Drugs produce their therapeutic effects by modulating specific targets, and there are 89 innovative targets of first-in-class drugs approved in 2004-17, each with information about drug clinical trial dated back to 1984. Analysis of the clinical trial timelines of these targets may reveal the trial-speed differentiating features for facilitating target assessment. Here we present a comprehensive analysis of all these 89 targets, following the earlier studies for prospective prediction of clinical success of the targets of clinical trial drugs. Our analysis confirmed the literature-reported common druggability characteristics for clinical success of these innovative targets, exposed trial-speed differentiating features associated to the on-target and off-target collateral effects in humans and further revealed a simple rule for identifying the speedy human targets through clinical trials (from the earliest phase I to the 1st drug approval within 8 years). This simple rule correctly identified 75.0% of the 28 speedy human targets and only unexpectedly misclassified 13.2% of 53 non-speedy human targets. Certain extraordinary circumstances were also discovered to likely contribute to the misclassification of some human targets by this simple rule. Investigation and knowledge of trial-speed differentiating features enable prioritized drug discovery and development.

Clinical trials, progression-speed differentiating features and swiftness rule of the innovative targets of first-in-class drugs.

Purpose To evaluate persistence and adherence of oral pharmacotherapy used in the treatment of overactive bladder (OAB) in a real-world setting. Materials and methods Systematic literature searches of six electronic publication databases were performed to identify observational studies of patients with OAB treated with antimuscarinics and/or mirabegron. Studies obtaining persistence and adherence data from sources other than electronic prescription claims were excluded. Reference lists of identified studies and relevant systematic reviews were assessed to identify additional relevant studies. Results The search identified 3897 studies, of which 30 were included. Overall, persistence ranged from 5% to 47%. In studies reporting data for antimuscarinics and mirabegron (n=3), 1-year persistence was 12%–25% and 32%–38%, respectively. Median time to discontinuation was Conclusion Most patients with OAB discontinued oral OAB pharmacotherapy and were non-adherent 1 year after treatment initiation. In general, mirabegron was associated with greater persistence and adherence compared with antimuscarinics. Combined with existing clinical trial evidence, this real-world review merits consideration of mirabegron for first-line pharmacological treatment among patients with OAB. PROSPERO registration number CRD42017059894.

https://bmjopen.bmj.com/content/bmjopen/8/11/e021889.full.pdf

Real-world persistence and adherence to oral antimuscarinics and mirabegron in patients with overactive bladder (OAB): a systematic literature review

Aims
We performed the first large population-based study to evaluate lower urinary tract symptoms (LUTS) in Brazil. The study objective was to assess the prevalence and bother of LUTS in the population aged ≥40 years in five major cities of Brazil.

Methods
This study was conducted as a telephone survey with assessment of LUTS using a standardized protocol, which included the International Prostate Symptom Score (IPSS) and, for overactive bladder (OAB), the OAB-V8 questionnaire. Participants were asked to rate how often they experienced individual LUTS and the degree of associated bother.

Results
Of the 5184 participants, 53% were women, and the age group with most participants (34%) was 50-59 years. The prevalence of LUTS (symptoms occurring less than half the time or more) was 75%: 69% in men and 82% in women. There was a statistically significant association between the frequency and bother intensity of each symptom (P < 0.001). The prevalence of OAB was similar in men and women (25% and 24%, respectively). According to the IPSS questionnaire, moderate-to-severe symptoms were present in 21% of men and 24% of women. LUTS detrimentally affected quality of life in many individuals: 39% would be “mostly dissatisfied,” “unhappy,” or consider it “terrible” to spend the rest of their life with their urinary condition as it is currently.

Conclusions
This was the first nationwide, population-based epidemiological study of LUTS to be performed in Brazil. LUTS are highly prevalent and often bothersome among men and women aged ≥40 years.

https://onlinelibrary.wiley.com/doi/pdf/10.1002/nau.23446

The prevalence of lower urinary tract symptoms (LUTS) in Brazil: Results from the epidemiology of LUTS (Brazil LUTS) study.

Mycoplasma species relevant to the urogenital tract include mycoplasma hominis, mycoplasma genitalia and ureaplasma urealyticum. Their occurrence in the context of urogynaecological disease has been demonstrated in urethritis, cystitis and upper renal tract infections. Their role in hyperactive bladder and interstitial cystitis/painful bladder syndrome is controversial. All the above-mentioned microorganisms can occur as commensals or as potential pathogens. In most cases their role in any particular pathology cannot be proven, only presumed. The aim of this systematic review was to summarise current knowledge on the influence of mycoplasma and ureaplasma in urogynaecological pathology and to provide clinical guidance on diagnosis (when and how is pathogen detection indicated?) and treatment. 377 relevant articles were analysed. In summary: a urethral swab for PCR analysis of the three bacteria should be performed in the context of symptomatic sterile leukocyturia, chronic urethritis and suspected hyperactive bladder or interstitial cystitis/painful bladder syndrome. Symptomatic women should be treated strictly according to results of the antibiogram.

/pdf/a-systematic-review-of-mycoplasma-and-ureaplasma-in-3rfi0vkr9f.pdf

A Systematic Review of Mycoplasma and Ureaplasma in Urogynaecology.

The prevalence of lower urinary tract symptoms (LUTS) and overactive bladder (OAB) has been measured by population-based investigations in many parts of the world. However, data are lacking for Eastern Europe, and there has not been any large population-representative study in any country of this region. Therefore, the aim of this study was to evaluate the prevalence and associated bother of LUTS and OAB in a population-representative sample of persons aged ≥ 40 years in Poland. This investigation was conducted as a computer-assisted telephone interview. The survey sample was stratified by age, sex, and place of residence to reflect the entire Polish population. LUTS and OAB were assessed by a standardized protocol based on the International Continence Society definitions and validated questionnaires. Of 6005 participants, 57% were women, and the mean age (range) was 60.7 (40–93) years. The prevalence of LUTS was 69.8% (men 66.2%; women 72.6%). There was no difference in prevalence between urban and rural areas. LUTS were often bothersome among men and women, but women were more likely to be bothered compared with men. There were also statistically significant correlations between the frequency and the bother intensity of each of the LUTS. The prevalence of OAB was higher in women (39.5%) than in men (26.8%), and OAB increased with age. Lastly, LUTS had detrimental effects on the quality of life because one third of the participants had concerns about their urinary-specific quality of life. This investigation was the first nationwide, population-representative epidemiological study of LUTS and OAB in an Eastern-European country. LUTS were highly prevalent, often bothersome, and had negative effects on the quality of life of men and women aged ≥ 40 years. Our findings are comparable with other epidemiologic studies of LUTS and OAB conducted in different regions of the world. Trial registration: NCT04121936.

/pdf/prevalence-and-bother-of-lower-urinary-tract-symptoms-and-3ow0k7p9pn.pdf

Prevalence and bother of lower urinary tract symptoms and overactive bladder in Poland, an Eastern European Study.

Overactive bladder (OAB) is common in both men and women. It is a symptom complex that causes significant detriment to quality of life in patients. Although the prevalence of OAB is similar in both sexes, there are sex-specific differences in individual symptoms and the impact on quality of life. The coexistence of benign prostatic hyperplasia with OAB can worsen quality of life in men. This review examines the major studies that looked at the epidemiology of OAB as it relates to both sexes. It focuses on both the overall prevalence rates and the incidence of individual symptoms. This paper also addresses the level of bother and quality of life in men and women with OAB. In addition, the relationship between OAB and benign prostatic hyperplasia is reviewed.

/pdf/review-of-the-epidemiology-of-overactive-bladder-3gsk9fuyta.pdf

Renu S Eapen

Papers

Review of the epidemiology of overactive bladder.