Systematic Reviews and Meta-analyses of the Procedure-specific Risks of Thrombosis and Bleeding in General Abdominal, Colorectal, Upper Gastrointestinal, and Hepatopancreatobiliary Surgery.

OBJECTIVE: To provide procedure-specific estimates of symptomatic venous thromboembolism (VTE) and major bleeding after abdominal surgery. BACKGROUND: The use of pharmacological thromboprophylaxis represents a trade-off that depends on VTE and bleeding risks that vary between procedures; their magnitude remains uncertain. METHODS: We identified observational studies reporting procedure-specific risks of symptomatic VTE or major bleeding after abdominal surgery, adjusted the reported estimates for thromboprophylaxis and length of follow-up, and estimated cumulative incidence at 4 weeks postsurgery, stratified by VTE risk groups, and rated evidence certainty. RESULTS: After eligibility screening, 285 studies (8,048,635 patients) reporting on 40 general abdominal, 36 colorectal, 15 upper gastrointestinal, and 24 hepatopancreatobiliary surgery procedures proved eligible. Evidence certainty proved generally moderate or low for VTE and low or very low for bleeding requiring reintervention. The risk of VTE varied substantially among procedures: in general abdominal surgery from a median of <0.1% in laparoscopic cholecystectomy to a median of 3.7% in open small bowel resection, in colorectal from 0.3% in minimally invasive sigmoid colectomy to 10.0% in emergency open total proctocolectomy, and in upper gastrointestinal/hepatopancreatobiliary from 0.2% in laparoscopic sleeve gastrectomy to 6.8% in open distal pancreatectomy for cancer. CONCLUSIONS: VTE thromboprophylaxis provides net benefit through VTE reduction with a small increase in bleeding in some procedures (eg, open colectomy and open pancreaticoduodenectomy), whereas the opposite is true in others (eg, laparoscopic cholecystectomy and elective groin hernia repairs). In many procedures, thromboembolism and bleeding risks are similar, and decisions depend on individual risk prediction and values and preferences regarding VTE and bleeding.

Risk of thrombosis and bleeding in gynecologic cancer surgery: systematic review and meta-analysis.

OBJECTIVE: This study aimed to provide procedure-specific estimates of the risk of symptomatic venous thromboembolism and major bleeding in the absence of thromboprophylaxis, following gynecologic cancer surgery. DATA SOURCES: We conducted comprehensive searches on Embase, MEDLINE, Web of Science, and Google Scholar for observational studies. We also reviewed reference lists of eligible studies and review articles. We performed separate searches for randomized trials addressing effects of thromboprophylaxis and conducted a web-based survey on thromboprophylaxis practice. STUDY ELIGIBILITY CRITERIA: Observational studies enrolling ≥50 adult patients undergoing gynecologic cancer surgery procedures reporting absolute incidence for at least 1 of the following were included: symptomatic pulmonary embolism, symptomatic deep vein thrombosis, symptomatic venous thromboembolism, bleeding requiring reintervention (including reexploration and angioembolization), bleeding leading to transfusion, or postoperative hemoglobin <70 g/L. METHODS: Two reviewers independently assessed eligibility, performed data extraction, and evaluated risk of bias of eligible articles. We adjusted the reported estimates for thromboprophylaxis and length of follow-up and used the median value from studies to determine cumulative incidence at 4 weeks postsurgery stratified by patient venous thromboembolism risk factors. The GRADE approach was applied to rate evidence certainty. RESULTS: We included 188 studies (398,167 patients) reporting on 37 gynecologic cancer surgery procedures. The evidence certainty was generally low to very low. Median symptomatic venous thromboembolism risk (in the absence of prophylaxis) was <1% in 13 of 37 (35%) procedures, 1% to 2% in 11 of 37 (30%), and >2.0% in 13 of 37 (35%). The risks of venous thromboembolism varied from 0.1% in low venous thromboembolism risk patients undergoing cervical conization to 33.5% in high venous thromboembolism risk patients undergoing pelvic exenteration. Estimates of bleeding requiring reintervention varied from <0.1% to 1.3%. Median risks of bleeding requiring reintervention were <1% in 22 of 29 (76%) and 1% to 2% in 7 of 29 (24%) procedures. CONCLUSION: Venous thromboembolism reduction with thromboprophylaxis likely outweighs the increase in bleeding requiring reintervention in many gynecologic cancer procedures (eg, open surgery for ovarian cancer and pelvic exenteration). In some procedures (eg, laparoscopic total hysterectomy without lymphadenectomy), thromboembolism and bleeding risks are similar, and decisions depend on individual risk prediction and values and preferences regarding venous thromboembolism and bleeding.

Risk of thrombosis and bleeding in gynecologic noncancer surgery: systematic review and meta-analysis.

OBJECTIVE: This study aimed to provide procedure-specific estimates of the risk for symptomatic venous thromboembolism and major bleeding in noncancer gynecologic surgeries. DATA SOURCES: We conducted comprehensive searches on Embase, MEDLINE, Web of Science, and Google Scholar. Furthermore, we performed separate searches for randomized trials that addressed the effects of thromboprophylaxis. STUDY ELIGIBILITY CRITERIA: Eligible studies were observational studies that enrolled ≥50 adult patients who underwent noncancer gynecologic surgery procedures and that reported the absolute incidence of at least 1 of the following: symptomatic pulmonary embolism, symptomatic deep vein thrombosis, symptomatic venous thromboembolism, bleeding that required reintervention (including re-exploration and angioembolization), bleeding that led to transfusion, or postoperative hemoglobin level <70 g/L. METHODS: A teams of 2 reviewers independently assessed eligibility, performed data extraction, and evaluated the risk of bias of the eligible articles. We adjusted the reported estimates for thromboprophylaxis and length of follow-up and used the median value from studies to determine the cumulative incidence at 4 weeks postsurgery stratified by patient venous thromboembolism risk factors and used the Grading of Recommendations Assessment, Development and Evaluation approach to rate the evidence certainty. RESULTS: We included 131 studies (1,741,519 patients) that reported venous thromboembolism risk estimates for 50 gynecologic noncancer procedures and bleeding requiring reintervention estimates for 35 procedures. The evidence certainty was generally moderate or low for venous thromboembolism and low or very low for bleeding requiring reintervention. The risk for symptomatic venous thromboembolism varied from a median of <0.1% for several procedures (eg, transvaginal oocyte retrieval) to 1.5% for others (eg, minimally invasive sacrocolpopexy with hysterectomy, 1.2%-4.6% across patient venous thromboembolism risk groups). Venous thromboembolism risk was <0.5% for 30 (60%) of the procedures; 0.5% to 1.0% for 10 (20%) procedures; and >1.0% for 10 (20%) procedures. The risk for bleeding the require reintervention varied from <0.1% (transvaginal oocyte retrieval) to 4.0% (open myomectomy). The bleeding requiring reintervention risk was <0.5% in 17 (49%) procedures, 0.5% to 1.0% for 12 (34%) procedures, and >1.0% in 6 (17%) procedures. CONCLUSION: The risk for venous thromboembolism in gynecologic noncancer surgery varied between procedures and patients. Venous thromboembolism risks exceeded the bleeding risks only among selected patients and procedures. Although most of the evidence is of low certainty, the results nevertheless provide a compelling rationale for restricting pharmacologic thromboprophylaxis to a minority of patients who undergo gynecologic noncancer procedures.

Timing of symptomatic venous thromboembolism after surgery: meta-analysis.

BACKGROUND: The timing at which venous thromboembolism (VTE) occurs after major surgery has major implications for the optimal duration of thromboprophylaxis. The aim of this study was to perform a systematic review and meta-analysis of the timing of postoperative VTE up to 4 weeks after surgery. METHODS: A systematic search of MEDLINE, Scopus, and CINAHL databases was performed between 1 January 2009 and 1 April 2022. Prospective studies that recruited patients who underwent a surgical procedure and reported at least 20 symptomatic, postoperative VTE events by time were included. Two reviewers independently selected studies according to the eligibility criteria, extracted data, and evaluated risk of bias. Data were analysed with a Poisson regression model, and the GRADE approach was used to rate the certainty of evidence. RESULTS: Some 6258 studies were evaluated, of which 22 (11 general, 5 urological, 4 mixed, and 2 orthopaedic postoperative surgical populations; total 1 864 875 patients and 24 927 VTE events) were eligible. Pooled evidence of moderate certainty showed that 47.1 per cent of the VTE events occurred during the first, 26.9 per cent during the second, 15.8 per cent during the third, and 10.1 per cent during the fourth week after surgery. The timing of VTE was consistent between individual studies. CONCLUSION: Although nearly half of symptomatic VTE events in first 4 weeks occur during the first postoperative week, a substantial number of events occur several weeks after surgery. These data will inform clinicians and guideline developers about the duration of postoperative thromboprophylaxis.

Hundreds of millions of surgical procedures are performed annually worldwide. Blood clots in legs and lungs represent serious, and sometimes fatal, complications of surgery. To prevent these complications, clinicians often give blood thinners to patients. To optimize the starting time and duration of use of blood thinners, it is crucial to know when blood clots occur after surgery. This study summarized the timing of blood clots after surgery based on a systematic review and meta-analysis of 22 prospective studies including thousands of patients with blood clots from various surgical fields. Of blood clots occurring within 4 weeks after surgery, 47 per cent occurred by the first, 74 per cent by the second, and 90 per cent by the third week after surgery. These research results are useful for patients, clinicians, and guideline developers to guide the starting time and duration of use of blood thinners after surgery.

Decision aids for localized prostate cancer treatment choice: Systematic review and meta-analysis.

Patients who are diagnosed with localized prostate cancer need to make critical treatment decisions that are sensitive to their values and preferences. The role of decision aids in facilitating these decisions is unknown. The authors conducted a systematic review of randomized trials of decision aids for localized prostate cancer. Teams of 2 reviewers independently identified, selected, and abstracted data from 14 eligible trials (n = 3377 men), of which 10 were conducted in North America. Of these, 11 trials compared decision aids with usual care, and 3 trials compared decision aids with other decision aids. Two trials suggested a modest positive impact on decisional regret. Results across studies varied widely for decisional conflict (4 studies), satisfaction with decision (2 studies), and knowledge (2 studies). No impact on treatment choices was observed (6 studies). In conclusion, scant evidence at high risk of bias suggests the variable impact of existing decision aids on a limited set of decisional processes and outcomes. Because current decision aids provide information but do not directly facilitate shared decision making, subsequent efforts would benefit from user-centered design of decision aids that promote shared decision making.

The effectiveness of parasympathomimetics for treating underactive bladder: A systematic review and meta-analysis.

AIMS: Biological rationale suggests that parasympathomimetics (cholinergic receptor stimulating agents) could be beneficial for patients with underactive bladder. However, no systematic review with meta-analysis addressing potential benefits or adverse effects exists. The aim of this review was to assess the effectiveness, both benefits and harms, of using parasympathomimetics for the treatment of underactive bladder. METHODS: The protocol was registered in PROSPERO, and searches undertaken in PubMed, Embase, and CENTRAL, including randomized and non-randomized controlled trials of patients with underactive bladder, comparing parasympathomimetic to placebo, no treatment, or other pharmaceuticals. Risk ratios, odds ratios, and mean differences were calculated. RESULTS: Twelve trials with 3024 participants were included. There was a significant difference between parasympathomimetics and comparators (favoring parasympathomimetics) in the number of patients with urinary retention (risk ratio 0.55, 95% confidence interval [CI] 0.3-0.98, p = 0.04, low quality of evidence). There was no difference in mean postvoid volume overall (MD -41.4 ml, 95% CI -92.0 to 9.1, p = 0.11, low quality of evidence). There was a significant difference at up to 1 week post-intervention, favoring parasympathomimetics (MD -77.5 ml, 95% CI -90.9 to -64.1, p < 0.001, low quality of evidence), but no difference at 1 month post-intervention. There was no difference in adverse events (odds ratio 1.19, 95% CI 0.62-2.28, p = 0.6, moderate quality of evidence). CONCLUSIONS: The evidence supporting the use of parasympathomimetics is of low quality, with relatively short follow-up durations. Overall, it is not possible to draw clear evidence-based conclusions from the current literature, presenting the use of parasympathomimetics for treating underactive bladder as a key area that requires future well-controlled clinical trials.

Genome-Wide Association Study Identifies Two Novel Loci Associated with Female Stress and Urgency Urinary Incontinence.

PURPOSE: Genome-wide association studies have not identified replicable genetic risk loci for stress or urgency urinary incontinence. MATERIALS AND METHODS: We carried out a discovery stage, case control, genome-wide association study in 3 independent discovery cohorts of European women (8,979) for stress incontinence, urgency incontinence, and any incontinence phenotypes. We conducted replication in 6 additional studies of European ancestry (4,069). We collected bladder biopsies from women with incontinence (50) to further investigate bladder expression of implicated genes and pathways and used symptom questionnaires for phenotyping. We conducted meta-analyses using inverse variance fixed effects models and whole transcriptome analyses using Affymetrix® arrays with replication with TaqMan® polymerase chain reaction. RESULTS: In the discovery stage, we identified 16 single nucleotide polymorphisms genotyped or imputed at 5 loci that reached genome-wide significance (p <5×10-8). In replication, rs138724718 on chromosome 2 near the macrophage receptor with collagenous structure (MARCO) gene (replication p=0.003) was associated with stress incontinence. In addition, rs34998271 on chromosome 6 near the endothelin 1 (EDN1) gene (replication p=0.0008) was associated with urgency incontinence. In combined meta-analyses of discovery and replication cohorts, associations with genome-wide significance for these 2 single nucleotide polymorphisms were confirmed. Transcriptomics analyses showed differential expression of 7 of 19 genes in the endothelin pathway between stress and urgency incontinence (p <0.0001). CONCLUSIONS: We uncovered 2 new risk loci near the genes endothelin 1 (EDN1), associated with urgency incontinence, and macrophage receptor with collagenous structure (MARCO), associated with stress incontinence. These loci are biologically plausible given their roles in smooth muscle contraction and innate host defense, respectively.

Self-Management for Men With Lower Urinary Tract Symptoms: A Systematic Review and Meta-Analysis.

PURPOSE: Lower urinary tract symptoms are very common in older men. We conducted a systematic review and meta-analysis to evaluate the effects of self-management interventions on these symptoms. METHODS: We included randomized controlled trials comparing the effect of self-management interventions (alone or combined with drug therapy) with usual care or drug therapy alone in men with lower urinary tract symptoms. Two independent reviewers screened retrieved articles, extracted data, and assessed the risk of bias of included studies. The primary outcome was lower urinary tract symptom severity. Where data were available, we calculated mean differences (MDs) between the interventions. RESULTS: Analyses were based on 8 studies among 1,006 adult men. Seven of these studies were judged to be at high risk in 2 of the 7 domains of bias. The nature of the self-management interventions varied across studies. There was a clinically important reduction in the 35-point International Prostate Symptom Score at 6 months favoring self-management interventions compared with usual care (MD = -7.4; 95% CI, -8.8 to -6.1; 2 studies). The reduction in score with self-management was similar to that achieved with drug therapy at 6 to 12 weeks (MD = 0.0; 95% CI, -2.0 to 2.0; 3 studies). Self-management had a smaller, additional benefit at 6 weeks when added to drug therapy (MD = -2.3; 95% CI, -4.1 to -0.5; 1 study). CONCLUSIONS: We found moderate-quality evidence (suggesting reasonable certainty in estimates) for the effectiveness of self-management for treating lower urinary tract symptoms in men. We therefore recommend the use of self-management interventions for this patient population.

The Impact of Nocturia on Mortality: A Systematic Review and Meta-Analysis.

PURPOSE: Nocturia (waking from sleep at night to void) is a common cause of sleep disruption associated with increased comorbidity and impaired quality of life. However, its impact on mortality remains unclear. We performed a systematic review and meta-analysis to evaluate the association of nocturia with mortality as a prognostic factor and a causal risk factor. MATERIALS AND METHODS: We searched PubMed®, Scopus®, CINAHL® (Cumulative Index of Nursing and Allied Health Literature) and major conference abstracts up to December 31, 2018. Random effects meta-analyses were done to address the adjusted RR of mortality in people with nocturia. Meta-regression was performed to explore potential determinants of heterogeneity, including the risk of bias. We applied the GRADE (Grades of Recommendation, Assessment, Development and Evaluation) framework to rate the quality of evidence for nocturia as a prognostic risk factor for mortality and separately as a cause of mortality. RESULTS: Of the 5,230 identified reports 11 observational studies proved eligible for inclusion. To assess nocturia 10 studies used symptom questionnaires and 1 used frequency-volume charts. Nocturia was defined as 2 or more episodes per night in 6 studies (55%) and as 3 or more episodes per night in 5 (45%). Pooled estimates demonstrated a RR of 1.27 (95% CI 1.16-1.40, I2=48%) with an absolute 1.6% and 4.0% 5-year mortality difference in individuals 60 and 75 years old, respectively. The pooled estimates of relative risk did not differ significantly across varying age, gender, followup, nocturia case definition, risk of bias or study region. We rated the quality of evidence for nocturia as a prognostic factor as moderate and as a cause of mortality as very low. CONCLUSIONS: Nocturia is probably associated with an approximately 1.3-fold increased risk of death.

The Impact of Nocturia on Falls and Fractures: A Systematic Review and Meta-Analysis.

PURPOSE: Although nocturia is associated with various comorbidities, its impact on falls and fractures remains unclear. We performed a systematic review and meta-analysis to evaluate the association between nocturia and falls and fractures as a prognostic and as a causal risk factor. MATERIALS AND METHODS: We searched PubMed®, Scopus®, CINAHL (Cumulative Index to Nursing and Allied Health Literature) and abstracts of major urological meetings up to December 31, 2018. We conducted random effects meta-analyses of adjusted relative risks of falls and fractures. We applied the GRADE (Grading of Recommendations, Assessment, Development and Evaluation) approach to rate the quality of evidence for nocturia as a prognostic and causal factor of falls and fractures. RESULTS: Among 5,230 potential reports 9 observational longitudinal studies provided data on the association between nocturia and falls or fractures (1 for both, 4 for falls, 4 for fractures). Pooled estimates demonstrated a risk ratio of 1.20 (95% CI 1.05-1.37, I2=51.7%, annual risk difference 7.5% among the elderly) for association between nocturia and falls and 1.32 (95% CI 0.99-1.76, I2=57.5%, annual risk difference 1.2%) for association between nocturia and fractures. Subgroup analyses showed no significant effect modification by age, gender, followup time, nocturia case definition or risk of bias. We rated the quality of evidence for nocturia as a prognostic factor as moderate for falls and low for fractures, and as very low as a cause of falls/fractures. CONCLUSIONS: Nocturia is probably associated with an approximately 1.2-fold increased risk of falls and possibly an approximately 1.3-fold increased risk of fractures.

Long-term risks of stress and urgency urinary incontinence after different vaginal delivery modes.

BACKGROUND: Although operative delivery increases the risk of immediate pelvic floor trauma, no previous studies have adequately compared directly the effects of different kinds of instrumental vaginal deliveries on stress urinary incontinence and/or urgency urinary incontinence. OBJECTIVE(S): The objectives of the study were to estimate and compare the impact of different kinds of vaginal deliveries, including spontaneous, vacuum, and forceps, on stress and urgency urinary incontinence. STUDY DESIGN: All women aged 20 years or older, living in 1 county in Norway were invited to participate in 2 surveys addressing stress and urgency urinary incontinence using validated questions, "Do you leak urine when you cough, sneeze, laugh, or lift something heavy?" and "Do you have involuntary loss of urine in connection with sudden and strong urge to void?" with response options yes or no. Incontinence data were linked to the Medical Birth Registry of Norway. For this study, we included only women who had a history of vaginal birth(s). Case definitions for stress and urgency urinary incontinence were moderate to severe based on Sandvik Severity Index (slight, moderate, severe). We adjusted analyses for age, parity, body mass index, and time since last delivery and addressed effect modification, including an age threshold of 50 years. RESULTS: The final analysis included 13,694 women of whom 12.7% reported stress urinary incontinence and 8.4% urgency urinary incontinence. Among women aged younger than 50 years, there was a statistically significant difference in the risk of stress urinary incontinence for forceps delivery (odds ratio, 1.42, 95% confidence interval, 1.09-1.86, absolute difference 5.0%) but not for vacuum (odds ratio, 0.80, 95% confidence interval, 0.59-1.09) when compared with spontaneous vaginal delivery. Among women aged younger than 50 years, forceps also had increased risk for stress urinary incontinence (odds ratio, 1.76, 95% confidence interval, 1.20-2.60) when compared with vacuum. There was no association of stress or urgency urinary incontinence with mode of delivery in women aged 50 years or older. CONCLUSION: For women aged younger than 50 years, forceps delivery is associated with significant increased long-term risk of stress urinary incontinence compared with other vaginal deliveries.

The impact of bariatric surgery on urinary incontinence: a systematic review and meta-analysis.

OBJECTIVES: To systematically review and meta-analyse the impact of bariatric surgery on obese patients with urinary incontinence (UI). METHODS: A search of the Medical Literature Analysis and Retrieval System Online (MEDLINE), the Excerpta Medica dataBASE (EMBASE), Web of Science, Cochrane Central Register of Controlled Trials (CENTRAL), and PubMed to June 2018 was performed using methods pre-published on the International Prospective Register of Systematic Reviews (PROSPERO). Reporting followed the Preferred Reporting Items for Systematic Review and Meta-analysis (PRISMA) guidelines. Studies comparing UI status in obese patients before and after bariatric surgery were included. Primary outcomes were the improvement or complete resolution of any UI, stress UI (SUI), and urgency UI (UUI). Secondary outcomes were validated UI questionnaire scores. The Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach assessed overall quality of evidence. RESULTS: In all, 33 cohort studies (2910 patients) were included (median follow-up 12 months). Bariatric surgery resulted in improvement or resolution of any UI in 56% (95% confidence interval [CI] 48-63%), SUI in 47% (95% CI 34-60%), and UUI in 53% (95% CI 32-73%) of patients. Moreover, bariatric surgery significantly decreased (P < 0.001) questionnaire scores such as: the Urogenital Distress Inventory by 13.4 points (95% CI 7.2-19.6), International Consultation on Incontinence Questionnaire by 4.0 points (95% CI 2.3-5.7), and Incontinence Impact Questionnaire by 5.3 points (95% CI 3.9-6.6). However, worsening or new onset of UI was present in 3% of patients. The quality of evidence was very low for all outcomes. CONCLUSION: Half of obese patients report improvement or resolution of UI after bariatric surgery, but overall the quality of evidence is very low. Comparative studies examining the benefits of bariatric surgery in obese patients with UI are warranted.

Efficacy and safety of artificial urinary sphincter (AUS): Results of a large multi-institutional cohort of patients with mid-term follow-up.

AIMS: To assess efficacy and safety as well as predictive factors of dry rate and freedom from surgical revision in patients underwent AUS placement. The artificial urinary sphincter (AUS) is still considered the standard for the treatment of moderate to severe post-prostatectomy stress urinary incontinence (SUI). However, data reporting efficacy and safety from large series are lacking. METHODS: A multicenter, retrospective study was conducted in 16 centers in Europe and USA. Only primary cases of AUS implantation in non-neurogenic SUI after prostate surgery, with a follow-up of at least 1 year were included. Efficacy data (continence rate, based on pad usage) and safety data (revision rate in case of infection and erosion, as well as atrophy or mechanical failure) were collected. Multivariable analyses were performed in order to investigate possible predictors of the aforementioned outcomes. RESULTS: Eight hundred ninety-two men had primary AUS implantation. At 32 months mean follow-up overall dry rate and surgical revision were 58% and 30.7%, respectively. Logistic regression analysis showed that patients without previous incontinence surgery had a higher probability to be dry after AUS implantation (OR: 0.51, P = 0.03). Moreover institutional case-load was positively associated with dry rate (OR: 1.18; P = 0.005) and freedom from revision (OR: 1.51; P = 0.00). CONCLUSIONS: The results of this study showed that AUS is an effective option for the treatment of SUI after prostate surgery. Moreover previous incontinence surgery and low institutional case-load are negatively associated to efficacy and safety outcomes.

Guideline of guidelines: primary monotherapies for localised or locally advanced prostate cancer.

Decisions regarding the primary treatment of prostate cancer depend on several patient- and disease-specific factors. Several international guidelines regarding the primary treatment of prostate cancer exist; however, they have not been formally compared. As guidelines often contradict each other, we aimed to systematically compare recommendations regarding the different primary treatment modalities of prostate cancer between guidelines. We searched Medline, the National Guidelines Clearinghouse, the library of the Guidelines International Network, and the websites of major urological associations for prostate cancer treatment guidelines. In total, 14 guidelines from 12 organisations were included in the present article. One of the main discrepancies concerned the definition of 'localised' prostate cancer. Localised prostate cancer was defined as cT1-cT3 in most guidelines; however, this disease stage was defined in other guidelines as cT1-cT2, or as any T-stage as long as there is no lymph node involvement (N0) or metastases (M0). In addition, the risk stratification of localised cancer differed considerably between guidelines. Recommendations regarding radical prostatectomy and hormonal therapy were largely consistent between the guidelines. However, recommendations regarding active surveillance, brachytherapy, and external beam radiotherapy varied, mainly as a result of the inconsistencies in the risk stratification. The differences in year of publication and the methodology (i.e. consensus-based or evidence-based) for developing the guidelines might partly explain the differences in recommendations. It can be assumed that the observed variation in international clinical practice regarding the primary treatment of prostate cancer might be partly due to the inconsistent recommendations in different guidelines.

α-Blockers for uncomplicated ureteric stones: a clinical practice guideline.

OBJECTIVE: To develop an evidence-based recommendation concerning the use of α-blockers for uncomplicated ureteric stones based on an up-to-date Cochrane review, as the role of medical expulsive therapy for uncomplicated ureteric stones remains controversial in the light of new contradictory trial evidence. METHODS: We applied the Rapid Recommendations approach to guideline development, which represents an innovative approach by an international collaborative network of clinicians, researchers, methodologists and patient representatives seeking to rapidly respond to new, potentially practice-changing evidence with recommendations developed according to standards for trustworthy guidelines. RESULTS: The panel suggests the use of α-blockers in addition to standard care over standard care alone in patients with uncomplicated ureteric stones (weak recommendation based on low-quality evidence). The panel judged that the net benefit of α-blockers was small and that there was considerable uncertainty about patients' values and preferences. This means that the panel expects that most patients would choose treatment with α-blockers but that a substantial proportion would not. This recommendation applies to both patients in whom the presence of ureteric stones is confirmed by imaging, as well as patients in whom the diagnosis is made based on clinical grounds only. CONCLUSION: The Rapid Recommendations panel suggests the use of α-blockers for patients with ureteric stones. Shared decision-making is emphasised in making the final choice between the treatment options.

Premature Discontinuation of Pediatric Randomized Controlled Trials: A Retrospective Cohort Study.

OBJECTIVES: To determine the proportion of pediatric randomized controlled trials (RCTs) that are prematurely discontinued, examine the reasons for discontinuation, and compare the risk for recruitment failure in pediatric and adult RCTs. STUDY DESIGN: A retrospective cohort study of RCTs approved by 1 of 6 Research Ethics Committees (RECs) in Switzerland, Germany, and Canada between 2000 and 2003. We recorded trial characteristics, trial discontinuation, and reasons for discontinuation from protocols, corresponding publications, REC files, and a survey of trialists. RESULTS: We included 894 RCTs, of which 86 enrolled children and 808 enrolled adults. Forty percent of the pediatric RCTs and 29% of the adult RCTs were discontinued. Slow recruitment accounted for 56% of pediatric RCT discontinuations and 43% of adult RCT discontinuations. Multivariable logistic regression analyses suggested that pediatric RCT was not an independent risk factor for recruitment failure after adjustment for other potential risk factors (aOR, 1.22; 95% CI, 0.57-2.63). Independent risk factors were acute care setting (aOR, 4.00; 95% CI, 1.72-9.31), nonindustry sponsorship (aOR, 4.45; 95% CI, 2.59-7.65), and smaller planned sample size (aOR, 1.05; 95% CI 1.01-1.09, in decrements of 100 participants). CONCLUSION: Forty percent of pediatric RCTs were discontinued prematurely, owing predominately to slow recruitment. Enrollment of children was not an independent risk factor for recruitment failure.

Agreements between Industry and Academia on Publication Rights: A Retrospective Study of Protocols and Publications of Randomized Clinical Trials.

BACKGROUND: Little is known about publication agreements between industry and academic investigators in trial protocols and the consistency of these agreements with corresponding statements in publications. We aimed to investigate (i) the existence and types of publication agreements in trial protocols, (ii) the completeness and consistency of the reporting of these agreements in subsequent publications, and (iii) the frequency of co-authorship by industry employees. METHODS AND FINDINGS: We used a retrospective cohort of randomized clinical trials (RCTs) based on archived protocols approved by six research ethics committees between 13 January 2000 and 25 November 2003. Only RCTs with industry involvement were eligible. We investigated the documentation of publication agreements in RCT protocols and statements in corresponding journal publications. Of 647 eligible RCT protocols, 456 (70.5%) mentioned an agreement regarding publication of results. Of these 456, 393 (86.2%) documented an industry partner's right to disapprove or at least review proposed manuscripts; 39 (8.6%) agreements were without constraints of publication. The remaining 24 (5.3%) protocols referred to separate agreement documents not accessible to us. Of those 432 protocols with an accessible publication agreement, 268 (62.0%) trials were published. Most agreements documented in the protocol were not reported in the subsequent publication (197/268 [73.5%]). Of 71 agreements reported in publications, 52 (73.2%) were concordant with those documented in the protocol. In 14 of 37 (37.8%) publications in which statements suggested unrestricted publication rights, at least one co-author was an industry employee. In 25 protocol-publication pairs, author statements in publications suggested no constraints, but 18 corresponding protocols documented restricting agreements. CONCLUSIONS: Publication agreements constraining academic authors' independence are common. Journal articles seldom report on publication agreements, and, if they do, statements can be discrepant with the trial protocol.

Premature Discontinuation of Randomized Trials in Critical and Emergency Care: A Retrospective Cohort Study.

OBJECTIVES: Randomized clinical trials that enroll patients in critical or emergency care (acute care) setting are challenging because of narrow time windows for recruitment and the inability of many patients to provide informed consent. To assess the extent that recruitment challenges lead to randomized clinical trial discontinuation, we compared the discontinuation of acute care and nonacute care randomized clinical trials. DESIGN: Retrospective cohort of 894 randomized clinical trials approved by six institutional review boards in Switzerland, Germany, and Canada between 2000 and 2003. SETTING: Randomized clinical trials involving patients in an acute or nonacute care setting. SUBJECTS AND INTERVENTIONS: We recorded trial characteristics, self-reported trial discontinuation, and self-reported reasons for discontinuation from protocols, corresponding publications, institutional review board files, and a survey of investigators. MEASUREMENTS AND MAIN RESULTS: Of 894 randomized clinical trials, 64 (7%) were acute care randomized clinical trials (29 critical care and 35 emergency care). Compared with the 830 nonacute care randomized clinical trials, acute care randomized clinical trials were more frequently discontinued (28 of 64, 44% vs 221 of 830, 27%; p = 0.004). Slow recruitment was the most frequent reason for discontinuation, both in acute care (13 of 64, 20%) and in nonacute care randomized clinical trials (7 of 64, 11%). Logistic regression analyses suggested the acute care setting as an independent risk factor for randomized clinical trial discontinuation specifically as a result of slow recruitment (odds ratio, 4.00; 95% CI, 1.72-9.31) after adjusting for other established risk factors, including nonindustry sponsorship and small sample size. CONCLUSIONS: Acute care randomized clinical trials are more vulnerable to premature discontinuation than nonacute care randomized clinical trials and have an approximately four-fold higher risk of discontinuation due to slow recruitment. These results highlight the need for strategies to reliably prevent and resolve slow patient recruitment in randomized clinical trials conducted in the critical and emergency care setting.