Partial Nephrectomy versus Thermal Ablation for Clinical Stage T1 Renal Masses: Systematic Review and Meta-Analysis of More than 3,900 Patients.

PURPOSE: A systematic review and meta-analysis of clinical trials was undertaken to compare percutaneous thermal ablation versus partial nephrectomy (PN) for stage T1 renal tumors. MATERIALS AND METHODS: A comprehensive search of major databases was conducted from October 2000 to July 2016. Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines were followed. Incidences of all-cause mortality (ACM), cancer-specific mortality (CSM), local recurrence (LR), and metastases, as well as complication rates and changes in estimated glomerular filtration rate (eGFR), were evaluated. RESULTS: Inclusion criteria were met by 15 of 961 papers. These studies represented 3,974 patients who had undergone an ablative procedure (cryoablation or radiofrequency ablation; n = 1,455; 37%) or PN (n = 2,519; 63%). ACM and CSM rates were higher for ablation than for PN (hazard ratio [HR], 2.11; 95% confidence interval [CI], 1.54-2.87 [P < .05]; HR, 3.84; 95% CI, 1.66-8.88 [P < .05], respectively). No statistically significant difference in LR rate or risk of metastasis was seen between ablation and PN (HR, 1.32; 95% CI, 0.79-2.22 [P = .22]; HR, 1.83; 95% CI, 0.67-5.01 [P = 0.23], respectively). Complication rates were lower for ablation than for PN (13% vs 17.6%; odds ratio, 0.49; 95% CI, 0.25-0.94; P < .05). A significantly greater decrease in eGFR was observed after PN (13.09 mL/min/1.73 m2) vs ablation therapy (4.47 mL/min/1.73 m2). CONCLUSIONS: Thermal ablation showed no significant difference in LR or metastases compared with PN. Thermal ablation was associated with a lower morbidity rate and a lesser reduction in eGFR compared with PN, but with higher ACM and CSM rates.

Dermatologic manifestations of solid organ transplantation-associated graft-versus-host disease: A systematic review.

BACKGROUND: Graft-versus-host-disease (GVHD) after solid organ transplantation (SOT) is extremely rare. OBJECTIVE: To investigate the dermatologic manifestations and clinical outcomes of SOT GVHD. METHODS: Systematic literature review of SOT GVHD. RESULTS: After full-text article review, we included 61 articles, representing 115 patients and 126 transplanted organs. The most commonly transplanted organ was the liver (n = 81). Among 115 patients, 101 (87.8%) developed skin involvement. The eruption appeared an average of 48.3 days (range, 3-243 days) posttransplant and was pruritic in 5 of 101 (4.9%) cases. The eruption was described as morbilliform in 2 patients (1.9%), confluent in 6 (5.9%), and desquamative in 4 (3.9%) cases. In many cases, specific dermatologic descriptions were lacking. The mortality rate was 72.2%. Relative time of death was reported in 23 patients who died during the follow-up period. These patients died an average of 99.2 days (range, 22-270 days) posttransplant, or 50.9 days after the appearance of dermatologic symptoms. Frequent causes of death were sepsis and multiorgan failure. LIMITATIONS: Incomplete descriptions of skin findings and potential publication bias resulting in publication of only the most severe cases. CONCLUSIONS: GVHD is a potentially fatal condition that can occur after SOT and often presents with a skin rash. We recommend that dermatologists have a low threshold to consider and pursue this diagnosis in the setting of post-SOT skin eruption.

Flat Epithelial Atypia on Core Biopsy and Upgrade to Cancer: a Systematic Review and Meta-Analysis.

BACKGROUND: No consensus exists on whether flat epithelial atypia (FEA) diagnosed percutaneously should be surgically excised. A systematic review and meta-analysis of the frequency of upgrade to cancer or an atypical ductal hyperplasia (ADH) at surgical excision of FEA was performed. METHODS: Embase, MEDLINE, Scopus, and Web of Science databases from January 2003 to November 2015 were searched. The inclusion criteria required a manuscript in English with original data on FEA diagnosed percutaneously, data including the presence or absence of other concurrent high-risk lesions, and data including outcome of cancer at surgical excision. Studies were assessed for quality, and two reviewers extracted data. Random-effects meta-analysis was used to pool estimates. The impact of study-level characteristics was assessed by stratified meta-analysis and meta-regression. RESULTS: The inclusion criteria was met by 32 studies. A total of 1966 core needle biopsies showed pure FEA, and 1517 (77%) showed surgical excision. The proportions of patients with upgrade to cancer varied from 0 to 42%, with an overall pooled estimate of 11.1%. Heterogeneity was observed, with the greatest impact based on whether a study included cases of FEA diagnosed before 2003. With restriction of the investigation to 16 higher-quality studies, the cancer upgrade pooled estimate was 7.5% (95% confidence interval [CI], 5.4-10.4%), and the rate of invasive cancer was 3% (95% CI 1.9-4.5%). For upgrade to ADH, data from 22 studies including 937 patients were analyzed. The proportion of patients upgraded to ADH ranged from 0 to 60%, with a pooled estimate of 17.9% overall and 18.6% among high-quality studies. CONCLUSIONS: With patient management change potential for approximately 25% of patients, this analysis supports a general recommendation for surgical excision of FEA diagnosed by core biopsy.

Clinicopathologic features of breast cancers that develop in women with previous benign breast disease.

BACKGROUND: Women with benign breast disease (BBD) have an increased risk of developing breast cancer (BC). Nearly 30% of all BCs develop in women with prior BBD. Information regarding features of the expected number of BCs after BBD would enhance individualized surveillance and prevention strategies for these women. In the current study, the authors sought to characterize BCs developing in a large cohort of women with BBD. METHODS: The current study cohort included 13,485 women who underwent breast biopsy for mammographic or palpable concerns between 1967 and 2001. Biopsy slides were reviewed and classified as nonproliferative disease, proliferative disease without atypia, or atypical hyperplasia. BCs were identified by follow-up questionnaires, medical records, and Tumor Registry data. BC tissues were obtained and reviewed. RESULTS: With median follow-up of 15.8 years, 1273 women developed BC. The majority of BCs were invasive (81%), of which 61% were ductal, 13% were mixed ductal/lobular, and 14% were lobular. Approximately two-thirds of the BC cases were intermediate or high grade, and 29% were lymph node positive. Cancer characteristics were similar across the 3 histologic categories of BBD, with a similar frequency of ductal carcinoma in situ, invasive disease, tumor size, time to invasive BC, histologic type of BC, lymph node positivity, and human epidermal growth factor receptor 2 positivity. Women with atypical hyperplasia were found to have a higher frequency of estrogen receptor-positive BC (91%) compared with women with proliferative disease without atypia (80%) or nonproliferative disease (85%) (P = .02). CONCLUSIONS: A substantial percentage of all BCs develop in women with prior BBD. The majority of BCs after BBD are invasive tumors of ductal type, with a substantial number demonstrating lymph node positivity. Of all the BCs in the current study, 84% were estrogen receptor positive. Prevention therapy should be strongly encouraged in higher-risk women with BBD.

Hysteroscopic Morcellation Versus Resection for the Treatment of Uterine Cavitary Lesions: A Systematic Review and Meta-analysis.

This systematic review and meta-analysis compares hysteroscopic morcellation with electrosurgical resection to treat uterine cavitary lesions. A search of Ovid MEDLINE, Ovid Embase, Scopus, and Web of Science was conducted through August 18, 2015, for randomized controlled trials (RCTs) and prospective and retrospective studies, regardless of surgical indication and study language or sample size. Seven studies were eventually included (4 RCTs and 3 retrospective observational studies), enrolling 650 women. The meta-analysis showed that the total procedure time was significantly shorter for morcellation than for resection (weighted mean difference = 9.36 minutes; 95% confidence interval [CI], -15.08 to -3.64). When reviewing RCTs only, intrauterine morcellation was associated with a smaller fluid deficit and lower odds of incomplete lesion removal. This difference was not statistically significant in observational studies. There was no significant difference in the odds of surgical complications (odds ratio = 0.72; 95% CI, 0.20-2.57) or the number of insertions (weighted mean difference = -3.04; 95% CI, -7.86-1.78). In conclusion, compared with hysteroscopic resection, hysteroscopic morcellation is associated with a shorter operative time and possibly lower odds of incomplete lesion removal. The certainty in evidence was limited by heterogeneity and the small sample size.

Misrepresentation in multidisciplinary pain medicine fellowship applications to a single academic program.

BACKGROUND AND OBJECTIVES: Publication misrepresentation by residency applicants has been well documented, but fewer studies have investigated it in fellowship applicants, specifically in pain medicine. We therefore sought to evaluate the demographics of pain medicine fellowship applicants and the type, number, and accuracy of referenced publications they reported. METHODS: Applications to the Multidisciplinary Pain Medicine fellowship program in the Mayo School of Graduate Medical Education, Rochester, Minnesota were reviewed for three consecutive academic years (2009-2012). Demographic information and publications claimed by applicants were compiled, and publications were scrutinized by a medical librarian for accuracy. RESULTS: Over a 3-year period, 179 fellowship applications were received. Of the 179 applicants, more than half (106 [59%]) listed at least one publication. Of 324 listed publications, 263 were verifiable; of these, 14 (5.3%) were deemed fraudulent, and six (2.3%) contained an inaccuracy possibly conferring a competitive advantage. In our small sample size, we found no difference in the rate of publications or in the accuracy of listed publications across subspecialties, or between US medical graduates and international medical graduates. CONCLUSIONS: The lack of national data, specifically on applicant misrepresentation, due to the heretofore absence of a universal application process or match, impedes assessment of the extent to which these findings are representative of the national applicant pool. We observed notable trends (few female applicants; numerous international medical graduate applicants) different from those reported by other specialties. Despite the low rate (5.3%) of fraudulent publications, fellowship program directors and selection committees should be aware of this possibility to ensure selection of fellows with the highest degree of professional and ethical integrity.

The effects of stretching on performance.

Stretching long has been commonplace in the training programs of recreational and competitive athletes. Its role in performance enhancement has been debated. This review discusses the literature concerning the effects of static, dynamic, and proprioceptive neuromuscular facilitation stretching on performance in three categories of sporting activity: strength- and power-dominant, speed- and agility-dominant, and endurance-dominant activities.

Converting an intranet site to the cloud: using CampusGuides to refresh a library portal.

After a major redesign project in 2002, Mayo Clinic Libraries' heavily used intranet portal remained largely static. Library staff were unable to make substantive design changes or introduce tools that would make the content more dynamic. CampusGuides offered a practical, user-friendly, web-based solution to add dynamic content to the library site. A task force was formed both to establish design and style guidelines that would integrate with the library site and to plan the conversion of content to CampusGuides. Converting intranet site content to CampusGuides gave the task force the opportunity to examine, re-imagine, and revitalize site content.

A problem of proportions: estimates of metabolic associated fatty liver disease and liver fibrosis in Australian adults in the nationwide 2012 AusDiab Study.

Metabolic Associated Fatty Liver Disease (MAFLD) is the most common cause of liver disease in Australia, but prevalence data are limited. We aimed to describe the frequency of alanine aminotransferase (ALT) elevation, and MAFLD within a large prospective Australian cohort. Cross-sectional analysis of the 2012 survey of the Australian Diabetes, Obesity and Lifestyle (AusDiab) study which included 4747 Australian adults (aged 34-97 yrs) was performed. Frequency of ALT elevation (men ≥ 40 IU/L, women ≥ 30 IU/L) and MAFLD (Fatty Liver Index (FLI) > 60 alongside metabolic risk factors) was determined and risk of advanced fibrosis stratified using the BARD score. Elevated ALT was found in 13% of the cohort, including 22% of people with diabetes, 18% with obesity, and 17% with the metabolic syndrome. 37% of the cohort had MAFLD, and those with MAFLD were more likely to be older (OR 1.01 per 1 year (95% CI 1.00-1.02)), male (OR 1.37 (95% CI 1.17-1.59)), have ALT elevation (OR 3.21 (95% CI 2.59-3.99)), diabetes (OR 3.39 (95% CI 2.61-4.39)), lower HDL-C (OR 0.15 per 1 mmol/L (95% CI 0.12-0.19)), higher diastolic blood pressure (OR 1.05 per 10 mmHg (95% CI 1.05-1.06)), a sedentary lifestyle (OR 1.99 (95% CI 1.59-2.50)) and less likely to have tertiary education (OR 0.81 (95% CI 0.7-0.94) compared to those without MAFLD. Of those with MAFLD, 61% had a BARD score suggesting risk of advanced fibrosis and 22% had an elevated ALT. Over 10% of this Australian cohort had elevated ALT, and 37% had MAFLD, with many at risk for advanced fibrosis.

Teaching Web 2.0 beyond the library: adventures in social media, the class.

Librarians at the Mayo Clinic developed customized Web 2.0 courses for library staff, health science faculty, and nurse educators. As demand for this type of training spread across the institution, a single, self-paced class was developed for all employees. The content covered the typical Web 2.0 and social media tools (e.g., blogs, really simple syndication [RSS], wikis, social networking tools) emphasizing the organization's social media guidelines. The team consulted with the public affairs department to develop the class and coordinate marketing and advertising. The eight-module, blog-based course was introduced to all employees in 2010. Employees completing each module and passing a brief assessment receive credit on their employee transcript. Libraries staff provided support to participants throughout the duration of the course through chat widgets, e-mail, and blog comments. The results show that even though a high number of learners accessed the course, the completion percentage was low since there was no requirement to complete the course. Deploying a single, self-paced course for a large institution is an enormous undertaking, requiring the support of high level administration, managers, and employees.

Association Between Egg Consumption and Risk of Cardiovascular Outcomes: A Systematic Review and Meta-Analysis.

INTRODUCTION: Considerable controversy remains on the relationship between egg consumption and cardiovascular disease risk. The objective of this systematic review and meta-analysis was to explore the association between egg consumption and overall cardiovascular disease events. METHODS: We systematically searched Ovid MEDLINE, Ovid Embase, Ovid Cochrane Database of Systematic Reviews, Scopus, and Web of Science from database inception in 1966 through January 2020 for observational studies that reported the association between egg consumption and cardiovascular disease events. Two investigators independently reviewed data. Conflicts were resolved through consensus. Random-effects meta-analyses were used. Sources of heterogeneity were analyzed. RESULTS: We identified 23 prospective studies with a median follow-up of 12.28 years. A total of 1,415,839 individuals with a total of 123,660 cases and 157,324 cardiovascular disease events were included. Compared with the consumption of no or 1 egg/day, higher egg consumption (more than 1 egg/day) was not associated with significantly increased risk of overall cardiovascular disease events (pooled hazard ratios, 0.99; 95% confidence interval, 0.93-1.06; P < .001; I² = 72.1%). Higher egg consumption (more than 1 egg/day) was associated with a significantly decreased risk of coronary artery disease (pooled hazard ratios, 0.89; 95% confidence interval, 0.86-0.93; P < .001; I² = 0%), compared with consumption of no or 1 egg/day. CONCLUSIONS: Our analysis suggests that higher consumption of eggs (more than 1 egg/day) was not associated with increased risk of cardiovascular disease, but was associated with a significant reduction in risk of coronary artery disease.

The association between sarcopenia and bladder cancer-specific mortality and all-cause mortality after radical cystectomy: A systematic review and meta-analysis.

Objective: To compare cancer-specific mortality (CSM) and all-cause mortality (ACM) between patients with and without sarcopenia who underwent radical cystectomy for bladder cancer. Materials and methods: We performed a systematic review and meta-analysis of original articles published from October 2010 to March 2019 evaluating the effect of sarcopenia on CSM and ACM. We extracted hazard ratios (HRs) and 95% confidence intervals (CIs) for CSM and ACM from the included studies. Heterogeneity amongst studies was measured using the Q-statistic and the I 2 index. Meta-analysis was performed using a random-effects model if heterogeneity was high and fixed-effects models if heterogeneity was low. Results: We identified 145 publications, of which five were included in the meta-analysis. These five studies represented 1447 patients of which 453 were classified as sarcopenic and 534 were non-sarcopenic. CSM and ACM were increased in sarcopenic vs non-sarcopenic patients (HR 1.64, 95% CI 1.30-2.08, P < 0.01 and HR 1.41, 95% CI 1.22-1.62, P < 0.01, respectively). Conclusions: Sarcopenia is significantly associated with increased CSM and ACM in bladder cancer. Identifying patients with sarcopenia will augment preoperative counselling and planning. Further studies are required to evaluate targeted interventions in patients with sarcopenia to improve clinical outcomes. Abbreviations: ACM: all-cause mortality; ASA: American Association of Anesthesiologists; BMI: body mass index; CCI: Charlson Comorbidity Index; CSM: cancer-specific mortality; CSS: cancer-specific survival; ECOG: Eastern Cooperative Oncology Group; HR: hazard ratio; NAC: neoadjuvant chemotherapy; NIH: National Institutes of Health; OS: overall survival; RC: radical cystectomy; RCT: randomised controlled trial; SMI: Skeletal Muscle Index.

Association between short and long sleep durations and cardiovascular outcomes: a systematic review and meta-analysis.

BACKGROUND: A shorter sleep duration has been identified as a risk factor for cardiovascular diseases and increased mortality. It has been hypothesized that a short sleep duration may be linked to changes in ghrelin and leptin production, leading to an alteration of stress hormone production. Here, we conducted a systematic review and meta-analysis to investigate the potential relationship between a sleep duration and cardiovascular disease mortality. METHODS: We conducted a comprehensive search of Ovid Medline In-Process and other non-indexed citations, Ovid MEDLINE, Ovid Embase, Ovid Cochrane Central Register of Controlled Trials, and Scopus from database inception to March 2017. Observational studies were included if the studies reported hazard ratios or odds ratios of the associations between sleep durations (short and long) and cardiovascular disease mortality. Data were extracted by a reviewer and then reviewed by two separate reviewers. Conflicts were resolved through consensus. Using the DerSimonian and Laird random effects models, we calculated pooled hazard ratios and pooled odds ratios with 95% confidence intervals (CI). Subgroup analyses were performed to explore potential sources of heterogeneity. The quality of the included studies and publication bias were assessed. RESULTS: In total, our meta-analysis included 19 studies (31 cohorts) with a total of 816,995 individuals with 42,870 cardiovascular disease mortality cases. In pooled analyses, both short (risk ratio 1.19; 95% CI 1.13 to 1.26, P<0.001, I2=30.7, Pheterogeneity=0.034), and long (risk ratio 1.37; 95% CI 1.23 to 1.52, P<0.001, I2=79.75, Pheterogeneity<0.001) sleep durations were associated with a greater risk of cardiovascular disease mortality. CONCLUSIONS: Both short (<7 hours) and long sleep durations (>9 hours) can increase the risk of overall cardiovascular disease mortality, particularly in Asian populations and elderly individuals. Future epidemiological studies would ideally include objective sleep measurements, rather than self-report measures, and all potential confounders, such as genetic variants.

Potentially Modifiable Risk Factors for Long-Term Cognitive Impairment After Critical Illness: A Systematic Review.

Long-term cognitive impairment is common in survivors of critical illness. Little is known about the etiology of this serious complication. We sought to summarize current scientific knowledge about potentially modifiable risk factors during intensive care unit (ICU) treatment that may play a substantial role in the development of long-term cognitive impairment. All searches were run on October 1, 2017. The search strategy included Ovid MEDLINE, Ovid Embase, Ovid CDR, Cochrane Central Register of Controlled Trials and Database of Abstracts of Reviews of Effect, Scopus, and Web of Science, and included MeSH headings and keywords related to intensive care, critical care, and cognitive disorders. Searches were restricted to adult subjects. Inclusion required follow-up cognitive evaluation at least 2 months after ICU discharge. Studies assessing patients with cardiac arrest, traumatic brain injury, and cardiac surgery history were excluded. The search strategy resulted in 3180 studies. Of these, 28 studies (.88%) met our inclusion criteria and were analyzed. Delirium and duration of delirium were associated with long-term cognitive impairment after ICU admission in 6 of 9 studies in which this factor was analyzed. Weaker and more inconsistent associations have been reported with hypoglycemia, hyperglycemia, fluctuations in serum glucose levels, and in-hospital acute stress symptoms. Instead, most of the studies did not find significant associations between long-term cognitive impairment and mechanical ventilation; use of sedatives, vasopressors, or analgesic medications; enteral feeding; hypoxia; extracorporeal membrane oxygenation; systolic blood pressure; pulse rate; or length of ICU stay. Prolonged delirium may be a risk factor for long-term cognitive impairment after critical illness, though this association has not been entirely consistent across studies. Other potentially preventable factors have not been shown to have strong or consistent associations with long-term cognitive dysfunction in survivors of critical illness.

Comparison of Abiraterone Acetate and Docetaxel with Androgen Deprivation Therapy in High-risk and Metastatic Hormone-naïve Prostate Cancer: A Systematic Review and Network Meta-analysis.

CONTEXT: Randomized clinical trials have recently examined the benefit of adding docetaxel or abiraterone to androgen deprivation therapy (ADT) in hormone-naïve advanced prostate cancer (PCa). OBJECTIVE: To perform a systematic review and network meta-analysis of randomized clinical trials, indirectly evaluating overall survival (OS) for men treated with abiraterone acetate plus prednisone/prednisolone with ADT (Abi-ADT) versus docetaxel with ADT (Doce-ADT) in hormone-naïve high-risk and metastatic PCa. EVIDENCE ACQUISITION: Medline, Embase, Web of Science, Scopus, and Clinicaltrials.gov databases were searched in August 2017. We pooled results using the inverse variance technique and random-effects models. The Bucher technique for indirect treatment comparison was used to compare Abi-ADT with Doce-ADT. A priori subgroup and sensitivity analyses were performed. EVIDENCE SYNTHESIS: Overall, 6067 patients from five trials were included: 1181 (19.5%) patients who received Doce-ADT, 1557 (25.7%) patients who received Abi-ADT, and 3329 (54.9%) patients who received ADT-alone. There was a total of 1921 deaths: 391 in the Doce-ADT group, 353 in the Abi-ADT group, and 1177 in the ADT-only group. The pooled hazard ratio (HR) for OS was 0.75 (95% confidence interval [CI]: 0.63-0.91, I2=51%, 3 trials, 2951 patients) for Doce-ADT versus ADT-alone and 0.63 (95% CI: 0.55-0.72, I2=0%, 2 trials, 3116 patients) for Abi-ADT versus ADT-alone. The indirect comparison of Abi-ADT to Doce-ADT demonstrated no statistically significant difference in OS between these approaches (HR: 0.84, 95% CI: 0.67-1.06). Findings were similar in various a priori subset analyses, including patients with metastatic disease. Bayesian analyses demonstrated comparable results (HR: 0.83, 95% CI: 0.63-1.16). Despite the lack of statistical significance, Surface Under the Cumulative Ranking Analysis demonstrated an 89% probability that Abi-ADT was preferred. CONCLUSIONS: We did not identify a significant difference in OS between Abi-ADT and Doce-ADT for men with hormone-naïve high-risk or metastatic PCa, although Bayesian analysis demonstrates a high likelihood that Abi-ADT was preferred. PATIENT SUMMARY: We synthesized the evidence available from studies examining the administration of docetaxel or abiraterone in combination with hormonal therapy for patients with newly diagnosed, advanced prostate cancer. While these studies did not directly compare these agents, we used methodological techniques to indirectly compare them and found no significant difference in overall survival.

Systematic review and meta-analysis of the effect of SGLT-2 inhibitors on microvascular outcomes in patients with type 2 diabetes: a review protocol.

INTRODUCTION: Sodium glucose cotransporter 2 (SGLT-2) inhibitors are a relatively new drug-class of glucose-lowering medications. Several trials and systematic reviews have demonstrated their beneficial effect on some macrovascular outcomes. Their effect on microvascular outcomes has been reported as positive in several trials, however, their effect remains uncertain. Therefore, we report the protocol of a systematic review and meta-analysis aimed at determining the effect of SGLT-2 inhibitors regarding patient-important and surrogate microvascular outcomes in patients with type 2 diabetes. METHODS AND ANALYSIS: A comprehensive search will be conducted to find eligible articles from each database's earliest inception to November 2017. These databases will include Ovid, MEDLINE, EMBASE, Web of Science, and Scopus. We will search for randomized controlled trials (RCTs) that compare any of the SGLT-2 inhibitors with any other active treatment or placebo assessing microvascular outcomes in either their primary or secondary outcomes. Reviewers working independently and in duplicate will review all abstracts, and full-text manuscripts for eligibility, and will systematically extract the data and will assess the risk of bias in the included studies. Random-effects models will also be used. ETHICS AND DISSEMINATION: The results of the systematic review will be disseminated via publication in a peer-reviewed journal regardless of outcome and will be presented at relevant conferences. The data we will use do not include individual patient data, so ethical approval is not required PROSPERO REGISTRATION NUMBER: CRD42017076460.

First-line Systemic Therapy for Metastatic Renal Cell Carcinoma: A Systematic Review and Network Meta-analysis.

CONTEXT: In the last decade, there has been a proliferation of treatment options for metastatic renal cell carcinoma (mRCC). However, direct comparative data are lacking for most of these agents. OBJECTIVE: To indirectly compare the efficacy and safety of systemic therapies used in the first-line treatment of mRCC. EVIDENCE ACQUISITION: Medline, EMBASE, Web of Science, and Scopus databases were searched using the OvidSP platform for studies indexed from database inception to October 23, 2017. Abstracts of conferences of relevant medical societies were included, and the systematic search was supplemented by hand search. For the systematic review, we identified any parallel-group randomized controlled trials assessing first-line systemic therapy. For network meta-analysis, we limited these to a clinically-relevant network based on standard practice patterns. Progression-free survival (PFS) was the primary outcome. Overall survival (OS) and grade 3 and 4 adverse events (AEs) were secondary outcomes. EVIDENCE SYNTHESIS: In total, 37 trials reporting on 13 128 patients were included in the systematic review. The network meta-analysis comprised 10 trials reporting on 4819 patients. For PFS (10 trials, 4819 patients), there was a high likelihood (SUCRA 91%) that cabozantinib was the preferred treatment. For OS (5 trials, 3379 patients), there was a 48% chance that nivolumab plus ipilimumab was the preferred option. There was a 67% likelihood that nivolumab plus ipilimumab was the best tolerated regime with respect to AEs. CONCLUSIONS: Cabozantinib and nivolumab plus ipilimumab are likely to be the preferred first-line agents for treating mRCC; however, direct comparative studies are warranted. These findings may provide guidance to patients and clinicians when making treatment decisions and may help inform future direct comparative trials. PATIENT SUMMARY: There are many treatment options for patients diagnosed with metastatic renal cell carcinoma. We indirectly compared the available options and found that cabozantinib and nivolumab plus ipilimumab are likely to be preferable choices as the first-line treatment in this situation.

An appraisal of published usability evaluations of electronic health records via systematic review.

OBJECTIVE: In this systematic review, we aimed to evaluate methodological and reporting trends present in the current literature by investigating published usability studies of electronic health records (EHRs). METHODS: A literature search was conducted for articles published through January 2015 using MEDLINE (Ovid), EMBASE, Scopus, and Web of Science, supplemented by citation and reference list reviews. Studies were included if they tested the usability of hospital and clinic EHR systems in the inpatient, outpatient, emergency department, or operating room setting. RESULTS: A total of 4848 references were identified for title and abstract screening. Full text screening was performed for 197 articles, with 120 meeting the criteria for study inclusion. CONCLUSION: A review of the literature demonstrates a paucity of quality published studies describing scientifically valid and reproducible usability evaluations at various stages of EHR system development. A lack of formal and standardized reporting of EHR usability evaluation results is a major contributor to this knowledge gap, and efforts to improve this deficiency will be one step of moving the field of usability engineering forward.

Efficacy of menopausal hormone therapy on sleep quality: systematic review and meta-analysis.

Sleep complaints are reported by 40-60 % of menopausal women. Poor sleep is a risk factor for cardiovascular disease, diabetes, and obesity. The effect of menopausal hormone therapy on sleep quality is unclear. A systematic review and meta-analysis were conducted to summarize the efficacy of menopausal hormone therapy on self-reported sleep quality. Electronic databases (PubMed, Scopus, Ovid MEDLINE, EMBASE, EBM Reviews CENTRAL, and PsycInfo) were searched from 2002 to October 2015. Randomized trials assessing the effect of menopausal hormone therapy with a minimum follow up of 8 weeks were included. Titles, abstracts, and full texts were screened independently and in duplicate. Primary outcome included sleep items within a questionnaire, scale or diary. Standardized mean differences across trials were pooled using random-effects models. The search identified 424 articles, from which 42 trials were included. Seven trials at a moderate to high risk of bias enrolling 15,468 women were pooled in meta-analysis. Menopausal hormone therapy improved sleep quality in women who had vasomotor symptoms at baseline [standardized mean difference -0.54 (-0.91 to -0.18), moderate quality evidence]. No difference was noted when women without such symptoms were analyzed separately or combined. Across 31 sleep quality questionnaires, daytime dysfunction was the most evaluated sleep domain. Menopausal hormone therapy improves sleep in women with concomitant vasomotor symptoms. Heterogeneity of trials regarding study population, formulations, and sleep scales; limit overall certainty in the evidence. Future menopausal hormone therapy trials should include assessment of self-reported sleep quality using standardized scales and adhere to reporting guidelines.

The Association Between Vasectomy and Prostate Cancer: A Systematic Review and Meta-analysis.

Importance: Despite 3 decades of study, there remains ongoing debate regarding whether vasectomy is associated with prostate cancer. Objective: To determine if vasectomy is associated with prostate cancer. Data Sources: The MEDLINE, EMBASE, Web of Science, and Scopus databases were searched for studies indexed from database inception to March 21, 2017, without language restriction. Study Selection: Cohort, case-control, and cross-sectional studies reporting relative effect estimates for the association between vasectomy and prostate cancer were included. Data Extraction and Synthesis: Two investigators performed study selection independently. Data were pooled separately by study design type using random-effects models. The Newcastle-Ottawa Scale was used to assess risk of bias. Main Outcomes and Measures: The primary outcome was any diagnosis of prostate cancer. Secondary outcomes were high-grade, advanced, and fatal prostate cancer. Results: Fifty-three studies (16 cohort studies including 2 563 519 participants, 33 case-control studies including 44 536 participants, and 4 cross-sectional studies including 12 098 221 participants) were included. Of these, 7 cohort studies (44%), 26 case-control studies (79%), and all 4 cross-sectional studies were deemed to have a moderate to high risk of bias. Among studies deemed to have a low risk of bias, a weak association was found among cohort studies (7 studies; adjusted rate ratio, 1.05; 95% CI, 1.02-1.09; P < .001; I2 = 9%) and a similar but nonsignificant association was found among case-control studies (6 studies; adjusted odds ratio, 1.06; 95% CI, 0.88-1.29; P = .54; I2 = 37%). Effect estimates were further from the null when studies with a moderate to high risk of bias were included. Associations between vasectomy and high-grade prostate cancer (6 studies; adjusted rate ratio, 1.03; 95% CI, 0.89-1.21; P = .67; I2 = 55%), advanced prostate cancer (6 studies; adjusted rate ratio, 1.08; 95% CI, 0.98-1.20; P = .11; I2 = 18%), and fatal prostate cancer (5 studies; adjusted rate ratio, 1.02; 95% CI, 0.92-1.14; P = .68; I2 = 26%) were not significant (all cohort studies). Based on these data, a 0.6% (95% CI, 0.3%-1.2%) absolute increase in lifetime risk of prostate cancer associated with vasectomy and a population-attributable fraction of 0.5% (95% CI, 0.2%-0.9%) were calculated. Conclusions and Relevance: This review found no association between vasectomy and high-grade, advanced-stage, or fatal prostate cancer. There was a weak association between vasectomy and any prostate cancer that was closer to the null with increasingly robust study design. This association is unlikely to be causal and should not preclude the use of vasectomy as a long-term contraceptive option.