in the major difficulties evident in the Health Service, difficulties that carry major risks of poor medical outcomes for the citizens of the country,” they say.
“At a time where there continues to be dangerous levels of Emergency Department (ED) crowding with admitted hospital inpatients, their seemingly exclusive preoccupation on a charging mechanism for the provision of domestic water is a very serious cause of concern and is proof of just how little interest is
“Not only does the ED crowding problem persist and worsen, there are a myriad of other welldescribed health service problems that seriously impact on patients’ lives and wellbeing amongst them difficulties in accessing mental health services and primary care services in many areas.
“Irrespective of what government the country ends up with, there is an inescapable need to finally and definitively tackle ED crowding unless the intention is to see further patients die unnecessarily. ED crowding is a problem that could be fixed with the necessary political focus; investment in bed capacity and taking steps to create the circumstances (adequate staffing and appropriate resources) to allow EDs to function optimally. “Before the General Election campaign, the Association launched the IAEM 10 , a road
map for what needs to be done to ensure that Ireland’s Emergency Departments are able to provide the level of service that those medical and nursing staff working in them aim to provide and are capable of delivering, provided the impediments to service delivery currently evident, particularly crowding with admitted inpatients, are removed. “The country undoubtedly deserves better from those it elects to provide political leadership to the Irish people,” they conclude.
Cross Party Health Motion The new Minister for Health, Simon Harris is positively considering the motion submitted earlier this month to establish a cross-party committee on developing a 10-year plan for the health service. "It is extremely encouraging in the 32nd Dail to see a consensus emerging on the health service. I have made it very clear that I want to see consensus on a 10-year plan for the health service and I am currently considering the motion with a view to encompassing thoughts and ideas of my own and reflecting the Programme for Government agreed with our Independent partners. I am committed to working positively with the opposition to make progress on establishing this committee as quickly as possible,” he said.
HPN • May 2016
NUI study on sleep paralysis The School of Psychology at NUI Galway is starting a study on the number of people affected by sleep paralysis and unusual sleep experiences. The researchers are seeking over 1,000 participants throughout Ireland to take part in the online study.
Previous studies at NUI Galway have found that about a quarter of its students have reported experiences of sleep paralysis. Sleep paralysis involves a person experiencing the inability to move when they are just falling asleep or when waking up from sleep.
This study is interested in looking at how people’s emotions and lifestyles relate to their sleep. It is also interested in understanding how and why people experience sleep difficulties like sleep paralysis. Sleep paralysis can happen when we are falling asleep or waking up and is often viewed as a distressing experience.
People who experience sleep paralysis often report seeing a shadow of a man or an old woman, or a sense of someone being present in their room. Sometimes the figure sits on their chest, or just simply moves towards them. Other people report their bed clothes being moved or their body being touched.
In some cases, the person reports that they feel as if they are looking down on themselves whilst being unable to scream or move. Most reported the experience as very frightening, but some will have pleasant recollections, such as a dead relative coming to caress their face or tuck-them-in. One student reported that she recalled the Easter Bunny jumping up on her bed! The study is being carried out by Michelle Tomas, a Doctoral student on the clinical psychology training programme at the School of Psychology in NUI Galway and her supervisor Dr Jonathan Egan,
Deputy Director of the clinical programme. Dr Jonathan Egan from the School of Psychology at NUI Galway, said, “We are interested in how general well-being, sleep quality, stress and mood are related to episodes of sleep paralysis. No study has addressed a large non-student population in Ireland before and we hope to get over a thousand people to participate in the research.”
Urgent need for new Minister to address issues The Irish Hospital Consultants Association (IHCA) have welcomed the appointment of Simon Harris, TD, as the new Minister for Health and said they look forward to collaborating with him on the important issues impacting patient care in Ireland. The association has written to Minister Harris to wish him success in his new role and highlight the need for immediate action to address critical capacity deficits.
In writing to the Minister, the IHCA outlined the urgent need for investment in frontline services to address the severe capacity constraints that exist in acute hospital and mental health services, as they are impacting adversely on the delivery of timely, high quality, safe care to patients. Dr Gerard Crotty, President of the IHCA, said, “International comparisons confirm that our acute services have one of the
lowest numbers of practising doctors, a relatively low number of acute hospital beds and an excessively high bed occupancy rate. In recent years, Ireland has suffered a damaging medical brain drain which has resulted in hundreds of approved hospital consultant posts remaining vacant or, at best, being filled on a temporary or agency basis.” Dr Crotty continued, “These factors are undermining the
provision of care to patients in Ireland. We welcome Minister Harris’s commitment to the development of a 10-year healthcare strategy and the plans he has to address healthcare funding in future but this should not delay immediate investment that is needed to address the capacity constraints that are severely curtailing the delivery of care to patients.”
RCSI hosts 2016 All Ireland Schools of Pharmacy Research Conference Approximately 100 delegates attended the 38th All Ireland Schools of Pharmacy Research Conference hosted by RCSI and supported by AbbVie on March 21st and 22nd 2016. The attendees comprised postgraduate students and faculty from all five Schools of Pharmacy in Ireland; RCSI, Trinity College Dublin, University College Cork, Queen's University Belfast and Ulster University. A total of 75 abstracts were included in the conference programme, with 18 oral presentations from postgraduate students scheduled over the two days. This year's conference programme also included two keynote speakers; Dr Margaret Watson (University of Aberdeen) and Professor Robbert Jan Kok (Utrecht University). Dr Watson's keynote address focussed on the importance of pharmacy practice-
May 2016 • HPN
based research in informing evidence-based pharmacy practice and policy. Professor Kok's keynote address outlined how the safety and efficacy of drugs could be improved through selective targeting and localised delivery. The winner of the best oral presentation was David Walsh, PhD in RCSI's Anatomy Department, who presented his research on novel gene-activated scaffolds for application in tissue engineering. The winner of the best poster presentation was Marine Chalanqui of Queen's University, for her research on a biologically loaded, thermosensitive hydrogel for the treatment of bone metastases. Speaking during the conferences prize-giving ceremony, Professor Paul Gallagher, Head of RCSI's School of Pharmacy, said, “The RCSI School of Pharmacy took
Daire Osborne (left) and Mark Phelan (first right) of AbbVie with poster prize winner Marine Chalanqui (QUB) and oral prize winner David Walsh (RCSI) great pleasure in hosting this year's All-Ireland Schools of Pharmacy Research Conference, which is a long established and important feature of the academic
calendar. I'd like to thank all of those who participated in the conference proceedings and thanks to AbbVie for their sponsorship of the event.”
CPD 21: Melanoma Continuing Professional Development
Kenneth M. Joyce, MB, BCh, BAO, MRCS, Cormac W. Joyce, MB, BCh, BAO, MRCS,* Deirdre M. Jones, MD, FRCS,* Paul Donnellan, MD,† Alan J. Hussey, MD, FRCS,*‡ Padraic J. Regan, MD, FRCS,*‡ and Jack L. Kelly, MD, FRCS*‡ From the *Department of Plastic and Reconstructive Surgery, Galway University Hospital, Galway, Ireland; †Department of Oncology, Galway University Hospital, Galway, Ireland; and ‡Discipline of Surgery, National University of Ireland, Galway, Ireland.
1. REFLECT - Before reading this module, consider the following: Will this clinical area be relevant to my practice.
3. PLAN - If I have identified a knowledge gap - will this article satisfy those needs or will more reading be required?
2. IDENTIFY - If the answer is no, I may still be interested in the area but the article may not contribute towards my continuing professional development (CPD). If the answer is yes, I should identify any knowledge gaps in the clinical area.
4. EVALUATE - Did this article meet my learning needs - and how has my practise changed as a result? Have I identified further learning needs?
60 Second Summary Melanoma in situ (MIS) is an early form of melanoma with the atypical melanocytes confined to the epidermis. MIS accounts for up to 27% of all melanomas, with over 60,000 cases of MIS diagnosed in the United States in 2013.1,2 The risk of MIS converting to invasive melanoma, if untreated, is unknown, but the lentigo maligna (LM) subgroup carries a 5–15% lifetime risk of progression. We reviewed a prospectively maintained pathology database of all patients with MIS excised at our institution over a 5-year period from December 2008 to January 2014. Selection criteria included all patients who had biopsy-proven (excisional or incisional) primary MIS. The finding of single scattered atypical melanocytes was not considered sufficient for diagnosis of LM. From 2009 to 2014, 458 patients were treated for primary MIS. Forty-eight patients (10.5%) were lost to follow-up and were excluded from the study. These patients were followed up by their referring physician. The final cohort consisted of 410 patients (52.2% female, 47.8% male) with a median age of 69 years (range, 22–98 years). The median follow-up was 23 months (range, 1–65 months). The number of MIS excised per year increased over the study period, with 45 cases in 2009 compared to 111 cases in 2013. Worldwide, MIS is becoming increasingly prevalent. Contributing to this increase is an ageing population with a significant history of sun exposure. In our institution, the number of cases excised increased by over 160% in the time period studied. National melanoma statistics show that overall there is an increasing prevalence of melanomas being diagnosed; however, the rate of increase of MIS is greater than that of invasive disease.9 This may reflect the benefit of public awareness campaigns.
5. WHAT NEXT - At this time you may like to record your learning for future use or
assessment. Follow the 4 previous steps, log and record your findings. Published by HPN, sponsored by MSD. Copies can be downloaded from www.irishpharmacytraining.ie Disclaimer: All material published is copyright, no part of this can be used in any other publication without permission of the publishers and author. MSD has no editorial oversight of the CPD programmes included in these modules.
An Assessment of Histological Margins and Recurrence of Melanoma In Situ Melanoma in situ (MIS) is an early form of melanoma with the atypical melanocytes confined to the epidermis. MIS accounts for up to 27% of all melanomas, with over 60,000 cases of MIS diagnosed in the United States in 2013.1,2 The risk of MIS converting to invasive melanoma, if untreated, is unknown, but the lentigo maligna (LM) subgroup carries a 5–15% lifetime risk of progression.3
with surgical margins of at least 9 mm. A further study by Akhtar et al8 suggested that narrow margin excisions are unlikely to lead to recurrence and that wide margins may be unnecessary. The aim of this study was to assess the impact of histological excision margins to recurrence and progression to invasive disease for MIS.
MIS is becoming increasingly prevalent as the population ages, with risk factors, including sun exposure and immunosuppression, becoming more widespread. Therefore, optimal treatment for patients with MIS is becoming increasingly necessary. Although MIS is a precursor for invasive disease, it has no potential for metastatic spread, and the aim should be to excise the lesion completely with a clear histological margin.4 LM often has wide invisible extensions resulting in frequent re-excision. Local recurrence of LM occurs in 5% of patients by 2 years.5
We reviewed a prospectively maintained pathology database of all patients with MIS excised at our institution over a 5-year period from December 2008 to January 2014. Selection criteria included all patients who had biopsy-proven (excisional or incisional) primary MIS. The finding of single scattered atypical melanocytes was not considered sufficient for diagnosis of LM. All patients were treated by wide local excision (WLE) or staged excision. Patients undergoing staged excision only had the final histologic margin included in the analysis of margins. Mohs micrographic surgery is not performed at our institution. Specimens were formalin fixed and underwent serial sectioning and immunohistochemical staining. All cases were discussed at a skin cancer multidisciplinary meeting, and consensus was reached for each individual case.
Current National Comprehensive Cancer Network guidelines for MIS recommend a 5-mm surgical margin of resection, but this margin is frequently insufficient to prevent recurrence.6 A large study by Kunishige et al7 in 2012 suggested that MIS should be treated similarly to early invasive melanoma,
MATERIALS AND METHODS
Clinicopathologic details recorded included
Continuous Professional Development Modules are sponsored by MSD MSD has no editorial oversight of the CPD programmes included in these modules.
CPD 21: Melanoma
patient demographics, anatomical location, melanoma subtype, histological excision margin, and recurrence. Histological excision margins were measured by the pathologist in formalin-fixed specimens following surgical excision. Surgical margins of excision were not recorded given the retrospective nature of the study. The standard margin of excision for MIS in our institution was 5 mm when possible, as per recommended guidelines.4 For those who underwent a WLE that was clear of disease, the narrowest width of the specimen was taken as the histological margin of excision. Recurrence was defined as reappearance of tumour within or adjacent to the scar, with an intraepidermal component, and represented inadequate initial excision. Follow-up period was determined by the last outpatient review. Those patients lost to follow-up were excluded. Statistical analyses were performed using Fisher’s exact test, with statistical significance determined as P < 0.05. RESULTS From 2009 to 2014, 458 patients were treated for primary MIS. Forty-eight patients (10.5%) were lost to follow-up and were excluded from the study. These patients were followed up by their referring physician. The final cohort consisted of 410 patients (52.2% female, 47.8% male) with a median age of 69 years (range, 22–98 years). The median followup was 23 months (range, 1–65 months). The number of MIS excised per year increased over the study period, with 45 cases in 2009 compared to 111 cases in 2013 (Fig. (Fig.11).
primary lesions varied according to gender, with men having a greater proportion on the scalp and neck area (14.8% vs 2.3%) (P = 0.001), whereas women had a greater proportion on the lower limb (14.0% vs 1.5%) (P < 0.001). Within our cohort, 324 cases of MIS were LM subtype (79%), with the majority of these occurring on the face (81.4%) and scalp and neck (5.9%).
was 2.2% (9/410), with a mean time to recurrence of 29.6 months (range, 8–47 months). This is comparable to recent international studies (Table1).1
Fig. 2: Location of primary melanoma in situ (Below)
The mean excision margin of those that recurred was 1.9 ± 1.3 mm compared with a mean of 3.8 ± 2.3 mm in those that did not. There was no case of recurrence with a histological
The average histological excision margin was 3.7 mm (range, 0.2– 14 mm). The rate of recurrence
LM had a similar rate of recurrence compared with non-lentigo MIS (2.3% vs 1.2%) (P = 0.69). The majority of recurrences occurred on the face (Table2).2
excision margin of ≥5 mm (Table3).3 The rate of recurrence of lesions with histological margin ≤3.00 mm was 3.8% compared with 0.5% in those lesions with a histological margin >3.00 mm (P = 0.03). One case of MIS recurred as invasive disease. Initial excision showed a LM MIS with involved peripheral resection margins. This recurred after 6 months, and further excision showed a pT1a LM melanoma of Breslow thickness 0.5 mm.
Fig. 1: Number of MIS excised per year (Above) The most common site for the primary lesion was the face (67.1%), followed by the upper limb (9%) and scalp and neck (8.3%) (Fig. (Fig.2)2. The anatomical distributions of
Continuous Professional Development Modules are sponsored by MSD MSD has no editorial oversight of the CPD programmes included in these modules.
29 Table 1: Comparison of Recurrence Rates in the Literature
Table 2: Clinicopathological Details of Lesions That Recurred
Table 3: Histological Excision Margin and Number of Recurrences
DISCUSSION Worldwide, MIS is becoming increasingly prevalent. Contributing to this increase is an ageing population with a significant history of sun exposure. In our institution, the number of cases excised increased by over 160% in the time period studied. National
melanoma statistics show that overall there is an increasing prevalence of melanomas being diagnosed; however, the rate of increase of MIS is greater than that of invasive disease.9 This may reflect the benefit of public awareness campaigns. The anatomical distributions of primary lesions varied according
to gender, with men having a greater proportion on the scalp and neck area, whereas women had a greater proportion on the lower limb. This may be explained, in part, by the differences in clothing between men and women. Rates of melanoma tend to be highest on intermittently exposed sites
among people under 40 years old (ie, trunk or lower limbs), whereas for men and women over 60 years, melanoma is most commonly found on more chronically exposed sites such as the head and neck.10 The rate of recurrence in our study is similar to recent international studies. There
Continuous Professional Development Modules are sponsored by MSD MSD has no editorial oversight of the CPD programmes included in these modules.
CPD 21: Melanoma
was no significant difference in the rate of recurrence of LM versus non-LM lesions. All excisions of MIS in this study were carried out by WLE or staged excision, which is common practice in many plastic surgery units in Great Britain and Ireland. Mohs micrographic surgery provides the advantages of complete margin assessment, tissue conservation, and high cure rates, but this technique is not carried out at our institution. Controversy exists regarding the use of Mohs surgery for the treatment of MIS, with some authors highlighting the difficulties in recognizing MIS on frozen sections.11 The histological evaluation of MIS, particularly LM, presents a challenge for pathologists as certain histological criteria are often difficult to distinguish from benign changes that occur secondary to sun exposure. The presence of widespread atypical melanocytes in the background of long-standing sun damage is highly indicative of LM.12 However, the significance of individual melanocytes at the tumour margin that remain after surgical excision is unclear. Gorman et al13 demonstrated that for LM, melanocyte count at the excision margin was predictive of recurrence. The propensity for LM to recur after apparently adequate surgery is associated with significant morbidity. Clinical recurrence may relate to both wide subclinical extension of atypical melanocytes and limitations in margin assessment. Our results demonstrate that for WLE or staged excision, a histological margin of >3.0 mm is required to achieve a low recurrence rate. The rate of progression of MIS to invasive disease is poorly understood, yet it has been reported that LM carries a 5–15% lifetime risk of developing an invasive disease.3 This risk of invasive progression may be related to the size of the primary lesion, with large lesions harbouring invasive nests.3 In our study, there was one case of MIS that recurred as invasive melanoma 6 months after initial excision. This was a pT1a LM melanoma. Previously reported studies have shown that 23% of recurrent MIS have an invasive component, with a mean Breslow thickness of 0.94 mm.14 It has also been postulated that recurrent lesions may track along the original scar, thereby resulting in larger wounds. Several limitations exist within this study. Surgical margins of excision were not recorded due to the retrospective nature of the study. Furthermore, all lesions excised were by staged excision and not by Mohs
micrographic surgery. In Mohs surgery, the entire margin of the specimen is examined compared to standard pathological assessments where only 0.5–5% of the margin is examined.15 Ideally, all specimens should be excised by Mohs, but this would be far too laborious and resource depleting. CONCLUSIONS In conclusion, this study demonstrates that, at institutions using WLE or staged excision, a histological margin of >3.0 mm is required to achieve a low recurrence rate. The difference in recurrence rates of LM and non-LM subtypes was not significant, and so we conclude that they do not require different histological clearance. Future prospective, randomised controlled trials comparing surgical treatment options and excision margins for MIS are warranted to develop evidence-based guidelines. REFERENCES 1. Siegel R, Naishadham D, Jemal A. Cancer statistics, 2013. CA Cancer J Clin. 2013;63:11–30. [PubMed] 2. Coory M, Baade P, Aitken J, et al. Trends for in situ and invasive melanoma in Queensland, Australia, 1982–2002. Cancer Causes Control. 2006;17:21–27. [PubMed] 3. Agarwal-Antal N, Bowen GM, Gerwels JW. Histologic evaluation of lentigo maligna with permanent sections: implications regarding current guidelines. J Am Acad Dermatol. 2002;47:743–748. [PubMed] 4. Marsden J, Newton-Bishop J, Burrows L, et al. Revised UK guidelines for the management of cutaneous melanoma 2010. Br J Dermatol. 2010;163:238– 256. [PubMed] 5. Bub JL, Berg D, Slee A, et al. Management of lentigo maligna and lentigo maligna melanoma with staged excision: a 5-year follow-up. Arch Dermatol. 2004;140:552–558. [PubMed] 6. Leilabadi SN, Chen A, Tsai S, et al. Update and review on the surgical management of primary cutaneous melanoma. Healthcare. 2014;2:234– 249. 7. Kunishige JH, Brodland DG, Zitelli JA. Surgical margins for melanoma in situ. J Am Acad Dermatol. 2012;66:438–444. [PubMed]
9. National Cancer Registry Ireland. Cancer trends No. 7 Melanoma of the skin 2011. Available at: http:// www.ncri.ie/sites/ncri/files/pubs/ CancerTrendsNo.7-MelanomaofSkin. pdf. Accessed August 11, 2014. 10. Youl PH, Youlden DR, Baade PD. Changes in the site distribution of common melanoma subtypes in Queensland, Australia over time: implications for public health campaigns. Br J Dermatol. 2013;168:136–144. [PubMed] 11. Shriner DL, McCoy DK, Goldberg DJ, et al. Mohs micrographic surgery. J Am Acad Dermatol. 1998;39:79–97. [PubMed] 12. Megahed M, Schön M, Selimovic D, et al. Reliability of diagnosis of melanoma in situ. Lancet. 2002;359:1921–1922. [PubMed] 13. Gorman M, Khan MA, Johnson PC, et al. A model for lentigo maligna recurrence using melanocyte count as a predictive marker based upon logistic regression analysis of a blinded retrospective review. J Plast Reconstr Aesthet Surg. 2014;67:1322–1332. [PubMed] 14. DeBloom JR, II, Zitelli JA, Brodland DG. The invasive growth potential of residual melanoma and melanoma in situ. Dermatol Surg. 2010;36:1251– 1257. [PubMed] 15. Clark GS, Pappas-Politis EC, Cherpelis BS, et al. Surgical management of melanoma in situ on chronically sun-damaged skin. Cancer Control. 2008;15:216–224. [PubMed] 16. Bricca GM, Brodland DG, Ren D, et al. Cutaneous head and neck melanoma treated with Mohs micrographic surgery. J Am Acad Dermatol. 2005;52:92–100. [PubMed] 17. Bene NI, Healy C, Coldiron BM. Mohs micrographic surgery is accurate 95.1% of the time for melanoma in situ: a prospective study of 167 cases. Dermatol Surg. 2008;34:660–664. [PubMed] 18. Huilgol SC, Selva D, Chen C, et al. Surgical margins for lentigo maligna and lentigo maligna melanoma: the technique of mapped serial excision. Arch Dermatol. 2004;140:1087–1092. [PubMed]
8. Akhtar S, Bhat W, Magdum A, et al. Surgical excision margins for melanoma in situ. J Plast Reconstr Aesthet Surg. 2014;67:320–323. [PubMed]
Real-world patients remain on Stelara® longer compared to anti-TNF therapies1,2 Newly published BADBIR* data shows better drug persistency for Stelara compared to anti-TNF therapies1 Adjusted drug survival in biologic-naïve patients**1
• Compared to adalimumab$: - Stelara was a predictor of drug survival - Infliximab† and Etanercept‡ were both predictors of discontinuation.
1.0 Adjusted drug persistence rate
• Predictors of discontinuation were analyzed using a multivariate Cox proportional hazards model.1
Years of follow up
Adapted from Warren RB et al. 2015
* BADBIR (British Association of Dermatologists Biologic Interventions Register) is a prospective, longitudinal, pharmacovigilance register for the UK and the Republic of Ireland. Over 3,500 biologic-naïve patients are enrolled, with a median 1.4 years of follow-up.1 ** Study limitations: BADBIR is primarily used as a pharmacovigilance register, therefore limitations include: the intention behind concomitant medication; potential variability in classifying reason for drug withdrawal across centres; recall and reporting bias may occur with patient-reported characteristics; non-randomisation may introduce selection bias; unmeasured confounders cannot be ruled out; patient adherence was not measured; the infliximab cohort is small.1 $ Adalimumab was the reference standard to which the other biologics were compared with because it was the most commonly prescribed biologic in the registry. † Infliximab was a predictor for discontinuation overall and due to adverse events. ‡ Etanercept was a predictor for discontinuation overall and due to ineffectiveness
STELARA® solution for injection PRESCRIBING INFORMATION ACTIVE INGREDIENT(S): Ustekinumab Please refer to Summary of Product Characteristics (SmPC) before prescribing. INDICATION(S): Plaque psoriasis adults: Treatment of moderate to severe plaque psoriasis in adults who failed to respond to, or who have a contraindication to, or are intolerant to other systemic therapies including ciclosporin, methotrexate or PUVA. Plaque psoriasis paediatrics: Moderate to severe plaque psoriasis in adolescent patients from the age of 12 years and older, who are inadequaely controlled by, or are intolerant to, other systemic therapies or phototherapies. Psoriatic arthritis: Alone or in combination with methotrexate for the treatment of active psoriatic arthritis in adult patients when the response to previous nonbiological disease-modifying anti-rheumatic drug (DMARD) therapy has been inadequate. DOSAGE & ADMINISTRATION: Under the guidance and supervision of a physician experienced in diagnosis and treatment of psoriasis or psoriatic arthritis. Subcutaneous injection. Avoid areas with psoriasis. Self-injecting patients or caregivers ensure appropriate training Physicians are required to follow-up and monitor patients. Plaque psoriasis, adults & elderly: Patients <100kg, 45 mg at week 0 followed by a 45 mg dose at week 4, then every 12 weeks. Patients >100 kg, 90 mg at week 0 followed by a 90 mg dose at week 4, then every 12 weeks (45 mg was less effective in these patients). Plaque psoriasis paediatrics (12 years and older): Patients <60 kg, 0.75 mg/kg at week 0, followed by 0.75 mg/kg at week 4 then every 12 weeks thereafter. Patients ≥60-<100kg, 45 mg at week 0 followed by 45 mg at week 4, then every 12 weeks. Patients >100 kg, 90mg at week 0, followed by 90mg at week 4, then every 12 weeks. Psoriatic arthritis, adults & elderly: 45 mg at week 0 followed by a 45 mg dose at week 4, then every 12 weeks. Alternatively, 90 mg may be used in patients with a body weight >100 kg. Consider discontinuation if no response after 28 weeks. Children <12 years: Not recommended. Renal & Hepatic impairment: Not studied. CONTRAINDICATIONS: Hypersensitivity to product; clinically important, active infection. SPECIAL WARNINGS & PRECAUTIONS: Infections: Potential to increase risk of infections and reactivate latent infections. Caution in patients with a chronic infection or history of recurrent infection, particularly TB. Patients should be evaluated for tuberculosis prior to initiation of STELARA. Consider anti-tuberculosis therapy prior to initiation of STELARA in
patients with past history of latent or active tuberculosis. Patients should seek medical advice if signs or symptoms suggestive of an infection occur. If a serious infection develops, they should be closely monitored and STELARA should not be administered until infection resolves. Malignancies: Potential to increase the risk of malignancy. No studies in patients with a history of malignancy or in patients who develop malignancy while receiving STELARA. Monitor all patients, in particular those older than 60, patients with a medical history of prolonged immunosuppressant therapy or those with a history of PUVA treatment for non-melanoma skin cancer. Concomitant immunosuppressive therapy: Caution, including when changing immunosuppressive biologic agents. Hypersensitivity reactions: Serious hypersensitivity reactions (anaphylaxis and angioedema) reported, in some cases several days after treatment. If these occur appropriate therapy should be instituted and, STELARA discontinued immediately. Latex sensitivity: Needle cover contains natural rubber (latex), may cause allergic reactions. Immunotherapy: Not known whether STELARA affects allergy immunotherapy. Serious skin conditions: Exfoliative dermatitis has been reported following treatment. Discontinue STELARA if a drug reaction is suspected. SIDE EFFECTS: Common: dental infections, upper respiratory tract infection, nasopharyngitis, dizziness, headache, oropharyngeal pain, diarrhoea, nausea, pruritus, back pain, myalgia, arthralgia, fatigue, injection site erythema, injection site pain, antibodies to ustekinumab. Other side effects include: cellulitis, serious hypersensitivity reactions (including anaphylaxis, angioedema), skin exfoliation, exfoliative dermatitis. Studies show adverse events reported in ≥12 year olds with plaque psoriasis were similar to those seen in previous studies in adults with plaque psoriasis. Refer to SmPC for other side effects. FERTILITY: The effect of ustekinumab has not been evaluated. PREGNANCY: Should be avoided. Women of childbearing potential: Use effective contraception during treatment and for at least 15 weeks post-treatment. LACTATION: Limited data in humans. INTERACTIONS: In vitro, STELARA had no effect on CYP450 activities. Vaccinations: Live vaccines should not be given concurrently with STELARA, and should be witheld for at least 15 weeks after last dose of STELARA. STELARA can resume at least 2 weeks after such vaccinations. No data on secondary transmission of infection by live vaccines in patients receiving STELARA. Concomitant immunosuppressive therapy: Psoriasis: The safety and efficacy of STELARA in combination with other
immunosuppressants, including biologics, or phototherapy have not been evaluated. Refer to SmPC for full details of interactions. LEGAL CATEGORY: Prescription Only Medicine. PRESENTATIONS, PACK SIZES, MARKETING AUTHORISATION NUMBER: 45 mg: 1 x vial. EU/1/08/494/001, 45mg: 1 x 0.5ml pre-filled syringe. EU/1/08/494/003. 90mg: 1 x 1.0ml pre-filled syringe. EU/1/08/494/004. MARKETING AUTHORISATION HOLDER: JANSSEN-CILAG INTERNATIONAL NV, Turnhoutseweg 30, B-2340 Beerse, Belgium. FURTHER INFORMATION IS AVAILABLE FROM: Janssen-Cilag Ltd, 50 – 100 Holmers Farm Way, High Wycombe, Buckinghamshire, HP12 4EG UK. © Janssen-Cilag Ltd 2015 Adverse events should be reported. Healthcare professionals are asked to report any suspected adverse events via: HPRA Pharmacovigilance, Earlsfort Terrace, IRL - Dublin 2, Tel: +353 1 6764971, Fax: +353 1 6762517, Website: www.hpra.ie, E-mail: email@example.com Adverse events should also be reported to Janssen-Cilag Ltd on +44 1494 567447. Prescribing information last revised: 06/2015 References: 1. Warren RB et al. J Inv Dermatol. Accepted article: June 2015; doi: 10.1038/jid.2015.208. 2. Menter A et al. P1705: Poster presented at the AAD Annual Meeting, 20-24 March 2015; San Francisco, California. 3.Stelara Summary of Product Characteristics, available at www. medicines.ie Date of preparation: March 2016 | PHIR/STE/1015/0007a
Awards 32 Awards
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Shire Excellence in Child Psychiatry Award 2016
This is a new Award for 2016. The Shire Excellence in Child Psychiatry Award seeks to recognise the pivotal role that psychiatric professionals and teams play in improving or innovating psychiatric services and care for children and adolescents. This Award will be looking for those individuals and/or teams that can demonstrate quality improvement, effective leadership, good teamwork and effective use of resources. Judges will be looking for submissions that address prevention, diagnosis, or treatment in the field of child psychiatry throughout Ireland. JUDGES WILL BE LOOKING FOR: Excellence and leadership within child psychiatry and its development Evidence of working effectively across organisational and departmental boundaries to deliver excellence in child psychiatry Evidence to show that innovative practice has markedly enhanced the field and its development An innovative project/development/service or new approach in the field or a research project involving child psychiatry A multidisciplinary approach to clinically using medicines HOW TO ENTER: For each award category you wish to enter you must fill in your full contact details in the spaces provided and ensure you answer all the questions. For an application form please contact Kelly Jo Eastwood via email on: firstname.lastname@example.org or by telephone on +353 1 6690562 / 0044 7876548989 or by visiting our website at www.pharmacyawardsireland.com
Deadline for Entries: Friday, June 29th, 2016 May 2016 • HPN
Awards The Hospital Professional News Ireland
Hospital Pharmacy Team of the Year Award 2016 There are many key elements to building a productive team, including communication and co-operation. Good communication means everyone is aware of their own responsibilities and what the team's goals are whilst co-operation leads to increased productivity. A team that excels is the one who, together, endlessly work to improve their efforts. They comprehend the importance of on-going improvements and how this helps support the overall objectives of the department. The Award is open to any hospital pharmacy team with a minimum of three team members. JUDGES WILL BE LOOKING FOR: Judges will want to see effective communication skills with both staff and customers Demonstration of a commitment to mentoring or other leadership activities Operation within their own pharmacy liaising with key staff members and management and developing key communication skills A dedication and commitment to furthering the profession into the future HOW TO ENTER: For each award category you wish to enter you must fill in your full contact details in the spaces provided and ensure you answer all the questions. For an application form please contact Kelly Jo Eastwood via email on: email@example.com or by telephone on +353 1 6690562 / 0044 7876548989 or by visiting our website at www.pharmacyawardsireland.com
Deadline for Entries: Friday, June 29th, 2016 HPN • May 2016
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Excellence in Respiratory Initiative of the Year 2016
This new Award category for 2016 has been established to recognise a respiratory clinician or team who is providing compassion care, over and beyond that usually undertaken in a respiratory career. The project can come from any background but must be involve those working predominately in the respiratory field. The judges will be looking for a project that demonstrates deliverable outcomes within respiratory care over that has really supported and evidenced the difference made to the patient experience in respiratory care. Entries can be self-nominated from but must be Consultant-led. JUDGES WILL BE LOOKING FOR: Entries that can clearly demonstrate defined objectives for quality improvement within a project Clearly described respiratory interventions Clear evidence of innovation and new ways of working Clarity of leadership and how the qualities have affected the team Quantifiable improvements in patient care, including clinical outcomes HOW TO ENTER: For each award category you wish to enter you must fill in your full contact details in the spaces provided and ensure you answer all the questions. For an application form please contact Kelly Jo Eastwood via email on: firstname.lastname@example.org or by telephone on +353 1 6690562 / 0044 7876548989 or by visiting our website at www.pharmacyawardsireland.com
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Awards The Hospital Professional News Ireland
Patient Organisation Educational Project of the Year 2016 This is a new Award for 2016. This Award seeks to recognise the innovative projects or campaigns undertaken by patient organisations within Ireland which are designed and implemented to improve the lives of patients and their families and address their health needs. Judges will be looking for an outstanding patient engagement project or initiative that is a collaboration with the hospital healthcare team, contributing to the improvement of care and overall health well-being for public, patients and caregivers. JUDGES WILL BE LOOKING FOR: A project or initiative that has delivered improvement(s) to healthcare delivery and overall well-being of patients and caregivers A project or initiative should be established and/or ongoing in the past 3 years Only healthcare institutions, establishments involved in patient care or caregiving resources and patient support/volunteer groups may apply HOW TO ENTER: For each award category you wish to enter you must fill in your full contact details in the spaces provided and ensure you answer all the questions. For an application form please contact Kelly Jo Eastwood via email on: email@example.com or by telephone on +353 1 6690562 / 0044 7876548989 or by visiting our website at www.pharmacyawardsireland.com
Deadline for Entries: Friday, June 29th, 2016 HPN • May 2016
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The Hospital Professional News Ireland
Hospital Specialist of the Year 2016
Speciality clinicians are essential components of service provision, providing a major share of the medical input in many teams. This award is to recognise Specialty Clinician who has demonstrated advanced clinical skills as well as excelling in service development, teaching, research and leadership. Their contribution may be at local, regional or national level in the past three years. This new Award for 2016 will seek to recognise exemplary leadership within a speciality that demonstrates a positive and sustained impact on patients, service users, carers and staff. Judges will want to see evidence of speciality skills and leadership which are focused on improvement, and enhancing the quality of experience. JUDGES WILL BE LOOKING FOR: Evidence of key competencies across areas such as team working, innovation, research and education Excellence in clinical work and/or medical education Parity of esteem Commitment to improving services for service users and/ or staff alongside evidence of measurable improvement as a result of the entrants/nominees work HOW TO ENTER: For each award category you wish to enter you must fill in your full contact details in the spaces provided and ensure you answer all the questions. For an application form please contact Kelly Jo Eastwood via email on: firstname.lastname@example.org or by telephone on +353 1 6690562 / 0044 7876548989 or by visiting our website at www.pharmacyawardsireland.com
Deadline for Entries: Friday, June 29th, 2016 May 2016 • HPN
Awards The Hospital Professional News Ireland
MSD Antimicrobial Pharmacist of the Year Award 2016
The MSD Antimicrobial Pharmacist of the Year Award will seek to recognise those pharmacy professionals that have displayed levels of excellence and dedication within antimicrobials in Ireland. Key roles for the antibiotic pharmacist include educating pharmacy, nursing and medical staff, auditing prescribing patterns and trends, monitoring antibiotic use, ensuring compliance with good antibiotic practices and managing infection control issues, all of which contribute to reducing hospital associated infections. Having a dedicated antibiotic pharmacist within the team can ensure better monitoring and compliance with hospital antibiotic guidelines, which are based on good practice and local assessment of microbiology in the hospital setting. JUDGES WILL BE LOOKING FOR: Evidence of long-term, consistent dedication and outstanding achievements that have led to the advancement of the profession of pharmacy and public health Evidence of a large variety of skills, attributes and accomplishments Evidence of an individual strong in character, cumulative professional accomplishments and the ability to properly represent and model what pharmacy as a profession encompasses Evidence of an understanding the goals of pharmacy, and significantly contributing to how these goals may be achieved HOW TO ENTER: For each award category you wish to enter you must fill in your full contact details in the spaces provided and ensure you answer all the questions. For an application form please contact Kelly Jo Eastwood via email on: email@example.com or by telephone on +353 1 6690562 / 0044 7876548989 or by visiting our website at www.pharmacyawardsireland.com
Deadline for Entries: Friday, June 29th, 2016 HPN • May 2016
Awards 38 Awards
The Hospital Professional News Ireland
Hospital Rising Star Award 2016
The Hospital Rising Star Award recognises rising talent – those individuals who despite being in the early stages of their hospital careers are already demonstrating that they can make a difference to the profession and the companies for whom they work and the patients they serve. This award is open to hospital professionals aged up to 30 - at the date of entry submission - who are working within any hospital department where their involvement has been greater than six months. It is the individual qualities that will be evaluated, rather than those of any of the projects worked on. JUDGES WILL BE LOOKING FOR: Judges will want to see effective communication skills with both staff and customers Demonstration of a commitment to mentoring or other leadership activities Operation within their own pharmacy liaising with key staff members and management and developing key communication skills A dedication and commitment to furthering the profession into the future HOW TO ENTER: For each award category you wish to enter you must fill in your full contact details in the spaces provided and ensure you answer all the questions. For an application form please contact Kelly Jo Eastwood via email on: firstname.lastname@example.org or by telephone on +353 1 6690562 / 0044 7876548989 or by visiting our website at www.pharmacyawardsireland.com
Deadline for Entries: Friday, June 29th, 2016 May 2016 • HPN
Awards The Hospital Professional News Ireland
Medisource Hospital Pharmacy Technician of the Year 2016
It is evident that hospital pharmacy technicians are playing an increasingly important supporting role as pharmacists are increasingly spending more time with patient consultations and engaging local stakeholders. The shift in emphasis from dispensing to healthcare provision has meant that the wider pharmacy team has to pull together – pharmacy technicians capture the essence of this in everything that they do. This Award will recognise the winner’s important contribution to the hospital pharmacy technician profession. The judges will be looking for those who can demonstrate promotion of the role of the Pharmacy Technician and those who continue to champion excellence through forward thinking and innovation. The winners’ achievements will be an inspiration to those pursuing innovative practice; to those striving to raise standards; and to pharmacists who, through their professionalism, provide models for others within pharmacy. JUDGES WILL BE LOOKING FOR: Evidence of long-term, consistent dedication and outstanding achievements that have led to the advancement of the profession of pharmacy and public health Evidence of a large variety of skills, attributes and accomplishments Evidence of an individual strong in character, cumulative professional accomplishments and the ability to properly represent and model what pharmacy technicians as a profession encompasses Evidence of an understanding the goals of pharmacy, and significantly contributing to how these goals may be achieved HOW TO ENTER: For each award category you wish to enter you must fill in your full contact details in the spaces provided and ensure you answer all the questions. For an application form please contact Kelly Jo Eastwood via email on: email@example.com or by telephone on +353 1 6690562 / 0044 7876548989 or by visiting our website at www.pharmacyawardsireland.com
Deadline for Entries: Friday, June 29th, 2016 HPN • May 2016
Awards 40 Awards
The Hospital Professional News Ireland
Innovation and Service Development Award 2016
The Innovation and Service Development Award is defined as the successful introduction of an idea, method or device that makes a genuine difference or positive change for the hospital pharmacy or patients, or both. The Innovation and Service Development Award will be presented to an individual or team from any hospital pharmacy department who has demonstrated an innovative pharmacy practice programme, resulting in improved patient care or safety, advancement of the profession enhanced pharmacy systems or other professional development. This Award will go to those that can best demonstrate an innovation or innovative approach that has created competitive advantage, contributed to growth, transformed the organisation, improved overall financial advantage or achieved operational excellence. JUDGES WILL BE LOOKING FOR: Activities that may involve pioneering new models or systems that improve pharmacists' impact as members of the health care team; patient safety and outcomes; patient care in general and other professional development A system or tool for pharmacy professionals that will directly or immediately impact patient care or the profession and/ or serve as an example or template for other pharmacy professionals to follow Cumulative achievements or a single outstanding programme/ project completed or carried out over the past twelve months HOW TO ENTER: For each award category you wish to enter you must fill in your full contact details in the spaces provided and ensure you answer all the questions. For an application form please contact Kelly Jo Eastwood via email on: firstname.lastname@example.org or by telephone on +353 1 6690562 / 0044 7876548989 or by visiting our website at www.pharmacyawardsireland.com
Deadline for Entries: Friday, June 29th, 2016 May 2016 • HPN
Awards The Hospital Professional News Ireland
Multidisciplinary Award 2016 Treatment of patients is, in most cases, a combined effort of several individuals and it is recognised that the outcome of a procedure is optimal when the professionals do indeed work together as a team. Obviously, pharmacists are part of treatment teams in healthcare establishments. With expertise of product and processes, they improve the therapeutic outcome and the quality of work flow. Although it seems obvious that a pharmacist form part of a team, this Award will seek to recognise those who can demonstrate added value by their contribution. The judging panel will want to see actual multidisciplinary healthcare working and actual examples of it in practice as well as an outline of what lessons have been learnt from its implementation. JUDGES WILL BE LOOKING FOR: Evidence of how the applicant/team has shown exemplary teamwork A clear dissemination of why this project as initiated, market research conducted on identifying need Details of the challenges/innovations they overcome/initiated. Judges will expect to see evidence of results A demonstration of the impact this applicant/project has had on the wider hospital team Demonstration of how this initiative might be rolled out in hospitals across Ireland HOW TO ENTER: For each award category you wish to enter you must fill in your full contact details in the spaces provided and ensure you answer all the questions. For an application form please contact Kelly Jo Eastwood via email on: email@example.com or by telephone on +353 1 6690562 / 0044 7876548989 or by visiting our website at www.pharmacyawardsireland.com
Deadline for Entries: Friday, June 29th, 2016 HPN • May 2016
Awards 42 Awards
The Hospital Professional News Ireland
Excellence in Patient Safety Award 2016
This Award will seek applicants who have shown commitment and dedication to improving patient safety/medication safety amongst patients in the secondary care setting. This may be through team working with consultants, nurses, pharmacy colleagues but the endpoint result will be to improve this area for patients in terms of medication efficacy and adherence, as just two examples of many. This Award will encompass all aspects of patient safety within the hospital pharmacy sector in Ireland and invites applications from those who have recently undertaken patient safety initiatives to the betterment of the profession; those who are or who have offered patient safety expertise to the profession perhaps in the line of lecturing; or even those who have undertaken a recent patient safety innovation or initiative within a field pertinent to hospital pharmacy that will have a positive effect on the whole profession. JUDGES WILL BE LOOKING FOR: Evidence of safety improvements and enhancements through collaborative working, introduction of new services, improved systems of work and/or new training standards Innovative application of new standards, systems, protocols or services Evidence of benefits to patients and colleagues Examples of potential roll-out across Ireland HOW TO ENTER: For each award category you wish to enter you must fill in your full contact details in the spaces provided and ensure you answer all the questions. For an application form please contact Kelly Jo Eastwood via email on: firstname.lastname@example.org or by telephone on +353 1 6690562 / 0044 7876548989 or by visiting our website at www.pharmacyawardsireland.com
Deadline for Entries: Friday, June 29th, 2016 May 2016 • HPN
Awards The Hospital Professional News Ireland
Roche Oncology Pharmacist of the Year 2016
Recognising those who provide quality patient care in relation to a patient’s oncologic diagnosis, prescribed treatment, age group and other identified needs and provides comprehensive pharmaceutical care to oncology patients to assure safe and effective drug therapy. The judging panel will be looking for a high calibre individual who can demonstrate organisation, management and quality of care and services that optimise outcomes in patients with malignant diseases. This person will be able to show how they coordinate the drug therapy process through drug selection, drug information, dosing, monitoring, outcomes management, and patient education/ counselling. JUDGES WILL BE LOOKING FOR: Evidence of a clinical role or a project that combines with developing a clinical service A new approach to managing a clinical team, delivering a service or producing outstanding clinical work within oncology Development of a new service or technique that refines/ changes clinical oncology practice Research involving a clinical oncology service/setting or a new method of teaching oncology skills Examples of a multi-disciplinary approach to oncology services HOW TO ENTER: For each award category you wish to enter you must fill in your full contact details in the spaces provided and ensure you answer all the questions. For an application form please contact Kelly Jo Eastwood via email on: email@example.com or by telephone on +353 1 6690562 / 0044 7876548989 or by visiting our website at www.pharmacyawardsireland.com
Deadline for Entries: Friday, June 29th, 2016 HPN • May 2016
Awards 44 Awards
The Hospital Professional News Ireland
Idis Hospital Pharmacist of the Year Award 2016
Part of the Clinigen Group
The Hospital Pharmacist of the Award recognises a hospital pharmacist who demonstrates leadership and exemplifies the evolution of the pharmacy profession toward an expanded role in health care. The winner will demonstrate significant contributions to the pharmacy industry overall resulting in meaningful improvements in the quality of patient care and improved delivery models and pharmacy’s role on the health care team. JUDGES WILL BE LOOKING FOR: Evidence of long-term, consistent dedication and outstanding achievements that have led to the advancement of the profession of pharmacy and public health Evidence of a large variety of skills, attributes and accomplishments Evidence of an individual strong in character, cumulative professional accomplishments and the ability to properly represent and model what pharmacy as a profession encompasses Evidence of an understanding the goals of pharmacy, and significantly contributing to how these goals may be achieved HOW TO ENTER: For each award category you wish to enter you must fill in your full contact details in the spaces provided and ensure you answer all the questions. For an application form please contact Kelly Jo Eastwood via email on: firstname.lastname@example.org or by telephone on +353 1 6690562 / 0044 7876548989 or by visiting our website at www.pharmacyawardsireland.com
Deadline for Entries: Friday, June 29th, 2016 May 2016 • HPN
Awards The Hospital Professional News Ireland
Hospital Team of the Year Award 2016 This Award will be given to the hospital team that demonstrates the best combination of team spirit and enhancement of patient care at all levels. The judges will be looking for those who encourage and support each other and those who have collectively demonstrated innovation and forward thinking. The key to any successful hospital department is team work and this award recognises the power and potential of a focused and unified approach to health care initiatives. Teams can be based within one organisation or spread over multiple organisations; but they must comprise individuals working towards the same objective or goal. JUDGES WILL BE LOOKING FOR: How the team has demonstrated their ability to deliver clear benefits to patients; and/or staff members through working together efficiently and effectively How the team has worked together to achieve its objectives over the past twelve months Projects that the team has successfully managed which demonstrate excellence in quality, innovation, productivity and prevention A clear display of the principles underpinning their success as a team HOW TO ENTER: For each award category you wish to enter you must fill in your full contact details in the spaces provided and ensure you answer all the questions. For an application form please contact Kelly Jo Eastwood via email on: email@example.com or by telephone on +353 1 6690562 / 0044 7876548989 or by visiting our website at www.pharmacyawardsireland.com
Deadline for Entries: Friday, June 29th, 2016 HPN • May 2016
Awards 46 Awards
The Hospital Professional News Ireland
Professional Contribution Award 2016
This is a new Award for 2016 and will be presented to those who can demonstrate outstanding contribution to the field of secondary care through work outside of the hospital setting. This may include those working in industry, academia, research & development or for trade and regulatory bodies or within the HSE. JUDGES WILL BE LOOKING FOR: Those who have shown dedication to their profession by contributing to the standards of practice for the profession as a whole Examples of bringing attention and awareness to the pharmacy profession throughout Ireland and further afield Evidence of significant collaboration between other allied healthcare professionals Demonstration of efforts to enhance the future of the profession through innovations, initiatives, standards, training and research WHO CAN ENTER: All Hospital professionals working outside the Irish hospital setting Previous Professional Contribution Award entrants, including winners HOW TO ENTER: For each award category you wish to enter you must fill in your full contact details in the spaces provided and ensure you answer all the questions. For an application form please contact Kelly Jo Eastwood via email on: firstname.lastname@example.org or by telephone on +353 1 6690562 / 0044 7876548989 or by visiting our website at www.pharmacyawardsireland.com
Deadline for Entries: Friday, June 29th, 2016 May 2016 • HPN
Our passion is in the detail There are occasions when your patients have to deal with difficult challenges and you may need to arrange for special medicines. PharmaSource can help you source these medicines in a timely, reliable and safe manner. With over 70% of Irish pharmacies ordering from us every day, we are Ireland’s leading supplier of unlicensed medicines, manufactured specials and once off procured items to the Irish market. Our service is tried and tested and valued by our loyal customers. PharmaSource can help reduce the valuable time our customers are spending searching for medicines that are currently in short supply or discontinued in the national market. We can source these products for you, simply give our team a call.
Our team is made up of qualified pharmacists and pharmacy technicians who understand the importance of delivering your order on time every time. When you call PharmaSource you will be speaking to your peers.
PharmaSource was the first to market with our website. Others have tried to mimic but none can compare. Our site allows you to check stock levels in real time, confirm pricing, reprint monthly invoices and keep a record of what unlicensed medicines you have ordered for audit purposes. Placing your order with PharmaSource has never been easier.
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Proud sponsors of the HPN Awards 2015
48 Clinical Update
Chronic Obstructive Pulmonary Disease 5. National advice and information helpline to be established for COPD This has been the aim of the HSE National Asthma Programme under the guidance of Prof Pat Manning, Consultant Respiratory Physician, Bon Secours Hospital, Dublin, since its inception in early 2012. According to Prof Manning, the Programme is seeking to maximise the health and quality of life of people with asthma and to prevent avoidable mortality due to asthma.
Chronic obstructive pulmonary disease (COPD) is the name for a collection of lung diseases including chronic bronchitis, emphysema and chronic obstructive airways disease. Epidemiologic studies examining the incidence of respiratory symptoms show that COPD is a major health problem in Europe. However, it is very difficult to have exact figures of COPD prevalence in Europe due to the heterogeneity of studied populations (general, “targeted”, selected age groups) the heterogeneity of methods (symptom-based, medical diagnosis & expert opinion, spirometry-based), underestimation of disease severity by the patients who report their smoking with a sense of guilt anxiety and depression that alter the perception of the disease and quality of life with less adherence to treatment, more exacerbations, and more reaction time when the symptoms worsen. As a consequence, COPD is often under-diagnosed; the true prevalence rates and the burden
May 2016 • HPN
of disease may be much higher than the currently available data suggest (Pauwels, 2000; Wouters, 2003; Halbert et al., 2003). Estimates of COPD prevalence rates vary widely, from 0.2% to 18.3%, partly as a result of real differences in prevalence among countries and regions, and partly because of other factors. Some well-designed studies have found a measured prevalence of COPD in Europe between 4% and 10% of adults (Halbert et al., 2003). COPD is expected to increase from almost 270,000 in 2005 to 338,000 deaths by 2030. This incurable, life-limiting but treatable disease affects 380,000 people in Ireland, yet only 110,000 people are diagnosed. The burden of care is substantial with 13,685 people hospitalised yearly and spending on average 9.5 days in hospital. The total cost of COPD hospitalisations was ¤70,813,040 in 2014. COPD affects more men than
women. However, according to the Irish Thoracic Society, rates of COPD in women are increasing. The statistics make for poor reading and demonstrate the urgent need to improve services and care for COPD patients in Ireland. COPD Support Ireland has devised a series of practical and fair recommendations for earlier diagnosis and access to services, better care and improved management of the disease that will result in a reduction of the current cost of care to the State. Their key Actions for Ireland’s next Government are: 1. Spirometry testing to be made available in primary care. 2. Pulmonary Rehabilitation Programmes to be made available in every acute hospital 3. Medical cards to be provided for people living with COPD 4. Outreach and integrated care programmes to be attached to every acute hospital
As a disorder, COPD is underrecognised and under-treated (World Health Organisation, 2009, GOLD, 2009). Although in the past, there was little that could be done to relieve COPD, in the past decade there has been significant research into the condition, leading to a number of new treatment options (NCGC – National Clinical Guideline Centre, 2009), including pharmacologic therapies such as long-acting bronchodilator drugs, and the development of respiratory rehabilitation services. Although the condition is not curable, the symptoms of the disease can be controlled with effective treatment. The Institute of Public Health (IPH) projects that by 2020 there is likely to be a 23% increase in the number of adults with clinically diagnosed chronic airflow obstruction with one third of this increase due to an increase in the size of the population and two thirds due to population ageing (including the increases in risk factor levels associated with ageing). A ten year study of trends in COPD mortality and in-patient admissions found that there has been a convergence in COPD deaths and COPD hospital inpatient discharges for men and women which mirrors the trend in the convergence of male and female smoking rates. This study highlights the substantial burden of COPD on
49 acute hospital services in Ireland with lengthy hospital stays and repeat admissions being common. It concludes that given our ageing population and the greater number of older women than men in Ireland, we need to prepare for the growing burden of COPD on our health services by ensuring that adequate resources and best evidence based practice is used to care for patients. COPD care spans both chronic disease management with pulmonary rehabilitation to acute care with newly developed COPD outreach programme. The latter programmes have reduced length of hospital stay but require close involvement by the respiratory consultant during acute exacerbations managed at home. This increased workload taken with the increasing prevalence of COPD will place increasing demands on respiratory physicians over the next ten years. This is a sentiment that Consultant Respiratory Physician Dr Deirdre O’Riordan concurs with. She says policymakers should promote meaningful changes to national COPD care standards. “The condition must be diagnosed and managed optimally in order to reduce hospitalisations, improve patient quality of life, and provide more complete healthcare while using health resources most efficiently and effectively.” One way to reduce hospital admissions, she says, is to discover undiagnosed COPD patients in the first place, so that they may be started earlier on appropriate therapy. That is where the biggest awareness gap is. She recommends healthcare colleagues learn to recognise that what might look like an isolated infection—such as acute bronchitis—is likely to be a complication of underlying COPD. She told HPN that another key problem for physicians lies in definitions. “Chronic obstructive pulmonary disease is a very common disease often punctuated by intermittent episodes of exacerbation. These exacerbations affect the
natural history of the disease, accelerating a decline in lung function. They affect the individual in many ways and affect the health service caring for these patients. “The definition of exacerbation varies and lacks clarity. The definitions used most are either symptom based, for example, breathlessness, sputum production and sputum purulence, or event driven, for example, an event causing a patient to seek healthcare input or change to medications.” Dr O’Riordan believes that application of a practical definition would aid in clinical management of patients with chronic obstructive pulmonary disease and facilitate developments in future therapeutic advances through clinical trials. The primary goal of chronic COPD management is stabilisation of chronic disease and prevention of acute exacerbations. Bronchodilators are the mainstay of COPD therapy. With more than 50 new medications in the pipeline for the treatment of COPD, optimal management will continue to evolve and grow more complex as benefits of therapy are balanced with the limitations and needs of each patient. Cycle of care In response to the high levels of hospitalisations in Ireland, the COPD National Programme supported the development of 12 new COPD Outreach sites. The COPD Outreach team consists of a Clinical Nurse Specialist and a Senior Physiotherapist. The core activities of COPD outreach are to offer early supported discharge, assisted discharge, admission avoidance and direct GP access. It is well known that COPD Outreach is a well-established and successful service in the UK. An local study (Tallaght) has been published that looks at the efficacy of COPD Outreach in reducing length of stay and improving quality of life for patients. Results show a reduction in length of stay for all COPD patients and improved CAT scores in Outreach patients. They found no reductions in
readmissions or mortality rates. This is evidence that COPD Outreach in Ireland is working as planned and it is in keeping with other international research on the effectiveness of a COPD Outreach service. Current COPD Outreach Centres are • Letterkenny General Hospital • Cavan General Hospital • Our Lady of Lourdes, Drogheda • Connolly Hospital • St. Vincent’s University Hospital • St. Michaels Hospital, Dun Laoghaire • Tallaght Hospital • Galway University Hospital • Limerick Regional Hospital • Wexford General Hospital • Cork University Hospital, and • Mercy University Hospital A recent study which looked at COPD Outreach activity from 2012- suggests that COPD Outreach is now effectively active in most hospitals. Patient numbers are increasing year on year and this is leading to a reduction in length of patient stay. But Dr O’Riordan reflects there is much more still to be done. “A lack of access to spirometry is a major impediment to successful management of many cases of COPD in primary care,” she says. “As a result, patients with a suspected diagnosis of COPD are often referred in to hospital for diagnosis and on-going management. “Pulmonary rehabilitation is a key component of management of patients with COPD and is well recognised to improve quality of life, shortness of breath and exercise tolerance in patients with COPD. Unfortunately due to resource issues it is not widely available at present. Where it is available there are severe capacity issues.”
progressing. The Asthma Society of Ireland and COPD Support Ireland submitted a proposal to the HSE to fund the advice line in 2016. Engagement with the HSE has also been undertaken, with a view to gaining support for which patients could receive high-cost therapies. Professor Tim McDonnell, HSE Lead for COPD and Consultant Respiratory Physician with St Vincent’s University Hospital says there is a “massive incentive for all those in the COPD community to tackle this disease head-on and reduce the amount of unnecessary deaths associated with the disease”. He adds, "It is crucial to catch COPD as early as possible for effective treatment. "COPD has a detrimental impact on the quality of patients' lives. However, even severe cases can be improved with treatment and correct management. It is important that those who have mild COPD in particular manage their symptoms to avoid their condition worsening over time.” Dr Deirdre O’Riordan returned to practice in Dublin in 2001 having trained in Respiratory Medicine at the New England Deaconess Hospital and Harvard Medical School in Boston and at the Mayo Clinic in Rochester, Minnesota. She subsequently worked as a Consultant Respiratory Physician at Leeds General Infirmary, Leeds, U.K., before returning to Dublin. Dr O’Riordan has been a Consultant in Respiratory Medicine at St. James’s Hospital and Trinity College Dublin since 2001. Dr O’Riordan became a member of the Royal College of Physicians in Ireland in 1989, was awarded an M.D. by the National University of Ireland in 1993 and became a Fellow of the Royal College of Physicians in Ireland in 2004.
Work on developing a joint asthma and COPD advice line commenced in 2015 and work on the venture is still
HPN • May 2016
Psoriasis 1916-2016: Reflecting on a century of discovery As the ceremonies to mark the centenary of the 1916 rising come to a close, we reflect on some of the advances in psoriasis treatment that have occurred during this period.
with good results. The active ingredient of Goa powder (obtained from the bark of the araroba tree found in South America), was found to be chrysarobin.
Until relatively recently, progress in the treatment of psoriasis had been steered by a succession of fortuitous accidental discoveries. A timeline for some of the most important of these chance findings (dithranol, methotrexate, vitamin D analogues and cyclosporin), is outlined below, beginning in 1916 when the effectiveness of dithranol was established.
During World War I, when natural supplies of this product were scarce, a synthetic form called anthralin (dithranol) was developed. In 1916, it was demonstrated that anthralin was effective in the treatment of psoriasis, and it subsequently came into widespread use.
While these agents still provide valuable treatment options, their identification paved the way for a better understanding of the disease process and the development of more targeted therapies. Dithranol (anthralin) In 1876, Balmanno Squire (the chief of surgery and medicine for the British Hospital for Diseases of the Skin in London), reported the beneficial effects of Goa powder for the treatment of psoriasis. One of his patients had applied the powder to an area of â€˜ringedâ€™ psoriasis, which he mistook for ringworm,
In 1953, British Dermatologist John Ingram, noted that the beneficial effects of anthralin could be enhanced by combining it with other ingredients (salicylic acid and zinc oxide), and exposure to ultraviolet light therapy. Antimetabolites (Methotrexate) Another chance finding was made in 1951, when Richard Gubner (a New York cardiologist) and colleagues, reported that a patient experienced a dramatic improvement in their psoriasis while being treated with a drug called aminopterin for rheumatoid arthritis. Aminopterin was originally used to treat patients with leukaemia. In 1958, methotrexate (a drug based on
aminopterin, but with less risk of side effects) was shown to be effective for the treatment of psoriasis by American dermatologists, Edmundson and Guy. Vitamin D Analogues In the 1980s, Japanese researchers Marimoto and Kumahara, noted that a patient who was prescribed an oral form of vitamin D (1 , 25-dihydroxyvitamin D3) for treatment of osteoporosis, experienced complete clearance of his psoriasis. This chance observation led to the development of topically applied vitamin D derivatives. Cyclosporin Cyclosporin is an immunosuppressant medication that was developed in the 1970s to prevent organ rejection in transplant patients. It was observed that when transplant patients who happened to have psoriasis were prescribed cyclosporin, their psoriasis improved. This observation helped to identify the important role played by T cells and more generally, by the immune system, in the development of psoriasis. This discovery paved the way for a better understanding of the disease process and for the development of more targeted therapies. Recent scientific advances During the last 2 decades, researchers have built on the
May 2016 â€˘ HPN
knowledge gained from these chance findings, resulting in the development of new classes of medication that target the regulation of the immune system. A number of biologic agents have been licenced for the treatment of psoriasis including: tumour necrosis factor inhibitors (e.g. adalimumab, etanercept and infliximab), the interleukin (IL) 12/23 compound ustekinumab, and the IL 17A antagonist, secukinumab. These agents have significantly broadened the range and efficacy of treatment options available, and revolutionised the care of psoriasis patients. The future Over the last one hundred years, therapeutic advances have been informed by chance observations and scientific research. With studies ongoing, more is being learned about the disease process and those insights are helping to shape the development of new medicines. For example, just last week, the U.S. Food and Drug Administration approved ixekizumab (a biologic that targets IL-17A), to treat adults with moderate-to-severe plaque psoriasis, providing another important treatment option. This new wave of improved, targeted therapies, heralds a new era in the treatment of psoriasis.
THE AIM IS CLEAR TARGET IL-17A
Introducing Cosentyx® • The first and only fully human IL-17A inhibitor approved in Ireland for the treatment of moderate to severe plaque psoriasis and psoriatic arthritis
At week 16: • Cosentyx 300mg demonstrated superior efficacy against both ustekinumab and etanercept2,3 • 8/10 patients achieved PASI 902 • 4/10 patients achieved PASI 1002
ABBREVIATED PRESCRIBING INFORMATION. t COSENTYX 150 mg solution for injection in pre-filled pen. This medicinal product is subject to additional monitoring. This will allow quick identification of new safety information. Healthcare professionals are asked to report any suspected adverse reactions. See section 4.8 of the SmPC for how to report adverse reactions. Please refer to the Summary of Product Characteristics (SmPC) before prescribing. Presentation: COSENTYX 150 mg solution for injection in pre-filled pen. Therapeutic Indications: The treatment of moderate to severe plaque psoriasis in adults who are candidates for systemic therapy; the treatment of active ankylosing spondylitis in adults who have responded inadequately to conventional therapy; the treatment, alone or in combination with methotrexate (MTX), of active psoriatic arthritis in adult patients when the response to previous disease modifying anti rheumatic drug (DMARD) therapy has been inadequate. Dosage & Method of Administration: Plaque Psoriasis: Recommended dose in adults is 300 mg given as two subcutaneous injections of 150 mg. Dosing at Weeks 0, 1, 2 and 3, followed by monthly maintenance dosing starting at Week 4. Ankylosing Spondylitis: The recommended dose is 150 mg by subcutaneous injection with initial dosing at Weeks 0, 1, 2 and 3, followed by monthly maintenance dosing starting at Week 4. Psoriatic Arthritis: For patients with concomitant moderate to severe plaque psoriasis or who are anti TNFa inadequate responders, the recommended dose is 300 mg by subcutaneous injection with initial dosing at Weeks 0, 1, 2 and 3, followed by monthly maintenance dosing starting at Week 4. Each 300 mg dose is given as two subcutaneous injections of 150 mg. For all other patients, the recommended dose is 150 mg by subcutaneous injection with initial dosing at Weeks 0, 1, 2 and 3, followed by monthly maintenance dosing starting at Week 4. For all of the above indications, available data suggest that a clinical response is usually achieved within 16 weeks of treatment. Consideration should be given to discontinuing treatment in patients who have shown no response up to 16 weeks of treatment. Some patients with initially partial response may subsequently improve with continued treatment beyond 16 weeks. The safety and efficacy in children below the age of 18 years have not yet been established. Contraindications: Severe hypersensitivity reactions to the active substance or to any of the excipients. Clinically important, active infection (e.g. active tuberculosis). Warnings/Precautions: Infections: Cosentyx has the potential to increase the risk of infections. Infections observed in clinical studies are mainly mild or moderate upper respiratory tract infections such as nasopharyngitis not requiring treatment discontinuation. Non serious mucocutaneous candida infections more frequently reported for secukinumab than placebo in psoriasis clinical studies. Caution in patients with a chronic infection or a history of recurrent infection. Instruct patients to seek medical advice if signs or symptoms suggestive of an infection occur. If a patient develops a serious infection, close monitoring and discontinue treatment until the infection resolves. Should not be given to patients with active tuberculosis. Anti tuberculosis therapy should be considered prior to initiation in patients with latent tuberculosis. Crohn’s disease: Caution should be exercised when prescribing to patients with Crohn’s disease as exacerbations of Crohn’s disease, in some cases serious, were observed in clinical studies. Close monitoring of patients with Crohn’s disease treated with Cosentyx. Hypersensitivity reactions: In clinical studies, rare cases of anaphylactic reactions have been observed in patients receiving Cosentyx. If an anaphylactic or other serious allergic reactions occur, administration should be discontinued immediately and appropriate therapy initiated. Latex-sensitive individuals: The removable cap of the Cosentyx pre filled pen contains a derivative of natural rubber latex. Vaccinations: Live vaccines should not be given concurrently with Cosentyx. Patients may receive concurrent inactivated or non live vaccinations. Concomitant immunosuppressive therapy: Use in combination with immunosuppressants, including biologics, or phototherapy have not been evaluated. Interactions: Live vaccines should not be given concurrently with Cosentyx. No interaction studies have been performed in humans. A clinically relevant effect on CYP450 substrates with a narrow therapeutic index, where the dose is individually adjusted (e.g. warfarin) cannot be excluded. Therapeutic monitoring should be considered on initiation in patients treated with these types of medicinal products. No interaction seen when administered concomitantly with methotrexate (MTX) and/or corticosteroids. Fertility, Pregnancy and Lactation: Women of childbearing potential should use an effective method of contraception during treatment and for at least 20 weeks after treatment. It is preferable to avoid the use of Cosentyx in pregnancy as there are no adequate data from the use of secukinumab in pregnant women. It is not known whether secukinumab is excreted in human milk. A decision on whether to discontinue breast feeding during treatment and up to 20 weeks after treatment or to discontinue therapy with Cosentyx must be made taking into account the benefit of breast feeding to the child and the benefit of Cosentyx therapy to the woman. The effect of secukinumab on human fertility has not been evaluated. Undesirable Effects: Very common (≥1/10); Upper respiratory tract infections. Common (≥1/100 to <1/10); Oral herpes, rhinorrhoea, diarrhoea, urticaria. Uncommon (≥1/1,000 to <1/100); Oral candidiasis, tinea pedis, otitis externa, neutropenia, conjunctivitis. Rare (≥1/10,000 to <1/1,000); Anaphylactic reactions. Please see Summary of Product Characteristics for further information on undesirable effects. Legal Category: POM. Marketing Authorisation Holder: Novartis Europharm Ltd, Frimley Business Park, Camberley, GU167SR, United Kingdom. Marketing Authorisation Numbers: EU/1/14/980/004-005. Date of Revision of Abbreviated Prescribing Information: November 2015. Full prescribing information is available upon request from: Novartis Ireland Limited, Vista Building, Elm Park Business Park, Elm Park, Dublin 4. Tel: 01-2204100 or at www.medicines.ie. Detailed information on this product is also available on the website of the European Medicines Agency http://www.ema.europa.eu References: 1. Cosentyx Summary of Product Characteristics, November 2015. 2. Thaci D et al. JAAD 2015:73 (3) 400-409. 3. Langley RG et al. N Eng J Med 2014: 371 (4) 326-338. Date of Preparation: April 2016. IE02/COS15-CNF034b
52 Event Gallery Pulmonary Hypertension Society Meeting The Pulmonary Hypertension Society of Ireland recently held their annual patient and family meeting in the Crowne Plaza Hotel, Blanchardstown. The programme featured talks from Professor Sean Gaine, Consultant Respiratory Physician at the Mater Misericordiae University Hospital (MMUH), Hospital Pharmacist at MMUH Patricia Ging giving an overview of PH drugs and President of PHA Norway Mr Hall Skara.
Dr Brian McCullough, Respiratory Consultant, Mater Hospital and Dr Catherine Norton, Consultant Neuropsychologist, Private Practice
Patricia Ging, Hospital Pharmacist and Dr Brian McCullagh, Consultant Respiratory Physician, both Mater Hospital with patient Maurice Gavin
Winners of NCHD Poster Presentation and Essay Competition 2016
Hall Skara, President, Norway and Professor Sean Gaine, Consultant Respiratory Physician, Mater Hospital
Deirdre Clerkin and Catriona Minnock, CNS, both MMUH
Winners of the NCHD poster presentation and the Faculty of Addiction Psychiatry Essay Competition were congratulated at the College of Psychiatrists Spring Conference 2016 for the usual high standards. Prizes were awarded to: NCHD Research Prize Poster 2016 – Dr Erik Kolshus, Department of Old Age Psychiatry, Limerick Mental Health Services & Trinity College Institute of Neuroscience for ‘Bitemporal versus high dose right unilateral electroconvulsive therapy for depression. A systematic review and meta-analysis’. Faculty of Addiction Psychiatry Essay Competition 2016 - ‘Should Ireland adopt the Portuguese drug model?’ – awarded to Dr Kevin Lally, University Hospital, Limerick.
Specialist Fertility Consultant appointed at Beacon Care Fertility Dr Bartlomiej Kuczera has been appointed as Specialist Fertility Consultant at Beacon CARE Fertility in Dublin. Dr Kuczera has worked in Ireland for many years as a senior medical consultant in fertility treatment and is recognised as a leading authority in reproductive medicine in Ireland and Poland. Dr Kuczera brings extensive experience to the role and his in-depth knowledge and focus on results will complement the existing team at Beacon CARE Fertility in delivering the highest quality and most advanced fertility treatments for patients. Dr Ahmed Omar, Medical Director at Beacon CARE Fertility, said “We are delighted to welcome Bartlomiej to our dedicated fertility team in Dublin. He is held in high esteem by patients and the medical community and I am delighted to be working with him as we grow our comprehensive service in Ireland.” Dr Kuczera’s experience includes working in reproductive medicine in Ireland for the past five years before which he worked in Poland in the area of gynecology, obstetrics and reproductive medicine for 12 years. May 2016 • HPN
HPAI Annual Conference 2016 The Hospital Pharmacists Association of Ireland (HPAI) held their Annual Conference from April 8 to 10 in the Crowne Plaza Hotel, Santry, Dublin, hearing presentations on a number of exciting and pioneering IT projects established in hospital pharmacies across the country. The conference also witnessed outgoing President Elaine Conyard welcoming new President, Chief Pharmacist in Cork University Hospital Ms Deirdre Lynch. Pictured below are some of those who attended.
New HPAI President Deirdre Lynch, Cork University Hospital with Mairead Casserly, Mater Hospital
Norma Daly, Brian McGee, Louise Hayes, Deirbhle Joyce, University Hospital Limerick
Outgoing President Elaine Conyard, Our Lady of Lourdes Hospital with Brian Rattigan, Sligo Hospital
Irish Heart Foundation Research Bursary Awards 2016 New research into the prevention of cardiovascular disease (CVD) has been recognised by educational bursaries awarded by the Irish Heart Foundation which included stroke prevention bursaries supported by Daiichi Sankyo which were presented at the Irish Heart Foundation Study Day recently. The Irish Heart Foundation is the largest voluntary funder of Cardiovascular and Stroke Research in Ireland, participating in the search for novel treatments and cures. The Irish Heart Foundation established the bursaries to promote original innovative work in the area of cardiovascular disease which is not easily funded by other sources. Dr Angie Brown, Medical Director of the Irish Heart Foundation and consultant cardiologist said: “Innovative thinking has produced some of the major advances in medicine but modern
Mr Aidan Curley Country Operations Manager Daiichi Sankyo Ireland, Dr Roger Preston, PhD, Institute of Molecular Medicine, Trinity College Dublin, St James’s Hospital and Mr Barry Dempsey Chief Executive Irish Heart Foundation
research funding is often geared towards major academic institutions, rather than towards young people with bright ideas. The Irish Heart Foundation Research Bursaries awarded for 2016 illustrate the value of taking this approach and we are grateful to our donors and Daiichi Sankyo for supporting these pioneering projects.” Research winners Roger Preston, PhD, Institute of Molecular Medicine, Trinity College Dublin, St James’s Hospital, James Street, Dublin 8. ‘Bioengineering inhibition-resistant activated protein C analogs to enhance thrombolytic therapy for stroke patients.’ Dr Stephen Tuohy, (Dr Joe Galvin), Electrophysiology Research Registrar, Mater Heart House, 54 Eccles Street, D7.
Mr Aidan Curley Country Operations Manager Daiichi Sankyo Ireland, Dr Stephen Tuohy, Electrophysiology Research Registrar, Mater Heart House and Mr Barry Dempsey Chief Executive Irish Heart Foundation
Left atrial voltage mapping as a prognostic marker for atrial fibrillation recurrence post atrial fibrillation ablation. Dr Eibhlís O’Connor, Department of Life Sciences, University of Limerick, Co. Limerick. Can Matrix Gla Protein (MGP) determine arterial plaque phenotype in ‘at risk’ cardiovascular patients? An investigation into the relationship between MGP and arterial plaque composition in endarterectomy patients. Dr. Ciara Mahon, St Vincent’s University Hospital. Histological evidence of spiral re-entry circuits within the myocardium that facilitate rotor drivers of atrial fibrillation- a histological appraisal of the cardiac atria in post-mortem patients with a history of atrial fibrillation.
Mr Aidan Curley Country Operations Manager Daiichi Sankyo Ireland, Ms. Hilary Barrett on behalf of Dr Eibhlís O’Connor, Department of Life Sciences, University of Limerick and Mr Barry Dempsey Chief Executive Irish Heart Foundation
HPN • May 2016
54 Clinical R&D 12TH ANNUAL CONGRESS OF THE EUROPEAN CARDIAC ARRHYTHMIA SOCIETY (ECAS) 2016: Bayer AG and its development partner Janssen Pharmaceuticals, Inc. have announced results from a new real-world study, REVISITUS. In REVISIT-US reduced rates of ischemic stroke accompanied by reduced rates of intracranial haemorrhage (ICH) were seen with Xarelto® (rivaroxaban) versus warfarin in patients with non-valvular atrial fibrillation (AF). These results complement and reaffirm findings from the Phase III ROCKET AF clinical trial as well as the non-interventional XANTUS study. Results from REVISIT-US, which analysed nearly 23,000 realworld patients in the United States, were presented at the 12th Annual Congress of the European Cardiac Arrhythmia Society. REVISIT-US was a retrospective claims analysis performed using US MarketScan claims data evaluating the real-world occurrence of ischemic stroke and intracranial haemorrhage (ICH) in patients with non-valvular AF taking either rivaroxaban or warfarin. In this real-world setting rivaroxaban (n=11,411) was seen to be associated with a non-significant 29% decrease in ischemic stroke accompanied by a significant 47% reduction in ICH vs. warfarin (n=11,411). Looking at the combined endpoint of ICH and ischemic stroke, rivaroxaban resulted in a significant 39% reduction vs. warfarin in REVISITUS. These results confirm the positive benefit-risk-profile of Xarelto as determined in the Phase III ROCKET AF clinical trial as well as the non-interventional XANTUS study. “In the management of patients with AF, ischemic stroke and intracranial haemorrhage are the two events both physicians and patients fear most,” said Professor Craig Coleman, Professor of Pharmacy Practice at the University of Connecticut, U.S. who presented the REVISITUS results at ECAS. “Finding the appropriate balance of benefit and risk is always the goal. It is therefore highly reassuring to see that results from the real world continue to confirm that rivaroxaban is striking the appropriate balance of reducing stroke whilst at the same time also reducing the risk of intracranial haemorrhage in patients with nonvalvular AF.” “Although pivotal Phase III studies like ROCKET AF remain the gold standard to evaluate the efficacy and safety of a drug, real-world evidence plays an important role in complementing the knowledge about the use and impact of our May 2016 • HPN
medicines in everyday clinical practice,” said Dr Michael Devoy, Head of Medical Affairs & Pharmacovigilance of Bayer AG’s Pharmaceuticals Division and Bayer Chief Medical Officer. “We are pleased that study after study evaluating Xarelto in the real world across the spectrum of approved indications continues to confirm the positive benefit-risk profile of Xarelto.” REVISIT-US adds to the extensive investigation of rivaroxaban, which by the time of its completion, is expected to include more than 275,000 patients in both clinical trials and real-world settings.
CHAMPIX® (VARENICLINE) RESULTS FROM THE LARGEST GLOBAL CLINICAL TRIAL OF SMOKING CESSATION MEDICINES PUBLISHED IN THE LANCET Pfizer have announced results published in The Lancet from the largest clinical trial of approved smoking cessation medicines, called EAGLES (Evaluating Adverse Events in a Global Smoking Cessation Study. This smoking cessation trial included 8,144 adult smokers and was designed to compare the neuropsychiatric safety of Champix® (varenicline) and bupropion with placebo and nicotine patch in adult smokers with and without a history of psychiatric disorders. The authors concluded that the trial did not show a significant increase in the incidence of the composite primary safety endpoint of serious neuropsychiatric adverse events with Champix® or bupropion compared to placebo and nicotine patch. Differences between incidence rates were considered significant if their associated 95% confidence intervals (CIs) were entirely above or below zero. Approximately half of the trial participants had a history of psychiatric disorders, either past and in remission or present and clinically stable.The psychiatric diagnoses included primarily depressive, bipolar, anxiety and psychotic disorders. The EAGLES trial also included an efficacy objective to determine smoking abstinence rates in patients treated with Champix® or bupropion, relative to placebo, during the last four weeks of the 12-week treatment period. Continuous abstinence was also evaluated relative to the nicotine patch.1 In addition, longer-term abstinence through a 12-week non-treatment follow-up period (weeks 9-24) was evaluated for all treatments. The results showed that patients with and without a history of psychiatric
disorders taking Champix® had significantly higher continuous abstinence rates than patients treated with bupropion or nicotine patch during both time periods.1 Patients treated with each of the medications had higher abstinence rates than those treated with placebo. This is the first placebocontrolled trial of this size to directly compare the efficacy of Champix®, bupropion and nicotine patch to help people quit smoking. The primary safety endpoint of the EAGLES trial was defined as the occurrence of at least one treatment-emergent severe adverse event of anxiety, depression, feeling abnormal, or hostility and/or the occurrence of at least one treatment-emergent moderate or severe adverse event of agitation, aggression, delusions, hallucinations, homicidal ideation, mania, panic, paranoia, psychosis, suicidal ideation, suicidal behavior or completed suicide. The incidence of the primary safety endpoint in patients without a history of psychiatric disorders was 1.3% (Champix®), 2.2% (bupropion), 2.5% (nicotine patch) and 2.4% (placebo).1 The incidence rates in patients with a history of psychiatric disorders were 6.5% (Champix®), 6.7% (bupropion), 5.2% (nicotine patch) and 4.9% (placebo).1 In patients without a history of psychiatric disorders, the Champix®–placebo and bupropion–placebo risk differences (RDs) for the primary safety endpoint were -1.28 (95% CI -2.40 to -0.15) and -0.08 (-1.37 to 1.21), respectively.1 The RDs for Champix®-nicotine patch and bupropion-nicotine patch comparisons were -1.07 (-2.21 to 0.08) and 0.13 (-1.19 to 1.45), respectively. In patients with a history of psychiatric disorders, the Champix®–placebo and bupropion–placebo RDs were 1.59 (-0.42 to 3.59) and 1.78 (-0.24 to 3.81), respectively; the RDs for Champix®-nicotine patch and bupropion-nicotine patch comparisons were 1.22 (-0.81 to 3.25) and 1.42 (-0.63 to 3.46), respectively. Across both patient cohorts, 95% CIs associated with these RDs were lower than or included zero. There were more neuropsychiatric adverse events in the psychiatric cohort than the non-psychiatric cohort across all treatment arms including placebo.
EMA MARKETING AUTHORISATION FOR COAGADEX Bio Products Laboratory, Limited (BPL) have announced that the European Medicines Agency has granted marketing authorisation for Coagadex. Coagadex is indicated for the treatment and prophylaxis of bleeding episodes and for perioperative management
in patients with hereditary factor X deficiency. Coagadex is the first and only treatment licensed specifically for this rare bleeding disorder in Europe. Factor X deficiency is a rare and serious condition caused by not having enough of the Factor X protein in the blood; this protein plays a crucial role in coagulation (blood clotting) which helps patients stop bleeding. People with Factor X deficiency are at increased risk of bleeding or experience excessive or prolonged bleeding. Severely affected individuals, usually children, have an increased risk of bleeding inside the brain, in the lungs or in the gastrointestinal tract, which can be life-threatening. Hereditary Factor X deficiency is very rare and affects approximately 700 patients in Europe. Coagadex was approved based upon data generated from two open-label, multicentre, prospective studies. The first study enrolled patients with moderate to severe hereditary factor X deficiency who were treated on-demand for spontaneous or traumatic bleeding episodes. The primary efficacy endpoints were pharmacokinetic measures including recovery rate and halflife, and secondary endpoints included overall assessment of efficacy and the number of infusions needed to treat a bleed. The criteria for treatment success were satisfied in the study, and the pharmacokinetic parameters were consistent with previously published data. The overall mean in-vivo recovery rate was 2.0 IU/ dl per IU/kg and the half-life was approximately 30 hours. There were 187 assessable bleeds in the study with patients rating the treatment as “excellent” in 170 (91%) cases, “good” in 14 (7.5%) cases, and “poor” in two (1.1%) cases. In addition, most bleeding episodes (155/187 [82.9%]) were effectively treated with only one infusion of Coagadex. Two patients in the study reported six adverse events considered possibly related to the medication: two events of fatigue in one patient, two events of infusion site erythema in one patient, and one of infusion site pain and back pain in each patient. There were no other drug-related adverse events, no serious drug-related adverse events, and no patients discontinued from the study due to adverse events. The second study collected data on two surgical patients receiving Coagadex perioperatively.
55 STUDY FINDS STERILE POST-TRAUMATIC IMMUNOSUPRESSION CAN LEAD TO POST-SURGICAL MORTALITY Scientists at NUI Galway completed a research study which has revealed that post-traumatic immunosuppression (PTI) is one of the leading causes of post-surgical mortality and makes patients vulnerable to hospital-acquired infections, multiple organ failure and many other complications. Lead author of the study, Professor Rhodri Ceredig, Director of the National Centre for Biomedical Engineering Science at NUI Galway, said, “An evolutionarily sophisticated and balanced immune system exists in our body whose equilibrium can be altered by different physical, environmental or psychological stresses. Trauma, including major surgery and accidental injury, leads to post-traumatic immunosuppression (PTI) increasing a patient’s vulnerability to hospital-acquired infections. Florence Nightingale initially raised this question during the Crimean War and great efforts were then made to improve hospital hygiene. Although sanitation has been improved in hospitals, an equivalent phenomenon of posttraumatic deaths from systemic infections persists to this day. ” Professor Ceredig added, “More and more new infections are still threatening major trauma patients. An important question remains, ‘why do wounded patients acquire systemic infections even in a hygienic environment?’ Research over the past two decades suggests that following trauma, a patient’s immune system is imbalanced, thereby increasing their vulnerability to acquired infections. However, the underlying mechanisms of PTI are poorly defined and as yet, there are no universally accepted treatments. Our study, carried out by Dr Md. Nahidul Islam at NUI Galway in collaboration with Professor Benjamin Bradley of the University of Bristol, used total knee replacement surgery as a model of sterile surgical trauma.”
ASTRA ZENECA PRESENTS POSITIVE OSIMERTINIB FOLLOW-UP DATA AstraZeneca have reported new Phase I extended follow-up data on osimertinib in both first- and second-line treatment of patients with non-small cell lung cancer (NSCLC), at the European Lung Cancer Conference (ELCC) 2016. Late-breaker presentations reinforced the efficacy and safety profile for osimertinib previously
seen in the AURA clinical trials programme. Phase I data from the AURA trial on osimertinib investigated as first-line treatment in 60 patients (pooled 80mg and 160mg dose cohorts) with epidermal growth factor receptor (EGFR) mutationpositive advanced NSCLC showed an objective response rate (ORR, a measurement of tumour shrinkage) of 77% (95% confidence interval (CI): 64%-87%) and a progressionfree survival (PFS) of 19.3 months, with 55% of patients remaining progression-free at 18 months (95% CI: 41%-67%). Median duration of response (DoR) was non-calculable (NC) (95% CI: 12.5 months to NC) at the time of data cut off, with 53% of patients continuing to respond at 18 months (95% CI: 36%-67%). Of the 60 first-line patients, five had tumours also harbouring the T790M mutation at diagnosis (known as de novo patients) and all five of these patients showed durable responses. The most common adverse events were rash (78% overall; 2% ≥Grade 3), diarrhoea (73% overall; 3% ≥Grade 3), dry skin (58% overall; 0 ≥Grade 3) and paronychia (50% overall; 3% ≥Grade 3). All of the Grade 3 or above events in these categories occurred at the 160mg dose. Updated pooled results from AURA Phase II studies in 411 pretreated patients with EGFR T790M mutation-positive NSCLC treated with osimertinib 80mg showed a median PFS of 11 months (95% CI: 9.6-12.4 months), an ORR of 66% (95% CI: 61%-71%) and a median DoR of 12.5 months (95% CI:11.1 months to NC).2 Pooled treatment-related adverse events data from the AURA Phase II studies included rash (41% overall; <1% ≥Grade 3), diarrhoea (38% overall; <1% ≥Grade 3), dry skin (30% overall; 0% ≥Grade 3) and paronychia (29% overall; 0% ≥Grade 3). Interstitial lung disease was seen in 12 patients (3% overall; 2% ≥Grade 3), hyperglycaemia in 1 patient (<1% overall; 0 ≥Grade 3) and QT prolongation in 14 patients (3% overall; 1% ≥Grade 3). Osimertinib recently received accelerated approval as the first indicated treatment for patients with EGFR T790M mutationpositive metastatic NSCLC in the US, EU and Japan. The ongoing confirmatory Phase III trial, AURA, is assessing the efficacy and safety of osimertinib versus platinum-based doublet chemotherapy in patients with EGFR T790M mutation-positive, locally advanced, or metastatic
NSCLC who have progressed following prior therapy with an EGFR-TKI. AstraZeneca is also continuing studies in the adjuvant and locallyadvanced/metastatic first-line EGFRm settings, in patients with and without brain metastases, in leptomeningeal disease, and in combination with other compounds.
GREATER SURVIVAL BENEFIT SHOWN IN MEN WITH EARLY AND LESS AGGRESSIVE METASTATIC CASTRATIONRESISTANT PROSTATE CANCER Janssen Ireland have announced that data from a post-hoc analysis of the Phase 3 COU-AA-302 trial showed that ZYTIGA® (abiraterone acetate) plus prednisone provided an 11.8 months overall survival (OS) benefit (53.6 months vs 41.8 months; HR = 0.61 [95% CI, 0.43-0.87]; p = 0.0055), compared to an active control of placebo plus prednisone, in men with early and less aggressive chemotherapy-naïve metastatic castration-resistant prostate cancer (mCRPC).[i] Data from the post-hoc analysis was presented recently at the European Association of Urology (EAU) 2016 Congress in Munich, Germany. The post-hoc analysis divided patients into two groups to identify which group experienced a greater treatment benefit. The patients in Group 1 were in an earlier, less advanced and less symptomatic stage of the disease (which was defined as having a Brief Pain Inventory [BPI] Short Form score of 0-1, prostatespecific antigen [PSA] below 80 ng/ml and a Gleason score [GS] of below 8). Those in Group 2 were in a later, more advanced and more symptomatic stage of the disease (defined as a having a BPI of 2 or over and/or PSA of 80 ng/ml or above, and/or a GS of 8 or more). The analysis revealed that patients in both groups experienced an OS benefit when treated with abiraterone acetate plus prednisone, compared to placebo plus prednisone (Group 1: 11.8 months; HR = 0.61 [95% CI, 0.43-0.87]; p = 0.0055) (Group 2: 2.8 months; HR = 0.84 [95% CI, 0.72-0.99]; p = 0.0321). “Post-hoc analyses such as this are very important in helping us to identify the patients who could benefit most from therapies such as novel hormone agents, and at what stage of a patient’s disease they could be most effective.” said Dr John Mc Caffrey, Consultant Medical Oncologist at Dublin's
Mater Hospital. “As men with prostate cancer are living longer, quality of life is an increasingly important factor for them and their families. It is therefore encouraging to see that when used earlier, patients can stay on abiraterone acetate for longer and delay the need for additional, more invasive treatments,” he continued. In addition to OS benefit, the post-hoc analysis data also revealed that both groups showed improvement in disease progression, cancer-related pain and treatment duration when treated with abiraterone acetate plus prednisone, compared to placebo plus prednisone: Time to chemotherapy use was increased by 12.7 months in Group 1 and 8.8 months in Group Group 1: 37.0 months vs 24.3 months; HR = 0.64 [95% CI, 0.46-0.89]; p = 0.0073 Group 2: 23.3 months vs 14.5 months; HR = 0.71 [95% CI, 0.60-0.85]; p = 0.0001 There was an improvement in median time to opiate use for cancer-related pain in both groups Group 1: not reached vs 41.0 months; HR = 0.69 [95% CI, 0.48-0.99]; p = 0.0409 Group 2: 30.5 months vs 19.3 months; HR = 0.70 [95% CI, 0.59-0.84]; p = 0.0001 Median time on treatment almost doubled in both groups Group 1: 20.4 months vs 11.2 months; HR = 0.41 [95% CI, 0.31-0.54]; p < 0.0001 Group 2: 12.3 months vs 7.2 months; HR = 0.54 [95% CI, 0.46-0.62]; p < 0.0001 Dr Leisha Daly, Country Director, Janssen Ireland said, “Janssen is proud that this study continues to deliver valuable insights as to how best to treat different stages of advanced prostate cancer. We hope that this additional analysis will help healthcare professionals to define the most effective treatment pathway for individual patients. We remain committed to continuing our research in this area with the aim of helping to improve outcomes for men affected by this disease now and in the future.”
HPN • May 2016