Twenty years of participation of racialised groups in type 2 diabetes randomised clinical trials: a meta-epidemiological review.

AIMS/HYPOTHESIS: Type 2 diabetes mellitus prevalence is increasing globally and the greatest burden is borne by racialised people. However, there are concerns that the enrolment of racialised people into RCTs is limited, resulting in a lack of ethnic and racial diversity. This may differ depending whether an RCT is government funded or industry funded. The aim of this study was to review the proportions of racialised and white participants included in large RCTs of type 2 diabetes pharmacotherapies relative to the disease burden of type 2 diabetes in these groups. METHODS: The Ovid MEDLINE database was searched from 1 January 2000 to 31 December 2020. English language reports of RCTs of type 2 diabetes pharmacotherapies published in select medical journals were included. Studies were included in this review if they had a sample size of at least 100 participants and all participants were adults with type 2 diabetes. Industry-funded trials must have recruited participants from at least two countries. Government-funded trials were not held to the same standard because they are typically conducted in a single country. Data including the numbers and proportions of participants by ethnicity and race were extracted from trial reports. The participation-to-prevalence ratio (PPR) was calculated for each trial by dividing the percentage of white and racialised participants in each trial by the percentage of white and racialised participants with type 2 diabetes, respectively, for the regions of recruitment. A random-effects meta-analysis was used to generate the pooled PPRs and 95% CIs across study types. A PPR <0.80 indicates under-representation and a PPR >1.20 indicates over-representation. Risk of bias assessments were not conducted for this study as the objective was to examine recruitment of racialised and white participants rather than evaluate the trustworthiness of clinical trial outcomes. RESULTS: A total of 83 trials were included, involving 283,122 participants, of which 15 were government-funded and 68 were industry-funded trials. In government-funded trials, the PPR for white participants was 1.11 (95% CI 0.99, 1.24) and the PPR for racialised participants was 0.72 (95% CI 0.60, 0.86). In industry-funded trials, the PPR for white participants was 1.95 (95% CI 1.74, 2.18) and the PPR for racialised participants was 0.36 (95% CI 0.32, 0.42). The limitations of this study include the reliance on investigator-reported ethnicity and race to classify participants as 'white' or 'racialised', the use of estimates for type 2 diabetes prevalence and demographic data, and the high levels of heterogeneity of pooled estimates. However, despite these limitations, the results were consistent with respect to direction. CONCLUSIONS/INTERPRETATION: Racialised participants are under-represented in government- and industry-funded type 2 diabetes trials. Strategies to improve recruitment and enrolment of racialised participants into RCTs should be developed. REGISTRATION: Open Science Framework registration no. f59mk ( https://osf.io/f59mk ) FUNDING: The authors received no financial support for this research or authorship of the article.

Resistance training prescription for muscle strength and hypertrophy in healthy adults: a systematic review and Bayesian network meta-analysis.

OBJECTIVE: To determine how distinct combinations of resistance training prescription (RTx) variables (load, sets and frequency) affect muscle strength and hypertrophy. DATA SOURCES: MEDLINE, Embase, Emcare, SPORTDiscus, CINAHL, and Web of Science were searched until February 2022. ELIGIBILITY CRITERIA: Randomised trials that included healthy adults, compared at least 2 predefined conditions (non-exercise control (CTRL) and 12 RTx, differentiated by load, sets and/or weekly frequency), and reported muscle strength and/or hypertrophy were included. ANALYSES: Systematic review and Bayesian network meta-analysis methodology was used to compare RTxs and CTRL. Surface under the cumulative ranking curve values were used to rank conditions. Confidence was assessed with threshold analysis. RESULTS: The strength network included 178 studies (n=5097; women=45%). The hypertrophy network included 119 studies (n=3364; women=47%). All RTxs were superior to CTRL for muscle strength and hypertrophy. Higher-load (>80% of single repetition maximum) prescriptions maximised strength gains, and all prescriptions comparably promoted muscle hypertrophy. While the calculated effects of many prescriptions were similar, higher-load, multiset, thrice-weekly training (standardised mean difference (95% credible interval); 1.60 (1.38 to 1.82) vs CTRL) was the highest-ranked RTx for strength, and higher-load, multiset, twice-weekly training (0.66 (0.47 to 0.85) vs CTRL) was the highest-ranked RTx for hypertrophy. Threshold analysis demonstrated these results were extremely robust. CONCLUSION: All RTx promoted strength and hypertrophy compared with no exercise. The highest-ranked prescriptions for strength involved higher loads, whereas the highest-ranked prescriptions for hypertrophy included multiple sets. PROSPERO REGISTRATION NUMBER: CRD42021259663 and CRD42021258902.

Medical treatments for idiopathic pulmonary fibrosis: a systematic review and network meta-analysis.

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a respiratory disorder with a poor prognosis. Our objective is to assess the comparative effectiveness of 22 approved or studied IPF drug treatments. METHODS: We searched MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials and clinicaltrials.gov from inception to 2 April 2021. We included randomised controlled trials (RCTs) for adult patients with IPF receiving one or more of 22 drug treatments. Pairs of reviewers independently identified randomised trials that compared one or more of the target medical treatments in patients with IPF. We assessed the certainty of evidence using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach for network meta-analysis. We calculated pooled relative risk (RR) ratios and presented direct or network estimates with 95% credibility intervals (95% CI), within the GRADE framework. RESULTS: We identified 48 (10 326 patients) eligible studies for analysis. Nintedanib [RR 0.69 (0.44 to 1.1), pirfenidone [RR 0.63 (0.37 to 1.09); direct estimate), and sildenafil [RR (0.44 (0.16 to 1.09)] probably reduce mortality (all moderate certainty). Nintedanib (2.92% (1.51 to 4.14)), nintedanib+sildenafil (157 mL (-88.35 to 411.12)), pirfenidone (2.47% (-0.1 to 5)), pamrevlumab (4.3% (0.5 to 8.1)) and pentraxin (2.74% (1 to 4.83)) probably reduce decline of overall forced vital capacity (all moderate certainty). Only sildenafil probably reduces acute exacerbation and hospitalisations (moderate certainty). Corticosteroids+azathioprine+N-acetylcysteine increased risk of serious adverse events versus placebo (high certainty). CONCLUSION AND RELEVANCE: Future guidelines should consider sildenafil for IPF and further research needs to be done on promising IPF treatments such as pamrevlumab and pentraxin as phase 3 trials are completed.

Nasal Intermittent Positive Pressure Ventilation versus Continuous Positive Airway Pressure and Apnea of Prematurity: A Systematic Review and Meta-Analysis.

OBJECTIVE: The study aimed to systematically review and analyze the impact of nasal intermittent positive pressure ventilation (NIPPV) versus continuous positive airway pressure (CPAP) on apnea of prematurity (AOP) in preterm neonates. STUDY DESIGN: In this systematic review and meta-analysis, experimental studies enrolling preterm infants comparing NIPPV (synchronized, nonsynchronized, and bi-level) and CPAP (all types) were searched in multiple databases and screened for the assessment of AOP. Primary outcome was AOP frequency per hour (as defined by authors of included studies). RESULTS: Out of 4,980 articles identified, 18 studies were included with eight studies contributing to the primary outcome. All studies had a high risk of bias, with significant heterogeneity in definition and measurement of AOP. There was no difference in AOPs per hour between NIPPV versus CPAP (weighted mean difference = -0.19; 95% confidence interval [CI]: -0.76 to 0.37; eight studies, 456 patients). However, in a post hoc analysis evaluating the presence of any AOP (over varying time periods), the pooled odds ratio (OR) was lower with NIPPV (OR: 0.46; 95% CI: 0.32-0.67; 10 studies, 872 patients). CONCLUSION: NIPPV was not associated with decrease in AOP frequency, although demonstrated lower odds of developing any AOP. However, definite recommendations cannot be made based on the quality of the published evidence. KEY POINTS: · AOP is a common clinical complication related to preterm birth.. · NIPPV is often used to mitigate AOP and complications.. · Relative impact of NIPPV and CPAP on AOP remains unclear..

Thromboprophylaxis after knee arthroscopy does not decrease the risk of deep vein thrombosis: a network meta-analysis.

PURPOSE: The primary aim of this network meta-analysis (NMA) is to compare the incidence of venous thromboembolisms (VTE) and bleeding risk following the use of pharmacological and non-pharmacological thromboprophylaxis for arthroscopic knee surgery (AKS). This study assumed the null hypothesis which was that there will be no difference in the incidence of VTE and bleeding risk when comparing no treatment, pharmacological treatment, and non-pharmacological treatment for preventing VTE events following AKS. METHODS: A systematic electronic search of CENTRAL, Medline, Embase, and ClinicalTrials.gov was carried out. All English language prospective randomized clinical trials published from date of database inception to November 21, 2021 were eligible for inclusion. All papers addressing arthroscopic knee surgery were eligible for inclusion regardless of timing of surgery, operation, surgical technique, or rehabilitation. Multiple random effects NMAs were conducted to compare all treatments for each outcome. The primary outcome was the incidence of pulmonary embolism (PE) and secondary outcomes consisted of overall deep vein thrombosis (DVT), symptomatic DVT, asymptomatic DVT, and all-cause mortality. Adverse outcomes consisted of major and minor bleeding, as well as adverse events. RESULTS: A total of nine studies with 4526 patients were included for analysis. There were 1054 patients in the no treatment/placebo group (NT/Placebo), 1646 patients in the graduated compression stockings, 810 patients in the extended-duration (> 10 days) low molecular weight heparin (Ext-LMWH) group, 650 patients in the short-duration (< 10 days) LMWH group (Short-LMWH), and 356 patients in the rivaroxaban group. GCS, Ext-LMWH, Short-LMWH and rivaroxaban all demonstrated low risks of PE, symptomatic DVT, asymptomatic DVT, combined DVT and all-cause mortality. Similarly, all interventions demonstrated a low risk of major bleeding. CONCLUSION: There is no significant difference in the risk reduction of PEs, symptomatic DVTs, major/minor bleeding, and/or all-cause mortality when using LWMH (including short or extended regimens), rivaroxaban, graduated compression stockings or no treatment following arthroscopic knee surgery. Future primary research on the efficacy of thromboprophylaxis following arthroscopic knee surgery should stratify outcomes based on key patient (i.e., age, sex, comorbidities) and surgical (i.e., major vs. minor surgery) characteristics and should include acetylsalicylic acid as an intervention. LEVEL OF EVIDENCE: I, network meta-analysis of Level I studies.

Bariatric interventions in obesity treatment and prevention in pediatric acute lymphoblastic leukemia: a systematic review and meta-analysis.

Most children are surviving acute lymphoblastic leukemia (ALL) today. Yet, the emergence of cardiometabolic comorbidities in this population may impact long-term outcomes including the quality of life and lifespan. Obesity is a major driver of cardiometabolic disorders in the general population, and in ALL patients it is associated with increased risk of hypertension, dysglycemia, and febrile neutropenia when compared with lean ALL patients undergoing therapy. This systematic review aims to assess the current evidence for bariatric interventions to manage obesity in children with ALL. The primary outcome for this systematic review was the change in BMI z-score with implementation of the interventions studied. Literature searches were conducted in several databases. Ten publications addressing the study question were included in this review, and five studies were used in the meta-analysis to assess the impact of the bariatric interventions on obesity. The BMI z-score did not change significantly with the interventions. However, the quality of evidence was low, which precluded the recommendation of their use. In conclusion, prospective, rigorous, adequately powered, and high-quality longitudinal studies are urgently needed to deliver effective lifestyle interventions to children with ALL to treat and prevent obesity. These interventions, if successful, may improves cardiometabolic health outcomes and enhance the quality of life and life expectancy in children with ALL.

Transepithelial versus Epithelium-off Corneal Collagen Cross-linking for Corneal Ectasia: A Systematic Review and Meta-analysis.

TOPIC: To evaluate the safety and efficacy of transepithelial corneal cross-linking in comparison with the established epithelium-off technique for corneal ectasia. CLINICAL RELEVANCE: Considerable debate exists regarding whether transepithelial and epithelium-off cross-linking are comparable in their safety and efficacy. METHODS: We searched 16 electronic databases, including Medline, Embase, Web of Science, and the grey literature, current to July 8, 2020, for randomized controlled trials comparing transepithelial and epithelium-off cross-linking for corneal ectasia. We excluded studies evaluating cross-linking for nonectatic indications, as well as non-randomized controlled trials. Our primary outcome was the change in maximal keratometry (Kmax) at 12 months after cross-linking, and we considered additional topographic, visual, and safety outcomes. We summarized our analyses by calculating weighted mean differences (MDs) with associated 95% confidence intervals (CIs) for continuous outcomes and relative risks (RRs) with corresponding 95% CIs for dichotomous outcomes. We conducted trial sequential analysis to determine whether the required information size was met for each outcome. The quality of individual trials was evaluated using the Cochrane Collaboration's risk of bias assessment tool, and the evidence was assessed at an outcome level using the Grading of Recommendations Assessment, Development, and Evaluation methodology. RESULTS: Twelve studies totaling 966 eyes were eligible. A significant difference was found between transepithelial and epithelium-off cross-linking groups in the change in Kmax at 12 months (MD, 0.75; 95% CI, 0.23-1.28; P = 0.004; primary outcome) and at longest follow-up (MD, 1.20; 95% CI, 0.62-1.77; P < 0.001; secondary outcome) after treatment. No significant difference was found between the 2 groups when examining uncorrected distance visual acuity (MD, 0.04; 95% CI, -0.06 to 0.14; P = 0.386) or corrected distance visual acuity (MD, 0.01; 95% CI, -0.06 to 0.09; P = 0.732). Transepithelial cross-linking was associated with significantly fewer complications than the epithelium-off approach (RR, 0.22; 95% CI, 0.06-0.79; P = 0.020), although it was associated with an increased rate of disease progression at 12 months after treatment (RR, 4.49; 95% CI, 1.24-16.25; P = 0.022). The required information size was met for our primary outcome and trial sequential analysis supported the conventional meta-analysis. The quality of evidence was rated as moderate using the Grading of Recommendations Assessment, Development, and Evaluation methodology. DISCUSSION: The efficacy of transepithelial cross-linking remains inferior to the epithelium-off approach, although it is significantly safer.

Financial toxicity associated with a cancer diagnosis in publicly funded healthcare countries: a systematic review.

PURPOSE: Financial toxicity related to cancer diagnosis and treatment is a common issue in developed countries. We seek to systematically summarize the extent of the issue in very high development index countries with publicly funded healthcare. METHODS: We identified articles published Jan 1, 2005, to March 7, 2019, describing financial burden/toxicity experienced by cancer patients and/or informal caregivers using OVID Medline Embase and PsychInfo, CINAHL, Business Source Complete, and EconLit databases. Only English language peer-reviewed full papers describing studies conducted in very high development index countries with predominantly publicly funded healthcare were eligible (excluded the USA). All stages of the review were evaluated in teams of two researchers excepting the final data extraction (CJL only). RESULTS: The searches identified 7117 unique articles, 32 of which were eligible. Studies were undertaken in Canada, Australia, Ireland, UK, Germany, Denmark, Malaysia, Finland, France, South Korea, and the Netherlands. Eighteen studies reported patient/caregiver out-of-pocket costs (range US$17-US$506/month), 18 studies reported patient/caregiver lost income (range 17.6-67.3%), 14 studies reported patient/caregiver travel and accommodation costs (range US$8-US$393/month), and 6 studies reported financial stress (range 41-48%), strain (range 7-39%), or financial burden/distress/toxicity among patients/caregivers (range 22-27%). The majority of studies focused on patients, with some including caregivers. Financial toxicity was greater in those with early disease and/or more severe cancers. CONCLUSIONS: Despite government-funded universal public healthcare, financial toxicity is an issue for cancer patients and their families. Although levels of toxicity vary between countries, the findings suggest financial protection appears to be inadequate in many countries.

Preparing for patient partnership: A scoping review of patient partner engagement and evaluation in research.

BACKGROUND: Realizing patient partnership in research requires a shift from patient participation in ancillary roles to engagement as contributing members of research teams. While engaging patient partners is often discussed, impact is rarely measured. OBJECTIVE: Our primary aim was to conduct a scoping review of the impact of patient partnership on research outcomes. The secondary aim was to describe barriers and facilitators to realizing effective partnerships. SEARCH STRATEGY: A comprehensive bibliographic search was undertaken in EBSCO CINAHL, and Embase, MEDLINE and PsycINFO via Ovid. Reference lists of included articles were hand-searched. INCLUSION CRITERIA: Included studies were: (a) related to health care; (b) involved patients or proxies in the research process; and (c) reported results related to impact/evaluation of patient partnership on research outcomes. DATA EXTRACTION AND SYNTHESIS: Data were extracted from 14 studies meeting inclusion criteria using a narrative synthesis approach. MAIN RESULTS: Patient partners were involved in a range of research activities. Results highlight critical barriers and facilitators for researchers seeking to undertake patient partnerships to be aware of, such as power imbalances between patient partners and researchers, as well as valuing of patient partner roles. DISCUSSION: Addressing power dynamics in patient partner-researcher relationships and mitigating risks to patient partners through inclusive recruitment and training strategies may contribute towards effective engagement. Further guidance is needed to address evaluation strategies for patient partnerships across the continuum of patient partner involvement in research. CONCLUSIONS: Research teams can employ preparation strategies outlined in this review to support patient partnerships in their work.

Bedside Optic Nerve Ultrasonography for Diagnosing Increased Intracranial Pressure: A Systematic Review and Meta-analysis.

Background: Optic nerve ultrasonography (optic nerve sheath diameter sonography) has been proposed as a noninvasive, quick method for diagnosing increased intracranial pressure. Purpose: To examine the accuracy of optic nerve ultrasonography for diagnosing increased intracranial pressure in children and adults. Data Sources: 13 databases from inception through May 2019, reference lists, and meeting proceedings. Study Selection: Prospective optic nerve ultrasonography diagnostic accuracy studies, published in any language, involving any age group or reference standard. Data Extraction: 3 reviewers independently abstracted data and performed quality assessment. Data Synthesis: Of 71 eligible studies involving 4551 patients, 61 included adults, and 35 were rated as having low risk of bias. The pooled sensitivity, specificity, positive likelihood ratio, and negative likelihood ratio of optic nerve ultrasonography in patients with traumatic brain injury were 97% (95% CI, 92% to 99%), 86% (CI, 74% to 93%), 6.93 (CI, 3.55 to 13.54), and 0.04 (CI, 0.02 to 0.10), respectively. Respective estimates in patients with nontraumatic brain injury were 92% (CI, 86% to 96%), 86% (CI, 77% to 92%), 6.39 (CI, 3.77 to 10.84), and 0.09 (CI, 0.05 to 0.17). Accuracy estimates were similar among studies stratified by patient age, operator specialty and training level, reference standard, sonographer blinding status, and cutoff value. The optimal cutoff for optic nerve sheath dilatation on ultrasonography was 5.0 mm. Limitation: Small studies, imprecise summary estimates, possible publication bias, and no evaluation of effect on clinical outcomes. Conclusion: Optic nerve ultrasonography can help diagnose increased intracranial pressure. A normal sheath diameter measurement has high sensitivity and a low negative likelihood ratio that may rule out increased intracranial pressure, whereas an elevated measurement, characterized by a high specificity and positive likelihood ratio, may indicate increased intracranial pressure and the need for additional confirmatory tests. Primary Funding Source: None. (PROSPERO: CRD42017055485).

Atraumatic versus conventional lumbar puncture needles: a systematic review and meta-analysis.

BACKGROUND: Atraumatic needles have been proposed to lower complication rates after lumbar puncture. However, several surveys indicate that clinical adoption of these needles remains poor. We did a systematic review and meta-analysis to compare patient outcomes after lumbar puncture with atraumatic needles and conventional needles. METHODS: In this systematic review and meta-analysis, we independently searched 13 databases with no language restrictions from inception to Aug 15, 2017, for randomised controlled trials comparing the use of atraumatic needles and conventional needles for any lumbar puncture indication. Randomised trials comparing atraumatic and conventional needles in which no dural puncture was done (epidural injections) or without a conventional needle control group were excluded. We screened studies and extracted data from published reports independently. The primary outcome of postdural-puncture headache incidence and additional safety and efficacy outcomes were assessed by random-effects and fixed-effects meta-analysis. This study is registered with the International Prospective Register of Systematic Reviews, number CRD42016047546. FINDINGS: We identified 20 241 reports; after exclusions, 110 trials done between 1989 and 2017 from 29 countries, including a total of 31 412 participants, were eligible for analysis. The incidence of postdural-puncture headache was significantly reduced from 11·0% (95% CI 9·1-13·3) in the conventional needle group to 4·2% (3·3-5·2) in the atraumatic group (relative risk 0·40, 95% CI 0·34-0·47, p<0·0001; I2=45·4%). Atraumatic needles were also associated with significant reductions in the need for intravenous fluid or controlled analgesia (0·44, 95% CI 0·29-0·64; p<0·0001), need for epidural blood patch (0·50, 0·33-0·75; p=0·001), any headache (0·50, 0·43-0·57; p<0·0001), mild headache (0·52, 0·38-0·70; p<0·0001), severe headache (0·41, 0·28-0·59; p<0·0001), nerve root irritation (0·71, 0·54-0·92; p=0·011), and hearing disturbance (0·25, 0·11-0·60; p=0·002). Success of lumbar puncture on first attempt, failure rate, mean number of attempts, and the incidence of traumatic tap and backache did not differ significantly between the two needle groups. Prespecified subgroup analyses of postdural-puncture headache revealed no interactions between needle type and patient age, sex, use of prophylactic intravenous fluid, needle gauge, patient position, indication for lumbar puncture, bed rest after puncture, or clinician specialty. These results were rated high-quality evidence as examined using the grading of recommendations assessment, development, and evaluation. INTERPRETATION: Among patients who had lumbar puncture, atraumatic needles were associated with a decrease in the incidence of postdural-puncture headache and in the need for patients to return to hospital for additional therapy, and had similar efficacy to conventional needles. These findings offer clinicians and stakeholders a comprehensive assessment and high-quality evidence for the safety and efficacy of atraumatic needles as a superior option for patients who require lumbar puncture. FUNDING: None.

Complete Resolution of Nonalcoholic Fatty Liver Disease After Bariatric Surgery: A Systematic Review and Meta-analysis.

BACKGROUND & AIMS: Bariatric surgery has been reported to lead to complete resolution of nonalcoholic fatty liver disease (NAFLD) following the sustained weight loss induced in obese patients. We performed a systematic review and meta-analysis to evaluate the effects of bariatric surgery on NAFLD in obese patients. METHODS: We searched MEDLINE, EMBASE, CENTRAL, and Web of Science databases through May 2018 for studies that compared liver biopsy results before and after bariatric surgery in obese patients. Primary outcomes were biopsy-confirmed resolution of NAFLD and NAFLD activity score. Secondary outcomes were worsening of NAFLD after surgery and liver volume. The Grading of Recommendations, Assessment, Development, and Evidence approach was conducted to assess overall quality of evidence. RESULTS: We analyzed data from 32 cohort studies comprising 3093 biopsy specimens. Bariatric surgery resulted in a biopsy-confirmed resolution of steatosis in 66% of patients (95% CI, 56%-75%), inflammation in 50% (95% CI, 35%-64%), ballooning degeneration in 76% (95% CI, 64%-86%), and fibrosis in 40% (95% CI, 29%-51%). Patients' mean NAFLD activity score was reduced significantly after bariatric surgery (mean difference, 2.39; 95% CI, 1.58-3.20; P < .001). However, bariatric surgery resulted in new or worsening features of NAFLD, such as fibrosis, in 12% of patients (95% CI, 5%-20%). The overall Grading of Recommendations, Assessment, Development, and Evidence quality of evidence was very low. CONCLUSIONS: Through this systematic review and meta-analysis, we found that bariatric surgery leads to complete resolution of NAFLD in obese patients. However, some patients develop new or worsened features of NAFLD. Randomized controlled trials are needed to further examine the therapeutic benefits of bariatric surgery for patients with NAFLD.

Trochleoplasty provides good clinical outcomes and an acceptable complication profile in both short and long-term follow-up.

PURPOSE: The purpose of this study is to report on the global distribution and clinical outcomes of published articles related to trochleoplasty. METHODS: The online databases OVID Medline, OVID EMBASE, and the Cochrane Library were searched for the literature assessing trochleoplasty performed for lateral patellofemoral instability (LPI). Study data were abstracted looking at global trends in the literature, as well as clinical and patient-reported outcomes following this technique. RESULTS: For the assessment of global distribution, 29 studies including 998 patients met the inclusion criteria. The majority of the studies were conducted in Europe (93%) and most used an open thin flap technique (52%). For the secondary analysis of clinical outcomes, 21 studies were included with significant heterogeneity in patient selection, reporting on the degree of trochlear dysplasia, and patient-reported outcomes. All trochleoplasty techniques showed statistically significant improvement in clinical outcomes at average 50 months (range 3-228 months) post-operative, with most patients being satisfied with their procedure. Re-dislocation and complication rates were low. CONCLUSIONS: European centers have published majority of data on trochleoplasty surgery, which has been shown to be an acceptable procedure for patients with high-grade trochlear dysplasia and LPI. Trochleoplasty has demonstrated good clinical outcomes, a low re-dislocation rate, and an acceptable complication profile in both short and long-term follow-up. This study highlights the difficulty in reporting outcomes in this group of patients due to heterogeneity in patient selection, grading of trochlear dysplasia, and the lack of disease-specific outcome measures. LEVEL OF EVIDENCE: IV.

Changes in Kidney Function Do Not Differ between Healthy Adults Consuming Higher- Compared with Lower- or Normal-Protein Diets: A Systematic Review and Meta-Analysis.

Background: Higher-protein (HP) diets are advocated for several reasons, including mitigation of sarcopenia, but their effects on kidney function are unclear. Objective: This meta-analysis was conducted to determine the effect of HP intakes on kidney function in healthy adults. Methods: We conducted a systematic review and meta-analysis of trials comparing HP (≥1.5 g/kg body weight or ≥20% energy intake or ≥100 g protein/d) with normal- or lower-protein (NLP; ≥5% less energy intake from protein/d compared with HP group) intakes on kidney function. Medline and EMBASE databases were searched. Randomized controlled trials comparing the effects of HP with NLP (>4 d duration) intakes on glomerular filtration rate (GFR) in adults without kidney disease were included. Results: A total of 2144 abstracts were reviewed, with 40 articles selected for full-text review; 28 of these were analyzed and included data from 1358 participants. Data were analyzed using random-effects meta-analysis (RevMan 5; The Cochrane Collaboration), meta-regression (STATA; StataCorp), and dose-response analysis (Prism; GraphPad). Analyses were conducted using postintervention (post) GFR and the change in GFR from preintervention to post. The post-only comparison showed a trivial effect for GFR to be higher after HP intakes [standardized mean difference (SMD): 0.19; 95% CI: 0.07, 0.31; P = 0.002]. The change in GFR did not differ between interventions (SMD: 0.11; 95% CI: -0.05, 0.27; P = 0.16). There was a linear relation between protein intake and GFR in the post-only comparison (r = 0.332, P = 0.03), but not between protein intake and the change in GFR (r = 0.184, P = 0.33). The main limitation of the current analysis is the unclear risk of selection bias of the included trials. Conclusions: Postintervention GFR comparisons indicate that HP diets result in higher GFRs; however, when changes in GFR were compared, dietary protein had no effect. Our analysis indicates that HP intakes do not adversely influence kidney function on GFR in healthy adults.

Digital Rectal Examination for Prostate Cancer Screening in Primary Care: A Systematic Review and Meta-Analysis.

PURPOSE: Although the digital rectal examination (DRE) is commonly performed to screen for prostate cancer, there is limited data to support its use in primary care. This review and meta-analysis aims to evaluate the diagnostic accuracy of DRE in screening for prostate cancer in primary care settings. METHODS: We searched MEDLINE, Embase, DARE (Database of Abstracts of Reviews of Effects), Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, and CINAHL (Cumulative Index to Nursing and Allied Health Literature) from their inception to June 2016. Six reviewers, in pairs, independently screened citations for eligibility and extracted data. Pooled estimates were calculated for sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of DRE in primary care settings using an inverse-variance meta-analysis. We used QUADAS-2 (Quality Assessment of Diagnostic Accuracy Studies 2) and GRADE (Grades of Recommendation Assessment, Development, and Evaluation) guidelines to assess study risk of bias and quality. RESULTS: Our search yielded 8,217 studies, of which 7 studies with 9,241 patients were included after the screening process. All patients analyzed underwent both DRE and biopsy. Pooled sensitivity of DRE performed by primary care clinicians was 0.51 (95% CI, 0.36-0.67; I2 = 98.4%) and pooled specificity was 0.59 (95% CI, 0.41-0.76; I2 = 99.4%). Pooled PPV was 0.41 (95% CI, 0.31-0.52; I2 = 97.2%), and pooled NPV was 0.64 (95% CI, 0.58-0.70; I2 = 95.0%). The quality of evidence as assessed with GRADE was very low. CONCLUSION: Given the considerable lack of evidence supporting its efficacy, we recommend against routine performance of DRE to screen for prostate cancer in the primary care setting.

A systematic review, meta-analysis and meta-regression of the effect of protein supplementation on resistance training-induced gains in muscle mass and strength in healthy adults.

OBJECTIVE: We performed a systematic review, meta-analysis and meta-regression to determine if dietary protein supplementation augments resistance exercise training (RET)-induced gains in muscle mass and strength. DATA SOURCES: A systematic search of Medline, Embase, CINAHL and SportDiscus. ELIGIBILITY CRITERIA: Only randomised controlled trials with RET ≥6 weeks in duration and dietary protein supplementation. DESIGN: Random-effects meta-analyses and meta-regressions with four a priori determined covariates. Two-phase break point analysis was used to determine the relationship between total protein intake and changes in fat-free mass (FFM). RESULTS: Data from 49 studies with 1863 participants showed that dietary protein supplementation significantly (all p<0.05) increased changes (means (95% CI)) in: strength-one-repetition-maximum (2.49 kg (0.64, 4.33)), FFM (0.30 kg (0.09, 0.52)) and muscle size-muscle fibre cross-sectional area (CSA; 310 µm2 (51, 570)) and mid-femur CSA (7.2 mm2 (0.20, 14.30)) during periods of prolonged RET. The impact of protein supplementation on gains in FFM was reduced with increasing age (-0.01 kg (-0.02,-0.00), p=0.002) and was more effective in resistance-trained individuals (0.75 kg (0.09, 1.40), p=0.03). Protein supplementation beyond total protein intakes of 1.62 g/kg/day resulted in no further RET-induced gains in FFM. SUMMARY/CONCLUSION: Dietary protein supplementation significantly enhanced changes in muscle strength and size during prolonged RET in healthy adults. Increasing age reduces and training experience increases the efficacy of protein supplementation during RET. With protein supplementation, protein intakes at amounts greater than ~1.6 g/kg/day do not further contribute RET-induced gains in FFM.

Resolution of Diplopia in Late Repair of Enophthalmos Following Facial Trauma.

Posttraumatic enophthalmos due to isolated or complex orbital fractures can contribute to diplopia. Current evidence recommends early repair. However, little is known about the outcome of enophthalmos correction when repair occurs beyond 30 days after trauma. In this systematic review, the authors aim to evaluate the current evidence on functional outcomes after delayed repair of posttraumatic enophthalmos.Two independent assessors undertook a systematic review of the literature using multiple databases. The authors' inclusion criteria identified studies involving patients at least 14 years of age who had surgical correction of persistent enophthalmos 30 days after initial trauma. Each eligible paper was included after critical appraisal using validated guidelines. Data on preoperative and postoperative enophthalmos and diplopia in each study was extracted. The pattern of fracture was also noted.The authors' search for the medical databases yielded 1053 articles, of which 6 eligible papers were included. Meta-analysis was performed. In patients with complex injuries involving orbital and mid-facial fractures, diplopia resolution was calculated to be 53%, and enophthalmos was corrected in 83% of the patients. In patients with isolated orbital fractures, 53% had resolution of their diplopia, and enophthalmos was corrected in 88% of the patients.Enophthalmos can be corrected to within 2 mm of the contralateral eye in both the isolated and complex orbital fractures in patients who present 30 days or greater after injury. Based on the studies reviewed, there is less predictability in diplopia resolution.

Ablative Therapies in Metastatic Breast Cancer: A Systematic Review.

PURPOSE: Patients with oligometastatic breast cancer are being increasingly offered ablative therapies, yet it is unclear which subpopulations may derive long-term benefit. This study sought to explore factors that could define a clinically relevant oligometastatic breast cancer population that benefits from ablative therapies. METHODS: A systematic review using MEDLINE for English language articles published between 1985 and April 2014 was undertaken. Criteria for review included studies that reported overall survival (OS) or progression-free survival (PFS) in breast cancer patients with distant metastases which also: quantified the extent of disease, had metachronous presentation of metastases, and reported on at least 5 patients. RESULTS: Of 59 674 screened studies, 41 studies of 1813 individual patients were identified. All studies were observational cohort studies (level 2B or 4 evidence) and underwent critical review. All outcomes pertaining to OS and PFS were extracted. Extracted data were too heterogeneous to facilitate a meta-analysis. The only factor that suggested worse outcomes was positive margins post-metastasectomy. There was no clear signal for improved outcomes in regards to age, disease extent, disease-free interval, or receptor status. CONCLUSION: Existing evidence does not provide meaningful direction on which metastatic breast cancer patients should have ablation of their residual disease due to heterogeneous reporting of disease factors, patient factors, and outcomes. Thorough demonstration of the absence of high- or moderate-level evidence and the absence of clinical data to guide patient selection suggests that metastatic breast cancer patients being treated with ablative modalities should be placed on clinical trial.

Suprascapular and Interscalene Nerve Block for Shoulder Surgery: A Systematic Review and Meta-analysis.

BACKGROUND: Interscalene block provides optimal shoulder surgery analgesia, but concerns over its associated risks have prompted the search for alternatives. Suprascapular block was recently proposed as an interscalene block alternative, but evidence of its comparative analgesic effect is conflicting. This meta-analysis compares the analgesic effect and safety of suprascapular block versus interscalene block for shoulder surgery. METHODS: Databases were searched for randomized trials comparing interscalene block with suprascapular block for shoulder surgery. Postoperative 24-h cumulative oral morphine consumption and the difference in the area under curve for pooled rest pain scores were designated as primary outcomes. Analgesic and safety outcomes, particularly block-related and respiratory complications, were evaluated as secondary outcomes. Results were pooled using random-effects modeling. RESULTS: Data from 16 studies (1,152 patients) were analyzed. Interscalene block and suprascapular block were not different in 24-h morphine consumption. The difference in area under the curve of pain scores for the 24-h interval favored interscalene block by 1.1 cm/h, but this difference was not clinically important. Compared with suprascapular block, interscalene block reduced postoperative pain but not opioid consumption during recovery room stay by a weighted mean difference (95% CI) of 1.5 cm (0.6 to 2.5 cm; P < 0.0001). Pain scores were not different at any other time. In contrast, suprascapular block reduced the odds of block-related and respiratory complications. CONCLUSIONS: This review suggests that there are no clinically meaningful analgesic differences between suprascapular block and interscalene block except for interscalene block providing better pain control during recovery room stay; however, suprascapular block has fewer side effects. These findings suggest that suprascapular block may be considered an effective and safe interscalene block alternative for shoulder surgery.