Dermatofibrosarcoma Protuberans Recurrence After Wide Local Excision Versus Mohs Micrographic Surgery: A Systematic Review and Meta-Analysis.

BACKGROUND: Local recurrence (LR) rates of dermatofibrosarcoma protuberans (DFSP) treated with different surgical modalities are unknown. OBJECTIVE: To evaluate the differences in LR rates of DFSP treated with wide local excision (WLE) versus Mohs micrographic surgery (MMS). MATERIALS AND METHODS: Pertinent studies of DFSP treated with either WLE or MMS were identified through a search of multiple databases, including Ovid MEDLINE (1946-2018), Embase (1988-2018), Web of Science (1975-2018), and Scopus (1970-2018). Comparative 2-arm and noncomparative single-arm studies were assessed through meta-analyses. RESULTS: Of the 517 studies identified, 88 met inclusion criteria (12 comparative studies; 76 single-arm studies). In the 12 comparative studies, 352 patients with DFSP underwent MMS and 777 patients with DFSP underwent WLE. The LR rate was 1.7% after MMS and 3.7% after WLE (odds ratio, 1.549; 95% CI, 0.710-3.381; p = .27). In the 76 noncomparative studies, 980 patients underwent MMS (LR rate, 1.5%; 95% CI, 0.9%-2.1%; p < .001), and 2,215 patients underwent WLE (LR rate, 9.4%; 95% CI, 7.5%-11.3%; p < .001). CONCLUSION: The LR rate of DFSP in patients treated with MMS is lower than in patients treated with WLE. Because of high rates of postoperative DFSP LR, MMS should be strongly considered when available.

Local Recurrence of Melanoma Is Higher After Wide Local Excision Versus Mohs Micrographic Surgery or Staged Excision: A Systematic Review and Meta-analysis.

BACKGROUND: Complete removal of melanoma is a primary goal of excision, and local recurrence is one measure to evaluate the efficacy of surgical technique. OBJECTIVE: To compare published local recurrence rates for melanoma treated with Mohs micrographic surgery (MMS) or staged excision versus wide local excision (WLE). METHODS AND MATERIALS: Search of 6 databases identified comparative and noncomparative studies that reported local recurrence rates after MMS, staged excision, or WLE for melanoma. Random-effects meta-analysis was used to estimate odds ratios and 95% confidence interval (CI) from comparative studies and event rates from noncomparative studies. RESULTS: Of the 71 studies included (16,575 patients), 12 were comparative studies (2,683 patients) and 56 were noncomparative studies (13,698 patients). Comparative studies showed increased recurrence after WLE compared with MMS or staged excision (odds ratio [OR], 2.5; 95% CI, 1.4-4.6) and compared with MMS alone (OR, 3.3; 95% CI, 1.8-5.9). Pooled data from comparative and noncomparative studies showed a local recurrence rate of 7% after WLE (95% CI, 5%-11%), 3% after staged excision (95% CI, 2%-4%), and less than 1% after MMS (95% CI, 0%-1%). Statistical heterogeneity was moderate to high. CONCLUSION: Local recurrence of melanoma is significantly lower after MMS (<1%) and staged excision (3%) compared with WLE (7%).

A Systematic Review on the Efficacy of Intravenous Racemic Ketamine for Bipolar Depression.

BACKGROUND: Ketamine, a glutamate N-methyl-d-aspartate receptor antagonist, has shown rapid antidepressant effects in treatment-resistant depression. We conducted a systematic review of studies evaluating the efficacy of intravenous ketamine augmentation in treatment-resistant depression patients with bipolar disorder. METHODS: Major databases were searched for open-label and randomized controlled trials (RCT). Two independent reviewers screened and selected the studies that met the inclusion criteria. Studies were selected following the standard Cochrane methodology, and the findings are reported according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses. Methodological quality of the included studies was assessed using standardized measures. RESULTS: A total of 1442 articles were screened. Five studies were included in the systematic review (3 RCTs and 2 open-label studies) enrolling 110 subjects (mean age, 45.54 ± 12.65 years; 68.18% female). All the RCTs and open-label studies showed improvement in depressions symptoms after receiving a single infusion of ketamine. Included studies also suggested improvement in suicidal ideation and anhedonia after ketamine infusion. Dissociation and transient increase in blood pressure were the most common reported adverse effects with ketamine. Ketamine infusions did not increase mania symptoms. CONCLUSIONS: Limited data show efficacy and feasibility of intravenous racemic ketamine in treatment-resistant bipolar depression. Further studies with larger sample size are required to strengthen the evidence.

Association of Thyroid Function with Suicidal Behavior: A Systematic Review and Meta-Analysis.

Thyroid disease is a very common condition that influences the entire human body, including cognitive function and mental health. As a result, thyroid disease has been associated with multiple neuropsychiatric conditions. However, the relationship between thyroid dysfunction and suicide is still controversial. We conducted a systematic review and meta-analysis to describe the association of thyroid function with suicidal behavior in adults. We searched four data bases (MEDLINE, EMBASE, PsycINFO, and Scopus) from their inception to 20 July 2018. Studies that reported mean values and standard deviation (SD) of thyroid hormone levels [Thyroid-stimulating hormone (TSH), free thyroxine (FT4), free triiodothyronine (FT3), total thyroxine (TT4), and total triiodothyronine (TT3)] in patients with suicidal behavior compared with controls were included in this meta-analysis. The abstracts and papers retrieved with our search strategies were reviewed independently and in duplicate by four reviewers for assessment of inclusion criteria and data extraction, as well as for evaluation of risk of bias. Random-effects models were used in this meta-analysis to establish the mean difference on thyroid function tests between groups. Overall, 2278 articles were identified, and 13 studies met the inclusion criteria. These studies involved 2807 participants, including 826 participants identified with suicidal behavior. We found that patients with suicide behavior had lower levels of FT3 (-0.20 pg/mL; p = 0.02) and TT4 (-0.23 µg/dL; p = 0.045) compared to controls. We found no differences in either TSH, FT4, or TT3 levels among groups. With our search strategy, we did not identify studies with a comparison of overt/subclinical thyroid disease prevalence between patients with and without suicide behavior. The studies included in this meta-analysis had a low-to-moderate risk of bias. In the available literature, the evidence regarding the association of thyroid disorders and suicidal behavior is limited. We found that patients with suicidal behavior have significantly lower mean FT3 and TT4 levels when compared to patients without suicidal behavior. The clinical implications and pathophysiologic mechanisms of these differences remain unknown and further research is needed.

Effects of Promotility Agents on Gastric Emptying and Symptoms: A Systematic Review and Meta-analysis.

BACKGROUND & AIMS: Studies have reported a lack of association between improvements in gastric emptying (GE) and upper gastrointestinal (UGI) symptoms with promotility drugs. However, GE test methods were suboptimal in some studies. We assessed improvements in GE and UGI symptoms in patients given promotility agents in studies with optimal or moderate test methods (scintigraphy or breath test, solid meal, >2 hours duration) compared to studies with suboptimal GE test methods. METHODS: With an expert librarian, we completed an extensive search of publications in the Ovid MEDLINE (1946 to present), EMBASE (1988 to January 2018), and EBM Reviews Cochrane Central Register of Controlled Trials, without restrictions on language or year. Two independent reviewers evaluated the following inclusion criteria: randomized, blinded, parallel, or crossover trials of 5HT4 agonists, D2 receptor antagonist, or ghrelin agonists; trials that measured change in GE (T1/2) or composite UGI symptoms; trials of patients with functional dyspepsia and gastroparesis; and trials of GE test methods. Standardized mean differences (units expressed as SD) were used to standardize symptom assessments that were not uniform across studies. Random effects model was used to analyze data and meta-regression was used to evaluate the association between change in GE and UGI symptoms. RESULTS: Of 899 studies considered, 22 studies assessed change in GE; 23 evaluated UGI symptoms; and 14 evaluated GE and UGI symptoms. Promotility agents significantly accelerated GE (T1/2) in all studies (mean reduction in T1/2, 16.3 minutes; 95% confidence interval, -22.1 to -10.6 minutes) and in studies that used optimal GE test methods (mean reduction in T1/2, 23.6 minutes; 95% confidence interval, -32.3 to -14.9 minutes). Promotility agents also significantly reduced UGI symptoms (mean reduction, 0.25 SD; 95% confidence interval, -0.37 to -0.13 SD). Meta-regression found no significant association between change in GE and UGI symptoms. However, when only studies with optimal GE test methods were evaluated, there was a significant positive association between improvement in GE and UGI symptoms (P = .02). CONCLUSIONS: In a meta-analysis of published trials, we found promotility agents to significantly accelerate GE (when optimal test methods were used) and to produce significant improvements in UGI symptoms.

Improving Blood Pressure Management in Primary Care Patients with Chronic Kidney Disease: a Systematic Review of Interventions and Implementation Strategies.

INTRODUCTION: Chronic kidney disease (CKD) is widely prevalent, associated with morbidity and mortality, but may be lessened with timely implementation of evidence-based strategies including blood pressure (BP) control. Nonetheless, an evidence-practice gap persists. We synthesize the evidence for clinician-facing interventions to improve hypertension management in CKD patients in primary care. METHODS: Electronic databases and related publications were queried for relevant studies. We used a conceptual model to address heterogeneity of interventions. We conducted a quantitative synthesis of interventions on blood pressure (BP) outcomes and a narrative synthesis of other CKD relevant clinical outcomes. Planned subgroup analyses were performed by (1) study design (randomized controlled trials (RCTs) or nonrandomized studies (NRS)); (2) intervention type (guideline-concordant decision support, shared care, pharmacist-facing); and (3) use of behavioral/implementation theory. RESULTS: Of 2704 manuscripts screened, 73 underwent full-text review; 22 met inclusion criteria. BP target achievement was reported in 15 and systolic BP reduction in 6 studies. Among RCTs, all interventions had a significant effect on BP control, (pooled OR 1.21; 95% CI 1.07 to 1.38). Subgroup analysis by intervention type showed significant effects for guideline-concordant decision support (pooled OR 1.19; 95% CI 1.12 to 1.27) but not shared care (pooled OR 1.71; 95% CI 0.96 to 3.03) or pharmacist-facing interventions (pooled OR 1.04; 95% CI 0.82 to 1.34). Subgroup analysis finding was replicated with pooling of RCTs and NRS. The five contributing studies showed large and significant reduction in systolic BP (pooled WMD - 3.86; 95% CI - 7.2 to - 0.55). Use of a behavioral/implementation theory had no impact, while RCTs showed smaller effect sizes than NRS. DISCUSSION: Process-oriented implementation strategies used with guideline-concordant decision support was a promising implementation approach. Better reporting guidelines on implementation would enable more useful synthesis of the efficacy of CKD clinical interventions integrated into primary care. PROSPERO REGISTRATION NUMBER: CRD42018102441.

Antifungal prophylaxis in lung transplant recipients: A systematic review and meta-analysis.

BACKGROUND: No consensus exists regarding optimal strategy for antifungal prophylaxis following lung transplant. OBJECTIVE: To review data regarding antifungal prophylaxis on the development of fungal infections. STUDY SELECTION/APPRAISAL: We searched MEDLINE, Embase, and Scopus for eligible articles through December 10, 2019. Observational or controlled trials published after January 1, 2001, that pertained to the prevention of fungal infections in adult lung recipients were reviewed independently by two reviewers for inclusion. METHODS: Of 1702 articles screened, 24 were included. Data were pooled using random effects model to evaluate for the primary outcome of fungal infection. Studies were stratified by prophylactic strategy, medication, and duration (short term < 6 months and long term ≥ 6 months). RESULTS: We found no difference in the odds of fungal infection with universal prophylaxis (49/101) compared to no prophylaxis (36/93) (OR 0.76, CI: 0.03-17.98; I2  = 93%) and preemptive therapy (25/195) compared to universal prophylaxis (35/222) (OR 0.91, CI: 0.06-13.80; I2  = 93%). The cumulative incidence of fungal infections within 12 months was not different with nebulized amphotericin (0.08, CI: 0.04-0.13; I2  = 87%) compared to systemic triazoles (0.07, CI: 0.03-0.11; I2  = 21%) (P = .65). Likewise, duration of prophylaxis did not impact the incidence of fungal infections (short term: 0.11, CI: 0.05-0.17; I2  = 89%; long term: 0.06, CI: 0.03-0.08; I2  = 51%; P = .39). CONCLUSIONS: We have insufficient evidence to support or exclude a benefit of antifungal prophylaxis.

Association of Thyroid Function with Posttraumatic Stress Disorder: a Systematic Review and Meta-Analysis.

OBJECTIVE: To conduct a systematic review and meta-analysis describing the association of thyroid function with posttraumatic stress disorder (PTSD) in adults. METHODS: The authors conducted a comprehensive search from databases' inception to July 20, 2018. The meta-analysis included studies that reported mean values and standard deviation (SD) of thyroid hormone levels (thyroid-stimulating hormone [TSH], free thyroxine [FT4], free triiodothyronine [FT3], total T4 [TT4], and total T3 [TT3]) in patients with PTSD compared with controls. Five reviewers worked independently, in duplicate, to determine study inclusion, extract data, and assess risk of bias. The mean value and SD of the thyroid function tests were used to calculate the mean difference for each variable. Random-effects models for meta-analyses were applied. RESULTS: The meta-analysis included 10 observational studies at low-to-moderate risk of bias. Studies included 674 adults (373 PTSD, 301 controls). The meta-analytic estimates showed higher levels of FT3 (+0.28 pg/mL; P = .001) and TT3 (+18.90 ng/dL; P = .005) in patients with PTSD compared to controls. There were no differences in TSH, FT4, or TT4 levels between groups. In the subgroup analysis, patients with combat-related PTSD still had higher FT3 (+0.36 pg/mL; P = .0004) and higher TT3 (+31.62 ng/dL; P<.00001) compared with controls. Conversely, patients with non-combat-related PTSD did not have differences in FT3 or TT3 levels compared with controls. CONCLUSION: There is scarce evidence regarding the association of thyroid disorders with PTSD. These findings add to the growing literature suggesting that thyroid function changes may be associated with PTSD.

Interventions to improve older adults' Emergency Department patient experience: A systematic review.

STUDY OBJECTIVE: To summarize interventions that impact the experience of older adults in the emergency department (ED) as measured by patient experience instruments. METHODS: This is a systematic review to evaluate interventions aimed to improve geriatric patient experience in the ED. We searched Ovid CENTRAL, Ovid EMBASE, Ovid MEDLINE and PsycINFO from inception to January 2019. The main outcome was patient experience measured through instruments to assess patient experience or satisfaction. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach was used to evaluate the confidence in the evidence available. RESULTS: The search strategy identified 992 studies through comprehensive literature search and hand-search of reference lists. A total of 21 studies and 3163 older adults receiving an intervention strategy aimed at improve patient experience in the ED were included. Department-wide interventions, including geriatric ED and comprehensive geriatric assessment unit, focused care coordination with discharge planning and referral for community services, were associated with improved patient experience. Providing an assistive listening device to those with hearing loss and having a pharmacist reviewing the medication list showed an improved patient perception of quality of care provided. The confidence in the evidence available for the outcome of patient experience was deemed to be very low. CONCLUSION: While all studies reported an outcome of patient experience, there was significant heterogeneity in the tools used to measure it. The very low certainty in the evidence available highlights the need for more reliable tools to measure patient experience and studies designed to measure the effect of the interventions.

Association between delayed gastric emptying and upper gastrointestinal symptoms: a systematic review and meta-analysis.

BACKGROUND: The relationship between delayed gastric emptying and upper GI symptoms (UGI Sx) is controversial. OBJECTIVE: To assess association between gastric emptying and UGI Sx, independent of treatment. DESIGN: We performed a systematic review and meta-analysis of the literature from 2007 to 2017, review of references and additional papers identified by content expert. We included studies evaluating the association between gastric emptying and nausea, vomiting, early satiety/postprandial fullness, abdominal pain and bloating. Covariate analyses included optimal gastric emptying test method, gastric emptying type (breath test or scintigraphy) and patient category. Meta-regression compared the differences based on type of gastric emptying tests. RESULTS: Systematic review included 92 gastric emptying studies (26 breath test, 62 scintigraphy, 1 ultrasound and 3 wireless motility capsule); 25 of these studies provided quantitative data for meta-analysis (15 scintigraphy studies enrolling 4056 participants and 10 breath test studies enrolling 2231 participants). Meta-regression demonstrated a significant difference between optimal and suboptimal gastric emptying test methods when comparing delayed gastric emptying with nausea and vomiting. On evaluating studies using optimal gastric emptying test methodology, there were significant associations between gastric emptying and nausea (OR 1.6, 95% CI 1.4 to 1.8), vomiting (OR 2.0, 95% CI 1.6 to 2.7), abdominal pain (OR 1.5, 95% CI 1.0 to 2.2) and early satiety/fullness (OR 1.8, 95% CI 1.2 to 2.6) for patients with UGI Sx; gastric emptying and early satiety/fullness in patients with diabetes; gastric emptying and nausea in patients with gastroparesis. CONCLUSIONS: The systematic review and meta-analysis supports an association between optimally measured delayed gastric emptying and UGI Sx.

Office-Based Mesenchymal Stem Cell Therapy for the Treatment of Musculoskeletal Disease: A Systematic Review of Recent Human Studies.

BACKGROUND: The use of mesenchymal stem cells (MSCs) in clinical applications for the treatment of musculoskeletal disease is steadily increasing in office-based practice. The so-called "first generation" of MSCs is defined as autologous stem cells that have undergone minimal manipulation and are used for a homologous purpose. Systematic reviews of the clinical trials completed to date of such MSCs enable practitioners to better understand what is currently known about the outcomes and side effects of such treatments. STUDY DESIGN: A systematic review of human clinical studies of office-based MSC therapy for the treatment of painful degenerative musculoskeletal conditions. METHODS: A search of the Ovid MEDLINE, EMBASE, and Scopus databases was conducted from 2006 through September 2016. Seven hundred sixty-one records were identified from database searching, and two records from reference review of included papers. Studies with human subjects that evaluated treatment of musculoskeletal disease with minimally manipulated MSCs were included. RESULTS: Eight studies were included in this review based on selection criteria. A total of 941 patients were included, 841 of whom received cellular products, and no significant adverse events were reported. Symptomatology generally improved, though no differences were seen over controls where present. CONCLUSION: Support in the literature is strongest for the use of bone marrow aspirate concentrate (BMAC) injections for the treatment of knee pain, but applications of the use of BMAC and peripheral blood-derived MSCs for the treatment of hip pain, tendon pain, and disc pain have all been reported. Further research is required, with large randomized controlled trials.

Safety and Efficacy of Intravenous Lidocaine for Pain Management in the Emergency Department: A Systematic Review.

STUDY OBJECTIVE: We evaluate the safety and efficacy of intravenous lidocaine in adult patients with acute and chronic pain who are undergoing pain management in the emergency department (ED). METHODS: We searched Ovid CENTRAL, Ovid EMBASE, and Ovid MEDLINE databases for randomized controlled trials and observational studies from inception to January 2017. Efficacy outcomes included reduction in pain scores from baseline to postintervention and need for rescue analgesia. Safety outcomes included incidence of serious (eg, cardiac arrest) and nonserious (eg, dizziness) adverse events. We used the Cochrane Collaboration tool and a modified Newcastle-Ottawa Scale to evaluate the risk of bias across studies. The Grading of Recommendations Assessment, Development and Evaluation approach was used to evaluate the confidence in the evidence available. RESULTS: From a total of 1,947 titles screened, 61 articles were selected for full-text review. Eight studies met the inclusion criteria and underwent qualitative analysis, including 536 patients. The significant clinical heterogeneity and low quality of studies precluded a meta-analysis. Among the 6 randomized controlled trials included, intravenous lidocaine had efficacy equivalent to that of active controls in 2 studies, and was better than active controls in 2 other studies. In particular, intravenous lidocaine had pain score reduction comparable to or higher than that of intravenous morphine for pain associated with renal colic and critical limb ischemia. Lidocaine did not appear to be effective for migraine headache in 2 studies. There were 20 adverse events reported by 6 studies among 225 patients who received intravenous lidocaine in the ED, 19 nonserious and 1 serious (rate 8.9%, 95% confidence interval 5.5% to 13.4% for any adverse event; and 0.4%, 95% confidence interval 0% to 2.5% for serious adverse events). The confidence in the evidence available for the outcomes evaluated was deemed to be very low because of methodological limitations, including risk of bias, inconsistency, and imprecision. CONCLUSION: There is limited current evidence to define the role of intravenous lidocaine as an analgesic for patients with acute renal colic and critical limb ischemia pain in the ED. Its efficacy for other indications has not been adequately tested. The safety of lidocaine for ED pain management has not been adequately examined.

Atypical fibroxanthoma: Systematic review and meta-analysis of treatment with Mohs micrographic surgery or excision.

BACKGROUND: Atypical fibroxanthoma (AFX) is a fibrohistiocytic tumor with relatively high local recurrence rates but low metastatic potential. Wide local excision (WLE) and Mohs micrographic surgery (MMS) are common treatments, although no consensus exists regarding optimal therapy. OBJECTIVE: To systematically review evidence of AFX recurrence and metastatic rates after different surgical modalities. METHODS: A comprehensive search was performed for articles published from 1946 or database inception to March 20, 2017. Studies selected included those that had 5 or more patients with atypical fibroxanthoma treated surgically. Two reviewers independently abstracted the data. Risk of bias was assessed with the Newcastle-Ottawa scale. Main outcomes and measures included recurrence and metastasis. RESULTS: In total, 23 studies were selected (907 patients and 914 tumors); 175 patients were treated with MMS (recurrence rate 2.0%, 95% confidence interval [CI] 0%-4.1%; metastatic rate 1.9%, 95% CI 0.1%-3.8%), and 732 were treated with WLE (recurrence rate 8.7%, 95% CI 5%-12.3%; metastasis rate 1%, 95% CI 0.2%-1.9%). Among immunocompromised patients, no recurrence or metastases developed in the MMS subgroup, although 4 of 10 recurred and 1 of 10 metastasized in the WLE subgroup. LIMITATIONS: Low quality of the studies published. CONCLUSION: MMS for atypical fibroxanthoma is associated with a lower recurrence rate than WLE.

Comparison of efficacy of pharmacological treatments for chronic idiopathic constipation: a systematic review and network meta-analysis.

OBJECTIVE: To compare efficacy of pharmacotherapies for chronic idiopathic constipation (CIC) based on comparisons to placebo using Bayesian network meta-analysis. DATA SOURCES: We conducted searches (inception to May 2015) of MEDLINE, EMBASE, Scopus and Cochrane Central, as well as original data from authors or drug companies for the medications used for CIC. STUDY SELECTION: Phase IIB and phase III randomised, placebo-controlled trials (RCT) of ≥4 weeks' treatment for CIC in adults with Rome II or III criteria for functional constipation; trials included at least one of four end points. DATA EXTRACTION AND SYNTHESIS: Two investigators independently evaluated all full-text articles that met inclusion criteria and extracted data for primary and secondary end points, risk of bias and quality of evidence. OUTCOMES: Primary end points were ≥3 complete spontaneous bowel movements (CSBM)/week and increase over baseline by ≥1 CSBM/week. Secondary end points were change from baseline (Δb) in the number of SBM/week and Δb CSBM/week. RESULTS: Twenty-one RCTs (9189 patients) met inclusion and end point criteria: 9 prucalopride, 3 lubiprostone, 3 linaclotide, 2 tegaserod, 1 each velusetrag, elobixibat, bisacodyl and sodium picosulphate (NaP). All prespecified end points were unavailable in four polyethylene glycol studies. Bisacodyl, NaP, prucalopride and velusetrag were superior to placebo for the ≥3 CSBM/week end point. No drug was superior at improving the primary end points on network meta-analysis. Bisacodyl appeared superior to the other drugs for the secondary end point, Δb in number of SBM/week. CONCLUSIONS: Current drugs for CIC show similar efficacy. Bisacodyl may be superior to prescription medications for Δb in the number of SBM/week in CIC.

Interventions to prevent and reduce physician burnout: a systematic review and meta-analysis.

BACKGROUND: Physician burnout has reached epidemic levels, as documented in national studies of both physicians in training and practising physicians. The consequences are negative effects on patient care, professionalism, physicians' own care and safety, and the viability of health-care systems. A more complete understanding than at present of the quality and outcomes of the literature on approaches to prevent and reduce burnout is necessary. METHODS: In this systematic review and meta-analysis, we searched MEDLINE, Embase, PsycINFO, Scopus, Web of Science, and the Education Resources Information Center from inception to Jan 15, 2016, for studies of interventions to prevent and reduce physician burnout, including single-arm pre-post comparison studies. We required studies to provide physician-specific burnout data using burnout measures with validity support from commonly accepted sources of evidence. We excluded studies of medical students and non-physician health-care providers. We considered potential eligibility of the abstracts and extracted data from eligible studies using a standardised form. Outcomes were changes in overall burnout, emotional exhaustion score (and high emotional exhaustion), and depersonalisation score (and high depersonalisation). We used random-effects models to calculate pooled mean difference estimates for changes in each outcome. FINDINGS: We identified 2617 articles, of which 15 randomised trials including 716 physicians and 37 cohort studies including 2914 physicians met inclusion criteria. Overall burnout decreased from 54% to 44% (difference 10% [95% CI 5-14]; p<0·0001; I2=15%; 14 studies), emotional exhaustion score decreased from 23·82 points to 21·17 points (2·65 points [1·67-3·64]; p<0·0001; I2=82%; 40 studies), and depersonalisation score decreased from 9·05 to 8·41 (0·64 points [0·15-1·14]; p=0·01; I2=58%; 36 studies). High emotional exhaustion decreased from 38% to 24% (14% [11-18]; p<0·0001; I2=0%; 21 studies) and high depersonalisation decreased from 38% to 34% (4% [0-8]; p=0·04; I2=0%; 16 studies). INTERPRETATION: The literature indicates that both individual-focused and structural or organisational strategies can result in clinically meaningful reductions in burnout among physicians. Further research is needed to establish which interventions are most effective in specific populations, as well as how individual and organisational solutions might be combined to deliver even greater improvements in physician wellbeing than those achieved with individual solutions. FUNDING: Arnold P Gold Foundation Research Institute.

Outcomes Following Complete Surgical Metastasectomy for Patients with Metastatic Renal Cell Carcinoma: A Systematic Review and Meta-Analysis.

PURPOSE: The benefit of complete surgical metastasectomy for patients with metastatic renal cell carcinoma remains controversial due to limited outcome data. We performed a systematic review and meta-analysis to determine whether complete surgical metastasectomy confers a survival benefit compared to incomplete or no metastasectomy for patients with metastatic renal cell carcinoma. MATERIALS AND METHODS: Ovid Embase®, MEDLINE®, Cochrane and Scopus® databases were searched for studies evaluating complete surgical metastasectomy for metastatic renal cell carcinoma through January 19, 2016. Only comparative studies reporting adjusted hazard ratios (aHRs) for all cause mortality of incomplete surgical metastasectomy vs complete surgical metastasectomy were included in the analysis. Generic inverse variance with random effects models was used to determine the pooled aHR. Risk of bias was assessed with the Newcastle-Ottawa Scale. RESULTS: Eight published cohort studies with a low or moderate potential for bias were included in the final analysis. The studies reported on a total of 2,267 patients (958 undergoing complete surgical metastasectomy and 1,309 incomplete surgical metastasectomy). Median overall survival ranged between 36.5 and 142 months for those undergoing complete surgical metastasectomy, compared to 8.4 to 27 months for incomplete surgical metastasectomy. Complete surgical metastasectomy was associated with a reduced risk of all cause mortality compared with incomplete surgical metastasectomy (pooled aHR 2.37, 95% CI 2.03-2.87, p <0.001), with low heterogeneity (I2 = 0%). Complete surgical metastasectomy remained independently associated with a reduction in mortality across a priori subgroup and sensitivity analyses, and regardless of whether we adjusted for performance status. CONCLUSIONS: Complete surgical metastasectomy for metastatic renal cell carcinoma is associated with improved survival compared with incomplete surgical metastasectomy based on meta-analysis of observational data. Consideration should be given to performing complete surgical metastasectomy, when technically feasible, in patients with metastatic renal cell carcinoma who are surgical candidates.

Effectiveness of surgical interventions for thoracic aortic aneurysms: A systematic review and meta-analysis.

OBJECTIVE: A systematic review and meta-analysis was conducted to evaluate the effectiveness of thoracic endovascular aortic repair (TEVAR) and open repair in patients with descending thoracic aortic aneurysms (TAAs). METHODS: PubMed, Ovid MEDLINE, Ovid Embase, EBSCO Cumulative Index to Nursing and Allied Health Literature, and Scopus were searched from each database's inception to January 29, 2016. We selected studies that compared the two approaches in adults with TAAs and reported 30-day mortality or procedure complications. Two reviewers independently extracted data, and conflicts were resolved by consensus. Random-effects meta-analysis was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs). The main outcomes and measures were all-cause 30-day mortality, 30-day paraplegia or spinal cord ischemia, stroke, pulmonary complications, and length of hospital and intensive care unit (ICU) stay. RESULTS: Twenty-seven studies of moderate methodologic quality were included. TEVAR was associated with lower 30-day mortality in ruptured (OR, 0.58; 95% CI, 0.38-0.88) and intact (OR, 0.6; 95% CI, 0.36-0.99) aneurysms. Paraplegia or spinal cord ischemia (OR, 0.35; 95% CI, 0.2-0.61) and pulmonary complications (OR, 0.41; 95% CI, 0.37-0.46) were reduced in patients undergoing TEVAR, whereas a reduction in stroke risk was not statistically significant (OR, 0.89; 95% CI, 0.76-1.03). Pooled mean difference in length of hospital and ICU stay was lower for TEVAR by -5.17 days (95% CI, -7.77 to -2.57) and -5.89 days (95% CI, -9.65 to -2.12), respectively. Three studies showed that compared with open repair, a hybrid approach reduced hospital stay (pooled mean difference, -8.83 days; 95% CI, -14.37 to -3.29) and ICU stay (pooled mean difference, -3.17 days (95% CI, -5.54 to -0.97), with minimal evidence on other outcomes studied. CONCLUSIONS: Observational evidence at high risk of confounding suggests that compared with open repair for TAA, TEVAR reduced risk of mortality, paraplegia, spinal cord ischemia, and pulmonary complications within 30 days of intervention. Patients undergoing TEVAR also had shorter length of hospital and ICU stay compared with patients undergoing open repair.

Effectiveness of Apneic Oxygenation During Intubation: A Systematic Review and Meta-Analysis.

STUDY OBJECTIVE: We conduct a systematic review and meta-analysis to evaluate the effectiveness of apneic oxygenation during emergency intubation. METHODS: We searched Ovid MEDLINE, Ovid EMBASE, Ovid CENTRAL, and Scopus databases for randomized controlled trials and observational studies from 2006 until July 2016, without language restrictions. Gray literature, clinicaltrials.gov, and reference lists of articles were hand searched. We conducted a meta-analysis with random-effects models to evaluate first-pass success rates, incidence of hypoxemia, and lowest peri-intubation SpO2 between apneic oxygenation and standard oxygenation cases. RESULTS: A total of 1,386 studies were screened and 77 selected for full-text review. A total of 14 studies were included for qualitative analysis, and 8 studies (1,837 patients) underwent quantitative analysis. In the meta-analysis of 8 studies (1,837 patients), apneic oxygenation was associated with decreased hypoxemia (odds ratio [OR] 0.66; 95% confidence interval [CI] 0.52 to 0.84), but was not associated with decreased severe hypoxemia (6 studies; 1,043 patients; OR 0.86; 95% CI 0.47 to 1.57) or life-threatening hypoxemia (5 studies; 1,003 patients; OR 0.90; 95% CI 0.52 to 1.55). Apneic oxygenation was associated with increased first-pass success rate (6 studies; 1,658 patients; OR 1.59; 95% CI 1.04 to 2.44) and increased lowest peri-intubation SpO2 (6 studies; 1,043 patients; weighted mean difference 2.2%; 95% CI 0.8% to 3.6%). CONCLUSION: In this meta-analysis, apneic oxygenation was associated with increased peri-intubation oxygen saturation, decreased rates of hypoxemia, and increased first-pass intubation success.

The effect of disease severity markers on quality of life in autosomal dominant polycystic kidney disease: a systematic review, meta-analysis and meta-regression.

BACKGROUND: Little is known about determinants of quality of life (QoL) in autosomal dominant polycystic kidney disease (ADPKD). Recent studies suggest that QoL in ADPKD is determined by more factors than mere renal function. We investigated the effect of ADPKD on QoL and evaluated how Qol is affected by disease severity markers renal function, kidney volume and liver volume. METHODS: We performed a systematic review, meta-analysis and meta-regression analyses of cohort studies and randomized controlled trials investigating patient-reported QoL in adult patients with ADPKD not yet on dialysis. EMBASE, MEDLINE, and Web of Science were searched to August 2015 without language restrictions. Two investigators independently reviewed title, abstracts and full text of potentially relevant citations to determine eligibility. We compared pooled QoL summary scores of ADPKD patients using a random-effects meta-analytic model. These scores were compared with mean and age-corrected reference scores of the general population. In a meta-regression analysis, we investigated the univariate effect of renal function, kidney volume and liver volume on QoL. RESULTS: We included nine studies in meta-analysis including 1623 patients who completed the SF-36 questionnaire. Pooled physical (PCS) and mental component scores (MCS) of the SF-36 of individuals with ADPKD were lower than those of the reference population (45.7 vs. 50.0 and 47.8 vs. 50.0 points, both P < 0.001). QoL of ADPKD patients remained lower after comparison with age-corrected reference values (age 35-44 year; PCS 52.2, MCS 49.9 points, both P < 0.05). Larger liver volume negatively impacted PCS (P < 0.001) and MCS (P = 0.001), whereas there was no association with renal function (PCS P = 0.1, MCS P = 0.9) and kidney volume (PCS P = 0.5, MCS P = 0. 5). Total liver and kidney volume had no impact on PCS (P = 0.1), but did have impact on MCS (P = 0.02). CONCLUSIONS: QoL reported by non-dialysis patients with ADPKD is impaired compared to the general population. Large liver volume was the most important factor that diminishes QoL. PROSPERO International Registry number CRD42015026428.

Vitamin D and food allergies in children: A systematic review and meta-analysis.

BACKGROUND: Vitamin D insufficiency has been associated with immune dysfunction and linked to the epidemic of atopic diseases in the Western hemisphere, yet there are studies with conflicting results, and the risk has not been quantified uniformly across studies. OBJECTIVE: To perform a systematic review and meta-analysis to evaluate and quantify if vitamin D deficiency is associated with the presence and persistence of food allergy. METHODS: A systematic review was undertaken to assess for the association between food allergy and vitamin D status in children. RESULTS: A total of 368 citations relevant to this systematic review were identified. In the whole review, 5105 children were included. We did not find a significant association between 25 hydroxy vitamin D (25(OH)D) status and risk of food allergy in children (odds ratio [OR] 1.35 [95% confidence interval {CI}, 0.79-2.29]; p = 0.27, I2 = 58.3%). We conducted subgroup analyses based on different cutoffs of the 25(OH)D status (20 versus 30 ng/mL). Only one study used 30 ng/mL and found that children with <30 ng/mL were more likely to report food allergy than children with a 25(OH)D status of ≥30 ng/mL (OR 2.04 [95% CI, 1.02-4.04]; p = 0.04). Four studies compared children with a 25(OH)D status of <20 ng/mL to children with a 25(OH)D status of ≥20 ng/mL and found no significant differences (OR 1.18 [95% CI, 0.62-2.27]; p = 0.62, I2 = 62.7%). CONCLUSION: Based on the studies analyzed, this systematic review did not identify a significant association between vitamin D status and food allergy. Interpretation of the included studies was limited by a lack of a standard definition for vitamin D deficiency and insufficient knowledge regarding the optimal vitamin D status needed to impact immune function. Longitudinal studies are warranted to assess if vitamin D might contribute to the development of food allergy.