Cardiovascular risk profiles of GnRH agonists and antagonists: real-world analysis from UK general practice.

PURPOSE: Androgen deprivation therapy (ADT) is the mainstay for the management of metastatic prostate cancer. Available pharmaceutical ADTs include gonadotropin-releasing hormone (GnRH) agonists and antagonists. Here, real-world data are presented from the UK general practitioner Optimum Patient Care Research Database. The study investigated the hypothesis that GnRH antagonists have lower cardiac event rates than GnRH agonists. METHODS: The incidence of cardiac events following initiation of GnRH antagonist or agonist therapy was investigated in a population-based cohort study conducted in UK primary care between 2010 and 2017. RESULTS: Analysis of real-world data from the UK primary care setting showed that relative risk of experiencing cardiac events was significantly lower with degarelix, a GnRH antagonist, compared with GnRH agonists (risk ratio: 0.39 [95% confidence interval 0.191, 0.799]; p = 0.01). Patients that received degarelix as first-line treatment switched treatment more frequently (33.7%), often to a GnRH agonist, than those who initiated treatment with a GnRH agonist (6.7-18.6%). CONCLUSION: Screening for known or underlying vascular disease and identifying those at high risk of a cardiac event is important for risk mitigation in patients with prostate cancer receiving hormone therapy. The GnRH antagonist degarelix conferred a significantly lower risk of cardiac events than GnRH agonists. Prior to treatment, patients should be stratified based on level of cardiovascular (CV) risk, and appropriate lifestyle, and pharmacological interventions to mitigate CV risk should be recommended. CV risk factors and patient response to the intervention should be monitored at regular intervals.

British Society for Sexual Medicine Guidelines on the Management of Erectile Dysfunction in Men-2017.

BACKGROUND: This is an update of the 2008 British Society for Sexual Medicine (BSSM) guidelines. AIM: To provide up-to-date guidance for U.K. (and international) health care professionals managing male sexual dysfunction. METHODS: Source information was obtained from peer-reviewed articles, meetings, and presentations. A search of Embase, MEDLINE, and Cochrane Reviews was performed, covering the search terms "hypogonadism," "eugonadal or hypogonadism or hypogonadal or gonadal," and "low or lower testosterone," starting from 2009 with a cut-off date of September 2017. OUTCOMES: We offer evidence-based statements and recommendations for clinicians. RESULTS: Expert guidance for health care professionals managing male sexual dysfunction is included. CLINICAL TRANSLATION: Current U.K. management has been largely influenced by non-evidence guidance from National Health Service departments, largely based on providing access to care limited by resources. The 2008 BSSM guidelines to date have been widely quoted in U.K. policy decision making. CONCLUSIONS: There is now overwhelming evidence that erectile dysfunction is strongly associated with cardiovascular disease, such that newly presenting patients should be thoroughly evaluated for cardiovascular and endocrine risk factors, which should be managed accordingly. Measurement of fasting serum glucose, lipid profile, and morning total testosterone should be considered mandatory in all newly presenting patients. Patients attending their primary care physician with chronic cardiovascular disease should be asked about erectile problems. There can no longer be an excuse for avoiding discussions about sexual activity due to embarrassment. Hackett G, Kirby M, Wylie K, et al. British Society for Sexual Medicine Guidelines on the Management of Erectile Dysfunction in Men-2017. J Sex Med 2018;15:430-457.

A practical approach to the management of nocturia.

AIM: To raise awareness on nocturia disease burden and to provide simplified aetiologic evaluation and related treatment pathways. METHODS: A multidisciplinary group of nocturia experts developed practical advice and recommendations based on the best available evidence supplemented by their own experiences. RESULTS: Nocturia is defined as the need to void ≥1 time during the sleeping period of the night. Clinically relevant nocturia (≥2 voids per night) affects 2%-18% of those aged 20-40 years, rising to 28%-62% for those aged 70-80 years. Consequences include the following: lowered quality of life; falls and fractures; reduced work productivity; depression; and increased mortality. Nocturia-related hip fractures alone cost approximately €1 billion in the EU and $1.5 billion in the USA in 2014. The pathophysiology of nocturia is multifactorial and typically related to polyuria (either global or nocturnal), reduced bladder capacity or increased fluid intake. Accurate assessment is predicated on frequency-volume charts combined with a detailed patient history, medicine review and physical examination. Optimal treatment should focus on the underlying cause(s), with lifestyle modifications (eg, reducing evening fluid intake) being the first intervention. For patients with sustained bother, medical therapies should be introduced; low-dose, gender-specific desmopressin has proven effective in nocturia due to idiopathic nocturnal polyuria. The timing of diuretics is an important consideration, and they should be taken mid-late afternoon, dependent on the specific serum half-life. Patients not responding to these basic treatments should be referred for specialist management. CONCLUSIONS: The cause(s) of nocturia should be first evaluated in all patients. Afterwards, the underlying pathophysiology should be treated specifically, alone with lifestyle interventions or in combination with drugs or (prostate) surgery.

Prevalence of metabolic syndrome and its components among men with and without clinical benign prostatic hyperplasia: a large, cross-sectional, UK epidemiological study.

OBJECTIVES: To compare the prevalence of metabolic syndrome and the components of metabolic syndrome in men aged ≥50 years with and without clinical benign prostatic hyperplasia (BPH). SUBJECTS AND METHODS: This was a cross-sectional study using the UK Clinical Practice Research Datalink (CPRD). Men were selected from the CPRD who were aged ≥50 years and still registered as of 31 December 2011. Cohort 1 included men with clinical BPH, and cohort 2 men without clinical BPH who were matched 1:1 to those in cohort 1 by general practice, year of birth and previous years of available history (1-<2, 2-<3, 3-<4, ≥4 years of available history). The prevalence of metabolic syndrome and its components (for men alive and still registered in the CRPD as of 31 December 2011) was calculated using all available history (lifetime prevalence) and medical history from 2010 and 2011 (current prevalence). Crude odds ratios and 95% confidence intervals for the occurrence of metabolic syndrome and the occurrence of the components of metabolic syndrome were calculated by comparing men with and without BPH. RESULTS: A total of 26.5% of men with clinical BPH had metabolic syndrome compared with 20.9% of matched controls without clinical BPH (absolute difference 5.6%; P < 0.001); men with clinical BPH were therefore significantly more likely to have metabolic syndrome than matched controls without clinical BPH. Significantly greater proportions of men with clinical BPH also had each component of metabolic syndrome compared with matched controls without clinical BPH. The presence of clinical BPH was associated with a 37% increased odds of having metabolic syndrome (for both lifetime prevalence and current prevalence) compared with matched controls without clinical BPH. CONCLUSIONS: There is a significant cross-sectional association between clinical BPH and metabolic syndrome in the UK primary care population.

The role of gonadotrophin-releasing hormone antagonists in the treatment of patients with advanced hormone-dependent prostate cancer in the UK.

PURPOSE: Comparing gonadotrophin-releasing hormone (GnRH) antagonists and agonists as androgen deprivation therapy for advanced prostate cancer (PC). METHODS: This article stems from a round-table meeting in December 2014 to compare the properties of GnRH agonists and antagonists in the published literature in order to identify the patient groups most likely to benefit from GnRH antagonist therapy. A broad PubMed and congress abstract search was carried out in preparation for the meeting to ensure that the latest data and opinion were available for the discussions. RESULTS: In randomised, controlled trials, GnRH antagonist therapy provides more rapid suppression of luteinising hormone, follicle-stimulating hormone and testosterone than GnRH agonist treatment. Compared with the GnRH agonist, there is evidence of improved disease control by a GnRH antagonist, with longer interval to prostate-specific antigen progression and greater reduction of serum alkaline phosphatase. In a post hoc analysis of six randomised trials, the risk of cardiac events within 1 year of initiating therapy was significantly lower among men receiving GnRH antagonist than agonist. Pre-clinical laboratory data suggest a number of mechanisms whereby GnRH antagonist therapy may benefit men with pre-existing cardiovascular disease (CVD), the most plausible hypothesis being that, unlike GnRH agonists, GnRH antagonists do not activate T lymphocytes, which act to increase atherosclerotic plaque rupture. CONCLUSION: When making treatment decisions, clinicians should consider comorbidities, particularly CVD, in addition to effects on PC. GnRH antagonists may be appropriate in patients with significant CV risk, existing osteopenia, lower urinary tract symptoms and significant metastatic disease.

A review of detrusor overactivity and the overactive bladder after radical prostate cancer treatment.

There are various forms of treatment for prostate cancer. In addition to oncologic outcomes, physicians, and increasingly patients, are focusing on functional and adverse outcomes. Symptoms of overactive bladder (OAB), including urinary frequency, urgency and incontinence, can occur regardless of treatment modality. This article examines the prevalence, pathophysiology and options for treating OAB after radical prostate cancer treatment. OAB seems to be more common and severe after radiation therapy than after surgical therapy and even persisted longer with complications, suggesting an advantage for surgery over radiotherapy. Because OAB that occurs after radical prostate surgery or radiotherapy can be difficult to treat, it is important that patients are made aware of the potential development of OAB during counselling before decisions regarding treatment choice are made. To ensure a successful outcome of both treatments, it is imperative that clinicians and non-specialists enquire about and document pretreatment urinary symptoms and carefully evaluate post-treatment symptoms.

Appropriateness of oral drugs for long-term treatment of lower urinary tract symptoms in older persons: results of a systematic literature review and international consensus validation process (LUTS-FORTA 2014).

AIM: we aimed to systematically review drugs to treat lower urinary tract symptoms (LUTS) regularly used in older persons to classify appropriate and inappropriate drugs based on efficacy, safety and tolerability by using the Fit fOR The Aged (FORTA) classification. METHODS: to evaluate the efficacy, safety and tolerability of drugs used for treatment of LUTS in older persons, a systematic review was performed. Papers on clinical trials and summaries of individual product characteristics were analysed regarding efficacy and safety in older persons (≥65 years). The most frequently used drugs were selected based on current prescription data. An interdisciplinary international expert panel assessed the drugs in a Delphi process. RESULTS: for the 16 drugs included here, a total of 896 citations were identified; of those, only 25 reported clinical trials with explicit data on, or solely performed in older people, underlining the lack of evidence in older people for drug treatment of LUTS. No drug was rated at the FORTA-A-level (indispensable). Only three were assigned to FORTA B (beneficial): dutasteride, fesoterodine and finasteride. The majority was rated FORTA C (questionable): darifenacin, mirabegron, extended release oxybutynin, silodosin, solifenacin, tadalafil, tamsulosin, tolterodine and trospium. FORTA D (avoid) was assigned to alfuzosin, doxazosin, immediate release oxybutynin, propiverine and terazosin. CONCLUSIONS: dutasteride, fesoterodine and finasteride were classified as beneficial in older persons or frail elderly people (FORTA B). For most drugs, in particular those from the group of α-blockers and antimuscarinics, use in this group seems questionable (FORTA C) or should be avoided (FORTA D).

Diagnosis and medical treatment of lower urinary tract symptoms in adult men: applying specialist guidelines in clinical practice.

UNLABELLED: What's known on the subject? and What does the study add? Several sets of comprehensive treatment guidelines (national and international) exist for managing male lower urinary tract symptoms (LUTS), but these are not widely adopted in primary and secondary care, and are not consistently applied across Europe. This paper will improve the consistency of treatment approaches for adult males with LUTS by providing a clear, concise summary of existing treatment guidelines that can be easily adopted by urologists and primary care specialists. OBJECTIVE: To review current treatment guidelines (international and national) on managing male lower urinary tract symptoms (LUTS) and to summarize them for easy application in clinical practice. METHODS: A group of European urology specialists from primary and secondary care reviewed current treatment guidelines for male LUTS. RESULTS: The most appropriate recommendations for managing male LUTS were identified from existing international and national guidelines, and were summarized and simplified for use as a quick reference guide for healthcare professionals managing LUTS in adult males. CONCLUSIONS: Current guidelines for managing male LUTS were developed by urologists and are too complex for easy application in routine practice. This brief summary of current guidance should help to achieve consistent adoption of recommendations for best practice, improve working relationships between primary care specialists and urologists and clarify which patients' treatments should be managed entirely by urology specialists.

A national survey of the radiotherapy dosimetrist workforce in the UK.

OBJECTIVES: To undertake a national survey of the Radiotherapy Dosimetrist workforce within the UK; examining different attributes and experiences, comparing results with published evidence within the literature. METHODS: A national, anonymised survey was undertaken between Dec 2020 and end of Feb 2021; employing a mixed-methods approach and blend of closed, open-ended answer choices and free-text comments. Questions included range of training routes and job titles; registration status; job tasks and engagement with Continuing Professional Development (CPD). RESULTS: A total of 223 individuals responded. Nearly half were trained via therapeutic radiography; approximately, a fifth through a clinical technologist/physics routes. Most (70%) had Dosimetrist in their job title. Nearly 70% were statutorily registered, and almost a fifth were in the voluntary register of Clinical Technologists. Most job tasks were in treatment planning - with 57% spending over 70% of their time there. Most notably, 29% were not involved in any CPD scheme. No published evidence showed the same aspects identified here. CONCLUSIONS: Our survey showed a unique profile of the Radiotherapy Dosimetrist workforce in the UK, with a variety of training routes and statutory registration status. Nearly, a third were not engaged in a CPD scheme - adding to the current discussion that perhaps all Dosimetrists should be statutorily registered, for ensuring safe and effective clinical practice. ADVANCES IN KNOWLEDGE: A novel and unique national survey of Dosimetrists working in Radiotherapy in the UK is presented, leading to new insights into current training routes, registration status, job tasks and CPD engagement and needs.

Examining the frequency and concomitant dose of geometric verification imaging for patients undergoing proton beam therapy for ocular tumours; an audit of current clinical practice.

OBJECTIVES: This paper uses clinical audit to determine the extent and dosimetric impact of additional imaging for patients undergoing ocular proton beam therapy who have no clips visible in the collimated beam. METHODS: An audit was conducted on 399 patients treated at The National Centre for Eye Proton Therapy between 3 July 2017 and 14 June 2019. The mean total number of image pairs over the course of treatment for patients with and without clips visible in the collimated beam were compared. RESULTS: Among 364 evaluable patients, 333 had clips visible in the collimated beam and 31 did not. There was a statistically significant increase of five image pairs required for patients with no clips visible compared with those with clips visible (mean 14.6 vs 9.6 image pairs, respectively; p = 2.74 × 10-6). This equated to an additional 1.5 mGy absorbed dose, representing an increase in secondary cancer induction risk from 0.0004 to 0.0007%. CONCLUSIONS: The small increase in concomitant dose and set-up time for patients with no clips visible in the collimated beam is not clinically significant. ADVANCES IN KNOWLEDGE: This novel work highlights clinical audit from real on-treatment geometric verification data and frequencies, rather than protocols, for ocular proton beam therapy; something not present in the literature. The simple and straightforward methodology is easily and equally applicable to clinical audits (especially those under Ionising Radiation (Medical Exposure) Regulations) for photon techniques.

A novel e-learning tool to improve knowledge and awareness of pelvic radiotherapy late effects: qualitative responses amongst therapeutic radiographers.

Objectives: This study aimed to investigate the effectiveness of a novel e-learning intervention to increase knowledge, awareness and confidence surrounding pelvic radiotherapy late effects amongst therapeutic radiographers (RTTs), and to change staff perceptions of responsibility in providing such information to patients. Methods: The e-learning intervention was developed using blended learning software (Articulate Global, New York). 23 therapeutic radiographers within a single UK radiotherapy institution received the e-learning. Semi-structured interviews and questionnaires were utilised pre- and post-intervention to obtain qualitative and quantitative results. Thematic analysis of coded interview responses identified recurring themes, whilst statistical analysis was conducted using a Wilcoxon signed-rank test. This first paper presents the qualitative results. Results: Thematic analysis revealed increased knowledge and awareness of pelvic radiotherapy late effects amongst participants. Five key themes were identified: Knowledge/Confidence; Consent; Professional Responsibility; Gaps within Practice and Time/Space. Whilst several staff reported increased confidence in discussing late effects with patients, further training utilising "blended" pedagogical approaches may be required to achieve longstanding improvements. Following e-learning, participants demonstrated increased professional responsibility to deliver late effects information to patients. Conclusion: The novel e-learning intervention increased staff knowledge, awareness and confidence surrounding pelvic radiotherapy late effects, whilst changing staff perceptions on professional responsibility in delivering such information. Advances in knowledge: The e-learning has been disseminated to all hospitals within the region including a new "Radiotherapy Late Effects Clinic", educating various healthcare professionals. Study recommendations have led to introduction of dedicated radiotherapy late effects modules on a novel MSc programme at a UK University.

Characteristics, behaviors, and attitudes of men bypassing the healthcare system when obtaining phosphodiesterase type 5 inhibitors.

INTRODUCTION: Men may choose to bypass the healthcare system to obtain a phosphodiesterase type 5 inhibitor (PDE5i). AIM: Evaluate the characteristics and purchasing patterns of men obtaining a PDE5i without prior healthcare professional (HCP) interaction. MAIN OUTCOME MEASURES: Prior HCP interaction, defined as having a prescription for any PDE5i, having a PDE5i sample from a physician, or buying the PDE5i in a retail pharmacy; and erectile dysfunction (ED, the Massachusetts Male Aging Study single-item question) were assessed. A multivariate regression analysis determined predictive factors for PDE5i purchase without prior HCP interaction. Methods. A Web-based observational study was conducted in the United Kingdom, Germany, and Italy. RESULTS: Of the 11,899 participants, 1,252 (10.5% [95% CI, 10.0-11.1%]) reported PDE5i use in the last 6 months. PDE5is were obtained without prior HCP interaction by 403 users (32.3% [95% CI, 29.6-34.8%]); 65.5% of them had ED. Overall prevalence of men using PDE5is without HCP interaction was 3.0% (95% CI, 2.6-3.5%), 4.1% (95% CI, 3.5-4.6%), and 2.8% (95% CI, 2.1-3.5%) for men aged 18-34, 35-50, and >50 years, respectively (P = 0.0045). Predictive factors for obtaining a PDE5i without prior HCP interaction were embarrassment to speak to a physician (P = 0.0009) and the perception that this would be the cheapest way to get the medicine (P = 0.03). CONCLUSIONS: Based on these findings, it can be estimated that approximately 6 million men in Europe might currently bypass the healthcare system to obtain a PDE5i. In addition to the risks associated with use of PDE5is from uncontrolled sources, because most of these men have ED, they also miss the opportunity for important health information or medical follow-up. HCPs should actively address ED and offer treatment to discourage men from seeking uncontrolled sources of ED medicines.

Development of a conceptual framework to improve sexual wellbeing communication in routine prostate cancer care.

OBJECTIVE: To systematically develop a framework to improve sexual wellbeing communication in routine prostate cancer care. METHODS: The Theoretical Domains Framework was used to guide a multi-phase process used to identify components of the framework based on evidence reviews, semi-structured interviews and stakeholder workshops. 'Think-aloud' testing was used to explore usability, potential barriers and other factors relevant to implementation. RESULTS: A conceptual communication framework consisting of 'Engagement' (E), 'Assessment' (A), information and 'Support' (S) and 'Sign-posting' (Si) sections was developed. The framework emphasises routine engagement to normalise sexual concerns, brief, non-sensitive assessment, personalised advice based on treatment type and relationship status, and a mechanism for referral to additional support or self-management resources in the form of a patient and partner handout. Usability testing identified strategies to promote implementation. CONCLUSIONS: The proposed framework is appropriate for use in routine practice and appears to be acceptable to patients, partners and healthcare professionals. Its use may help address gaps in sexual wellbeing support for men and partners living with prostate cancer. Further work will be conducted evaluating an online engagement tool, modelled on the framework. PRACTICE IMPLICATIONS: The EASSi framework can facilitate and structure sexual wellbeing conversations and ensure fundamental but individualised support is provided routinely in prostate cancer care.

Management of erectile dysfunction after prostate cancer treatment: cross-sectional surveys of the perceptions and experiences of patients and healthcare professionals in the UK.

OBJECTIVES: Erectile dysfunction (ED) is known to be a common consequence of radical treatment for prostate cancer (PCa) but is often under-reported and undertreated. This study aimed to explore how ED in patients with PCa is managed in real-life clinical practice, from the perspective of patients and healthcare professionals (HCPs). DESIGN AND SETTING: This is a UK-wide cross-sectional survey of men with ED after treatment for PCa which covered assessment and discussion of erectile function, provision of supportive care and satisfaction with management. Parallel surveys of primary and secondary HCPs were also conducted. RESULTS: Responses were received from 546 men with ED after PCa treatment, 167 primary (general practitioners and practice nurses) and 94 secondary care HCPs (urologists and urology clinical nurse specialists). Survey findings revealed inadequate management of ED in primary care, particularly underprescribing of effective management options. A fifth of men (21%) were not offered any ED management, and a similar proportion (23%) were not satisfied with the way HCPs addressed their ED concerns. There was poor communication between HCPs and men, including failure to initiate discussions about ED and/or involve partners, with 12% of men not told that ED was a risk factor of PCa treatment. These issues seemed to reflect poor access to effective ED management or services and lack of primary HCP confidence in managing ED, as well as confusion over the roles and responsibilities among both HCPs and men. CONCLUSIONS: This study confirms the need for better support for men from HCPs and more tailored and timely access to effective ED management after treatment for PCa. A clearly defined pathway is required for the discussion and management of ED, starting from the planning stage of PCa treatment. Improved adherence to ED management guidelines and better education and training for primary care HCPs are areas of priority.

A review of adherence to drug therapy in patients with overactive bladder.

Drug therapy for overactive bladder (OAB) is associated with improvements in symptoms and quality of life, but the short- and long-term adherence and persistence is suboptimal. In this review we outline methods of measuring, and factors affecting, adherence to pharmacotherapy in patients with OAB. Clinical practice suggests that adherence rates reported in clinical trials are much greater than in real practice. Factors affecting adherence include psychological and social variables that might alter patients' perception of the benefits of taking medication, and the effect of comorbidity and polypharmacy. Whilst there is some evidence that lack of efficacy and side-effects are contributory, these additional factors are also important.

A computationally efficient method for automatic registration of orthogonal x-ray images with volumetric CT data.

The paper presents a computationally efficient 3D-2D image registration algorithm for automatic pre-treatment validation in radiotherapy. The novel aspects of the algorithm include (a) a hybrid cost function based on partial digitally reconstructed radiographs (DRRs) generated along projected anatomical contours and a level set term for similarity measurement; and (b) a fast search method based on parabola fitting and sensitivity-based search order. Using CT and orthogonal x-ray images from a skull and a pelvis phantom, the proposed algorithm is compared with the conventional ray-casting full DRR based registration method. Not only is the algorithm shown to be computationally more efficient with registration time being reduced by a factor of 8, but also the algorithm is shown to offer 50% higher capture range allowing the initial patient displacement up to 15 mm (measured by mean target registration error). For the simulated data, high registration accuracy with average errors of 0.53 mm +/- 0.12 mm for translation and 0.61 +/- 0.29 degrees for rotation within the capture range has been achieved. For the tested phantom data, the algorithm has also shown to be robust without being affected by artificial markers in the image.