Prevalence, Comorbidities, and Risk Factors of Erectile Dysfunction: Results from a Prospective Real-World Study in the United Kingdom.

Objectives: Assessment of erectile dysfunction (ED) burden could improve health outcomes associated with underlying cardiometabolic and psychological causes of ED. This study provided updated real-world evidence (RWE) on ED epidemiology and quantified healthcare resource utilization (HCRU) and health-related quality of life (HRQoL) burden among men with ED in the UK. Methods: This cross-sectional, prospective real-world evidence study was conducted via a self-reported Internet survey in 2018 in the UK general population. Prevalence of ED was estimated; HCRU and HRQoL were compared between men with ED versus without ED via bivariate analysis. Results: Of 12,490 men included, 41.5% reported ED; 7.5% of men reported severe ED; ED was most prevalent in Wales (44.3%). Men with ED were older (54.1 ± 14.5 vs. 46.8 ± 14.1 years) and often reported modifiable lifestyle risk factors, including smoking (32.8% vs. 26.3%), drinking alcohol (76.1% vs. 71.0%), not exercising (21.7% vs. 19.4%), and being overweight or obese (64.9% vs. 54.6%). Additionally, men with ED more often reported ≥1 comorbid chronic conditions (73.7% vs. 47.7%), including hypertension (31.8% vs. 16.3%), hyperlipidemia (27.6% vs. 14.0%), depression (24.3% vs. 14.6%), anxiety (23.3% vs. 16.6%), and diabetes (15.9% vs. 6.1%) versus men without ED (all, p < 0.001). Nearly half of men with ED (45.3%) were not undergoing treatment for cardiometabolic or psychological comorbidities. Furthermore, men with ED more often reported ≥1 visit to physicians/nurse practitioners and pharmacists in the past year and had significantly lower SEAR total and domain scores than men without ED (all, p < 0.001). Conclusion: ED was highly prevalent in the UK affecting over a quarter of younger men. Cardiometabolic and psychological conditions were common among men with ED and often remained untreated. Higher proportions of modifiable lifestyle risk factors observed among men with ED present an opportunity for healthcare providers to help mitigate the risk of cardiometabolic diseases and incidence of ED.

Increasing access to erectile dysfunction treatment via pharmacies to improve healthcare provider visits and quality of life: Results from a prospective real-world observational study in the United Kingdom.

OBJECTIVES: The Medicines and Healthcare Products Regulatory Agency in the United Kingdom (UK) formally reclassified sildenafil citrate 50 mg tablets as a pharmacy medicine (sildenafil-P) in 2017 for adult men with erectile dysfunction (ED). A 1-year prospective real-world observational study was conducted to track men's health behaviour, particularly their healthcare resource utilisation (HCRU) and quality of life (QoL) before and after the availability of sildenafil-P. METHODS: Adult men with ED aged ≥18 years provided data at baseline (prior to launch of sildenafil-P) and every 3 months after the launch. Demographics, health characteristics, treatments at baseline and HCRU, including number of pharmacist and physician/nurse practitioner visits over time are reported. QoL-related outcomes were assessed via the Self-Esteem and Relationship Questionnaire (SEAR), 2-Item Patient Health Questionnaire and ratings of sexual satisfaction. Generalised linear models were used to assess the association of sildenafil-P use with total physician/nurse practitioner and pharmacist visits and QoL-related outcomes at 12 months. RESULTS: Overall, 1162 men completed the survey at all 5 time points. The mean ± SD age was 59.02 ± 12.06 years; 55.42% reported having a moderate-to-severe ED. Hypertension (37.52%) and hypercholesterolaemia (31.50%) were the most common risk factors for ED. At baseline, 62.99% were not using any ED treatment. After adjusting for baseline visits/other covariates, mean physician/nurse practitioner (3.68 vs 2.87; P = .003) and pharmacist visits for any reason (2.10 vs 1.34; P < .001) at 12 months were significantly higher among sildenafil-P users than those who never used sildenafil-P. Sildenafil-P users also had significantly higher SEAR total and domain (sexual relationship and self-esteem) scores at 12 months. CONCLUSION: Following the reclassification to a pharmacy medicine in the UK, sildenafil-P was associated with a higher number of physician/nurse practitioner and pharmacist visits for any reason. Sildenafil-P use was also associated with better QoL, although group differences were small in magnitude.

Impact of sertraline daily treatment regimen on adherence, persistence and healthcare resource utilisation in patients with major depressive disorder or obsessive-compulsive disorder: A real-world evidence analysis from the United States.

OBJECTIVE: To generate real-world evidence (RWE) from the United States to assess the impact of pill burden and the importance of achieving a stable daily dose of sertraline (time taken, number of dose adjustments needed) on adherence/persistence and healthcare resource utilisation (HCRU). METHODS: Retrospective analysis of the PharMetrics® Plus database (1 October 2012 to 31 March 2020) in the United States. Eligible patients had major depressive disorder (MDD) or obsessive-compulsive disorder (OCD) and ≥1 claim for sertraline during index period (1 April 2013 to 31 March 2019, allowing 6-months prior, 1-year post-index follow-up). Patients who achieved stable daily dose of sertraline (>90 days on same dose) were categorised into five cohorts, depending on pill burden/daily dose: Cohort (1): 1 × 50 mg/d; Cohort (2): 1 × 100 mg/d; Cohort (3): 2 × 50 mg/d; Cohort (4): 1.5 × 100 mg/d; Cohort (5): 3 × 50 mg/d. Impact of pill burden on adherence/persistence and HCRU was assessed among cohorts using logistic regression analysis, and between patients who did vs did not stabilise on therapy. P < .05 was considered significant for all analyses. RESULTS: Of 224 412 eligible patients, 108 729 stabilised on sertraline (50, 100 or 150 mg/d) and formed Cohorts 1-5. Stabilised patients on lower pill burden had statistically higher adherence and were more likely to remain persistent throughout 1-year post-index period vs patients on higher pill burden but same overall dose (100 mg/d [Cohort 2 vs 3] and 150 mg/d [Cohort 4 vs 5], respectively). Patients who did not stabilise had significantly lower adherence/persistence vs patients who achieved stable daily dose (Cohorts 1-5 combined). Persistence improved when stable daily dose was achieved quickly (within 1-4 months) and efficiently (within 1-3 dose adjustments). Probability of HCRU increased for patients who did not stabilise on their initial prescription. CONCLUSION: Simplifying treatment regimen and decreasing pill burden improved adherence and/or persistence with sertraline therapy (100 or 150 mg/d). Patients achieving stable daily dose of sertraline in an efficient and timely manner were more likely to remain persistent throughout 1-year follow-up.

Health and functional status, health events, use of healthcare services and costs associated with overactive bladder among the medically complex vulnerable elderly in the US.

AIMS: To assess the prevalence of overactive bladder (OAB) among medically complex vulnerable elderly (MCVE) patients in the United States and to compare health status measures, functional status, healthcare events, use of healthcare services and costs between MCVE patients with and without OAB. METHODS: Using the 2001-2010 Medicare Current Beneficiary Surveys, we defined the MCVE as those respondents who were ≥65 years old with scores ≥3 on the Vulnerable Elders Survey-13. OAB diagnosis codes or self-reported use of antimuscarinic medications were used to identify MCVE individuals with OAB. Multiple regression analyses were used to estimate the adjusted relationship between OAB and the outcome measures. RESULTS: The annual prevalence of OAB among the MCVE increased from 9.6% in 2001 to 13.5% in 2010. MCVE individuals with OAB were more likely to have experienced falls or fractures (odds ratio [OR] = 1.6; 95% confidence interval [CI]: 1.3-2.0), urinary tract infections (OR = 4.3; 95% CI: 3.5-5.4), institutionalization (OR = 1.9; 95% CI: 1.4-2.5), limitations in activity of daily living (ADL) (OR = 1.4; 95% CI: 1.1-1.7) and instrumental ADL (OR = 1.5; 95% CI: 1.2-2.0), hospital admission (OR = 1.6; 95% CI: 1.3-2.0) and emergency department admissions (OR = 1.6; 95% CI: 1.3-2.0) than those without OAB. MCVE individuals with OAB incurred, on average, $7188 (2013 dollars) more in healthcare costs than those without OAB. DISCUSSION/CONCLUSIONS: The prevalence of OAB in the MCVE population increased over time. OAB is associated with substantial clinical and economic burden. Further research is warranted to understand whether better management of the MCVE population with OAB may reduce healthcare resource use.

Systematic literature review of clinical trials evaluating pharmacotherapy for overactive bladder in elderly patients: An assessment of trial quality.

AIMS: Overactive bladder (OAB) disproportionately affects older-aged adults, yet most randomized controlled trials (RCTs) underrepresent patients ≥65. This systematic literature review (SLR) identified RCTs evaluating ß-3 adrenergic agonists or muscarinic antagonists in elderly patients with OAB, and compared study quality across trials. METHODS: MEDLINE® , Embase® , and Cochrane Collaboration Central Register of Clinical Trials databases were searched from inception through April 28, 2015 to identify published, peer-reviewed RCT reports evaluating ß-3 adrenergic agonists or muscarinic antagonists in elderly OAB patients (either ≥65 years or study-described as "elderly"). To assess study quality of RCT reports, we focused on internal/external validity, assessed via two scales: the validated Effective Public Health Practice Project [EPHPP]): Quality Assessment Tool for Quantitative Studies, and a tool commissioned by the Agency for Healthcare Research and Quality (AHRQ). RESULTS: Database searches yielded 1380 records that were then screened according to predefined inclusion/exclusion criteria. We included eight papers meeting study criteria. Despite scientific community efforts to improve RCT reporting standards, published reports still include incomplete and inconsistent reporting-of subject attrition, baseline patient characteristics, inclusion/exclusion criteria, and other important details. Only three of the eight OAB RCTs in this review received quality ratings of Strong (EPHPP) or Fair (AHRQ) and were multicenter with large samples. CONCLUSIONS: Despite the prevalence of OAB among older age individuals, relatively few RCTs evaluate OAB treatments explicitly among elderly subjects. The findings from this quality assessment suggest some areas for improvement in both conduct and reporting of future RCTs assessing OAB treatment in elderly.

Patterns of medical management of overactive bladder (OAB) and benign prostatic hyperplasia (BPH) in the United States.

AIMS: Overactive bladder (OAB) and benign prostatic hyperplasia (BPH) are highly prevalent conditions that place a large burden on the United States (US) health care system. We sought to analyze patterns of prescription medication usage for incident OAB in men and women, and for incident BPH in men using US health insurance claims data. MATERIALS AND METHODS: This study used Truven Health MarketScan® Commercial and Medicare Supplemental Research databases. The data were pooled from diverse points of care. BPH subjects included men age 18+ with the first and last two diagnoses of BPH ≥30 days apart and no BPH diagnosis for 1 year prior. OAB subjects included men and women age 18+, who were diagnosed similarly with incident OAB. The type of medication, medication continuation (persistence), and switching to a different medication were analyzed through September 30, 2013. RESULTS: Medication persistence was much higher overall for BPH than OAB (56% vs 34%, respectively, P < 0.0001), and was highest among men with BPH age 65+ (62%). Patients age 18-64 were less likely to continue medication than older adults (age 65+) for both BPH and OAB. A 9.4% of patients in the OAB cohort and 6.9% of men with BPH switched from one medication to another. CONCLUSIONS: Persistence was higher with BPH than OAB medications overall, whereas switching rates were higher in the OAB group. The lower persistence of OAB medication may be due to less efficacy or tolerability. The possibility of under treatment of OAB also warrants future investigations.

Benefits of quitting smoking on work productivity and activity impairment in the United States, the European Union and China.

BACKGROUND: Smoking has important health and economic consequences for individuals and society. This study expands the understanding of work-related burden associated with smoking and benefit of smoking cessation across the US, European Union (EU) and China using large-scale, representative survey methodology. METHODS: Data utilised the 2013 National Health and Wellness Survey in United States (US), EU5 (UK, France, Germany, Italy, and Spain) and China. Working-aged respondents 18-64 were used in the analyses (US N=58 500; EU5 N=50 417; China N=17 987) and were categorised into: current smokers, trying to quit, former smokers and never smokers. Generalised linear models controlling for demographics and health characteristics examined the relationship of smoking status with work productivity and activity impairment (WPAI-GH). The WPAI-GH measures were: absenteeism, presenteeism, overall work impairment, and activity impairment. Separately, current smokers were compared with those who quit 0-4, 5-10 and 11 or more years ago on WPAI-GH end-points. RESULTS: Current smokers reported greater absenteeism in the US and China and greater presenteeism, overall work impairment, and activity impairment than former and never smokers across the three regions. Those who quit even 0-4 years ago demonstrated lower absenteeism, presenteeism, and activity impairment in China and lower presenteeism, overall work impairment, and activity impairment in the US and EU5. CONCLUSIONS: Smoking was associated with significant work productivity loss in the US, EU5 and China. The results suggest that quitting benefits extend to work productivity rapidly after cessation, serving to further encourage and promote the implementation of workplace cessation programs.

Patterns of Care for Newly Diagnosed Benign Prostatic Hyperplasia in the United States.

PURPOSE: We examined diagnostic tests and treatment patterns in men with new onset benign prostatic hyperplasia using consolidated national electronic health record data. MATERIALS AND METHODS: The Humedica® electronic health record database consists of de-identified patient records from approximately 25 million patients in the United States. Using this database, men with a new benign prostatic hyperplasia diagnosis (benign prostatic hyperplasia, bladder neck obstruction, urinary retention and incomplete bladder emptying) between July 1, 2009 and June 30, 2012 were included in study. Exclusion criteria included conditions such as genitourinary cancers, radiation cystitis, neurogenic bladder and urological pain diagnoses. Diagnostic tests and treatments were summarized and stratified by age (less than 65 vs 65 years or greater) and serum prostate specific antigen level. RESULTS: A total of 38,252 men met inclusion criteria. Mean followup was 1,020 days. Serum creatinine in 92% of patients, serum prostate specific antigen in 76% and urinalysis in 52% were the most common tests. Invasive testing was obtained in less than 20% of patients. Treatments included watchful waiting in 40% of patients, pharmacological therapy in 59.4% and surgery in 2.2%. α-Blockers were prescribed in 50.7% of men. Men older than 65 years and with higher prostate specific antigen levels were less likely to be treated with watchful waiting. Therapy with a 5-ARI (5-α reductase inhibitor) was prescribed in 23% to 29% of men across all prostate specific antigen categories. CONCLUSIONS: The majority of clinical care for new onset benign prostatic hyperplasia was in concordance with guideline recommendations. Based on prostate specific antigen values, 5-ARI therapy was underutilized in men with large prostates and was over utilized in men with small prostates.

Relationship between age and erectile dysfunction diagnosis or treatment using real-world observational data in the USA.

AIMS: With self-reporting of erectile dysfunction (ED) in population-based surveys, men with ED may not represent men who are bothered sufficiently to seek an ED diagnosis and treatment. We used real-world observational data to assess: 1) the prevalence of ED diagnosis or treatment by age subgroups; and 2) the relationship of age with ED diagnosis or treatment after controlling for ED-related comorbidities in the USA. METHODS: This cross-sectional study used de-identified claims data (MarketScan® databases; primary analysis). Sensitivity analysis was conducted using electronic health records (Humedica® database). Inclusion criteria were men aged ≥18 years with a 360-day continuous enrollment before the index date. We assessed the prevalence of ED diagnosis or phosphodiesterase type 5 inhibitor (PDE5I) prescription by age and the risk for ED diagnosis or treatment by age after controlling for comorbidities (hypertension, other cardiovascular disease, diabetes mellitus, depression and benign prostatic hyperplasia). RESULTS: Of 19,833,939 men meeting inclusion criteria in the primary analysis, only 1 108 842 (5.6%) had an ED diagnosis or PDE5I prescription (mean [SD] age: 55.2 [11.2] years). Prevalence of ED diagnosis or treatment increased from age 18-29 years (0.4%) to 60-69 years (11.5%), then decreased in the seventh (11.0%), eighth (4.6%), and ninth (0.9%) decades. Men with ED diagnosis or treatment had a higher prevalence of any comorbidity (63.1% vs 29.3% for men without ED) and of each comorbid condition. In multivariate analyses, age was an independent risk factor for ED diagnosis or treatment. Sensitivity analysis provided consistent results. CONCLUSIONS: In a real-world setting in the USA, the prevalence of ED diagnosis or PDE5I treatment is generally low, increases with age, decreases in very old men, and is associated with increased prevalence of comorbidities. Age is an independent risk factor for ED diagnosis or treatment after controlling for comorbidities.

Meta-analysis of Air Versus Liquid Enema for Intussusception Reduction in Children.

OBJECTIVE: The purpose of this study was to assess the effectiveness and safety of air versus liquid enema reduction in the treatment of intussusception in children. MATERIALS AND METHODS: Literature searches of the PubMed, Embase, and Cochrane Library databases were conducted from January 1, 1966, through May 31, 2013. Articles on the use of air or liquid enema in children with a confirmed diagnosis of intussusception and reporting either a success rate for enema reduction of intussusception or a perforation rate were selected. Enema reduction success rate, perforation rate, and recurrence rate were the main outcomes and were calculated by random effects modeling. RESULTS: One hundred two articles (101 reporting success rate, 71 reporting perforation rate) were included that presented results for 32,451 children (age range, 1 day-22 years; boys, 66%; girls, 34%). In 44 studies (16,187 children), the combined estimate for success rate of air enema was 82.7% (95% CI, 79.9-85.6%; inconsistency index [I(2)] = 97%), and in 52 studies (13,081 children) of liquid enema, it was 69.6% (95% CI, 65.0-74.1%; I(2) = 98%). In 38 studies (15,752 children), the combined estimate of perforation rate for air enema was 0.39% (95% CI, 0.23- 0.55%; I(2) = 40%), and in 30 studies (9429 children) of liquid enema, it was 0.43% (95% CI, 0.24- 0.62%; I(2) = 9%). Among 10,494 children (26 studies) undergoing air enema reduction, the rate of first intussusception recurrence was 6% (95% CI, 4.5-7.5%; I(2) = 89%), similar to the 7.3% (95% CI, 5.8-8.8%; I(2) = 71%) found for 4004 children (24 studies) undergoing liquid enema reduction. CONCLUSION: Air enema was superior to liquid enema for intussusception reduction. The success rate was higher without a difference in perforation rate. Limitations included heterogeneity and publication bias.

When Will Real-World Data Fulfill Its Promise to Provide Timely Insights in Oncology?

Randomized trials provide high-quality, internally consistent data on selected clinical questions, but lack generalizability for the aging population who are most often diagnosed with cancer and have comorbid conditions that may affect the interpretation of treatment benefit. The need for high-quality, relevant, and timely data is greater than ever. Promising solutions lie in the collection and analysis of real-world data (RWD), which can potentially provide timely insights about the patient's course during and after initial treatment and the outcomes of important subgroups such as the elderly, rural populations, children, and patients with greater social health needs. However, to inform practice and policy, real-world evidence must be created from trustworthy and comprehensive sources of RWD; these may include pragmatic clinical trials, registries, prospective observational studies, electronic health records (EHRs), administrative claims, and digital technologies. There are unique challenges in oncology since key parameters (eg, cancer stage, biomarker status, genomic assays, imaging response, side effects, quality of life) are not recorded, siloed in inaccessible documents, or available only as free text or unstructured reports in the EHR. Advances in analytics, such as artificial intelligence, may greatly enhance the ability to obtain more granular information from EHRs and support integrated diagnostics; however, they will need to be validated purpose by purpose. We recommend a commitment to standardizing data across sources and building infrastructures that can produce fit-for-purpose RWD that will provide timely understanding of the effectiveness of individual interventions.

A Web-Based Survey of Patients Dispensed Viagra Connect® Behind the Counter in UK: An Evaluation of Effectiveness of Additional Risk Minimization Measures.

Purpose: A national additional risk minimization measures (aRMMs) program was implemented to train pharmacists for safe supply of non-prescription Viagra Connect® (VC) to erectile dysfunction (ED) patients in United Kingdom (UK). A survey aimed to evaluate the effectiveness of aRMMs. Methods: A cross-sectional, web-based survey enrolled ED patients who purchased at least 1 supply of VC in UK, using a structured self-administered questionnaire. Patients were assessed for the suitability of VC and received appropriate advice from pharmacists. Descriptive statistics were used. Results: The final sample had 297 patients, who reported that pharmacists inquired about blood pressure and heart comorbidities (91.9%), relevant illnesses (87.9%), medications (86.5%), ED diagnosis (82.2%), and were advised to consult their doctor regarding ED (51.2%). Furthermore, 85.5% of patients were advised on how to take VC correctly, 82.2% on possible side effects for which they might have to discontinue taking VC and consult their doctor, 80.1% on being informed that ED could be caused by underlying conditions. About 65.0% reported that they had visited (19.2%) or planned to visit (45.8%) their doctor. A majority (68.7%) also indicated that they had received advice on lifestyle modifications to manage their ED-related health risks. Conclusion: This survey provided a reasonable confirmation of the effectiveness of the VC aRMMs program and assurance that ED patients, when requesting and purchasing VC in UK pharmacies, are assessed appropriately for suitability of VC and receive the appropriate advice from pharmacists.

A national additional risk minimization measures (aRMMs) program was implemented to train pharmacists for safe supply of non-prescription VC to erectile dysfunction (ED) patients in United Kingdom (UK). A cross-sectional, web-based survey enrolled ED patients who purchased at least 1 supply of VC in UK, using a structured self-administered questionnaire. Patients were assessed for the suitability of VC and received appropriate advice from pharmacists. The final sample had 297 patients, who reported that pharmacists inquired about blood pressure and heart comorbidities, relevant illnesses, medications, ED diagnosis, and were advised to consult their doctor regarding ED. Additionally, most of the patients had consulted or planned to consult their doctors, on how to take VC correctly, on possible side effects for which they might have to discontinue taking VC and consult their doctor, on being informed that ED could be caused by underlying conditions, and on lifestyle modifications. A majority also indicated that they had received advice on lifestyle modifications to manage their ED-related health risks. This survey provided a reasonable confirmation of the effectiveness of the VC aRMMs program and assurance that ED patients, when requesting and purchasing VC in UK pharmacies, are assessed appropriately for suitability of VC and receive the appropriate advice from pharmacists.

The Next Horizon of Drug Development: External Control Arms and Innovative Tools to Enrich Clinical Trial Data.

Conducting clinical trials (CTs) has become increasingly costly and complex in terms of designing and operationalizing. These challenges exist in running CTs on novel therapies, particularly in oncology and rare diseases, where CTs increasingly target narrower patient groups. In this study, we describe external control arms (ECA) and other relevant tools, such as virtualization and decentralized clinical trials (DCTs), and the ability to follow the clinical trial subjects in the real world using tokenization. ECAs are typically constructed by identifying appropriate external sources of data, then by cleaning and standardizing it to create an analysis-ready data file, and finally, by matching subjects in the external data with the subjects in the CT of interest. In addition, ECA tools also include subject-level meta-analysis and simulated subjects' data for analyses. By implementing the recent advances in digital health technologies and devices, virtualization, and DCTs, realigning of CTs from site-centric designs to virtual, decentralized, and patient-centric designs can be done, which reduces the patient burden to participate in the CTs and encourages diversity. Tokenization technology allows linking the CT data with real-world data (RWD), creating more comprehensive and longitudinal outcome measures. These tools provide robust ways to enrich the CT data for informed decision-making, reduce the burden on subjects and costs of trial operations, and augment the insights gained for the CT data.

Cumulative response curves to enhance interpretation of treatment differences on the Self-Esteem And Relationship questionnaire for men with erectile dysfunction.

UNLABELLED: What's known on the subject? and What does the study add? Studies on erectile dysfunction (ED) therapies rely heavily on patient-reported outcomes (PROs) to measure efficacy on treatment response. A challenge when using PROs is interpretation of the clinical meaning of changes in scores. A responder analysis provides a threshold score to indicate whether a change in score qualifies a patient as a responder. However, a major consideration with responder analysis is the sometimes arbitrary nature of defining the threshold for a response. By contrast, cumulative response curves (CRCs) display patient response rates over a continuum of possible thresholds, thus eliminating problems with a rigid threshold definition, allowing for a variety of response thresholds to be examined simultaneously, and encompassing all data. With respect to the psychosocial factors addressed in the Self-Esteem And Relationship questionnaire in ED, CRCs clearly, distinctly, and meaningfully highlighted the favourable profiles of responses to sildenafil compared with placebo. CRCs for PROs in urology can provide a clear, transparent and meaningful visual depiction of efficacy data that can supplement and complement other analyses. OBJECTIVE: To use cumulative response curves (CRCs) to enrich meaning and enhance interpretation of scores on the Self-Esteem And Relationship (SEAR) questionnaire with respect to treatment differences for men with erectile dysfunction (ED). PATIENTS AND METHODS: This post hoc analysis used data from all patients who took at least one dose of study drug and had at least one post-baseline efficacy evaluation in a previously published 12-week, multicentre, randomized, double-blind, placebo-controlled trial of flexible-dose (25, 50, or 100 mg) sildenafil citrate (Viagra) in adult men with ED who had scored ≤ 75 out of 100 on the Self-Esteem subscale of the SEAR questionnaire. CRCs were used on the numeric change in transformed SEAR scores from baseline to end-of-study for each SEAR component. The horizontal axis of the CRC represented change from baseline on the SEAR score, and the vertical axis represented the percentage of patients experiencing that change or greater. The differences between CRCs for the sildenafil group vs the placebo group were assessed using the Kolmogorov-Smirov test. RESULTS: For each of the SEAR components, there was essentially no overlap in the CRCs between the sildenafil group (n = 113) and placebo group (n = 115 or 116, depending on the component), showing that a greater percentage of sildenafil recipients compared with placebo recipients had a more favourable change across the spectrum of response thresholds (P ≤ 0.01). Previous research showed that a 10-point score increase is the minimal clinically meaningful improvement for most SEAR components. In the sildenafil vs placebo groups, a ≥10-point score increase occurred in 72 vs 37% of patients, respectively, on the Sexual Relationship Satisfaction domain, 71 vs 41% on the Confidence domain, 76 vs 49% on the Self-Esteem subscale, 60 vs 44% on the Overall Relationship Satisfaction subscale, and 75 vs 38% on the Overall score. CONCLUSIONS: With respect to the psychosocial factors addressed in the SEAR questionnaire, CRCs clearly, distinctly, and meaningfully highlighted the favourable profiles of responses to sildenafil compared with placebo. CRCs for patient-reported outcomes in urology can provide a clear, transparent, and meaningful visual depiction of efficacy data that can supplement and complement other analyses.

Effect of varenicline on individual nicotine withdrawal symptoms: a combined analysis of eight randomized, placebo-controlled trials.

INTRODUCTION: Concerns exist that varenicline may cause neuropsychiatric side effects. Some of these symptoms (e.g., depression, irritability) have been measured in clinical trials using nicotine withdrawal scales. This study assessed the effect of varenicline on neuropsychiatric and other symptoms, as measured by the Minnesota Nicotine Withdrawal Scale (MNWS). METHODS: We analyzed weekly individual MNWS symptom ratings in 8 randomized double-blind, placebo-controlled smoking cessation trials funded by Pfizer with similar methodology (n = 2,403 varenicline; n = 1,434 placebo). Ratings for the past 24hr were obtained prior to quitting and starting treatment and at Weeks 1-6 and 11 after the quit date. RESULTS: In repeated measures analyses controlling for baseline values, ratings for 5 neuropsychiatric symptoms (depressed mood, irritability, anxiety, difficulty concentrating, and restlessness) and urge to smoke were lower (p < .01) for varenicline than placebo at each timepoint. Worsening in scores from 0-2 (baseline) to 4 was less frequent on varenicline than placebo for all ratings except appetite- (significantly more frequent for varenicline, p < .0001) and sleep-related items. Repeated measures analysis for individuals with low levels of exhaled carbon monoxide revealed similar patterns except for a nonsignificant difference for increased appetite. CONCLUSIONS: Use of varenicline while trying to quit smoking reduces and does not increase neuropsychiatric symptoms such as depressed mood and irritability measured on the MNWS in smokers without current psychiatric disorders. It is associated with increases in sleep disturbance and appetite although the latter appears due to enabling more subjects to abstain from smoking.

T2 hyperintensity of medial lemniscus is an indicator of small-vessel disease.

OBJECTIVE: Small-vessel disease is a common MRI finding that can be difficult to differentiate from other white matter (WM) diseases because of the lack of a specific pattern of brain involvement. The purpose of our study was to evaluate medial lemniscus hyperintensity seen on FLAIR images as an imaging marker for small-vessel disease. MATERIALS AND METHODS: Two blinded neuroradiologists retrospectively reviewed 103 consecutive outpatient brain MRI studies. Medial lemniscus signal in the dorsal pons was evaluated visually on FLAIR images and after placing regions of interest (ROIs) on T2-weighted images. On the basis of the original interpretations, scans were divided into three categories: small-vessel disease, multiple sclerosis (MS), and normal or nonspecific WM changes. Cardiovascular risk factors were recorded. Analysis of variance and Fisher exact tests were used to determine group differences, and kappa statistics was used to determine interrater agreement. RESULTS: Thirty-seven patients had small-vessel disease, 14 patients had MS, and 52 had nonspecific WM changes. Medial lemniscus hyperintensity was seen in about 20% of patients with small-vessel disease and was generally bilateral. Although ROI analyses identified a slightly higher number of patients with medial lemniscus signal > 20% of adjacent to normal-appearing brainstem, interrater reliability was moderate, and there were false-positive and false-negative cases in comparison with visual data. When small-vessel disease patients were further subdivided into mild or advanced subgroups, medial lemniscus hyperintensity was selectively seen in advanced small-vessel disease. Patients with medial lemniscus hyperintensity were older (p < 0.001) and had higher prevalence of diabetes (p = 0.03), hypertension (p = 0.009), and hypercholesterolemia (p = 0.03). CONCLUSION: Medial lemniscus hyperintensity seen on FLAIR images is a reliable radiologic marker of advanced small-vessel disease.

The impact of COPD on quality of life, productivity loss, and resource use among the elderly United States workforce.

Abstract To address the gap in knowledge about the impact of chronic obstructive pulmonary disease (COPD) on older working adults, this study examined quality of life, worker productivity, and healthcare resource utilization among employed adults aged 65 and older with and without COPD. Among 2009 National Health and Wellness Survey (a cross-sectional, internet-based survey representative of the US adult population) respondents, employed adults aged 65 years and older, with COPD (n = 297) and without COPD (n = 3061), were included in analyses. Impact of self-reported COPD diagnosis on mean quality of life (using health utilities and mental, MCS, and physical, PCS, component summary scores from SF-12v2), work productivity and activity impairment (using the WPAI questionnaire), and resource use were examined. Adjusting for demographic and health characteristics such as co-morbidities (weighted to project to the US population) in regression models (linear, negative binomial, or logistic, as appropriate given the outcome measure), older workers with COPD reported significantly lower MCS (52.1 vs. 53.4, p < .05), PCS (40.3 vs. 47.2, p < .05), and health utilities (0.72 vs. 0.79, p < .05) than those without COPD, and significantly greater percentages of impairment while at work (presenteeism) (12.6% vs. 8.7%, p < .0001), overall work impairment (absenteeism and presenteeism combined) (19.3% vs. 10.0%, p < .05), and impairment in daily activities (23.9% vs. 13.7%, p < .05). There were no significant differences in absenteeism or healthcare use. Quality of life and work productivity suffered among employed adults aged 65 years and older with COPD, emphasizing the need for disease management in this population.

Comparison of adjustment methods for stratified two-sample tests in the context of ROC analysis.

We compare several nonparametric and parametric weighting methods for the adjustment of the effect of strata. In particular, we focus on the adjustment methods in the context of receiver-operating characteristic (ROC) analysis. Nonparametrically, rank-based van Elteren's test and inverse-variance (IV) weighting using the area under the ROC curve (AUC) are examined. Parametrically, the stratified t-test and IV AUC weighted method are applied based on a binormal monotone transformation model. Stratum-specific, pooled, and adjusted estimates are obtained. The pooled and adjusted AUCs are estimated. We illustrate and compare these weighting methods on a multi-center diagnostic trial and through extensive Monte-Carlo simulations.

Enhanced Patient-Centricity: How the Biopharmaceutical Industry Is Optimizing Patient Care through AI/ML/DL.

Technologies utilizing cutting-edge methodologies, including artificial intelligence (AI), machine learning (ML) and deep learning (DL), present powerful opportunities to help evaluate, predict, and improve patient outcomes by drawing insights from real-world data (RWD) generated during medical care. They played a role during and following the Coronavirus Disease 2019 (COVID-19) pandemic by helping protect healthcare providers, prioritize care for vulnerable populations, predict disease trends, and find optimal therapies. Potential applications across therapeutic areas include diagnosis, disease management and patient journey mapping. Use of fit-for-purpose datasets for ML models is seeing growth and may potentially help additional enterprises develop AI strategies. However, biopharmaceutical companies often face specific challenges, including multi-setting data, system interoperability, data governance, and patient privacy requirements. There remains a need for evolving regulatory frameworks, operating models, and data governance to enable further developments and additional research. We explore recent literature and examine the hurdles faced by researchers in the biopharmaceutical industry to fully realize the promise of AI/ML/DL for patient-centric purposes.

Clinical Practice Management of Primary Open-Angle Glaucoma in the United States: An Analysis of Real-World Evidence.

Purpose: To investigate clinical management of primary open-angle glaucoma (POAG) in the United States using real-world evidence and to examine healthcare resource utilization (HCRU), medication adherence/persistence, and procedure use. Design: A cross-sectional, retrospective analysis of Optum's de-identified Market Clarity Dataset (July 1, 2013-December 31, 2019). Patients and Methods: Patients ≥18 years with POAG diagnosis and continuous enrollment for 1-year pre- and post-index were eligible and categorized into four mutually exclusive cohorts: CH1, treated with antiglaucoma medication(s) only; CH2, underwent glaucoma procedure(s) only; CH3, treated with antiglaucoma medication(s) and underwent procedure(s); and CH4, received no treatment for POAG. Adherence and persistence with antiglaucoma medications, and disease-specific HCRU were analyzed. Pairwise two-sample comparisons and multivariate regressions were conducted. Results: Examined 232,572 eligible patients (CH1=60,895; CH2=4330; CH3=6027; CH4=161,320). Prostaglandin analogs were most prescribed antiglaucoma medications (CH1: 69.7%; CH3: 62.7%), of which latanoprost was most common (CH1: 51.3%; CH3: 46.1%). Disease-specific office visits occurred in 26.3%, 78.2%, 75.0%, 23.8%, and surgical services visits occurred in 3.8%, 36.3%, 42.5%, 3.3%, in CH1-CH4, respectively. Adherence was higher (medication possession ratio: 47.1% vs 39.4%; P<0.0001), and more patients remained persistent across 1-year post-index period in CH1 vs CH3 (25.4% vs 16.1%; P<0.0001). Positive predictors of medication persistence included being female, ≥55 years, and history of dyslipidemia or thyroid disease (all P≤0.0003). Conclusion: Overall, 70% POAG patients might not have received antiglaucoma treatment. Since POAG is a slowly progressive blinding disease, the lack of antiglaucoma treatment and suboptimal adherence/persistence with medications are of major concerns. Targeted screening and educational approaches are needed to improve POAG management.