Persistence on biologic DMARD monotherapy after achieving rheumatoid arthritis disease control on combination therapy: retrospective analysis of corrona registry data.

Biological disease-modifying antirheumatic drugs (bDMARDs) monotherapy may enhance adherence and decrease adverse events compared to combination therapy with conventional synthetic DMARDs (csDMARDs); however, persistence with bDMARD monotherapy has not been extensively studied. We explore persistence of etanercept monotherapy and monotherapy with other tumor necrosis factor inhibitors (TNFis) among patients first achieving remission/low disease activity (LDA) while on combination therapy with csDMARDs and a TNFi. Using Corrona registry data, the percentage of patients persistent with the index TNFi (etanercept versus other TNFis) over 6 and 12 months was determined. Factors influencing persistence and treatment patterns at 6 and 12 months were examined. Among 617 eligible patients, 56% of 182 patients on etanercept and 45% of 435 patients on other TNFis persisted with monotherapy at 6 months, 46% and 33%, respectively, at 12 months. Across first-line and subsequent biologic DMARDs, etanercept persistence was greater than other TNFi persistence by 10.8% (95% CI 2.1%, 19.6%) at 6 months and 11.4% (95% CI 0.9%, 21.9%) at 12 months. Patients on other TNFis were more likely to require reintroduction of csDMARD after 6 months (45% versus 35% for etanercept). Remission was the key predictor of persistence for both etanercept and other TNFi monotherapies. This retrospective, cohort study of registry data reflecting real-world practice indicates patients who achieve remission/LDA with combination csDMARD and TNFi therapy may successfully transition to TNFi monotherapy. Patients on etanercept monotherapy experienced greater persistence and less frequent reintroduction of a csDMARD than was observed for patients on other TNFi monotherapies.

High Prevalence of Eosinophilic Gastrointestinal Disease in Children With Intestinal Failure.

OBJECTIVES: The aim of the present study was to describe the prevalence and clinical features of gastrointestinal (GI) eosinophilic inflammation among pediatric patients with intestinal failure (IF). METHODS: Medical records of all patients studied in our institution's IF program who underwent GI endoscopy over a 15-year period were reviewed, and clinical, pathologic, nutrition, and laboratory data collected. RESULTS: One hundred five patients underwent 208 GI endoscopic procedures with biopsy. The overall prevalence of eosinophilic inflammation, defined as increased eosinophils in at least 1 tissue type on at least 1 endoscopy, was 39 of 105 (37%). The tissue-specific prevalence of eosinophilic inflammation ranged widely, with the colon/rectosigmoid being the most common (18/68, 26%), followed by the esophagus (17/83, 20%), ileum (9/54, 17%), duodenum (4/83, 5%), and stomach (3/83, 4%). Higher peripheral eosinophil count and hematochezia were associated with eosinophilic inflammation in the colon (P = 0.002 and 0.0004, respectively). The use of a strict elemental diet for 3 months before endoscopy was not associated with a decreased frequency of eosinophilic inflammation in any tissue. CONCLUSIONS: Eosinophilic inflammation is a common histopathological finding in patients with IF. Colonic eosinophilic inflammation is associated with clinical symptoms of GI blood loss, and peripheral eosinophilia, and was not abrogated by a strict elemental diet.

A randomized trial of urodynamic testing before stress-incontinence surgery.

BACKGROUND: Urodynamic studies are commonly performed in women before surgery for stress urinary incontinence, but there is no good evidence that they improve outcomes. METHODS: We performed a multicenter, randomized, noninferiority trial involving women with uncomplicated, demonstrable stress urinary incontinence to compare outcomes after preoperative office evaluation and urodynamic tests or evaluation only. The primary outcome was treatment success at 12 months, defined as a reduction in the score on the Urogenital Distress Inventory of 70% or more and a response of "much better" or "very much better" on the Patient Global Impression of Improvement. The predetermined noninferiority margin was 11 percentage points. RESULTS: A total of 630 women were randomly assigned to undergo office evaluation with urodynamic tests or evaluation only (315 per group); the proportion in whom treatment was successful was 76.9% in the urodynamic-testing group versus 77.2% in the evaluation-only group (difference, -0.3 percentage points; 95% confidence interval, -7.5 to 6.9), which was consistent with noninferiority. There were no significant between-group differences in secondary measures of incontinence severity, quality of life, patient satisfaction, rates of positive provocative stress tests, voiding dysfunction, or adverse events. Women who underwent urodynamic tests were significantly less likely to receive a diagnosis of overactive bladder and more likely to receive a diagnosis of voiding-phase dysfunction, but these changes did not lead to significant between-group differences in treatment selection or outcomes. CONCLUSIONS: For women with uncomplicated, demonstrable stress urinary incontinence, preoperative office evaluation alone was not inferior to evaluation with urodynamic testing for outcomes at 1 year. (Funded by the National Institute of Diabetes and Digestive and Kidney Diseases and the Eunice Kennedy Shriver National Institute of Child Health and Human Development; ClinicalTrials.gov number, NCT00803959.).

5-year longitudinal followup after retropubic and transobturator mid urethral slings.

PURPOSE: Few studies have characterized longer-term outcomes after retropubic and transobturator mid urethral slings. MATERIALS AND METHODS: Women completing 2-year participation in a randomized equivalence trial who had not undergone surgical re-treatment for stress urinary incontinence were invited to participate in a 5-year observational cohort. The primary outcome, treatment success, was defined as no re-treatment or self-reported stress incontinence symptoms. Secondary outcomes included urinary symptoms and quality of life, satisfaction, sexual function and adverse events. RESULTS: Of 597 women 404 (68%) from the original trial enrolled in the study. Five years after surgical treatment success was 7.9% greater in women assigned to the retropubic sling compared to the transobturator sling (51.3% vs 43.4%, 95% CI -1.4, 17.2), not meeting prespecified criteria for equivalence. Satisfaction decreased during 5 years but remained high and similar between arms (retropubic sling 79% vs transobturator sling 85%, p=0.15). Urinary symptoms and quality of life worsened with time (p <0.001), and women with a retropubic sling reported greater urinary urgency (p=0.001), more negative impact on quality of life (p=0.02) and worse sexual function (p=0.001). There was no difference in the proportion of women experiencing at least 1 adverse event (p=0.17). Seven new mesh erosions were noted (retropubic sling 3, transobturator sling 4). CONCLUSIONS: Treatment success decreased during 5 years for retropubic and transobturator slings, and did not meet the prespecified criteria for equivalence with retropubic demonstrating a slight benefit. However, satisfaction remained high in both arms. Women undergoing a transobturator sling procedure reported more sustained improvement in urinary symptoms and sexual function. New mesh erosions occurred in both arms over time, although at a similarly low rate.

Predictors of Enteral Autonomy in Children with Intestinal Failure: A Multicenter Cohort Study.

OBJECTIVES: In a large cohort of children with intestinal failure (IF), we sought to determine the cumulative incidence of achieving enteral autonomy and identify patient and institutional characteristics associated with enteral autonomy. STUDY DESIGN: A multicenter, retrospective cohort analysis from the Pediatric Intestinal Failure Consortium was performed. IF was defined as severe congenital or acquired gastrointestinal diseases during infancy with dependence on parenteral nutrition (PN) >60 days. Enteral autonomy was defined as PN discontinuation >3 months. RESULTS: A total of 272 infants were followed for a median (IQR) of 33.5 (16.2-51.5) months. Enteral autonomy was achieved in 118 (43%); 36 (13%) remained PN dependent and 118 (43%) patients died or underwent transplantation. Multivariable analysis identified necrotizing enterocolitis (NEC; OR 2.42, 95% CI 1.33-4.47), care at an IF site without an associated intestinal transplantation program (OR 2.73, 95% CI 1.56-4.78), and an intact ileocecal valve (OR 2.80, 95% CI 1.63-4.83) as independent risk factors for enteral autonomy. A second model (n = 144) that included only patients with intraoperatively measured residual small bowel length found NEC (OR 3.44, 95% CI 1.36-8.71), care at a nonintestinal transplantation center (OR 6.56, 95% CI 2.53-16.98), and residual small bowel length (OR 1.04 cm, 95% CI 1.02-1.06 cm) to be independently associated with enteral autonomy. CONCLUSIONS: A substantial proportion of infants with IF can achieve enteral autonomy. Underlying NEC, preserved ileocecal valve, and longer bowel length are associated with achieving enteral autonomy. It is likely that variations in institutional practices and referral patterns also affect outcomes in children with IF.

Comparison of flowrates and voided volumes during non-instrumented uroflowmetry and pressure-flow studies in women with stress incontinence.

AIMS: The Blaivas-Groutz nomogram defines voiding obstruction in women using Qmax from the NIF and the maximum detrusor pressure (Pdetmax ) from the PFS. The aim of this study was to understand the relationship between NIF and PFS maximum flow rates in women with stress incontinence. METHODS: We analyzed the UDS of 597 women with stress-dominant urinary incontinence. Each subject underwent a NIF and then a PFS. Mixed model was used to test the hypothesis that the relationship between flow rates and voided volume (VV) were similar for NIF and PFS. RESULTS: There were 452 subjects with both NIF and PFS studies that met the inclusion criteria and had max flow rate (Qmax ) for both NIF and PFS. The mean age was 53. Overall, higher VV were observed during PFS compared to NIF and subjects had higher Qmax with NIF compared to PFS. The relationship between Qmax and VV was significantly different between NIF and PFS (P < 0.004). At 200 ml, NIF Qmax was 14% higher than PFS Qmax and this difference increased to 30% at 700 ml. CONCLUSION: The difference between PFS Qmax and NIF Qmax increases as VV increase. As a result, values from PFS and NIF cannot be used interchangeably as has been suggested in the Blaivas-Groutz nomogram for obstruction in women.

Perceptions of gender equality in work-life balance, salary, promotion, and harassment: results of the NASPGHAN task force survey.

OBJECTIVES: Gender equality in the workplace has not been described in pediatric gastroenterology. METHODS: An electronic survey that explored perceptions of career parity, work-life balance, and workplace harassment was sent to all members of the North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition. Reponses were anonymous. RESULTS: Of the 303 respondents (21%), there was an even distribution across geographic region, age, and gender (54% men). Gender affected perception of salary and promotion; 46% of men but only 9% of women feel that "women earn the same as men" (P < 0.001). Similarly, 48% of men but only 12% of women feel that "women rise at the same rate as men" (P < 0.001). Both genders of academic practice respondents, compared with other practice models, perceived men were promoted more quickly than women (P = 0.008). Women had higher dissatisfaction with mentoring than men (29% vs 13%, P = 0.03). Significantly more men than women reported spouses with "flexible jobs" (35% vs 14%, P < 0.001). Having a spouse with "flexible job" or having children (preschool or school age), however, did not affect satisfaction with work-life balance for either gender. Overall, women are more likely to be dissatisfied with work-life balance than men (P = 0.046). CONCLUSIONS: Satisfaction with work-life balance is lower among women versus men pediatric gastroenterologists, but does not correlate with flexibility of spouse's job or caring for young children. Gender-divergent perception of promotion, parity of compensation, and mentoring requires further investigation.

Missing data frequency and correlates in two randomized surgical trials for urinary incontinence in women.

INTRODUCTION AND HYPOTHESIS: Missing data is frequently observed in clinical trials; high rates of missing data may jeopardize trial outcome validity. PURPOSE: We determined the rates of missing data over time, by type of data collected and compared demographic and clinical factors associated with missing data among women who participated in two large randomized clinical trials of surgery for stress urinary incontinence, the Stress Incontinence Surgical Treatment Efficacy Trial (SISTEr) and the Trial of Midurethral Sling (TOMUS). METHODS: The proportions of subjects who attended and missed each follow-up visit were calculated. The chi-squared test, Fisher's exact test and t test were used to compare women with and without missing data, as well as the completeness of the data for each component of the composite primary outcome. RESULTS: Data completeness for the primary outcome computation in the TOMUS trial (62.3%) was nearly double that in the SISTEr trial (35.7%). The follow-up visit attendance rate decreased over time. A higher proportion of subjects attended all follow-up visits in the TOMUS trial and overall there were fewer missing data for the period that included the primary outcome assessment at 12 months. The highest levels of complete data for the composite outcome variables were for the symptoms questionnaire (SISTEr 100 %, TOMUS 99.8%) and the urinary stress test (SISTEr 96.1%, TOMUS 96.7%). In both studies, the pad test was associated with the lowest levels of complete data (SISTEr 85.1%, TOMUS 88.3%) and approximately one in ten subjects had incomplete voiding diaries at the time of primary outcome assessment. Generally, in both studies, a higher proportion of younger subjects had missing data. This analysis lacked a patient perspective as to the reasons for missing data that could have provided additional information on subject burden, motivations for adherence and study design. In addition, we were unable to compare the effects of the different primary outcome assessment time-points in an identically designed trial. CONCLUSIONS: Missing visits and data increased with time. Questionnaire data and physical outcome data (urinary stress test) that could be assessed during a visit were least prone to missing data, whereas data for variables that required subject effort while away from the research team (pad test, voiding diary) were more likely to be missing. Older subjects were more likely to provide complete data.

Effect of aging on storage and voiding function in women with stress predominant urinary incontinence.

PURPOSE: We investigated age related changes in urodynamic parameters in 2 large cohorts of women planning stress urinary incontinence surgery. MATERIALS AND METHODS: Using a standardized protocol we obtained urodynamic parameters for participants in SISTEr (Stress Incontinence Surgical Treatment Efficacy Trial) and TOMUS (Trial of Mid-Urethral Slings) undergoing baseline noninvasive flow followed by filling cystometrogram and pressure flow study. The bladder contractility index (defined as detrusor pressure at maximum flow+5×maximum flow) and detrusor hypocontractility (defined as detrusor pressure at maximum flow less than 10 cm H2O) were also characterized. Patients excluded from analysis had undergone prior stress urinary incontinence surgery or had prolapse stage greater than II. Propensity score analysis controlled for the potential bias of combining participants from 2 clinical trials. Linear and logistic regression analysis adjusting for propensity score quintile was done to assess the association of age and an age cutoff (less than 65 vs 65 or greater years) with urodynamic parameters. RESULTS: A total of 945 women (468 in SISTEr and 477 in TOMUS) were included in analysis. Mean age was 50 years in SISTEr (range 27 to 75) and 51 years (range 24 to 82) in TOMUS. Noninvasive maximum urinary flow decreased significantly with age (26.2 vs 22 ml per second, p=0.002). Noninvasive flow voiding time increased 2.7 seconds for each 10-year age increment and detrusor pressure at maximum flow decreased 2.1 cm H2O for each 10-year increase in age (each p=0.003). Hypocontractility was more likely in women 65 years old or older (OR 2.89, 95% CI 1.59, 5.27). The bladder contractility index was inversely related to age, decreasing a mean±SD of 7.68±1.96 cm H2O for each 10-year age increase (p<0.001). CONCLUSIONS: In these 2 cohorts the observed changes in voiding parameters suggest that detrusor contractility and efficiency decrease with age.

Pre-operative urodynamics in women with stress urinary incontinence increases physician confidence, but does not improve outcomes.

AIMS: To determine if pre-operative urodynamic testing (UDS) affects physicians' diagnostic confidence and if physician confidence affects treatment outcomes at 1 year. METHODS: The Value of Urodynamic Evaluation (ValUE) trial randomized 630 women with predominant stress urinary incontinence (SUI) to office evaluation (OE) or OE plus UDS prior to surgery. After OE, physicians completed a checklist of five clinical diagnoses: SUI, overactive bladder (OAB) wet and dry, voiding dysfunction (VD), and intrinsic sphincter deficiency (ISD), and reported their confidence in each. Responses ranged from 1 to 5 with; 1 = "not very confident (<50%)" to 5 = "extremely confident (95 + %)." After UDS, investigators again rated their confidence in these five clinical diagnoses. Logistic regression analysis correlated physician confidence in diagnosis with treatment success. RESULTS: Of 315 women who received OE plus UDS, 294 had complete data. Confidence improved after UDS in patients with baseline SUI (4.52-4.63, P < 0.005), OAB-wet (3.55-3.75, P < 0.001), OAB-dry (3.55-3.68 P < 0.005), VD (3.81-3.95, P < 0.005), and suspected ISD (3.63-3.92, P < 0.001). Increased confidence after UDS was not associated with higher odds of treatment success although mean changes in confidence were slightly higher for those who achieved treatment success. Physician diagnoses shifted more from not confident to confident for ISD and OAB-wet after UDS (McNemar's P-value <0.001 for both). CONCLUSIONS: In women undergoing UDS for predominant SUI, UDS increased physicians' confidence in their clinical diagnoses; however, this did not correlate with treatment success.

Comparison of body composition assessment methods in pediatric intestinal failure.

OBJECTIVES: The aim of the study was to examine the agreement of multifrequency bioelectric impedance analysis (BIA) and anthropometry with reference methods for body composition assessment in children with intestinal failure (IF). METHODS: We conducted a prospective pilot study in children 14 years or younger with IF resulting from either short bowel syndrome or motility disorders. Bland-Altman analysis was used to examine the agreement between BIA and deuterium dilution in measuring total body water (TBW) and lean body mass (LBM), and between BIA and dual-energy x-ray absorptiometry (DXA) techniques in measuring LBM and fat mass (FM). FM and percent body fat (%BF) measurements by BIA and anthropometry were also compared in relation to those measured by deuterium dilution. RESULTS: Fifteen children with IF, median (interquartile range) age 7.2 (5.0, 10.0) years, and 10 (67%) boys, were studied. BIA and deuterium dilution were in good agreement with a mean bias (limits of agreement) of 0.9 (-3.2 to 5.0) for TBW (L) and 0.1 (-5.4 to 5.6) for LBM (kg) measurements. The mean bias (limits) for FM (kg) and %BF measurements were 0.4 (-3.8 to 4.6) kg and 1.7 (-16.9 to 20.3)%, respectively. The limits of agreement were within 1 standard deviation of the mean bias in 12 of 14 (86%) subjects for TBW and LBM, and in 11 of 14 (79%) for FM and %BF measurements. Mean bias (limits) for LBM (kg) and FM (kg) between BIA and DXA were 1.6 (-3.0 to 6.3) kg and -0.1 (-3.2 to 3.1) kg, respectively. Mean bias (limits) for FM (kg) and %BF between anthropometry and deuterium dilution were 0.2 (-4.2 to 4.6) and -0.2 (-19.5 to 19.1), respectively. The limits of agreement were within 1 standard deviation of the mean bias in 10 of 14 (71%) subjects. CONCLUSIONS: In children with IF, TBW and LBM measurements by multifrequency BIA method were in agreement with isotope dilution and DXA methods, with small mean bias and clinically acceptable limits of agreement. In comparison with deuterium dilution, BIA was comparable to anthropometry for FM and %BF assessments with small mean bias, but the limits of agreement were large. BIA is a reliable method for TBW and LBM assessments in population studies; however, its reliability in individual patients, especially for FM assessments, cannot be guaranteed.

Patterns in the Sequential Treatment of Patients With Rheumatoid Arthritis Starting a Biologic or Targeted Synthetic Disease-Modifying Antirheumatic Drug: 10-Year Experience From a US-Based Registry.

OBJECTIVE: Developing and evaluating new treatment guidelines for rheumatoid arthritis (RA) based on observational data requires a quantitative understanding of patterns in current treatment practice with biologic and targeted synthetic disease-modifying antirheumatic drugs (b/tsDMARDs). METHODS: We used data from the CorEvitas RA registry to study patients starting their first b/tsDMARD therapy, defined as the first line of therapy, between 2012 and the end of 2021. We identified treatment patterns as unique sequences of therapy changes following and including the first-line therapy. Therapy cycling was defined as switching back to a treatment from a previously used therapeutic class. RESULTS: A total of 6015 b/tsDMARD-naïve patients (77% female) were included in the analysis. Their median age was 58 years, and their median disease duration was 3 years. In 2012-2014, 80% of the patients started a tumor necrosis factor inhibitor (TNFi) as their first b/tsDMARD. However, the use of TNFi decreased in favor of Janus kinase inhibitors since 2015. Although the number of treatment patterns was large, therapy cycling was relatively common. For example, 601 patterns were observed among 1133 patients who changed therapy at least four times, of whom 85.3% experienced therapy cycling. Furthermore, the duration of each of the first three lines of therapy decreased over the past decade. For example, the median duration of the first-line therapy was 153 days in 2018-2021 compared to 208 days in 2015-2017 (P < 0.001). CONCLUSION: First-line therapy was almost always TNFi, but diversity in treatment choice was high after that. This practice variation allows for proposing and evaluating new guidelines for sequential treatment of RA. It also presents statistical challenges to compare patients with different treatment sequences.

Retropubic versus transobturator midurethral slings for stress incontinence.

BACKGROUND: Midurethral slings are increasingly used for the treatment of stress incontinence, but there are limited data comparing types of slings and associated complications. METHODS: We performed a multicenter, randomized equivalence trial comparing outcomes with retropubic and transobturator midurethral slings in women with stress incontinence. The primary outcome was treatment success at 12 months according to both objective criteria (a negative stress test, a negative pad test, and no retreatment) and subjective criteria (self-reported absence of symptoms, no leakage episodes recorded, and no retreatment). The predetermined equivalence margin was +/-12 percentage points. RESULTS: A total of 597 women were randomly assigned to a study group; 565 (94.6%) completed the 12-month assessment. The rates of objectively assessed treatment success were 80.8% in the retropubic-sling group and 77.7% in the transobturator-sling group (3.0 percentage-point difference; 95% confidence interval [CI], -3.6 to 9.6). The rates of subjectively assessed success were 62.2% and 55.8%, respectively (6.4 percentage-point difference; 95% CI, -1.6 to 14.3). The rates of voiding dysfunction requiring surgery were 2.7% in those who received retropubic slings and 0% in those who received transobturator slings (P=0.004), and the respective rates of neurologic symptoms were 4.0% and 9.4% (P=0.01). There were no significant differences between groups in postoperative urge incontinence, satisfaction with the results of the procedure, or quality of life. CONCLUSIONS: The 12-month rates of objectively assessed success of treatment for stress incontinence with the retropubic and transobturator approaches met the prespecified criteria for equivalence; the rates of subjectively assessed success were similar between groups but did not meet the criteria for equivalence. Differences in the complications associated with the two procedures should be discussed with patients who are considering surgical treatment for incontinence. (ClinicalTrials.gov number, NCT00325039.)

The effect of urodynamic testing on clinical diagnosis, treatment plan and outcomes in women undergoing stress urinary incontinence surgery.

PURPOSE: We evaluated the influence of preoperative urodynamic studies on diagnoses, global treatment plans and outcomes in women treated with surgery for uncomplicated stress predominant urinary incontinence. MATERIALS AND METHODS: We performed a secondary analysis from a multicenter, randomized trial of the value of preoperative urodynamic studies. Physicians provided diagnoses before and after urodynamic studies and global treatment plans, defined as proceeding with surgery, surgery type, surgical modification and nonoperative therapy. Treatment plan changes and surgical outcomes between office evaluation and office evaluation plus urodynamic studies were compared by the McNemar test. RESULTS: Of 315 subjects randomized to urodynamic studies after office evaluation 294 had evaluable data. Urodynamic studies changed the office evaluation diagnoses in 167 women (56.8%), decreasing the diagnoses of overactive bladder-wet (41.6% to 25.2%, p <0.001), overactive bladder-dry (31.4% to 20.8%, p = 0.002) and intrinsic sphincter deficiency (19.4% to 12.6%, p = 0.003) but increasing the diagnosis of voiding dysfunction (2.2% to 11.9%, p <0.001). After urodynamic studies physicians canceled surgery in 4 of 294 women (1.4%), changed the incontinence procedure in 13 (4.4%) and planned to modify mid urethral sling tension (more or less obstructive) in 20 women (6.8%). Nonoperative treatment plans changed in 40 of 294 women (14%). Urodynamic study driven treatment plan changes were not associated with treatment success (OR 0.96, 95% CI 0.41, 2.25, p = 0.92) but they were associated with increased postoperative treatment for urge urinary incontinence (OR 3.23, 95% CI 1.46, 7.14, p = 0.004). CONCLUSIONS: Urodynamic studies significantly changed clinical diagnoses but infrequently changed the global treatment plan or influenced surgeon decision to cancel, change or modify surgical plans. Global treatment plan changes were associated with increased treatment for postoperative urgency urinary incontinence.

Nonresponders, partial responders, and complete responders to PDE5 inhibitors therapy according to IIEF criteria: validation of an anchor-based treatment responder classification.

INTRODUCTION: Despite widespread use of the International Index of Erectile Function (IIEF) in erectile dysfunction (ED) research, there are no published criteria for classifying ED treatment responders in clinical trials or patient management settings. A new classification for treatment response in men with ED has been developed and validated in a large clinical trial database. AIM: The study aims to test discriminant and convergent validity of the responder classification and examine the role of covariates. METHOD: Treatment assignment was used to test discriminant validity. The diary-based Sexual Encounter Profile (SEP) question ("Did your erection last long enough for you to have successful intercourse?") and Global Assessment Question (GAQ) ("Has the treatment you have been taking over the past study interval improved your erections?") were used to evaluate convergent validity. Chi-square and Cochran-Armitage trend tests were used to examine outcome associations. Logistic regression was used to further assess the relationship of outcomes controlling for covariates. MAIN OUTCOME MEASURE: The classification measure was developed and validated in a database from 17 clinical trials in 3,252 men with ED randomized to placebo or tadalafil. The treatment responder is defined as complete (erectile function [EF] ≥ 26); partial (EF < 26; met minimal clinically important difference [MCID] criteria); or nonresponder following treatment (EF < 26; did not meet MCID). RESULTS: The new responder definition performed consistently well in all prespecified tests of validity. Eighty-nine percent of subjects classified as complete responders were in the treatment group, and the responder definition was associated with changes on the SEP and GAQ measures, respectively (SEP odds ratio [OR] = 14, 95% confidence intervals [CI] 11-17; GAQ OR = 50, 95% CI 39-88; complete vs. nonresponders). CONCLUSIONS: We developed and validated a novel method of defining an ED treatment responder based on multiple IIEF criteria and using other measures (SEP, GAQ) for validation. The results have implications for understanding results of clinical trials in ED, and in monitoring response to treatment in the clinic.

The role of initial success rates and other factors in determining reliability of outcomes of phosphodiesterase inhibitor therapy for erectile dysfunction: a pooled analysis of 17 placebo-controlled trials of tadalafil for use as needed.

INTRODUCTION: Reliability of successful outcomes in men with erectile dysfunction (ED) on phosphodiesterase type 5 inhibitors is an important aspect of patient management. AIMS: We examined reliability of successful outcomes in a large integrated dataset of randomized tadalafil trials. MAIN OUTCOME MEASURES: Success rates, time to success, subsequent success after first success, and probability of success were analyzed based on Sexual Encounter Profile questions 2 and 3. METHODS: Data from 3,254 ED patients treated with tadalafil 10 mg (N = 510), 20 mg (N = 1,772), or placebo (N = 972) were pooled from 17 placebo-controlled studies. RESULTS: Tadalafil patients had significantly higher first-attempt success rates vs. placebo. This effect was consistent across most subgroups; however, patients with severe ED experienced a greater response to tadalafil than patients with mild-moderate ED. Approximately 80% of patients achieved successful penile insertion within two attempts with either tadalafil dose and successful intercourse within eight attempts for tadalafil 10 mg and four attempts for tadalafil 20 mg. However, approximately 70% of tadalafil-treated patients achieved successful intercourse even by the second attempt. Subsequent success rates were higher for patients with first-attempt success (81.5% for 10 mg and 86.1% for 20 mg vs. 66.2% for placebo, P < 0.001) vs. patients with later initial success (53.2% for 10 mg and 56.4% for 20 mg vs. 39.9% for placebo, P < 0.001). Among patients treated with tadalafil, intercourse success rates at early attempts were similar to rates at later attempts (i.e., attempts 5 and 10 vs. 25), although insertion success rates were significantly lower earlier in treatment. CONCLUSIONS: The findings affirm the reliability of successful outcomes with tadalafil treatment and that first-attempt success is a critical factor affecting subsequent outcomes. The results further show that even among men who did not succeed on first attempt, a substantial proportion will have successful outcomes if treatment is maintained.

Preoperative clinical, demographic, and urodynamic measures associated with failure to demonstrate urodynamic stress incontinence in women enrolled in two randomized clinical trials of surgery for stress urinary incontinence.

INTRODUCTION AND HYPOTHESIS: The unexpected absence of urodynamic stress incontinence (USI) in women planning surgery for stress urinary incontinence (SUI) is a challenge to surgeons. We examined the prevalence and clinical and demographic factors associated at baseline (preoperatively) with the unexpected absence of USI among study participants of two multicenter randomized clinical trials of surgery for treating SUI. METHODS: Women with SUI symptoms and positive stress tests on physical examination enrolled in two separate clinical trials-one comparing the autologous fascial sling with the Burch colposuspension [Stress Incontinence Surgical Treatment Efficacy Trial (SISTEr), and the other comparing the retropubic mid-urethral sling with the transobturator midurethral sling [Trial of Mid-Urethral Slings (TOMUS)]-were evaluated for USI preoperatively. The association of clinical, demographic, and urodynamic parameters was examined in women without USI in univariate and multivariate analyses. RESULTS: Overall, 144 of 1,233 women (11.7 %) enrolled in the two studies showed no USI. These women had a significantly lower mean volume at maximum cystometric capacity than those with USI (347.5 vs. 395.8 in SISTEr, p = 0.012), (315.2 vs. 358.2 in TOMUS, p = 0.003) and a lower mean number of daily accidents reported on a 3-day diary (2.2 vs 2.7 in SISTEr, p = 0.030) (1.7 vs 2.7 in TOMUS, p < 0.001). Additionally, those without demonstrable USI were more likely to have Pelvic Organ Prolapse Quantification (POP-Q) stage III/IV (31.7 % vs 14.4 % in SISTEr, p = 0.002), (15.5 % vs 6.9 % in TOMUS, p = 0.025). SUI severity as recorded on the Urogenital Distress Inventory (UDI) correlated strongly with the presence of USI in both studies. CONCLUSIONS: We observed that about one of eight women planning surgery for SUI does not show USI. Stage 3/4 POP was strongly associated with the unexpected absence of USI. A diminished urodynamic bladder capacity among women who did not display USI may reflect an inability to reach the limits of capacity during urodynamics, at which these women normally leak.

Prevalence and overlap of childhood and adult physical, sexual, and emotional abuse: a descriptive analysis of results from the Boston Area Community Health (BACH) survey.

Abuse is associated with a wide variety of health problems, yet comprehensive population-based data are scant. Existing literature focuses on a single type of abuse, population, or lifestage. Using a racially/ethnically diverse community-based sample, we document the prevalence of physical, emotional, and sexual abuse by lifestage and gender, assess variation in abuse by sociodemographics; establish overlap of abuses; and examine childhood abuse relationships with abuse in adulthood. Prevalence of abuse ranges from 15% to 27%; women report more adulthood emotional abuse and lifetime sexual abuse than men; reports of abuse can vary by race/ethnicity and poverty status, particularly in women; there is overlap between types of abuse; and a history of childhood abuse is associated with a greater risk of abuse as an adult.

Assessing clusters of comorbidities in rheumatoid arthritis: a machine learning approach.

BACKGROUND: Comorbid conditions are very common in rheumatoid arthritis (RA) and several prior studies have clustered them using machine learning (ML). We applied various ML algorithms to compare the clusters of comorbidities derived and to assess the value of the clusters for predicting future clinical outcomes. METHODS: A large US-based RA registry, CorEvitas, was used to identify patients for the analysis. We assessed the presence of 24 comorbidities, and ML was used to derive clusters of patients with given comorbidities. K-mode, K-mean, regression-based, and hierarchical clustering were used. To assess the value of these clusters, we compared clusters across different ML algorithms in clinical outcome models predicting clinical disease activity index (CDAI) and health assessment questionnaire (HAQ-DI). We used data from the first 3 years of the 6-year study period to derive clusters and assess time-averaged values for CDAI and HAQ-DI during the latter 3 years. Model fit was assessed via adjusted R2 and root mean square error for a series of models that included clusters from ML clustering and each of the 24 comorbidities separately. RESULTS: 11,883 patients with RA were included who had longitudinal data over 6 years. At baseline, patients were on average 59 (SD 12) years of age, 77% were women, CDAI was 11.3 (SD 11.9, moderate disease activity), HAQ-DI was 0.32 (SD 0.42), and disease duration was 10.8 (SD 9.9) years. During the 6 years of follow-up, the percentage of patients with various comorbidities increased. Using five clusters produced by each of the ML algorithms, multivariable regression models with time-averaged CDAI as an outcome found that the ML-derived comorbidity clusters produced similarly strong models as models with each of the 24 separate comorbidities entered individually. The same patterns were observed for HAQ-DI. CONCLUSIONS: Clustering comorbidities using ML algorithms is not computationally complex but often results in clusters that are difficult to interpret from a clinical standpoint. While ML clustering is useful for modeling multi-omics, using clusters to predict clinical outcomes produces models with a similar fit as those with individual comorbidities.