49 minute read
Why is Healthcare still not Safe?
PEER REVIEW: PATIENT SAFETY
Why is Healthcare Still not Safe?
In the turn of the century a report was published recognising ‘to err is human’. It recognised the fallible nature of humans, and how error-making is a part of work. Nonetheless, ongoing discussions exist in the media and literature as to ‘why is healthcare still not safe?’.
In this article, I will give an executive overview, based on empirical evidence and broad disciplinary considerations, that such issues exist to a myriad of intertwining complex and historically associated variables. There will be reference to the foundations of the safety for patients movement, the growing influence of medical bureaucracy, the flaws in research design and assessment of progress, and an overemphasis on leveraging change at the individual level and not the organisational level.
Foundations of patient safety
First – we need to look back to fully understand the causal factors which led to the formation of focus on healthcare safety. While this article questions why healthcare is still not safe, and could be argued from the lens of injury to practitioners in their work, the focus of this article is on the end user of healthcare work – the patient. Patient Safety is a healthcare discipline that emerged with the evolving complexity in health care systems and the resulting rise of patient harm in health care facilities. As a discipline it aims to prevent and reduce risks, errors and harm that occur to patients during provision of health care. A cornerstone of the discipline is continuous improvement based on learning from errors and adverse events. Written by Dr Dale Whelehan, PhD in Behaviour Sciences, Trinity College Dublin, the University of Dublin
Day to day adverse events create a burden of harm which can lead to safety issues for our patients. These include things such as medication errors, diagnostic errors and health-care associated infections.
The issue of patient safety was first raised in 1847 by Semmelweiss who documented the difference in rates of medical harm across two wards of care. Coupled with disparate amounts of research over the coming decades, a seminal study conducted by Moser in the 1960’s called ‘Diseases of Medical Progress’ as well as the Harvard medical practice study first began to succinctly identify instances of safety concern in healthcare. This was the beginning of the research movement and founded with input from the safety sciences. A successful application of this research, and considered a gold standard example to this day, was the application of human factors and safety science research to the discipline of Anaesthesia by a researcher called Jeff Cooper. Large scale reductions in patient harm were recorded from this initial movement.
Alongside this stream of work, a parallel movement was forming, motivated by milestone cases relating to medical error. Confounded by several variables, including media, these cases created a political uproar as each played on a different public fear. Libby Zion, who died as a result of poor supervision and overworked staff. Willie King, whose wrong leg was amputated. Josie King, who went to a prestigious and highly rated hospital for cancer treatment and received a dose that was too high. Elaine Bromley, who went in for a routine nasal operation and died soon after. Growing hostility towards the healthcare professions ensued, with large blame being placed on individuals within systems. There was a true desire to prevent such cases from ever happening again, leading to successful events such as the Annenberg 1 and 2 conferences. These brought together a broad range of stakeholders under the impetus to make healthcare safe in the turn of the century. A third movement emerged around this time, fuelled in part by both aforementioned movements, but also by publication of significant reports such as the ‘To Err is Human’ report which estimated 44,000-98,000 deaths/year U.S citizens died due to medical error every year. Political will to deal with these issues through ‘shaking up healthcare’ resulted, leading to application of managerialism style interventions. Medical practitioners became managers to deal with issues of safety, leading to the formation of an in-group thinktank for patient safety assurance. Industralisation of medicine ensued, creating a corporate elite of healthcare staff who utilized superficial principles of evidencebased approaches from the safety sciences, in conjunction with Taylorism principles of scientific management, to create faux solutions which were branded as scientific interventions. This has become the dominant movement, and despite efforts, a 2016 John Hopkins Study concluded that little progress has been made and safety issues are the 3rd leading cause of death.
Research design
A discourse has been ongoing in academic institutions since the biomedicalisation of patient safety research. A twenty year review has found that, using retrospective analysis of charts, there exists little shifts in the metrics previously used to define safety in healthcare – whether they be harm, adverse events, or medical error. The interchanging utilisation of these terms has meant the research is heterogenous, and often poorly understood. Utilisation of inappropriate research methods to make sweeping generalisation and conclusions has become a normal issue in the discipline of research, further conflating the difficulty in truly understanding the effective interventions to make healthcare safer.
Along the journey since the publication of To Err is Human, we have lost one of the pivotal segments of the research puzzle – to involve the experts of safety sciences – the psychologists, anthropologists, human factor engineers – as our methodological experts. Instead we have biomedicalised the discipline, broadening its parameters to include aligned disciplines such as infection control, which has led to a forever squeezing of opportunity for the nonepidemiological disciplines. This positivist approach has meant many disciplines have been effectively silenced. A fundamental realignment to recognise that medicine needs these disciplines to make evidence-based interventions is important. Organisational behaviourist Dr. Kathleen Sutcliffe has conducted extensive research on the issue of healthcare safety and concludes healthcare is a mindless and vulnerable system. She identifies a series of confounding variables influencing healthcare issues – ranging from micro-issues such as individual performance, mezzo issues such as interpersonal skills, as macro issues such as organisation design and culture. These manifested themselves through behaviours which led to individualism, siloed ways of working, hierarchical governance, and inability to meet growing public service needs. The growing focus on performance science in recent decades from psychologists has also identified a link between staff wellbeing and patient safety. While healthcare workers have always worked above and beyond their vocational requirements, the confounding role that COVID has played on levels of burnout in the healthcare workforce is likely to significantly influence healthcare safety efforts.
Culture
One of the growing issues around patient safety is the risk of poor patient safety culture. When individuals work together, in teams, and not just groups with individuals with personal
interests, then a richer and fuller understanding of phenomena can be achieved. Unfortunately healthcare has a long way to go in achieving this vision. Ethnographic research conducted by Dr. Sutcliffe identified that healthcare workers continue to perform well at the individual level, but fail to form a level of team cognition which would allow them to communicate at a system level, and thus towards the higher system-level requirement of patient safety assurance. Leadership should be the focus going forward, at all levels, with a reduced emphasis on quality reporting as the only metric of safety evaluation, and instead increased effort on system resilience capability building. Supporting such strategic endeavours is the need to build a culture of patient safety which is honest, reflective, constructive and ethically-driven. Viewing the blackbox analogy used in the airline industry as an example of opportunity to learn from adverse event causal effects instead of as an oversight regulatory intervention is where we need to get to in healthcare. To ensure that first, we need to build psychological safety in our teams, where blame culture is removed, and individuals are recognised as just one cog in a complex machine which attempts to make a system as hazardous free as possible. Too long the blame has been on scapegoating the individual as the causal outcome of an egregious error, and instead system ownership to build authentic safety culture, away from biomedicalization and managerialism approaches is needed.
The Solution: A highly-reliable system
So how do we build such desired states? We have two approaches to safety. Safety 1, which focuses on accident causation in risk management. This identifies root causes which differ from normal work. It is managed through regulation. It is bio-medically driven and bureaucratically positivist and includes Heinrich’s pyramid and Swiss cheese models of linear sequential chain models. This approach alone is problematic as it assumes relationships between causes but ultimately blames people for making healthcare not safe.
Safety 2 on the other hand, utilises aspects of accident and high reliability organisation theories. It is interpretative in approach, and focuses on making authentic risks and consequences more apparent, so that they can become reversible. This resilience engineering also enables capabilities in people to adapt to dynamic responses. It recognises that people are performing exceptionally well despite trying conditions. Instead of focusing on causal outcomes, accidents and errors are thought to happen naturally in complex systems. A high reliability organisation is one which can reduce such failures where they might be normally expected. Serious accidents in high risk and hazardous operations can be prevented through a combination of organizational design, culture, management, and human choice. High reliability organisations seek to organize in ways that increase the quality of attention across the organization, thereby enhancing people's alertness and awareness to details so that they can detect subtle ways in which contexts vary and call for collective mindfulness. There are particular behaviours needed to build a HRO: Treat anomalies as symptoms of a problem with the system and building anticipation and learning opportunities. Building situational awareness is extremely important Refusing to simplify complex problems. Commiting to resilience - developing the capability to detect, contain, and recover from errors. Errors will happen, but we are not paralysed by them. Deference to expertise - follow typical communication hierarchy during routine operations, but defer to the person with the expertise to solve the problem during upset conditions. These behaviours are particularly important as safety is a dynamic non-event. It is dynamically preserved by human adjustment, and a non-event because successful outcomes aren’t visible.
Conclusion
To conclude this article I rephrase the question from ‘why is healthcare still not safe’ to ‘how do complex healthcare organisations achieve safe, reliable, resilience performance under trying conditions’. This allows us to focus on the organisational and behavioural levers we need to pull to evoke effective change. It is a fundamental rethinking of the patient safety discipline that is needed. A focus on not scrutinising the people within the system as the cause of safety issues, but the system itself. The "medicalisation" of the patient safety movement has placed it under the hegemony of bureaucratic-industrialized medicine and rendered the movement with little hope of truly understanding the basis (social and psychological as opposed to medical) of accidents in healthcare delivery. If we want to make healthcare safe, we need to: 1. Achieve greater consilience and reducing scientific bureaucratic technocracy. Making the human factors the subject matter experts, and the healthcare workers the content experts 2. Focus on new behaviours and culture – rejecting approaches where rule bound organisations are considered safe, and instead focus on safety culture.
Reduce hubristic behaviours and build capability to prepare for the unknown. Safety is not an objective quality, but an activity created and destroyed every minute. 3. Reshift the research towards the evidence-base and not just cherry picking the parts of patient safety we like such as checklists. Redefine our understanding of what is patient safety research and what isn’t. Similarly, create greater understanding of different latent constructs such as medical harm, medical error – and understand the implications of these terminologies for media dissemination. Foster the energy of the patient safety movement and engage in meaningful patient engagement to design studies. 4. Start with understanding the dynamic nature of people and system interaction to influence safety. There is a need for focusing on supra organisational interventions which transcend both the individual behavioural and organisational levers of patient safety. 5. Be driven by science and not by popular movement.
Safety in healthcare has a fluid and fractured intellectual history. Vested interests, cognitive dissonance, and oversimplification of complex systems does nothing in the end to make healthcare safer.
PEER REVIEW: GOUT
Written by Dr. Emma Dorris (Scientist, UCD), Mariosa Kieran (Pharmacist, Mater Misericordiae University Hospital), Professor Nicola Dalbeth (Consultant Rheumatologist, University of Auckland) and Professor Geraldine McCarthy (Consultant Rheumatologist, Mater Misericordiae University Hospital/UCD)
Dr. Emma Dorris (Scientist, UCD) Professor Geraldine McCarthy (Consultant Rheumatologist, Mater Misericordiae University Hospital/UCD)
Mariosa Kieran (Pharmacist, Mater Misericordiae University Hospital) Professor Nicola Dalbeth (Consultant Rheumatologist, University of Auckland)
Gout is the most common form of inflammatory arthritis in adults. The incidence of gout is rising. People with gout have an increased risk of cardiovascular disease, and gout is associated with a number of comorbidities including diabetes and renal impairment. The increased incidence of gout together with increased cardiovascular risk and comorbidities is a significant public health challenge. Unlike other common rheumatic diseases, the underlying cause of gout is well understood. Gout is caused by hyperuricaemia, too much uric acid in the body. This can occur due an underexcretion and/or overproduction of urate, which leads to monosodium urate (MSU) crystal formation and deposition in joints and tissues in susceptible individuals (figure 1). Acute gout flares occur as an inflammatory response to the MSU crystals. The goal of urate lowering therapy is to reduce serum urate to a therapeutic target level, thereby permitting MSU crystals to dissolve, in addition to preventing further crystal formation and deposition. An important issue in urate lowering therapy is that paradoxically, initiation of urate lowering therapy can actually induce a gout attack. This happens because the urate lowering therapy causes MSU crystals to be shed from the articular cartilage into the joint space, resulting in acute inflammation. To prevent this, a low dose of anti-inflammatory prophylaxis, such as colchicine, is recommended for at least the first three to six months following initiation of urate lowering therapy. Community pharmacists are the most easily accessible members of a patient’s health care team. Pharmacists are often a key source of information on disease management and patients have confidence in them. Pharmacists act as a critical resource for effective management of disease, particularly when chronic such as gout. Thus, open communication and education between the pharmacy and prescriber communities is essential to provide the most up-to-date and appropriate patient care. However, pharmacists frequently report a lack of patient treatment plan information and clinical connection to other healthcare professionals as barriers to providing optimal care to patients. The use of low dose colchicine as a prophylaxis is an example of this gap in knowledge translation. Colchicine use in gout is most commonly used in the treatment of acute gout flares in a strictly time limited fashion. Legacy prescribing, whereby short or intermediate-term medications are not appropriately discontinued, is prevalent. Patients, and indeed pharmacists, can be unsure whether the prescribed colchicine is intended as a prophylaxis or is a legacy prescription that was previously prescribed in case of flare. This confusion can be magnified by lack of clear, definitive statements on updated best practices from national bodies and the time lag in incorporating professional body recommendations into readily accessible drug information sources, e.g. the product Summary of Product Characteristics, the British National Formulary. Pharmacists have reported that the advice on use of colchicine as a prophylaxis in their typical reference manuals is poorly defined in comparison to its use for acute flares. This can lead to conflicting advice being given to patients from their pharmacists and rheumatologists about gout management, particularly in relation to colchicine use. This prompted research into the pharmacist knowledge of gout management, leading to the development of an educational intervention for pharmacists. Our research showed that pharmacist-knowledge of gout management in Ireland was not in line with current European (EULAR) gout management guidelines. However, we also demonstrated that pharmacists do not typically use disease management guidelines as standard sources of information. As such, there is a knowledge gap in the most up to date recommendations for gout management. Given the wide number of conditions encountered on a daily basis in community pharmacy, this is somewhat understandable. As such, a dedicated effort must be made by prescribers and professional societies to communicate treatment standards to pharmacists.
In response to our initial findings, an education intervention was co-developed by two consultant rheumatologists and gout specialists, a pharmacist and general practitioner. We worked closely with the site founder of Pharmabuddy, the eLearning platform designed for and used by pharmacists. A thirteen minute video tutorial on the pharmaceutical management of gout was produced and is hosted on the Pharmabuddy eLearning platform. Nine months after the initial launch of the video, the impact of the educational intervention was assessed. Pharmacists who had watched the tutorial had significantly greater knowledge of gout management than the pharmacists who had not. Importantly, pharmacists who had watched the tutorial had greater knowledge about colchicine and its use as prophylaxis following initiation of ULT. This demonstrates that low-cost educational interventions can greatly improve pharmacist knowledge of gout management. Gout management recommendations can be impeded if translation into pharmacy practice is neglected. Our research acts as a proof of concept that a co-designed educational intervention on gout management is effective. The Pharmacy Act 2007 requires that all pharmacists in Ireland undertake continuing professional development (CPD). For wider implementation, our intervention could be integrated into a CPD for gout management. This could increase the reach of this information to pharmacists. Pharmacists, particularly community pharmacists, have a hugely broad remit. The onus is on the rheumatology community to communicate to pharmacists and other health care providers about up-to-date recommendations for gout management. Improved pharmacist knowledge can in turn empower patients to assume selfmanagement of gout. The original research paper is available open access at BMC Rheumatology: Pharmacist knowledge of gout management: impact of an educational intervention. ER Dorris, M. Kieran, N. Dalbeth & G. McCarthy. BMC Rheumatol 6, 30 (2022). https://doi.org/10.1186/s41927022-00259-x
Figure 1: Pathophysiology of Gout
Both the overproduction of urate and the underexcretion of urate can contribute to hyperuricaemia, leading to gout. The goal of urate lowering therapy is to reduce serum uric acid levels below its saturation point, thereby preventing crystal formation and deposition. The rate of crystal reduction is dependent upon both the total crystal load and reduction in serum uric acid. Urate lowering therapy initiation can cause rapid dissolution of crystal deposits and may lead to increased flare rate and associated pain due to the removal of protein deposits protecting the underlying surface from attack by inflammatory cells. Thus an anti-inflammatory prophylaxis, such as Colchicine, is recommended for the first six months following initiation of urate lowering therapy. Image Copyright: Emma Dorris
Figure 1
PEER REVIEW: ERECTILE DYSFUNCTION
Management of Erectile Dysfunction in Ireland
Erectile dysfunction (ED) is a common condition occurring in males over 40 years of age, although it can occur earlier. It is estimated that at least 150 million men globally have ED. It is difficult to obtain accurate values for the true prevalence of erectile dysfunction however, as many patients fail to seek medical attention, and many clinicians are reluctant to ask patients about their sexual health.
We recently spoke to Theresa Lowry Lehnen, RGN, GPN, RNP, BSc, MSc, M. Ed, PhD Clinical Nurse Specialist and Associate Lecturer South East Technological University to understand more about this condition and its impact on males in Ireland.
ED can have a substantial negative impact on a man’s quality of life, Theresa reflects. She says, “Erectile dysfunction is the inability to achieve or maintain an erection for satisfactory sexual performance, and affects a considerable proportion of men at least occasionally. It is often treatable, however, if left untreated, ED can be a source of severe emotional stress for both the man and their partner.” Theresa notes that erectile dysfunction is often an under recognised, yet important, cardiovascular risk factor. She says, “Owing to its strong association with metabolic An interview with Theresa LowryLehnen (PhD), CNS, GPN, RNP, South East Technological University
syndrome and cardiovascular disease, cardiac assessment is warranted in men with symptoms of ED.”
Aetiology of Erectile Dysfunction
Although most men will experience periodic episodes of erectile dysfunction, it tends to become more frequent with advancing age. “Many factors can contribute to sexual dysfunction in older men, including physical and psychological conditions, comorbidities and polypharmacy,” she adds. “Aspects of an ageing man’s lifestyle behaviour and androgen deficiency, most often decreasing testosterone levels, can affect sexual function.
“Studies have shown that the percentage of men who engage in some form of sexual activity, decreases from 73% in men aged 57–64 years to 26% for men aged 75–85 years. The aetiology for this decline in male sexual activity is multifactorial, and is in part related to female partners menopause at approximately 52 years of age, leading to a significant decline in female libido and desire to engage in sexual activity.” While ED is associated with ageing, many studies and largescale surveys have concluded that ED is a major health concern among young men. Theresa adds, “One study in 2013 reported that 1: 4 men seeking medical help for erectile dysfunction in the real-life setting, is < 40 years of age. Another study in 2016 concluded that 22.1% of men < 40 years of age had low (<21) Sexual Health Inventory for Men (SHIM) scores. “In the past, erectile dysfunction was almost always considered a psychogenic disorder. However, evidence now suggests that more than 80% of cases have an organic aetiology. While most patients with ED have organic disease, some do have a primary psychological cause, particularly younger men. Even when ED is organic in nature, there are almost always psychological consequences regarding relationship issues, cultural norms and expectations, loss of self-esteem, shame, and anxiety and depression related to sexual performance.” Erectile dysfunction is multidimensional in nature, and Theresa says it can be broadly divided into endocrine and nonendocrine causes.
“The condition can be caused by any disease process which affects penile arteries, nerves, hormone levels, smooth muscle tissue, corporal endothelium, or tunica albuginea. It is closely related to cardiovascular disease, diabetes mellitus, hyperlipidaemia, hypertension, and endothelial dysfunction,” she explains. “Erectile dysfunction and vascular disease are thought to be linked at the level of the endothelium. Endothelial dysfunction, results in the inability of smooth muscle cells lining the arterioles to relax and prevents vasodilatation. The endothelial cell is known to affect vascular tone and impact the process of atherosclerosis and impacting ED, CVD and peripheral vascular disease. Cardiovascular disease and hypertension are very significant risk factors for erectile dysfunction.” Besides cardiovascular disease, there are strong correlations between ED and hyperlipidaemia, diabetes, hypogonadism, obesity, smoking, alcoholism, benign prostatic hyperplasia (BPH) with lower urinary symptoms (LUTS), depression, and premature ejaculation. Diabetes is a common aetiology of sexual dysfunction, because it can affect both the blood vessels and the nerves that supply the penis. Men with diabetes are four times more likely to experience erectile dysfunction, and on average, experience it 15 years earlier than men without diabetes. “Obesity is also correlated to the development of several types of dysfunction, including a decrease in sex drive and an increase in episodes of ED,” she continues. “Neurogenic erectile dysfunction is caused by a deficit in nerve signalling to the corpora cavernosa. Such deficits can be secondary to spinal cord injury, multiple sclerosis, Parkinson disease, lumbar disc disease, traumatic brain injury, radical pelvic surgery and diabetes. Men being treated for prostate cancer with treatments such as radical prostatectomy, radiation therapy or the use of lutenising hormonereleasing hormone (LHRH) agonists and antagonists often experience ED.”
Numerous medications are listed with erectile dysfunction and/ or a decreased libido as a side effect. Drugs that can cause ED include hydrochlorothiazide’s and beta-blocking agents. Medications used to treat depression, particularly the SSRIs such as citalopram, escitalopram, fluoxetine, fluvoxamine, paroxetine and sertraline, can also contribute to ED. The severity of erectile dysfunction is often described as mild, moderate or severe according to the five-item International Index of Erectile Function (IIEF-5) questionnaire, with a score of 1–7 indicating severe, 8–11 moderate, 12–16 mild–moderate, 17–21 mild and 22–25 no erectile dysfunction.
The International Index of Erectile Function (IIEF-5) Questionnaire
The IIEF is a multidimensional validated questionnaire with 15 questions in the five domains of sexual function (erectile and orgasmic functions, sexual desire, satisfaction with intercourse and overall sexual satisfaction), and there is also an abbreviated format of five questions in the Sexual Health Inventory for Men (SHIM).
Investigations and Diagnosis
Theresa continues, “A thorough medical history, detailed sexual history, and physical examination are required before commencing treatment or further investigations. It is important to distinguish between psychological and
SUSPECT ATTR-CM
(TRANSTHYRETIN AMYLOID CARDIOMYOPATHY)
A LIFE-THREATENING DISEASE THAT CAN GO UNDETECTED
Life-threatening, underrecognized, and underdiagnosed, ATTR-CM is a rare condition found in mostly older patients in which misfolded transthyretin proteins deposit in the heart.1-7 It is vital to recognize the diagnostic clues so you can identify this disease.
CONSIDER THE FOLLOWING CLINICAL CLUES, ESPECIALLY IN COMBINATION, TO RAISE SUSPICION FOR ATTR-CM AND THE NEED FOR FURTHER TESTING
HFpEF heart failure with preserved ejection fraction in patients typically over 60 years old5-7 INTOLERANCE to standard heart failure therapies (ACEi, ARBs, and beta blockers)8-10 DISCORDANCE between QRS voltage and left ventricular (LV) wall thickness11-13 DIAGNOSIS of carpal tunnel syndrome or lumbar spinal stenosis3,8,14-20 ECHO showing increased LV wall thickness6,13,16,21,22 NERVOUS SYSTEM —autonomic nervous system dysfunction-including gastrointestinal complaints or unexplained weight loss6,16,23,24
LEARN HOW TO RECOGNIZE THE CLUES OF ATTR-CM AT: S U S P E C T A N D D E T E C T . I E
References
1. Sipe JD, Benson MD, Buxbaum JN, et al. Amyloid fibril proteins and amyloidosis: chemical identification and clinical classification International Society of Amyloidosis 2016 Nomenclature Guidelines. Amyloid. 2016;23(4):209-213. 2. Maurer MS, Elliott P, Comenzo R, Semigran M, Rapezzi C. Addressing common questions encountered in the diagnosis and management of cardiac amyloidosis. Circulation. 2017;135(14):1357-1377. 3. Connors LH, Sam F, Skinner M, et al. Heart failure due to age-related cardiac amyloid disease associated with wild-type transthyretin: a prospective, observational cohort study. Circulation. 2016;133(3):282-290. 4. Pinney JH, Whelan CJ, Petrie A, et al. Senile systemic amyloidosis: clinical features at presentation and outcome. J Am Heart Assoc. 2013;2(2):e000098. 5. Mohammed SF, Mirzoyev SA, Edwards WD, et al. Left ventricular amyloid deposition in patients with heart failure and preserved ejection fraction. JACC Heart Fail. 2014;2(2):113-122. 6. Maurer MS, Hanna M, Grogan M, et al. Genotype and phenotype of transthyretin cardiac amyloidosis: THAOS (Transthyretin Amyloid Outcome Survey). J Am Coll Cardiol. 2016;68(2):161-172. 7. González-López E, Gallego-Delgado M, Guzzo-Merello G, et al. Wild-type transthyretin amyloidosis as a cause of heart failure with preserved ejection fraction. Eur Heart J. 2015;36(38):2585-2594. 8. Narotsky DL, Castano A, Weinsaft JW, Bokhari S, Maurer MS. Wild-type transthyretin cardiac amyloidosis: novel insights from advanced imaging. Can J Cardiol. 2016;32(9):1166.e1-1166.e10. 9. Brunjes DL, Castano A, Clemons A, Rubin J, Maurer MS. Transthyretin cardiac amyloidosis in older Americans. J Card Fail. 2016;22(12):996-1003. 10. Castaño A, Drach BM, Judge D, Maurer MS. Natural history and therapy of TTR-cardiac amyloidosis: emerging disease-modifying therapies from organ transplantation to stabilizer and silencer drugs. Heart Fail Rev. 2015;20(2):163-178. 11. Carroll JD, Gaasch WH, McAdam KP. Amyloid cardiomyopathy: characterization by a distinctive voltage/mass relation. Am J Cardiol. 1982;49:9-13. 12. Cyrille NB, Goldsmith J, Alvarez J, Maurer MS. Prevalence and prognostic significance of low QRS voltage among the three main types of cardiac amyloidosis. Am J Cardiol. 2014;114(7):1089-1093. 13. Quarta CC, Solomon D, Uraizee I, et al. Left ventricular structure and function in transthyretin-related versus light-chain cardiac amyloidosis. Circulation. 2014;129(18):1840-1849. 14. Connors LH, Prokaeva T, Lim A, et al. Cardiac amyloidosis in African Americans: Comparison of clinical and laboratory features of transthyretin V122I amyloidosis and immunoglobulin light chain amyloidosis. Am Heart J. 2009;158(4):607-614. 15. Nakagawa M, Sekijima Y, Yazaki M, et al. Carpal tunnel syndrome: a common initial symptom of systemic wild-type ATTR (ATTRwt) amyloidosis. Amyloid. 2016;23(1):58-63. 16. Rapezzi C, Merlini G, Quarta CC, et al. Systemic cardiac amyloidoses: disease profiles and clinical courses of the 3 main types. Circulation. 2009;120(13):1203-1212. 17. Sperry BW, Reyes BA, Ikram A, et al. Tenosynovial and cardiac amyloidosis in patients undergoing carpal tunnel release. J Am Coll Cardiol. 2018;72(17): 2040-2050. 18. Westermark P, Westermark GT, Suhr OB, Berg S. Transthyretin-derived amyloidosis: probably a common cause of lumbar spinal stenosis. Ups J Med Sci. 2014;119(3):223-228. 19. Yanagisawa A, Ueda M, Sueyoshi T, et al. Amyloid deposits derived from transthyretin in the ligamentum flavum as related to lumbar spinal canal stenosis. Mod Pathol. 2015;28(2):201-207. 20. Sueyoshi T, Ueda M, Jono H, et al. Wild-type transthyretin-derived amyloidosis in various ligaments and tendons. Hum Pathol. 2011;42(9):1259-1264. 21. Phelan D, Collier P, Thavendiranathan P, et al. Relative apical sparing of longitudinal strain using two-dimensional speckle-tracking echocardiography is both sensitive and specific for the diagnosis of cardiac amyloidosis. Heart. 2012;98(19):1442-1448. 22. Ternacle J, Bodez D, Guellich A, et al. Causes and consequences of longitudinal LV dysfunction assessed by 2D strain echocardiography in cardiac amyloidosis. JACC Cardiovasc Imaging. 2016;9(2):126-138. 23. Coelho T, Maurer MS, Suhr OB. THAOS - The Transthyretin Amyloidosis Outcomes Survey: initial report on clinical manifestations in patients with hereditary and wild-type transthyretin amyloidosis. Curr Med Res Opin. 2013;29(1):63-76. 24. Swiecicki PL, Zhen DB, Mauermann ML, et al. Hereditary ATTR amyloidosis: a single-institution experience with 266 patients. Amyloid. 2015;22(2):123-131.
The severity of erectile dysfunction is often described as mild, moderate or severe according Patient Name: _________________ to the five-item International Index of Erectile Function (IIEF-5) questionnaire, with a score of PEER REVIEW: ERECTILE DYSFUNCTION 1–7 indicating severe, 8–11 moderate, 12–16 mild–moderate, 17–21 mild and 22–25 no erectile dysfunction.2, 4 Date of Birth __________________ Date Completed: The International Index of Erectile Function (IIEF_______________ -5) Questionnaire 4,5 The IIEF is a multidimensional validated questionnaire with 15 questions in the five domains of sexual function (erectile and orgasmic functions, sexual desire, satisfaction with intercourse and overall sexual satisfaction), and there is also an abbreviated format of five questions in the Sexual Health Inventory for Men (SHIM). 5
Sexual Health Inventory for Men (SHIM)
Over the past 6 months:
1. How do you rate your confidence that you could get and keep an erection?
Very low 1 Low 2 Moderate 3 High 4 Very high 5
Sexual Health Inventory for Men (SHIM)
2. When you had erections with sexual stimulation, how often were your erections hard enough for penetration? Almost never/never 1 A few times (much less than half the time) 2 Sometimes (about half the time) 3 Most times (much more than half the time) 4 Almost always/always 5
3. During sexual intercourse, how often were you able to maintain your erection after you had penetrated (entered) your partner? Almost never/never 1 A few times (much less than half the time) 2 Sometimes (about half the time) 3 Most times (much more than half the time)4 Almost always/always 5
4. During sexual intercourse, how difficult was it to maintain your erection to completion of intercourse? Extremely difficult 1 Very difficult 2 Difficult 3 Slightly difficult 4 Not difficult 5
5. When you attempted sexual intercourse, how often was it satisfactory for you? Almost never/never 1 A few times (much less than half the time) 2 Sometimes (about half the time) 3 Most times (much more than half the time) 4 Almost always/always 5
IIEF-5 scoring:
The IIEF-5 score is the sum of the ordinal responses to the 5 items. 22-25: No erectile dysfunction 17-21: Mild erectile dysfunction 12-16: Mild to moderate erectile dysfunction 8-11: Moderate erectile dysfunction 5-7: Severe erectile dysfunction
Total Score __________
organic causes of ED, as well as to ensure that the patient has erectile dysfunction and not another disorder. History that points towards a psychological aetiology include, sudden onset of erectile dysfunction especially if it is related to a new partner or a major life-changing event, situational ED, normal erections with masturbation or a different partner, presence of morning erections and high daily variability in erectile rigidity. “The main differential diagnosis for erectile dysfunction is hypogonadism, loss of libido, depression with low mood, and other psychological conditions. It may also be the first manifestation of diabetes or cardiovascular disease as well as depression. It is important to differentiate between true erectile dysfunction and other sexual disorders such as premature ejaculation, and this is usually assessed by obtaining a good sexual history. “A complete medication list including supplements should be checked with the patient. ED can be a result of prescription or other medications. Prescription drugs that can cause ED include, antidepressants especially SSRIs, cimetidine, ketoconazole, spironolactone, sympathetic blockers, thiazide diuretics, and other antihypertensives. ACE inhibitors and calcium channel blockers are the least likely to cause ED. Beta-blockers are only a minor contributor, while alpha-blockers can improve erectile function.”
Vascular risk factors such as hypertension and diabetes and lifestyle factors such as smoking, activity level, alcohol intake, and the use of any recreational drugs should be assessed, Theresa adds. A full general and cardiovascular examination should be undertaken, as erectile dysfunction can be the first symptom of underlying vascular disease. Peripheral pulses should be checked and blood pressure measured. The genitalia should be carefully inspected for hypogonadism, signs of infection, the presence of penile fibrosis or plaques, and phimosis. Theresa continues, “The role of testosterone replacement therapy (TRT) as a potential to improve erectile function in ED remains an issue for clinicians who are comfortable treating androgen deficiency. Androgens are known to have a significant impact on the function of the smooth musculature within the corpus spongiosum. “Testosterone supplementation is more effective as a treatment for low libido than for ED. For most men with both ED and
https://www.urologypartners.co.uk/repository/originals/The_International_Index_of_Erectile_Function.pdf
Investigations and Diagnosis
A thorough medical history, detailed sexual history, and physical examination are required before commencing treatment or further investigations. It is important to distinguish between psychological and organic causes of ED, as well as to ensure that the patient has erectile dysfunction and not another disorder. History that points towards a psychological
WOULD YOU CONSIDER BOTH EFFICACY AND SAFETY?
Choose both efficacy and safety with ELIQUIS®
ELIQUIS is a factor Xa inhibitor that offers superior risk reduction in stroke and systemic embolism, with significantly less major bleeding vs. warfarin in non-valvular AF patients.1,*
• Superiority demonstrated on stroke / systemic embolism vs. warfarin1 • Superiority demonstrated on major bleeding vs. warfarin1
ELIQUIS® (apixaban) PRESCRIBING INFORMATION Ireland Consult Summary of Product Characteristics (SmPC) before prescribing PRESENTATION: Film-coated tablets; 5 mg and 2.5 mg apixaban. INDICATION (SPC section 4.1): Prevention of stroke and systemic embolism in adults with non-valvular atrial fi brillation (NVAF) with one or more risk factors, such as prior stroke or transient ischaemic attack (TIA), age ≥ 75 years, hypertension, diabetes mellitus or symptomatic heart failure (NYHA Class ≥ II). Treatment of deep vein thrombosis (DVT) and pulmonary embolism (PE), and prevention of recurrent DVT and PE in adults (see Special warnings and precautions for information on haemodynamically unstable PE patients). Prevention of venous thromboembolic events (VTE) in adults who have undergone elective hip or knee replacement surgery (2.5 mg only). DOSAGE AND ADMINISTRATION (SPC section 4.2): Oral. Taken with water, with or without food. Prevention of stroke and systemic embolism in patients with NVAF: The recommended dose is 5 mg twice a day. In patients who meet at least two of the following criteria: serum creatinine ≥ 1.5 mg/dL (133 micromole/L), age ≥ 80 years, or body weight ≤ 60 kg the recommended dose is Eliquis, 2.5 mg twice daily. Patients with severe renal impairment (creatinine clearance 15-29 ml/min) should receive Eliquis 2.5 mg twice daily. Therapy should be continued long term. Treatment of DVT, treatment of PE and prevention of recurrent DVT and PE (VTEt): The recommended dose for the treatment of acute DVT and treatment of PE is 10 mg twice daily for the fi rst 7 days followed by 5 mg twice daily. As per available medical guidelines, short duration of treatment (at least 3 months) should be based on transient risk factors (e.g. recent surgery, trauma, immobilisation). The recommended dose for the prevention of recurrent DVT and PE is 2.5 mg twice daily. When prevention of recurrent DVT and PE is indicated, the 2.5 mg twice daily dose should be initiated following completion of 6 months of treatment with Eliquis 5 mg twice daily or with another anticoagulant. The duration of overall therapy should be individualised after careful assessment of the treatment benefi t against the risk for bleeding. Prevention of VTE (VTEp): elective hip or knee replacement surgery: The recommended dose is 2.5 mg twice a day. The initial dose should be taken 12 to 24 hours after surgery. Hip replacement surgery, the recommended duration of treatment is 32 to 38 days. Knee replacement surgery, the recommended duration of treatment is 10 to 14 days. Missed Dose for All Indications: If a dose is missed, Eliquis should be taken immediately and then continue with twice daily dose as before. Switching: Switching treatment from parenteral anticoagulants to Eliquis (and vice versa) can be done at the next scheduled dose. These medicinal products should not be administered simultaneously. Switching treatment from VKA therapy to Eliquis: Warfarin or other VKA therapy should be discontinued and Eliquis started when the international normalized ratio (INR) is < 2. Switching treatment from Eliquis to VKA therapy: Administration of Eliquis should be continued for at least 2 days after beginning VKA therapy. After 2 days of co- administration of Eliquis with VKA therapy, an INR should be obtained prior to next scheduled dose of Eliquis. Co-administration of Eliquis and VKA therapy should be continued until the INR is ≥2. Renal Impairment - mild or moderate renal impairment: For the prevention of VTE in elective hip or knee replacement surgery (VTEp), for the treatment of DVT, treatment of PE and prevention of recurrent DVT and PE (VTEt), no dose adjustment is necessary. For the prevention of stroke and systemic embolism in patients with NVAF and serum creatinine ≥ 1.5 mg/dL (133 micromole/L) associated with age ≥ 80 years or body weight ≤ 60 kg, a dose reduction is necessary. In the absence of other criteria for dose reduction (age, body weight), no dose adjustment is necessary. Severe renal impairment (creatinine clearance 15-29 mL/min): For the prevention of VTE in elective hip or knee replacement surgery (VTEp), for the treatment of DVT, treatment of PE and prevention of recurrent DVT and PE (VTEt), Eliquis is to be used with caution. For the prevention of stroke and systemic embolism in patients with NVAF, patients should receive the lower dose of Eliquis 2.5mg twice daily. In patients with creatinine clearance < 15 mL/min, or in patients undergoing dialysis, there is no clinical experience therefore Eliquis is not recommended. See SmPC for further details. Hepatic impairment: Contraindicated in patients with hepatic disease associated with coagulopathy and clinically relevant bleeding risk. Not recommended in patients with severe hepatic impairment. Use with caution in patients with mild or moderate hepatic impairment (Child Pugh A or B). No dose adjustment is required in patients with mild or moderate hepatic impairment. Use with caution in patients with elevated liver enzymes (ALT/AST >2 x ULN) or total bilirubin ≥ 1.5 x ULN. Prior to initiating Eliquis, liver function testing should be performed. Catheter ablation (NVAF): Patients can continue Eliquis use while undergoing catheter ablation. Cardioversion (NVAF): Eliquis can be initiated or continued in NVAF patients who may require cardioversion. See SmPC for further details. Patients with NVAF and acute coronary syndrome (ACS) and/or percutaneous coronary intervention (PCI): There is limited experience of treatment with apixaban at the recommended dose for NVAF patients when used in combination with antiplatelet agents in patients with ACS and/or undergoing PCI after haemostasis is achieved. See SmPC for further details. Paediatric population: Eliquis is not recommended in children and adolescents below the age of 18. CONTRAINDICATIONS (SPC section 4.3): Hypersensitivity to active substance or to excipients, active clinically signifi cant bleeding, hepatic disease associated with coagulopathy and clinically relevant bleeding risk, lesion or condition if considered a signifi cant risk factor for major bleeding, see SmPC for further details. Concomitant treatment with any other anticoagulant agent except under specifi c circumstances of switching anticoagulant therapy or when unfractionated heparin (UFH) is given at doses necessary to maintain an open central venous or arterial catheter or when UFH is given during catheter ablation for atrial fi brillation, see SmPC for further details. WARNINGS AND PRECAUTIONS (SPC section 4.4): Haemorrhage risk: Carefully observe for signs of bleeding. Use with caution in conditions with increased risk of haemorrhage. Discontinue administration if severe haemorrhage occurs. An agent to reverse the anti-factor Xa activity of apixaban is available. For information on reversal and managing bleeding, see SmPC for further details. Interaction with other medicinal products affecting haemostasis: Concomitant treatment with any other anticoagulant is contraindicated (see contraindications). Concomitant use of Eliquis with antiplatelet agents increases the risk of bleeding. Care with concomitant SSRIs, SNRIs or NSAIDs, including acetylsalicylic acid. Following surgery, other platelet aggregation inhibitors are not recommended concomitantly with Eliquis. In patients with atrial fi brillation and conditions that warrant mono or dual antiplatelet therapy, a careful assessment of the potential benefi ts against the potential risks should be made before combining this therapy with Eliquis. A clinical trial enrolled patients with atrial fi brillation with ACS and/or undergoing PCI and a planned treatment period with a P2Y12 inhibitor, with or without ASA, and oral anticoagulant (either apixaban or VKA) for 6 months. Concomitant use of ASA increased the risk of ISTH (International Society on Thrombosis and Hemostasis) major or CRNM (Clinically Relevant Non-Major) bleeding in apixaban-treated subjects. See SmPC for further details. Use of thrombolytic agents for the treatment of acute ischemic stroke: Limited experience. Patients with prosthetic heart valves: safety and effi cacy of Eliquis have not been studied in patients with prosthetic heart valves, with or without atrial fi brillation. Therefore, the use of Eliquis is not recommended in this setting. Patients with antiphospholipid syndrome: Direct acting Oral Anticoagulants (DOACs), including Eliquis, are not recommended for patients with a history of thrombosis who are diagnosed with antiphospholipid syndrome (see SmPC for further details). Surgery and invasive procedures: Discontinue at least 48 hours prior to elective surgery or invasive procedures with a moderate or high risk of bleeding. Discontinue at least 24 hours prior to elective surgery or invasive procedures with a low risk of bleeding. If surgery or invasive procedures cannot be delayed, appropriate caution should be exercised, taking into consideration an increased risk of bleeding. Eliquis should be restarted after the invasive procedure or surgical intervention as soon as possible provided the clinical situation allows and adequate haemostasis has been established. For patients undergoing catheter ablation for atrial fi brillation, Eliquis treatment does not need to be interrupted. Temporary discontinuation: Discontinuing anticoagulants, including Eliquis, for active bleeding, elective surgery, or invasive procedures places patients at an increased risk of thrombosis. Lapses in therapy should be avoided and if anticoagulation with Eliquis must be temporarily discontinued for any reason, therapy should be restarted as soon as possible. Spinal/ epidural anaesthesia or puncture: Patients treated with antithrombotic agents for prevention of thromboembolic complications are at risk of developing an epidural or spinal haematoma which can result in long- term or permanent paralysis. The risk of these events may be increased by the post- operative use of indwelling epidural catheters or the concomitant use of medicinal products affecting haemostasis. Indwelling epidural or intrathecal catheters must be removed at least 5 hours prior to the fi rst dose of Eliquis. The risk may also be increased by traumatic or repeated epidural or spinal puncture. Patients are to be frequently monitored for signs and symptoms of neurological impairment (e.g., numbness or weakness of the legs, bowel or bladder dysfunction). If neurological compromise is noted, urgent diagnosis and treatment is necessary. Prior to neuraxial intervention the physician should consider the potential benefi t versus the risk in anticoagulated patients or in patients to be anticoagulated for thromboprophylaxis. There is no clinical experience with the use of Eliquis with indwelling intrathecal or epidural catheters. See SmPC for further details. Haemodynamically unstable PE patients or patients who require thrombolysis or pulmonary embolectomy: Eliquis is not recommended as an alternative to unfractionated heparin in patients with pulmonary embolism who are haemodynamically unstable or may receive thrombolysis or pulmonary embolectomy since the safety and effi cacy of Eliquis have not been established. Patients with active cancer: Patients with active cancer can be at high risk of both venous thromboembolism and bleeding events. When apixaban is considered for DVT or PE treatment in cancer patients, a careful assessment of the benefi ts against the risks should be made. Renal impairment: see dosage and administration section. Elderly patients: Increasing age may increase haemorrhagic risk. Also, the co-administration of Eliquis with ASA in elderly patients should be used cautiously because of a potentially higher bleeding risk. Body weight: Low body weight (< 60 kg) may increase haemorrhagic risk. Hepatic impairment: see dosage and administration section. Interaction with Inhibitors of CYP3A4 and P-gp: Not recommended with strong inhibitors of both CYP3A4 and P-gp. These medicinal products may increase Eliquis exposure by 2-fold or greater in the presence of additional factors that increase Eliquis exposure (e.g. severe renal impairment) see SmPC for further details. Interaction with Inducers of CYP3A4 and P-gp: Eliquis should not be used for the treatment of DVT and PE in patients receiving concomitant systemic treatment with strong inducers of both CYP3A4 and P-gp since effi cacy may be compromised. Concomitant systemic treatment with strong inducers of both CYP3A4 and P-gp, Eliquis should be used with caution for the prevention of VTE in elective hip or knee replacement surgery, for the prevention of stroke and systemic embolism in patients with NVAF and for the prevention of recurrent DVT and PE, though no dose adjustment for Eliquis is required during concomitant therapy with such medicinal products. Hip fracture surgery: Eliquis has not been studied in clinical trials in patients undergoing hip fracture surgery. Therefore, it is not recommended in these patients. Laboratory parameters: Clotting tests (PT, INR, and aPTT) are affected by the mechanism of action of apixaban. Changes observed at the expected therapeutic dose are small and subject to a high degree of variability, see SmPC for further details. Information about excipients: Eliquis contains lactose. Patients with galactose intolerance, total lactase defi ciency or glucose-galactose malabsorption should not take Eliquis. DRUG INTERACTIONS (SPC Section 4.5): Eliquis should be used with caution when co-administered with SSRIs/SNRIs, NSAIDs, ASA and/or P2Y12 inhibitors because these medicinal products typically increase the bleeding risk. There is limited experience of co-administration with other platelet aggregation inhibitors (such as GPIIb/IIIa receptor antagonists, dipyridamole, dextran or sulfi npyrazone) or thrombolytic agents. As such agents increase the bleeding risk, co-administration of these products with Eliquis is not recommended. See SmPC for further details.Due to an increased bleeding risk, concomitant treatment with any other anticoagulants is contraindicated, except under specifi c circumstances of switching anticoagulant therapy, when UFH is given at doses necessary to maintain an open central venous or arterial catheter or when UFH is given during catheter ablation for atrial fi brillation. Administration of activated charcoal reduces Eliquis exposure. Also see contraindications and special warnings and precautions section; Consult SmPC (contraindications, special warnings and precautions and drug interactions) for full details on interactions. PREGNANCY AND LACTATION (SPC section 4.6): Pregnancy: As a precautionary measure, it is preferable to avoid the use of apixaban during pregnancy. Breastfeeding: A decision must be made whether to discontinue breast-feeding or to discontinue/abstain from apixaban therapy taking into account the benefi t of breast-feeding for the child and the benefi t of therapy for the woman. UNDESIRABLE EFFECTS (SPC section 4.8): Increased risk of occult or overt bleeding from any tissue or organ, which may result in post haemorrhagic anaemia. The signs, symptoms, and severity will vary according to the location and degree or extent of the bleeding. Frequencies: common (≥ 1/100 to < 1/10); uncommon (≥ 1/1,000 to < 1/100); rare (≥ 1/10,000 to < 1/1,000); very rare (< 1/10,000); not known (cannot be estimated from the available data). Prevention of VTE in adult patients who have undergone elective hip or knee replacement surgery (VTEp): Common: anaemia; haemorrhage*; haematoma*; nausea; contusion. Uncommon: thrombocytopenia*; epistaxis*; haematochezia*; liver function test abnormal (including blood bilirubin increased*); haematuria*; specifi c haemorrhage such as gastrointestinal*, abnormal vaginal*, urogenital*, post procedural*, wound secretion*, incision site*, operative*. Rare: hypersensitivity*; anaphylaxis*; haemoptysis*; gingival bleeding*; specifi c haemorrhage such as eye (including conjunctival)*, rectal*, muscle*. Not known: angioedema*; specifi c haemorrhage such as brain (encompassing intracranial, intraspinal)*, intra-abdominal*, respiratory tract*, haemorrhoidal*, mouth*, retroperitoneal*, traumatic*, erythema multiforme*. Prevention of stroke and systemic embolism in adult patients with NVAF, with one or more risk factors (NVAF): Common: anaemia; haemorrhage*; haematoma*; hypotension (including procedural hypotension); epistaxis*; nausea; gingival bleeding*; gamma-glutamyltransferase increased; haematuria*; contusion; specifi c haemorrhage such as eye (including conjunctival)*, gastrointestinal*, rectal*. Uncommon: thrombocytopenia*; hypersensitivity*; anaphylaxis*; haemoptysis*; haematochezia*; liver function test abnormal (including blood bilirubin increased*); specifi c haemorrhage such as brain (encompassing intracranial, intraspinal)*, intra-abdominal*, haemorrhoidal*, mouth*, abnormal vaginal*, urogenital*, post procedural*, wound secretion*, incision site*, operative*, traumatic*. Rare: specifi c haemorrhage such as respiratory tract*, retroperitoneal*, muscle*. Very Rare: erythema multiforme*. Not known: angioedema*. Treatment of DVT and PE, and prevention of recurrent DVT and PE (VTEt): Common: anaemia; thrombocytopenia*; haemorrhage*; haematoma*; epistaxis*; nausea; gingival bleeding*; gamma-glutamyltransferase increased; alanine aminotransferase increased; skin rash; haematuria*; contusion; specifi c haemorrhage such as gastrointestinal*, mouth*, rectal*, abnormal vaginal*, urogenital*. Uncommon: hypersensitivity*; anaphylaxis*; haemoptysis*; haematochezia*; liver function test abnormal (including blood bilirubin increased*); specifi c haemorrhage such as eye (including conjunctival)*, haemorrhoidal*, muscle*, post procedural*, wound secretion*, incision site*, operative*, traumatic*. Rare: specifi c haemorrhage such as brain (encompassing intracranial, intraspinal)*, respiratory tract*. Not Known: angioedema*; specifi c haemorrhage such as intra-abdominal* and retroperitoneal*, erythema multiforme*. *Denotes serious adverse reaction Refer to SmPC for all other adverse events LEGAL CATEGORY: POM. MARKETING AUTHORISATION NUMBER (SPC section 8): EU/1/11/691/002-3, EU/1/11/691/008, EU/1/11/691/014 PACKAGE QUANTITIES: Carton of 20 fi lm-coated tablets 2.5 mg, 60 fi lm-coated tablets 2.5 mg, 56 fi lm-coated tablets 5 mg, 28 fi lm- coated tablets 5 mg. MARKETING AUTHORISATION HOLDER (SPC section 7): Bristol-Myers Squibb/Pfi zer EEIG, Plaza 254, Blanchardstown Corporate Park 2, Dublin 15, D15 T867, Ireland FOR FURTHER INFORMATION CONTACT: medical.information@bms.com or 1 800 749 749 (Ireland) DATE OF PREPARATION: April 2021 ADDITIONAL INFORMATION AVAILABLE ON REQUEST Approval Code: 432-IE-2100041
Adverse events should be reported. Reporting forms and information can be found at: Ireland - via HPRA Pharmacovigilance at www.hpra.ie Adverse events should also be reported to Bristol-Myers Squibb via medical.information@bms.com or 1 800 749 749 (Ireland)
* with one or more risk factors, such as prior stroke or transient ischaemic attack (TIA); age≥ 75 years; hypertension; diabetes mellitus; symptomatic heart failure (NYHA Class ≥ II)
AF = Atrial Fibrillation. Reference: 1. Granger CB et al. N Engl J Med 2011; 365: 981–992. Date of approval: May 2021 Job code: PP-ELI-IRL-0497
www.eliquis.ie
considered safe.6 Practice with the device improves outcomes and some degree of manual 32dexterity is required. VCD devices are the most inexpensive long-term therapy for ED, and a non-invasive option for patients who deem it acceptable. While the efficacy rates of VCD devices are high, patient satisfaction rates are lower. 1 PEER REVIEW: ERECTILE DYSFUNCTION Other second-line therapy includes the use of either intracavernosal injection (ICI) or intraurethral suppositories (IUS). A small needle is used to inject the ICI medication into the lateral aspect of the penis through a small-gauge needle. These vasoactive agents include prostaglandin E1, papaverine and phentolamine and sometimes atropine, which work alone or in combination to elicit an erection. Response is dose related, usually occurs within 10–15 minutes, and does not require stimulation. A concern with ICI use is priapism, and if this occurs the patient will need to seek urgent medical attention. Bruising can also occur, due to it being an injected medication. The intraurethral suppository consists of a tiny pellet of prostaglandin E1 inserted into the urethral meatus. Response is dose related, and onset usually occurs within 10–15 minutes. Patients need to be trained on the technique of the IUS before use, and should be advised that pain or burning may occur with this medication. 2, 6 In men who fail to respond to first or second-line therapy, or who are not interested in conservative therapies, penile prosthesis implantation is available. Penile implants include malleable and inflatable devices, although most implants used are of the inflatable variety. Adverse effects including malfunction and infection are rare, and patient satisfaction is high.6
hypogonadism, oral PDE5 inhibitors alone are recommended as the initial therapy. Testosterone supplementation is reasonable in men with proven hypogonadism and ED who have already failed PDE5 inhibitor therapy or who also have low libido. Hypogonadal patients with borderline erectile rigidity are most likely to benefit from testosterone supplementation. “Testosterone replacement therapy may cause increased levels of haemoglobin or haematocrit which is associated with an increased risk of heart attack, stroke and blood clots. Testosterone treatment can also cause an enlarged prostate or other prostate disorders. During TRT treatment, the prostate specific antigen (PSA) will be measured to monitor for any changes and this is particularly important in men over 45 years of age. “As a result of using testosterone replacement, natural production of testosterone may be reduced. This may lead to a reduction in sperm production and fertility. Other side effects of TRT include: weight gain, increased appetite, hot flushes, acne, depression, restlessness, irritability, aggression, tiredness, general weakness and excessive sweating. Lifestyle modifications are considered first-line therapy for ED, and men should be encouraged to make the necessary changes to benefit both their sexual function and their overall health. “PDE5 inhibitors are highly effective and have an overall success rate of up to 76%. PDE5 inhibitors are contraindicated in patients taking nitrates, but otherwise are safe and effective. When PDE5 inhibitors are co-administered with nitrates, pronounced systemic vasodilation and severe hypotension can occur. “PDE5 inhibitors and α-adrenergic receptor blockers, often used for treatment of BPH, need to be taken at least 4 hours apart. Among second-line therapies, external vacuum devices (VCDs) are a good, non-surgical option for patients with ED. VCDs are clear plastic chambers placed over the penis, tightened against the lower abdomen with a mechanism to create a vacuum inside the chamber. This directs blood into the penis. If an adequate erection occurs inside the chamber, the patient slips a small constriction band off the end of the VCD and onto the base of the penis. An erection beyond 30 minutes is not recommended. While cumbersome, these devices are considered safe. “Other second-line therapy includes the use of either intracavernosal injection (ICI) or intraurethral suppositories (IUS). A small needle is used to inject the ICI medication into the lateral aspect of the penis through a small-gauge needle. These vasoactive agents include prostaglandin E1, papaverine and phentolamine and sometimes atropine, which work alone or in combination to elicit an erection. Response is dose related, usually occurs within 10– 15 minutes, and does not require stimulation. A concern with ICI use is priapism, and if this occurs the patient will need to seek urgent medical attention. Bruising can also occur, due to it being an injected medication. The intraurethral suppository consists of a tiny pellet of prostaglandin E1 inserted into the urethral meatus. Response is dose related, and onset usually occurs within 10–15 minutes. Patients need to be trained on the technique of the IUS before use, and should be advised that pain or burning may occur with this medication. “In men who fail to respond to first or second-line therapy, or who are not interested in conservative therapies, penile prosthesis implantation is available. Penile implants include malleable and inflatable devices, although most implants used are of the inflatable variety. Adverse effects including malfunction and infection are rare, and patient satisfaction is high.”
Outlook
Theresa told us that future Therapies for ED Clinical studies in gene therapy are looking towards replacing proteins that may not be functioning properly in the penile tissue of men with erectile dysfunction. She says, “Replacement of these proteins may result in improvement in ED. Experimental animal models have demonstrated improvement in erectile function with gene therapy. Human studies may demonstrate success with this therapy in the future, however, gene therapy in humans is controversial, and can take a long time for regulatory approval and public acceptance. “Stem cell studies may also provide advancements in the treatment of ED in the future. The mechanism of action of stem cells is to generate angiogenesis with subsequent increase in cavernosal smooth muscle cells within the corporal bodies. “The clinical studies published to date provide encouraging results, with improvement of sexual function reported with no side effects. Although pioneering, stem cell studies to date are small scale, with a short follow up period, various aetiologies of ED and without a control group. Melanocortin activators are drugs that act through the central nervous system, and have been shown in animal studies to produce an erection. Initial studies in humans suggest that the drug (PT-141) can be effective if given intranasally in men with psychological rather than physical causes, and mild to moderate ED. “Larger studies are necessary, however,to demonstrate the safety and overall effectiveness of these drugs. Another potential new treatment for ED, is penile lowintensity shock wave lithotripsy. This consists of 1500 shocks twice a week for 3–6 weeks. The purpose is to stimulate neovascularisation to the corporal bodies with improvement in penile blood flow and endothelial function. The use of low-intensity shock wave lithotripsy may convert PDE5 inhibitor nonresponders to responders.”
Erectile Dysfunction. JAMA. 2016;316(17):1838. doi:10.1001/ jama.2016.12284
