Tag Archive for: epidemiology

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Article of the week: A longitudinal analysis of urological chronic pelvic pain syndrome flares in the Multidisciplinary Approach to the Study of Chronic Pelvic Pain (MAPP) Research Network

Every week, the Editor-in-Chief selects an Article of the Week from the current issue of BJUI. The abstract is reproduced below and you can click on the button to read the full article, which is freely available to all readers for at least 30 days from the time of this post.

In addition to the article itself, there is an editorial written by a prominent member of the urological community. These are intended to provoke comment and discussion and we invite you to use the comment tools at the bottom of each post to join the conversation. 

If you only have time to read one article this week, it should be this one.

A longitudinal analysis of urological chronic pelvic pain syndrome flares in the Multidisciplinary Approach to the Study of Chronic Pelvic Pain (MAPP) Research Network

Siobhan Sutcliffe*, Robert Gallop, Hing Hung Henry Lai§, Gerald L. Andriole, Catherine S. Bradley**††, Gisela Chelimsky‡‡, Thomas Chelimsky§§, James Quentin Clemens¶¶, Graham A. Colditz*, Bradley Erickson††, James W. Griffith***, Jayoung Kim†††, John N. Krieger‡‡‡, Jennifer Labus§§§, Bruce D. Naliboff§§§, Larissa V. Rodriguez¶¶¶, Suzette E. Sutherland‡‡‡, Bayley J. Taple*** and John Richard Landis

 

*Division of Public Health Sciences, Department of Surgery and the Alvin J. Siteman Cancer Center, Washington University School of Medicine, St. Louis, MO, Department of Biostatistics and Epidemiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, Division of Urologic Surgery, Department of Surgery, §Department of Anesthesiology, Washington University School of Medicine, St. Louis, MO, Department of Obstetrics and Gynecology, Carver College of Medicine University of Iowa, **Department of Epidemiology, College of Public Health, ††Department of Urology, Carver College of Medicine, University of Iowa, Iowa City, IA, ‡‡Department of Pediatrics, Division of Pediatric Gastroenterology, §§Department of Neurology, Medical College of Wisconsin, Milwaukee, WI, ¶¶Division of Neurourology and Pelvic Reconstructive Surgery, Department of Urology, University of Michigan, Ann Arbor, MI, ***Department of Medical Social Sciences, Northwestern University Feinberg School of Medicine, Chicago, IL, †††Departments of Surgery and Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, CA, ‡‡‡Department of Urology, University of Washington, Seattle, WA, §§§Oppenheimer Center for Neurobiology of Stress and Resilience and Division of Digestive Diseases, Department of Medicine, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, and ¶¶¶Institute of Urology, University of Southern California, Beverly Hills, CA, USA

Abstract

Objective

To describe the frequency, intensity and duration of urological chronic pelvic pain syndrome symptom exacerbations (‘flares’), as well as risk factors for these features, in the Multidisciplinary Approach to the Study of Chronic Pelvic Pain Epidemiology and Phenotyping longitudinal study.

Participants and Methods

Current flare status (‘urological or pelvic pain symptoms that are much worse than usual’) was ascertained at each bi‐weekly assessment. Flare characteristics, including start date, and current intensity of pelvic pain, urgency and frequency (scales of 0–10), were assessed for participants’ first three flares and at three randomly selected times when they did not report a flare. Generalized linear and mixed effects models were used to investigate flare risk factors.

Results

Of the 385 eligible participants, 24.2% reported no flares, 22.9% reported one flare, 28.3% reported 2–3 flares, and 24.6% reported ≥4 flares, up to a maximum of 18 during the 11‐month follow‐up (median incidence rate = 0.13/bi‐weekly assessment, range = 0.00–1.00). Pelvic pain (mean = 2.63‐point increase) and urological symptoms (mean = 1.72) were both significantly worse during most flares (60.6%), with considerable within‐participant variability (26.2–37.8%). Flare duration varied from 1 to 150 days (94.3% within‐participant variability). In adjusted analyses, flares were more common, symptomatic, and/or longer‐lasting in women and in those with worse non‐flare symptoms, bladder hypersensitivity, and chronic overlapping pain conditions.

Conclusion

In this foundational flare study, we found that pelvic pain and urological symptom flares were common, but variable in frequency and manifestation. We also identified subgroups of participants with more frequent, symptomatic, and/or longer‐lasting flares for targeted flare management/prevention and further study.

Article of the week: Cluster analysis of multiple chronic conditions associated with urinary incontinence among women in the USA

Every week, the Editor-in-Chief selects an Article of the Week from the current issue of BJUI. The abstract is reproduced below and you can click on the button to read the full article, which is freely available to all readers for at least 30 days from the time of this post.

In addition to the article itself, there is an accompanying editorial written by a prominent member of the urological community. These are intended to provoke comment and discussion and we invite you to use the comment tools at the bottom of each post to join the conversation. There is also a new residents’ podcast focussing on this article. 

If you only have time to read one article this week, it should be this one.

Cluster analysis of multiple chronic conditions associated with urinary incontinence among women in the USA

Alayne D. Markland*, Camille P. Vaughan§, Ike S. Okosun, Patricia S. Goode*, Kathryn L. Burgio*and Theodore M. Johnson II§

 

*Department of Medicine, Division of Gerontology, Geriatrics and Palliative Care, University of Alabama-Birmingham UAB School of Medicine, Birmingham/Atlanta VA Geriatric Research, Education and Clinical Center, Birmingham VA Medical Center, Birmingham, AL, Birmingham/Atlanta VA Geriatric Research, Education and Clinical Center, Atlanta VA Medical Center, Decatur, §Department of Medicine, Division of General Medicine and Geriatrics, Emory University School of Medicine and Division of Epidemiology and Biostatistics, School of Public Health, Georgia State University, Atlanta, GA, USA

 

Abstract

Objective

To identify patterns of prevalent chronic medical conditions among women with urinary incontinence (UI).

Materials and Methods

We combined cross‐sectional data from the 2005–2006 to 2011–2012 US National Health and Nutrition Examination Surveys, and identified 3 800 women with UI and data on 12 chronic conditions. Types of UI included stress UI (SUI), urgency UI (UUI), and mixed stress and urgency UI (MUI). We categorized UI as mild, moderate or severe using validated measures. We performed a two‐step cluster analysis to identify patterns between clusters for UI type and severity. We explored associations between clusters by UI subtype and severity, controlling for age, education, race/ethnicity, parity, hysterectomy status and adiposity in weighted regression analyses.

Results

Eleven percent of women with UI had no chronic conditions. Among women with UI who had at least one additional condition, four distinct clusters were identified: (i) cardiovascular disease (CVD) risk‐younger; (ii) asthma‐predominant; (iii) CVD risk‐older; and (iv) multiple chronic conditions (MCC). In comparison to women with UI and no chronic diseases, women in the CVD risk‐younger (age 46.7 ± 15.8 years) cluster reported the highest rate of SUI and mild UI severity. In the asthma‐predominant cluster (age 51.5 ± 10.2 years), women had more SUI and MUI and more moderate UI severity. Women in the CVD risk‐older cluster (age 57.9 ± 13.4 years) had the highest rate of UUI, along with more severe UI. Women in the MCC cluster (age 61.0 ± 14.8 years) had the highest rates of MUI and the highest rate of moderate/severe UI.

Conclusions

Women with UI rarely have no additional chronic conditions. Four patterns of chronic conditions emerged with differences by UI type and severity. Identification of women with mild UI and modifiable conditions may inform future prevention efforts.

 

 

Article of the Week: Association of HDI with global bladder, kidney, prostate and testis cancer

Every Week the Editor-in-Chief selects an Article of the Week from the current issue of BJUI. The abstract is reproduced below and you can click on the button to read the full article, which is freely available to all readers for at least 30 days from the time of this post.

In addition to the article itself, there is an accompanying editorial written by a prominent member of the urological community. This blog is intended to provoke comment and discussion and we invite you to use the comment tools at the bottom of each post to join the conversation.

If you only have time to read one article this week, it should be this one.

Association of Human Development Index with global bladder, kidney, prostate and testis cancer incidence and mortality

Alyssa K. Greiman*, James S. Rosoff† and Sandip M. Prasad*

 

*Department of Urology, Medical University of South Carolina, Charleston, SC, Department of Urology, Yale School of Medicine, New Haven, CT, and Department of Surgery, Ralph M. Johnson VA Medical Center, Charleston, SC, USA

 

Abstract

Objectives

To describe contemporary worldwide age-standardized incidence and mortality rates for bladder, kidney, prostate and testis cancer and their association with development.

Materials and Methods

We obtained gender-specific, age-standardized incidence and mortality rates for 184 countries and 16 major world regions from the GLOBOCAN 2012 database. We compared the mortality-to-incidence ratios (MIRs) at national and regional levels in males and females, and assessed the association with socio-economic development using the 2014 United Nations Human Development Index (HDI).

Results

Age-standardized incidence rates were 2.9 (bladder) to 7.4 (testis) times higher for genitourinary malignancies in more developed countries compared with less developed countries. Age-standardized mortality rates were 1.5–2.2 times higher in more vs less developed countries for prostate, bladder and kidney cancer, with no variation in mortality rates observed in testis cancer. There was a strong inverse relationship between HDI and MIR in testis (regression coefficient 1.65, R2 = 0.78), prostate (regression coefficient −1.56, R2 = 0.85), kidney (regression coefficient −1.34, R2 = 0.74), and bladder cancer (regression coefficient −1.01, R2 = 0.80).

Conclusion

While incidence and mortality rates for genitourinary cancers vary widely throughout the world, the MIR is highest in less developed countries for all four major genitourinary malignancies. Further research is needed to understand whether differences in comorbidities, exposures, time to diagnosis, access to healthcare, diagnostic techniques or treatment options explain the observed inequalities in genitourinary cancer outcomes.

Editorial: Human development and its impact on genitourinary cancers

Using the extensive data from the WHO International Agency for Research on Cancer and the United Nations Human Development Report, Greiman et al. [1] aimed to investigate how human development is associated with incidence and mortality of genitourinary cancers. Even though they generate some interesting descriptive findings, we have to remain critical of these descriptive statistics and carefully assess what needs to be investigated next.

Firstly, despite having highlighted the need for attention to indicators of longevity, education, and income per head when assessing human development, the human development index (HDI) is a rather crude measurement. As a geometric mean of normalised indices for each of these three domains, the HDI simplifies but only captures part of what human development entails. Important indicators of health care such as inequalities, poverty, human security, and empowerment are not reflected in the HDI (www.hdr.undp.org). In the context of cancer incidence and mortality this is an important limitation, as it has for instance been shown that socioeconomic status affects early phase cancer trial referrals, which can be considered as a proxy for access to health care [2]. This inequality has been hypothesised to be linked to more comorbidities and lower education in those who are most deprived – a complex interaction which may not be completely captured by the HDI.

Secondly, registration of incidence and mortality of cancers may vary substantially between countries based on both medical practice and governance. These differences are important when trying to generate hypotheses following the ecological study of Greiman et al. [1]. In the case of bladder cancer, for instance, mortality has been estimated to be 17% in the Netherlands, compared to 22% in the USA, and 50% in the UK. As cancer treatments are expected to be similar in these developed countries, it has been thought that a lower registration of non-muscle-invasive bladder cancer in the UK could explain this higher proportion [3]. Thus, discrepancies in cancer registration, even between developed countries, may limit our awareness of cancer burden.

Thirdly, the study design suffers from ‘ecological fallacy’. The latter refers to the inability to draw causal inference about the effect of the HDI on genitourinary cancer at the individual level, in conjunction with the underlying problem of heterogeneity of exposure levels [4]. This limitation was not mentioned by Greiman et al. [1], but affects their conclusions. The lack of information on, for instance, smoking data, comorbidities, and ethnicity make it difficult to understand how development is affecting cancer incidence or mortality. It would have been interesting to also investigate cancers other than genitourinary cancers because a comparison of different tumour types might have shed light on differences in medical practice or risk factors across countries and help tease out the ecological effect of human development.

Despite the aforementioned limitations, the descriptive analysis by Greiman et al. [1] can be helpful for generating hypotheses – as also outlined by the authors. This ecological effect of human development on incidence and mortality rates of genitourinary cancers is particularly relevant when evaluating the impacts of prevention and intervention programmes for these cancers. Their findings suggest that further investigation is required to examine the hypothesis regarding human development and incidence/mortality of genitourinary cancers. To further elucidate this association, methodological challenges will need to be overcome, as HDI assessment has been criticised for being too crude. Nevertheless, it should be possible to collect more detailed information to allow for an understanding of which components of a country’s collective resources affect cancer incidence and mortality the most, e.g. differences in resources used for cancer detection and treatment.

Mieke Van Hemelrijck
Division of Cancer Studies, Translational Oncology and Urology Research (TOUR), Kings College London, London, UK

 

References

 

1 Greiman AKRosoff JSPrasad SM. Association of Human Development Index with global bladder, kidney, prostate and testis cancer incidence and mortality. BJU Int2017; 120: 799-807

 

2 Mohd Noor A Sarker DVizor S et al. Effect of patient socioeconomic status on access to early-phase cancer trials. J Clin Oncol 2013; 31: 224– 30.

 

3 Boormans JLZwarthoff EC. Limited funds for bladder cancer research and what can we do about it. Bladder Cancer 2016; 2: 4951

 

4 Morgenstern H . Ecologic studies in epidemiology: concepts, principles, and methods. Annu Rev Public Health 1995; 16: 618

 

Article of the Month: Immortal-Time Bias in Urological Research

Every Month the Editor-in-Chief selects an Article of the Month from the current issue of BJUI. The abstract is reproduced below and you can click on the button to read the full article, which is freely available to all readers for at least 30 days from the time of this post.

In addition to the article itself, there is an accompanying editorial written by a prominent member of the urological community. This blog is intended to provoke comment and discussion and we invite you to use the comment tools at the bottom of each post to join the conversation.

Finally, the third post under the Article of the Week heading on the homepage will consist of additional material or media. This week we feature a video discussing the paper.

If you only have time to read one article this week, it should be this one.

Estimating the effect of immortal-time bias in urological research: a case example of testosterone-replacement therapy

 

Christopher J.D. Wallis*Rek Saskin†‡, Steven A. Narod§, Calvin Law, Girish S. Kulkarni† **, Arun Seth†† and Robert K. Nam*

 

*Division of Urology, Sunnybrook Health Sciences Centre, Institute for Health Policy, Management and Evaluation, University of Toronto, Institute of Clinical Evaluative Sciences, Sunnybrook Health Sciences Centre, §Department of Public Health Sciences, University of Toronto, Division of General Surgery, Sunnybrook Health Sciences Centre, **Division of Urology, University Health Network, University of Toronto, and ††Department of Anatomic Pathology, Platform Biological Sciences, Sunnybrook Health Sciences Centre, Toronto, ON, Canada

 

Abstract

Objective

To quantify the effect of immortal-time bias in an observational study examining the effect of cumulative testosterone exposure on mortality.

Patients and Methods

We used a population-based matched cohort study of men aged ≥66 years, newly treated with testosterone-replacement therapy (TRT), and matched-controls from 2007 to 2012 in Ontario, Canada to quantify the effects of immortal-time bias. We used generalised estimating equations to determine the association between cumulative TRT exposure and mortality. Results produced by models using time-fixed and time-varying exposures were compared. Further, we undertook a systematic review of PubMed to identify studies addressing immortal-time bias or time-varying exposures in the urological literature and qualitatively summated these.

Results

Among 10 311 TRT-exposed men and 28 029 controls, the use of a time-varying exposure resulted in the attenuation of treatment effects compared with an analysis that did not account for immortal-time bias. While both analyses showed a decreased risk of death for patients in the highest tertile of TRT exposure, the effect was overestimated when using a time-fixed analysis (adjusted hazard ratio [aHR] 0.56, 95% confidence interval [CI]: 0.52–0.61) when compared to a time-varying analysis (aHR 0.67, 95% CI: 0.62–0.73). Of the 1 241 studies employing survival analysis identified in the literature, nine manuscripts met criteria for inclusion. Of these, five used a time-varying analytical method. Each of these was a large, population-based retrospective cohort study assessing potential harms of pharmacological agents.

Conclusions

Where exposures vary over time, a time-varying exposure is necessary to draw meaningful conclusions. Failure to use a time-varying analysis will result in overestimation of a beneficial effect. However, time-varying exposures are uncommonly utilised among manuscripts published in prominent urological journals.

Article of the week: Bladder and bowel: the link between OAB and IBS

Every week the Editor-in-Chief selects the Article of the Week from the current issue of BJUI. The abstract is reproduced below and you can click on the button to read the full article, which is freely available to all readers for at least 30 days from the time of this post.

In addition to the article itself, there is an accompanying editorial written by a prominent member of the urological community. This blog is intended to provoke comment and discussion and we invite you to use the comment tools at the bottom of each post to join the conversation.

If you only have time to read one article this week, it should be this one

Relationship between overactive bladder and irritable bowel syndrome: a large-scale internet survey in Japan using the overactive bladder symptom score and Rome III criteria

Seiji Matsumoto, Kazumi Hashizume, Naoki Wada, Jyunichi Hori, Gaku Tamaki, Masafumi Kita, Tatsuya Iwata and Hidehiro Kakizaki

Asahikawa Medical University, Renal and Urological Surgery, Asahikawa, Hokkaidou, Japan

OBJECTIVE

• To investigate the association between overactive bladder (OAB) and irritable bowel syndrome (IBS) by using an internet-based survey in Japan.

SUBJECTS AND METHODS

• Questionnaires were sent via the internet to Japanese adults.

• The overactive bladder symptom score was used for screening OAB, and the Japanese version of the Rome III criteria for the diagnosis of IBS was used for screening this syndrome.

RESULTS

• The overall prevalence of OAB and IBS was 9.3% and 21.2%, respectively.

• Among the subjects with OAB, 33.3% had concurrent IBS.

• The prevalence of OAB among men was 9.7% and among women it was 8.9%, while 18.6% of men and 23.9% of women had IBS.

• Concurrent IBS was noted in 32.0% of men and 34.8% of women with OAB.

CONCLUSION

• Taking into account a high rate of concurrent IBS in patients with OAB, it seems to be important for physicians to assess the defaecation habits of patients when diagnosing and treating OAB.

 

Read Previous Articles of the Week

Editorial: Think irritable bowel syndrome when treating overactive bladder

The bladder and bowel are functionally related organs; they lie in close proximity, have similar innervations and some structural similarities, albeit having different functional characteristics; they are both critical for the storage, collection and expulsion of waste products. Several previous clinical reports have suggested that LUTS, such as overactive bladder syndrome (OAB), can occur concurrently with disorders of the colon, such as irritable bowel syndrome (IBS).

In the study entitled ‘Relationship between overactive bladder and irritable bowel syndrome: a large-scale internet survey in Japan using the overactive bladder symptom score and Rome III criteria’, Matsumoto et al. investigate the prevalence of OAB and IBS in Japan using a large scale internet based survey. In all, 10 000 randomly selected participants completed the surveys with equal numbers of men and women. Subjects were grouped according to age and gender and the prevalence and severity of OAB was assessed using the OAB symptom score (OABSS). The OABSS as an assessment tool combines OAB symptoms into a single score. Four main criteria were examined (daytime frequency, night-time frequency, urgency and urgency incontinence) and disease severity was assessed by overall score value (5, mild; 6–11, moderate; and >12 severe). Similar epidemiological studies have been conducted in the past; however, this is the first study to use the OABSS to assess OAB in a general population. IBS was assessed using the IBS module of the ROME III criteria.

The study found that in the population studied, the overall prevalence of OAB was 9.3% (with 9.7% of men and 8.9% of women affected) and increased with advancing age. Of those affected, 59% reported mild symptoms, 40% reported moderate symptoms and 1% reported sever symptoms. The prevalence of IBS was greater, with 21.2%  of people reporting symptoms (18.6% of men and 23.9% of women); however, conversely the incidence of IBS was reduced with age. Consistent with previous epidemiological studies conducted in Europe and the USA, 33.3% of participants reporting OAB symptoms also had concurrent IBS (32.0% men and 34.8% women), interestingly though, the prevalence of concurrent IBS and OAB was unaffected by age, suggesting that age is not a contributing factor to this relationship.

The exact aetiology of OAB and IBS, by virtue of the non-specific nature of both symptom syndromes, cannot be clearly defined. However, both disorders are characterised by at least increased frequency of visceral emptying due to increased sensation and in many cases motor hyperactivity. In the LUT this takes the form of urgency with associated detrusor overactivity in 40–90% of patients and in the bowel it manifests as pain and discomfort. Experimental studies in rodent models have shown that initiation of bladder overactivity using chemical agents, such as cyclophosphamide, can induce hypersensitivity of the colon and conversely induction of colitis can lead to altered bladder function resembling OAB (Bielefeldt K et al., Brumovsky PR et al., Pezzone MA et al.). The concurrence of these disorders suggests that there may be a common underlying pathology or dysfunction at least in a subset of patients.

One theory put forward to explain the concurrence of OAB and IBS is that of cross-organ sensitisation, whereby sensory innervation of the bladder and bowel interact. These interactions can occur at multiple levels. In the periphery, there is evidence for afferent fibres, which extensively branch and innervate multiple target structures. These dichotomising afferents converge at a single neurone in the dorsal root ganglion (DRG). Studies using retrograde tracers injected into the colon and bladder wall have identified specific DRGs neurones that receive projections from both organs, although the numbers or these neurones are low. Sensitisation of the endings in one organ by local inflammation damage or injury would probably impact on overall sensitivity after upregulation in excitability in all terminal receptive fields.

In addition to peripheral mechanisms, sensitisation of central pathways could also be a contributing factor in cross-organ sensitisation. Spinal neurones receiving afferent input from the bladder have been shown to respond to afferent input from other pelvic structures including the colon. Second-order neurones in the spinal cord therefore receive convergent input from various visceral structures, as well as somatic inputs. This theory provides an explanation for the phenomenon of referred pain, where sensations from the viscera are experienced in the associated somatic sensory fields. Such viscero-somatic convergence has been extensively investigated (the most common example of this is angina), but only recently has viscero-visceral referral received attention. Clearly much research is still required to understand these interactions; however; this study clearly highlights the concurrence of bladder and bowel disorders. Understanding the mechanism(s) involved could have important implications for future therapeutic interventions aimed at treating both OAB and IBS.

Donna Daly and Christopher Chapple*

Department of Biomedical Science, University of Sheffeld and *Department of Urology, The Royal Hallamshire Hospital, Sheffeld Teaching Hospitals NHS Foundation Trust, Sheffield, UK

Article of the Week: Does tadalafil improve ejaculatory dysfunction?

Every week the Editor-in-Chief selects the Article of the Week from the current issue of BJUI. The abstract is reproduced below and you can click on the button to read the full article, which is freely available to all readers for at least 30 days from the time of this post.

In addition to the article itself, there is an accompanying editorial written by a prominent member of the urological community. This blog is intended to provoke comment and discussion and we invite you to use the comment tools at the bottom of each post to join the conversation.

Finally, the third post under the Article of the Week heading on the homepage will consist of additional material or media. This week we feature a video of  Darius Paduch discussing his paper.

If you only have time to read one article this week, it should be this one.

Effects of 12 weeks of tadalafil treatment on ejaculatory and orgasmic dysfunction and sexual satisfaction in patients with mild to severe erectile dysfunction: integrated analysis of 17 placebo-controlled studies

Darius A. Paduch*†, Alexander Bolyakov*†, Paula K. Polzer‡ and Steven D. Watts‡

*Department of Urology and Reproductive Medicine,Weill Cornell Medical College, New York, NY, †Consulting Research Services, Inc., Red Bank, NJ, and ‡Lilly Research Laboratories, Eli Lilly, Indianapolis, IN, USA


Weill Cornell Medical College Press Release

OBJECTIVES

• To compare effects of tadalafil on ejaculatory and orgasmic function in patients presenting with erectile dysfunction (ED).

• To determine the effects of post-treatment ejaculatory dysfunction (EjD) and orgasmic dysfunction (OD) on measures of sexual satisfaction.

PATIENTS AND METHODS

• Data from 17 placebo-controlled 12-week trials of tadalafil (5, 10, 20 mg) as needed in patients with ED were integrated.

• EjD and OD severities were defined by patient responses to the International Index of Erectile Function, question 9 (IIEF-Q9; ejaculation) and IIEF-Q10 (orgasm), respectively.

• Satisfaction was evaluated using the intercourse and overall satisfaction domains of the IIEF and Sexual Encounter Profile question 5.

• Analyses of covariance were performed to compare mean ejaculatory function and orgasmic function, and chi-squared tests evaluated differences in endpoint responses to IIEF-Q9 and IIEF-Q10.

RESULTS

• A total of 3581 randomized subjects were studied.

• Treatment with tadalafil 10 or 20 mg was associated with significant increases in ejaculatory and orgasmic function (vs placebo) across all baseline ED, EjD, and OD severity strata.

• In the tadalafil group, 66% of subjects with severe EjD reported improved ejaculatory function compared with 36% in the placebo group (P < 0.001).

• Similarly, 66% of the tadalafil-treated subjects (vs 35% for placebo; P < 0.001) with severe OD reported improvement.

• Residual severe EjD and OD after treatment had negative impacts on sexual satisfaction.

• Limitations of the analysis include its retrospective nature and the use of an instrument (IIEF) with as yet unknown performance in measuring treatment responses for EjD and OD.

CONCLUSIONS

• Tadalafil treatment was associated with significant improvements in ejaculatory function, orgasmic function and sexual satisfaction.

• Proportions of subjects reporting improved ejaculatory or orgasmic function were ª twofold higher with tadalafil than with placebo.

• These findings warrant corroboration in prospective trials of patients with EjD or OD (without ED).

 

Read Previous Articles of the Week

Editorial: Phosphodiesterase Inhibitors (PDEi) improve orgasm. The power of meta-analysis?

Ever since the potential utility of meta-analyses in the assessment of clinical data was brought to the notice of the urological community by Peter Boyle [1], they have been used increasingly. Indeed this approach to evaluation of drug effects has become de rigueur for healthcare providers and regulatory bodies. In particular, invaluable insight has been given into the benefit : risk ratios of drugs in BPH/LUTS and overactive bladder. Even to the extent, where sufficiently large databases have been made available, it has been possible to identify characteristics predictive of subpopulations of responders and non-responders [1].

The most recent example of the power of meta-analysis is the rigorous statistical dissection of the impact tadalafil on sexual function in erectile dysfunction (ED) by the Department of Urology atWeill Cornell published in BJUI [2]. As would be anticipated from previously published individual clinical trials, there was confirmation in this review of 3581 subjects in 17 placebo-controlled studies, of the positive effect of tadalafil (exemplifying the phosphodiesterase inhibitor [PDEi] class) on erectile function. It could perhaps be argued that with a clinical effect as large and clear-cut as that of PDEi in ED, the meta-analysis was superfluous. Only in situations where the clinical impact beyond that of placebo was of lower magnitude does it come to the fore, e.g. a-adrenoceptor antagonists in the treatment of LUTS [3]. However, at this point the following health warning should be issued, PDEi in the hands of the skilled meta-analysts and marketeers: caveat lector (let the reader beware).
Returning, however, to the material in hand, the analysis of the tadalafil data also shows unequivocally that there is an additional positive effect of the drug (and presumably the PDEi class) on orgasm and sexual satisfaction. These products and class attributes have often been alluded to with varying degrees of conviction, but this is the first time convincing evidence has been tabulated and documented.

Also described is the positive effect of tadalafil on co-morbid ejaculatory dysfunction (EjD) which, at first sight, would tend to provide supportive evidence for the off-label use of tadalafil and other PDEi in the treatment of premature ejaculation (PE). Although the words in the manuscript [3] fall short of advocating this practice, the inference is there for all to read and potentially be detailed astutely by the field-force.We now move into the ‘grey’ area between caveat lector and caveat emptor (let the buyer beware). EjD can mean different things to different men and can represent a continuum from premature to delayed or even anejaculation. Almost certainly most of the patients in the clinical trials analysed would not meet the definition of PE crafted by the International Society for Sexual Medicine (ISSM) [4], so little conclusion about the benefit to men with PE can be drawn.

Ironically, a meta-analysis on the impact of PDEi on men with unequivocal PE (or at least meet the ISSM definition) has just been published [5]. The conclusion was that there is no clinically or statistically significant improvement in PE with acute or chronic treatment with PDEi.

Although, at least in the case of ejaculatory function the conclusion of the two meta-analyses appear to be at variance, in actuality they are addressing different questions. It remains, that, although in the use of meta-analysis we have the means of creating a level playing field, we have to be careful to consider what questions are being asked, by whomand with what objective.

References
1 Boyle P, Gould AL, Roehrborn CG. Prostate volume predicts outcome of treatment of benign prostatic hyperplasia with finasteride: meta-analysis of randomized clinical trials. Urology 1996; 48: 398–405
2 Paduch DA, Bolyakov A, Polzer PK, Watts SD. Effects of 12 weeks of tadalafil treatment on ejaculatory and orgasmic dysfunction and sexual satisfaction in patients with mild to severe erectile dysfunction: integrated analysis of 17 placebo-controlled studies. BJU Int 2013; 111: 333–42
3 Boyle P, Robertson C, Manski R, Padley RJ, Roehrborn CG. Meta-analysis of randomized trials of terazosin in the treatment of benign prostatic hyperplasia. Urology 2001; 58: 717–22
4 McMahon CG, Althof S, Waldinger MD et al. International Society for Sexual Medicine Ad Hoc Committee for Definition of Premature Ejaculation. An evidence-based definition of lifelong premature ejaculation: report of the International Society for Sexual Medicine Ad Hoc Committee for the Definition of Premature Ejaculation. BJU Int 2008; 102: 338–50
5 Asimakopoulos AD, Miano R, Agrò EF, Vespasiani G, Spera E. Does current scientific and clinical evidence support the use of phosphodiesterase type 5 inhibitors for the treatment of premature ejaculation? A systematic review and meta-analysis. J Sex Med 2012; 9: 2404–16

Mike Wyllie
Plethora Solutions Ltd London, London, UK.
e-mail: [email protected]

Dr Paduch’s commentary on tadalafil and ejaculatory dysfunction

 

 

Effects of 12 weeks of tadalafil treatment on ejaculatory and orgasmic dysfunction and sexual satisfaction in patients with mild to severe erectile dysfunction: integrated analysis of 17 placebo-controlled studies

Darius A. Paduch*†, Alexander Bolyakov*†, Paula K. Polzer‡ and Steven D. Watts‡

*Department of Urology and Reproductive Medicine,Weill Cornell Medical College, New York, NY, †Consulting Research Services, Inc., Red Bank, NJ, and ‡Lilly Research Laboratories, Eli Lilly, Indianapolis, IN, USA

OBJECTIVES

• To compare effects of tadalafil on ejaculatory and orgasmic function in patients presenting with erectile dysfunction (ED).

• To determine the effects of post-treatment ejaculatory dysfunction (EjD) and orgasmic dysfunction (OD) on measures of sexual satisfaction.

PATIENTS AND METHODS

• Data from 17 placebo-controlled 12-week trials of tadalafil (5, 10, 20 mg) as needed in patients with ED were integrated.

• EjD and OD severities were defined by patient responses to the International Index of Erectile Function, question 9 (IIEF-Q9; ejaculation) and IIEF-Q10 (orgasm), respectively.

• Satisfaction was evaluated using the intercourse and overall satisfaction domains of the IIEF and Sexual Encounter Profile question 5.

• Analyses of covariance were performed to compare mean ejaculatory function and orgasmic function, and chi-squared tests evaluated differences in endpoint responses to IIEF-Q9 and IIEF-Q10.

RESULTS

• A total of 3581 randomized subjects were studied.

• Treatment with tadalafil 10 or 20 mg was associated with significant increases in ejaculatory and orgasmic function (vs placebo) across all baseline ED, EjD, and OD severity strata.

• In the tadalafil group, 66% of subjects with severe EjD reported improved ejaculatory function compared with 36% in the placebo group (P < 0.001).

• Similarly, 66% of the tadalafil-treated subjects (vs 35% for placebo; P < 0.001) with severe OD reported improvement.

• Residual severe EjD and OD after treatment had negative impacts on sexual satisfaction.

• Limitations of the analysis include its retrospective nature and the use of an instrument (IIEF) with as yet unknown performance in measuring treatment responses for EjD and OD.

CONCLUSIONS

• Tadalafil treatment was associated with significant improvements in ejaculatory function, orgasmic function and sexual satisfaction.

• Proportions of subjects reporting improved ejaculatory or orgasmic function were ª twofold higher with tadalafil than with placebo.

• These findings warrant corroboration in prospective trials of patients with EjD or OD (without ED).

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