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Ireland ‘far from where it should be’ in Diabetes care
Ireland is "very far from where it should be" in the treatment of children with Type 1 diabetes, an expert in the disease has claimed. A co-ordinated national strategy is vital to confronting the chronic condition, said Consultant Dr Colin Hawkes ahead of World Diabetes Day held in November past. He and the team at Cork University Hospital treats almost 500 children with Type 1 diabetes, but insufficient resources mean it is not possible to see children every three months, as recommended - with some waiting six-eight months between appointments. “We are also totally unequipped to address the psychological burden Dr Colin Hawkes, Consultant Paediatric Endocrinologist, Cork University Hospital
of this disease," said Dr Hawkes, a paediatric endocrinologist at CUH. “We are very far from where we should be, there is a lot more that we need to be doing to meet the needs of these children and their families. “In CUH alone, we have an exceptional team but we should have six diabetes nurses for the number of children we care for and we only have three. We have submitted a business case requesting three more. It is extremely difficult to provide the care these children deserve at such low staffing levels. “We also should be at the forefront of research in this condition and are working to generate energy and funding to build a research team and programme. This will help change the future of this condition.” In Type 1 diabetes, the immune system attacks the pancreas, destroying cells that make insulin - crucial for sending glucose (sugars) to the body's cells for energy. When a child is diagnosed, they must learn to detect glucose levels and administer insulin throughout the day and night. Advances in technology, however, have largely replaced the fingerstick glucose checks with glucose monitors and insulin injections with insulin pumps. Possible signs of diabetes in children include increased thirst, frequent urination, bed wetting, reduced energy, unexplained weight loss, extreme hunger (possibly with craving for sugary foods) and vaginal thrush. “We know that if it is not properly controlled, it increases the risk of heart disease, blindness and kidney failure in adulthood. It is extremely important to get it right. This is critical in childhood, where we are setting the child on a life-long journey in managing this condition.
“The aspiration should be that every child should have access to the same and the best standard of care, regardless of where they live. There is not equity in Ireland in access to a full diabetes multidisciplinary team. “Cork is the largest centre in Ireland without a dedicated psychologist to support these families. “CUH is a regional centre of excellence for children with type 1 diabetes in the South/Southwest Hospital Group. In addition to our local children, we provide diabetes expertise for children in Kerry and as far as Clonmel (Tipperary). “Rather than bringing children long distances to us, appropriate staffing of the diabetes programme at Cork would allow our diabetes team to perform regional outreach clinics. In my view, that should be the model.”
Body Clock and Inflammatory Disease Link
New research from RCSI has demonstrated the significant role that an irregular body clock plays in driving inflammation in the body’s immune cells, with implications for the most serious and prevalent diseases in humans. The research was led by the School of Pharmacy and Biomolecular Sciences at RCSI University of Medicine and Health Sciences. The circadian body clock generates 24-hour rhythms that keep humans healthy and in time with the day/night cycle. This includes regulating the rhythm of the body's own (innate) immune cells called macrophages. When these cell rhythms are disrupted (due to things like erratic eating/ sleeping patterns or shift work), the cells produce molecules which drive inflammation. This can lead to chronic inflammatory diseases such as heart disease, obesity, arthritis, diabetes and cancer, and also impact our ability to fight infection. In this study, the researchers looked at these key immune cells called macrophages with and without a body clock under laboratory conditions. They were interested to understand if macrophages without a body clock might use or 'metabolise' fuel differently, and if that might be the reason these cells produce more inflammatory products. The researchers found that macrophages without a body clock took up far more glucose and broke it down more quickly than normal cells. They also found that, in the mitochondria (the cells energy powerhouse), the pathways by which glucose was further broken down to produce energy were very different in macrophages without a clock. This led to the production of reactive oxygen species (ROS) which further fuelled inflammation. Dr George Timmons, lead author on the study, said, “Our results add to the growing body of work showing why disruption of our body clock leads to inflammatory and infectious disease, and one of the aspects is fuel usage at the level of key immune cells such as macrophages.”
The Next Line Is Clear¹
LORVIQUA as monotherapy is indicated for the treatment of adult patients with anaplastic lymphoma kinase (ALK)-positive advanced non-small cell lung cancer (NSCLC) whose disease has progressed after:
References: 1. Lorviqua® Summary of Product Characteristics.
PRESCRIBING INFORMATION
▼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. Refer to section 4.8 of the SPC for how to report adverse reactions.
Lorviqua®▼ 25 mg and 100 mg film-coated tablets IE Prescribing Information: Before prescribing Lorviqua (lorlatinib) please refer to the full Summary of Product Characteristics (SmPC). Presentation: Each 25 mg film-coated tablet contains 25 mg lorlatinib; Each 100 mg film-coated tablet contains 100 mg lorlatinib. Indications: Lorviqua as monotherapy is indicated for the treatment of adult patients with anaplastic lymphoma kinase (ALK) positive advanced non small cell lung cancer (NSCLC) whose disease has progressed after alectinib or ceritinib as the first ALK tyrosine kinase inhibitor (TKI) therapy, or crizotinib and at least one other ALK TKI. Dosage and Administration: Treatment should be initiated and supervised by a physician experienced in the use of anticancer medicinal products. The recommended dose is 100 mg lorlatinib taken orally once daily. Treatment is recommended as long as the patient is deriving clinical benefit from therapy without unacceptable toxicity. If a dose is missed, then it should be taken as soon as the patient remembers unless it is less than 4 hours before the next dose. Patients should not take 2 doses at the same time to make up for a missed dose. To manage adverse reaction, dose interruption or dose reduction see SmPC section 4.2. Concurrent use of lorlatinib with medicinal products that are strong CYP3A4/5 inhibitors and grapefruit juice products may increase lorlatinib plasma concentrations, see SmPC section 4.2 for further information. Special populations: Elderly (≥ 65 years): There are limited data on this population, no dose recommendation can be made for patients aged 65 years and older (see section 5.2). Renal impairment: See SmPC section 4.2. No dose adjustment is required for patients with mild or moderate renal impairment. A reduced dose of lorlatinib is recommended in patients with severe renal impairment (absolute eGFR < 30 mL/min), e.g. a once daily starting dose of 75 mg taken orally (see SmPC section 5.2). No information is available for patients on renal dialysis. Hepatic impairment: See SmPC section 4.2. No dose adjustment is required for patients with mild hepatic impairment. No information is available for lorlatinib in patients with moderate or severe hepatic impairment. Therefore, lorlatinib is not recommended in patients with moderate to severe hepatic impairment (see section 5.2). Paediatric population: The safety and efficacy of lorlatinib in children and adolescents < 18 years of age have not been established. Method of administration: Lorlatinib is for oral use. Patients should be encouraged to take their dose of lorlatinib at approximately the same time each day with or without food (see SmPC section 5.2). The tablets should be swallowed whole (tablets should not be chewed, crushed or split prior to swallowing). No tablet should be ingested if it is broken, cracked, or otherwise not intact. Contra-indications: Hypersensitivity to the active substance or to any of the excipients. Concomitant use of strong CYP3A4/5 inducers (see SmPC sections 4.4 and 4.5). Special Warnings and Precautions:Hyperlipidaemia: The use of lorlatinib has been associated with increases in serum cholesterol and triglycerides (see SmPC section 4.8). Serum cholesterol and triglycerides should be monitored before initiation of lorlatinib; 2, 4 and 8 weeks after initiating lorlatinib and regularly thereafter. Initiate or increase the dose of lipid lowering medicinal products, if indicated (see SmPC section 4.2). Central nervous system (CNS) effects: CNS effects have been observed in patients receiving lorlatinib, including psychotic effects and changes in cognitive function, mood, mental status or speech (see SmPC section 4.8). Dose modification or discontinuation may be required for those patients who develop CNS effects (see SmPC section 4.2). Atrioventricular block: Lorlatinib was studied in a population of patients that excluded those with second degree or third degree AV block (unless paced) or any AV block with PR interval > 220 msec. PR interval prolongation and AV block have been reported in patients receiving lorlatinib (see SmpC section 5.2). Monitor electrocardiogram (ECG) prior to initiating lorlatinib and monthly thereafter, particularly in patients with predisposing conditions to the occurrence of clinically significant cardiac events. Dose modification may be required for those patients who develop AV block (see SmPC section 4.2). Left ventricular ejection fraction decrease: Left ventricular ejection fraction (LVEF) decrease has been reported in patients receiving lorlatinib who had baseline and at least one follow-up LVEF assessment. In patients with cardiac risk factors and those with conditions that can affect LVEF, cardiac monitoring, including LVEF assessment at baseline and during treatment, should be considered. In patients who develop relevant cardiac signs/symptoms during treatment, cardiac monitoring, including LVEF assessment, should be considered. Lipase and amylase increase: Elevations of lipase and/or amylase have occurred in patients receiving lorlatinib (see SmPC section 4.8). Risk of pancreatitis should be considered in patients receiving lorlatinib due to concomitant hypertriglyceridemia and/or a potential intrinsic mechanism. Patients should be monitored for lipase and amylase elevations prior to the start of lorlatinib treatment and regularly thereafter as clinically indicated (see SmPC section 4.2). Interstitial lung disease/Pneumonitis: Severe or life threatening pulmonary adverse reactions consistent with ILD/pneumonitis have occurred with lorlatinib (see SmPC section 4.8). Any patient who presents with worsening of respiratory symptoms indicative of ILD/ pneumonitis (e.g. dyspnoea, cough and fever) should be promptly evaluated for ILD/pneumonitis. Lorlatinib should be withheld and/or permanently discontinued based on severity (see SmPC section 4.2). Hypertension: Hypertension has been reported in patients receiving lorlatinib (see SmPC section 4.8). Blood pressure should be controlled prior to initiation of lorlatinib. Blood pressure should be monitored after 2 weeks and at least monthly thereafter during treatment with lorlatinib. Lorlatinib should be withheld and resumed at a reduced dose or permanently discontinued based on severity (see SmPC section 4.2). Hyperglycaemia: Hyperglycaemia has occurred in patients receiving lorlatinib (see SmPC section 4.8). Fasting serum glucose should be assessed prior to initiation of lorlatinib and monitored periodically thereafter according to national guidelines. Lorlatinib should be withheld and resumed at a reduced dose or permanently discontinued based on severity (see SmPC section 4.2). Interactions: Concomitant use of a strong CYP3A4/5 inducer is contraindicated (see SmPC sections 4.3 and 4.5). No clinically meaningful changes in liver function tests were seen in healthy subjects after receiving a combination of lorlatinib with the moderate CYP3A4/5 inducer modafinil (see section 4.5). Concurrent administration of lorlatinib with CYP3A4/5 substrates with narrow therapeutic indices, including but not limited to alfentanil, ciclosporin, dihydroergotamine, ergotamine, fentanyl, hormonal contraceptives, pimozide, quinidine, sirolimus and tacrolimus, should be avoided since the concentration of these medicinal products may be reduced by lorlatinib (see SmPC section 4.5). Lorlatinib is a weak inducer of CYP2B6, no dose adjustment is necessary when lorlatinib is used in combination with medicinal products that are mainly metabolised by CYP2B6 (see SmPC section 4.5). Lorlatinib is a weak inducer of CYP2C9, no dose adjustment is required for medicinal products that are mainly metabolised by CYP2C9. Patients should be monitored in case of concomitant treatment with medicinal products with narrow therapeutic indices metabolised by CYP2C9 (e.g. coumarin anticoagulants) (see SmPC section 4.5). Lorlatinib is a weak inducer of UGT, no dose adjustment is required for medicinal products that are mainly metabolised by UGT. Patients should be monitored in case of concomitant treatment with medicinal products with narrow therapeutic indices metabolised by UGT (see SmPC Section 4.5). Lorlatinib is a moderate inducer of P gp. Medicinal products that are P gp substrates with narrow therapeutic indices (e.g. digoxin, dabigatran etexilate) should be used with caution in combination with lorlatinib due to the likelihood of reduced plasma concentrations of these substrates. Lorlatinib should be used with caution in combination with substrates of BCRP, OATP1B1, OATP1B3, OCT1, MATE1 and OAT3 as clinically relevant changes in the plasma exposure of these substrates cannot be ruled out (see SmPC section 4.5). Fertility, pregnancy and Breast-feeding: Fertility: Male fertility may be compromised during treatment with lorlatinib (see SmPC section 5.3). Men should seek advice on effective fertility preservation before treatment. It is not known whether lorlatinib affects female fertility. Pregnancy: Lorlatinib is not recommended during pregnancy or for women of childbearing potential not using contraception. Women of childbearing potential should be advised to avoid becoming pregnant while receiving lorlatinib. A highly effective non hormonal method of contraception is required for female patients during treatment because lorlatinib can render hormonal contraceptives ineffective (see SmPC sections 4.5 and 4.6). If a hormonal method of contraception is unavoidable, then a condom must be used in combination with the hormonal method. Effective contraception must be continued for at least 35 days after completing therapy (see SmPC section 4.6). During treatment and for at least 14 weeks after the final dose, male patients with female partners of childbearing potential must use effective contraception, including a condom, and male patients with pregnant partners must use condoms (see SmPC section 4.6). Breast-feeding: Lorlatinib should not be used during breast feeding. Breast feeding should be discontinued during treatment and for 7 days after the final dose. Lactose intolerance: This medicinal product contains lactose as an excipient. Patients with rare hereditary problems of galactose intolerance, total lactase deficiency, or glucose galactose malabsorption should not take this medicinal product. Effects on ability to drive and use machines: Lorlatinib has moderate influence on the ability to drive and use machines. Caution should be exercised when driving or operating machines as patients may experience CNS effects (see SmPC section 4.8). Undesirable Effects: See SmPC section 4.8. The overall safety profile of lorlatinib is presented from data from 295 adults treated with lorlatinib 100 mg once daily with advanced NSCLC from Study A (Phase II 1001 (n=275), Phase I (n=17), Japanese Cohort (n=3)). The most common (≥2%) Grade ≥3 adverse reactions of lorlatinib were Anaemia, Hypercholesterolaemia, Hypertriglyceridaemia, Cognitive effects, Peripheral neuropathy, Oedema, Weight increased, Lipase increased, Amylase increased. Commonly reported adverse events (≥ 1/100 to < 1/10) were Hyperglycaemia, Psychotic effects, Mental status changes, Speech effects, Pneumonitis. Dose reductions due to adverse reactions occurred in 23.4% of patients receiving lorlatinib. Very common (≥ 1/10) adverse reactions in patients receiving lorlatinib in this study were Anaemia, Hypertension, Hypercholesterolaemia, Hypertriglyceridaemia, Mood effects, Cognitive effects, Peripheral neuropathy, Headache, Vision disorder, Diarrhoea, Nausea, Constipation, rash, Arthralgia, Myalgia, Oedema, Fatigue, Weight increased, Lipase increased, Amylase increased. Common (≥ 1/100 to < 1/10) adverse effects were Speech effects, Pneumonitis. Legal Category: S1A. Package quantities and Marketing Authorisation Numbers: Lorviqua 25 mg film-coated tablets EU/1/19/1355/003, 90 tablets. Lorviqua 100 mg film-coated tablets EU/1/19/1355/002, 30 tablets. For further information on this medicine please contact: Pfizer Medical Information on 1800 633 363 or at EUMEDINFO@pfizer.com For queries regarding product availability please contact: Pfizer Healthcare Ireland, Pfizer Building 9, Riverwalk, National Digital Park, Citywest Business Campus, Dublin 24 + 353 1 4676500. Marketing Authorisation Holder: Pfizer Europe MA EEIG, Boulevard de la Plaine 17, 1050 Bruxelles, Belgium.
First in Prostate Cancer at Blackrock
Blackrock Clinic is now providing a new type of scan for prostate cancer. The PSMA (Protein Specific Membrane Antigen) is labelled with F-18 and the PET/ CT scan is used to detect the F-18 PSMA within the body for the first time in Ireland. PSMA provides the most accurate staging evaluation for men with prostate cancer. The scan is most popular for patients who have previously had prostate cancer and are now representing with concern of disease recurrence, most frequently with elevated prostate-specific antigen (PSA). PSMA can also be used as a staging tool to more accurately detect the spread of prostate cancer in a newly diagnosed patient. Due to difficulties accessing this scan in Ireland, many Irish patients currently have to go overseas to the UK or Europe for these scans. The PSMA PET/CT Scan uses nuclear isotopes in Fluorine-18 to detect certain proteins in the body by attaching to and “lighting up” on a scan when they come into contact with cancerous growths. Professor Stephen Connolly, a Consultant Urologist at the Blackrock Clinic said, “This is very good news for men with prostate cancer. This simple and effective scan will help to quickly and accurately evaluate prostate cancer, which in turn will lead to better precision in treatment and improvements in outcome.” CEO of the Blackrock Clinic, James O’Donoghue welcomed
'Normal PSMA' scan - Citation: R.W. Foley, S.L. Redman, R.N. Graham, W.W. Loughborough, D. Little, Fluorine-18 labelled prostate-specific membrane antigen (PSMA)-1007 positron-emission tomography–computed tomography: normal patterns, pearls, and pitfalls, Clinical Radiology, Volume 75, Issue 12, 2020, Pages 903-913, ISSN 0009-9260, https://doi. org/10.1016/j.crad.2020.06.031. (https://www.sciencedirect.com/science/ article/pii/S0009926020302737) Blackrock Clinic CEO James O'Donoghue
the development saying, “At the Blackrock Clinic we strive to provide the most advanced care to all of our patients. The PSMA PET/CT scan using the Fluorine-18 radioisotope is the latest technology we have introduced specifically to improve men’s health and wellbeing.” Blackrock Clinic is the only private hospital in the country offering such a scan and agreement has been reached with the VHI to fund this diagnostic test for members on certain plans. If a patient’s insurer does not cover the cost of this scan, it is available on a selfpay basis. Internationally, these scans are widespread in the evaluation of prostate cancer. PSMA PET/CT is now considered the best staging tool for the most common cancer affecting men, representing a new standard of care. However, in Ireland, only one public hospital is currently providing PSMA PET/CT scanning which means that there are long delays in accessing this important diagnostic tool. Being the first hospital to provide PET/CT in Ireland in 2000, Blackrock Clinic is delighted with this development as it will significantly improve access to these valuable scans for patients and consultants.
HIQA Advises NSAC on Ethics Frameworks
The Health Information and Quality Authority (HIQA) has published a review of international ethics frameworks to help inform the work of the National Screening Advisory Committee (NSAC). NSAC is developing an ethics framework to support its evaluations and deliberations in relation to population-based screening programmes in Ireland. The development of this framework follows the recommendations of the Scoping Inquiry into the CervicalCheck Screening Programme by Dr Gabriel Scally ('the Scally Report'), which emphasised the role of ethics in the consideration of programmes. HIQA’s review identified and described ethics frameworks used internationally for policy-making in the context of screening. Sources for the review included bodies with responsibility for screening policy-making, public health agencies, national ethics bodies, and international agencies. While considerable variation was found in the content and structure of the frameworks identified, consistencies were noted in the ethical principles and procedural values that are considered. Several frameworks highlighted the need to consider the relevance and relative importance of values or principles within different contexts of screening (for example, adult versus child programmes), and the possibility that some values and principles may conflict with each other. Furthermore, as public health decisions related to screening are taken at the population or community level, the values and principles that guide these decisions differ from those that guide traditional clinical decision-making. Therefore, it is important to balance the consideration of the benefits and harms of screening as they relate to the overall population and for the individual.
