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Excessive opioid prescribing after surgery has contributed to the current opioid crisis; however, the value of prescribing opioids at surgical discharge remains uncertain. We aimed to estimate the extent to which opioid prescribing after discharge affects self-reported pain intensity and adverse events in comparison with an opioid-free analgesic regimen.In this systematic review and meta-analysis, we searched MEDLINE, Embase, the Cochrane Library, Scopus, AMED, Biosis, and CINAHL from Jan 1, 1990, until July 8, 2021. We included multidose randomised controlled trials comparing opioid versus opioid-free analgesia in patients aged 15 years or older, discharged after undergoing a surgical procedure according to the Physiological and Operative Severity Score for the Enumeration of Mortality and Morbidity definition (minor, moderate, major, and major complex). We screened articles, extracted data, and assessed risk of bias (Cochrane's risk-of-bias tool for randomised trials) in duplicate. The primary outcomes of interest were self-reported pain intensity on day 1 after discharge (standardised to 0-10 cm visual analogue scale) and vomiting up to 30 days. Pain intensity at further timepoints, pain interference, other adverse events, risk of dissatisfaction, and health-care reutilisation were also assessed. We did random-effects meta-analyses and appraised evidence certainty using the Grading of Recommendations, Assessment, Development, and Evaluations scoring system. The review was registered with PROSPERO (ID CRD42020153050).47 trials (n=6607 patients) were included. 30 (64%) trials involved elective minor procedures (63% dental procedures) and 17 (36%) trials involved procedures of moderate extent (47% orthopaedic and 29% general surgery procedures). Compared with opioid-free analgesia, opioid prescribing did not reduce pain on the first day after discharge (weighted mean difference 0·01cm, 95% CI -0·26 to 0·27; moderate certainty) or at other postoperative timepoints (moderate-to-very-low certainty). Opioid prescribing was associated with increased risk of vomiting (relative risk 4·50, 95% CI 1·93 to 10·51; high certainty) and other adverse events, including nausea, constipation, dizziness, and drowsiness (high-to-moderate certainty). Opioids did not affect other outcomes.Findings from this meta-analysis support that opioid prescribing at surgical discharge does not reduce pain intensity but does increase adverse events. Evidence relied on trials focused on elective surgeries of minor and moderate extent, suggesting that clinicians can consider prescribing opioid-free analgesia in these surgical settings. Data were largely derived from low-quality trials, and none involved patients having major or major-complex procedures. Given these limitations, there is a great need to advance the quality and scope of research in this field.The Canadian Institutes of Health Research.

Background The purpose of this study was to determine if observational therapy is noninferior to antibiotics for acute uncomplicated diverticulitis according to clinically relevant margins. Methods MEDLINE, EMBASE, and Cochrane were systematically searched by 2 independent reviewers to identify comparative studies of observational therapy versus antibiotics for acute uncomplicated diverticulitis. Non-inferiority margins (ΔNI) for each outcome were based on Delphi consensus including 50 patients and 55 physicians: persistent diverticulitis (ΔNI = 4.0%), progression to complicated diverticulitis (ΔNI = 3.0%), and time to recovery (ΔNI = 5 days). Risk differences and mean differences were pooled using random-effects meta-analysis. One-sided 90% confidence intervals and Z-tests were used to determine non-inferiority. A sensitivity analysis was performed, excluding patients post hoc determined to have complicated diverticulitis. Results Nine studies (3 randomized controlled trials, 6 observational studies) met inclusion criteria: observational therapy (n = 2,011) versus antibiotics (n = 1,144). Observational therapy was noninferior to antibiotics regarding the risk of persistent diverticulitis (pooled risk differences: -0.39%, 90% CI -3.22 to 2.44%, ΔNI: 4.0%, PNI Conclusion According to clinically relevant ΔNIs, observational therapy was noninferior to antibiotics for the treatment of acute uncomplicated diverticulitis with regard to persistent diverticulitis and progression to complicated diverticulitis.

Background Pneumocystis jirovecii pneumonia (PCP) is an opportunistic infection commonly affecting immunocompromised people. Diagnosis usually requires invasive techniques to obtain respiratory specimens. Minimally invasive detection tests have been proposed, but their operating characteristics are poorly described. Objectives To systematically review and meta-analyse the performance of minimally invasive PCP detection tests to inform diagnostic algorithms. Data sources Medline, Embase, Cochrane Library (inception to 15 October 2020). Study eligibility criteria Studies of minimally invasive PCP detection tests were included if they contained a minimum of ten PCP cases. Participants Adults at risk of PCP. Tests Non-invasive PCP detection tests. Reference standard Diagnosis using the combination of clinical and radiographical features with invasive sampling. Assessment of risk bias Using the QUADAS-2 tool. Methods We used bivariate and, when necessary, univariate analysis models to estimate diagnostic test sensitivity and specificity. Results Fifty-two studies were included; most studies (40) comprised exclusively human immunodeficiency virus (HIV) -infected individuals; nine were mixed (HIV and non-HIV), two were non-HIV and one study did not report HIV status. Sampling sites included induced sputum, nasopharyngeal aspirate, oral wash and blood. The four testing modalities evaluated were cytological staining, fluorescent antibody, PCR and lactate dehydrogenase. Induced sputum had the most data available; this modality was both highly sensitive at 99% (95% CI 51%–100%) and specific at 96% (95% CI 88%–99%). Induced sputum cytological staining had moderate sensitivity at 50% (95% CI 39%–61%) and high specificity at 100% (95% CI 100%–100%), as did fluorescent antibody testing with sensitivity 74% (95% CI 62%–87%) and specificity 100% (95% CI 91%–100%). Conclusion There are several promising minimally invasive PCP diagnostic tests available, some of which may reduce the need for invasive respiratory sampling. Understanding the operating characteristics of these tests can augment current diagnostic strategies and help establish a more confident clinical diagnosis of PCP. Further studies in non-HIV infected populations are needed.

Background Iron administration has been evaluated in several randomized controlled trials for the potential of increasing baseline hemoglobin values and decreasing the incidence of red blood cell transfusion during cardiac surgery. We describe the protocol for a study aiming to evaluate the efficacy and safety of perioperative iron administration in patients undergoing cardiac surgery. Methods We will search MEDLINE, Embase, the Cochrane Central Register of Controlled Trials and the Web of Science, from inception to Nov. 19, 2020, for randomized controlled trials in any language evaluating the perioperative administration of iron in adult patients undergoing cardiac surgery; we will also include the first 50 results from Google Scholar. The primary outcome will be the incidence of red blood cell transfusion from the study intervention time until 8 weeks postoperatively. The secondary outcomes will be the number of red blood cell units transfused; change in ferritin level, reticulocyte count and hemoglobin concentration after iron administration; and adverse events. We will assess the risk of bias with the Cochrane Collaboration Risk of Bias Tool, and will analyze the primary and secondary outcomes using a random-effects model. Interpretation This study will summarize the current evidence about perioperative iron administration in patients undergoing cardiac surgery, help determine whether this intervention should be included in enhanced-recovery protocols, and shape future research if needed. The final manuscript will be submitted to a peer-reviewed journal. Trial registration PROSPERO no. CRD42020161927.

Safe and timely access to cesarean section (CS) in low- and middle-income countries (LMIC) remains a significant challenge.To compare maternal and perinatal outcomes of CS by non-physician clinicians (NPCs) versus physicians in LMIC.A systematic search of Ovid MEDLINE, EMBASE, Cochrane Library (including CENTRAL), Web of Science, and LILACS was performed from inception to January 2022.Data were extracted by two independent reviewers and meta-analysis was performed when possible.Ten studies from seven African countries were included. There was no significant difference in maternal mortality for CS performed by NPCs versus physicians (odds ratio [OR] 1.09, 95% confidence interval [CI] 0.56-2.14, P = 0.8, INPCs have comparable maternal and neonatal outcomes for CS compared with standard providers, albeit with increased odds of wound complication.CRD42020217966.

In low- and lower middle-income countries (LMICs), timely access to primary care following thermal injury is challenging. Children with deep burns often fail to receive specialized burn care until months or years post-injury, thus suffering impairments from hypertrophic scarring or joint and soft tissue contractures. We aimed to examine the correlation between limited access to care following burn injury and long-term disability in children in LMICs and to identify specific factors affecting the occurrence of late burn complications. A systematic literature search was conducted to retrieve articles on pediatric burns in LMICs using Medline, Embase, the Cochrane Library, LILACS, Global Health, African Index Medicus, and others. Articles were assessed by two reviewers and reported in accordance with PRISMA guidelines. Of 2896 articles initially identified, 103 underwent full-text review and 14 met inclusion criteria. A total of 991 children who developed long-term burn sequelae were included. Time from injury to consultation ranged from a few months to 17 years. Factors associated with late complications included total body surface area burned, burn depth, low socio-economic status, limited infrastructure, perceived inability to pay, lack of awareness of surgical treatment, low level of maternal education, and time elapsed between burn injury and reconstructive surgery.

Background Alvimopan is a Food and Drug Administration–approved treatment to accelerate gastrointestinal recovery after abdominal surgery; however, benefits may vary across different procedures and contexts of care. The purpose of this study is to summarize the evidence regarding the effect of alvimopan on postoperative outcomes after abdominal surgery. Methods Major databases (Medline, Embase, Biosis, Cochrane, Web of Science, and Scopus) were searched for randomized controlled trials and nonrandomized studies comparing alvimopan versus control. Risk of bias was assessed using Cochrane’s risk of bias tool 2.0 (for randomized controlled trials) and Risk of Bias in Nonrandomized Studies-of Intervention tool (for nonrandomized studies). Results were appraised descriptively as heterogeneity in reporting and risk of bias hindered meta-analysis. Quality of evidence across different surgical procedures and contexts of care (ie, open versus minimally invasive surgery, traditional care versus enhanced recovery pathway) was evaluated using Grading of Recommendations Assessment, Development, and Evaluation. Results Nine randomized controlled trials and 35 nonrandomized studies were identified. Evidence of low to moderate certainty supports that alvimopan reduces length of stay and improves gastrointestinal recovery after open bowel resection and open radical cystectomy. Limited evidence supports alvimopan for surgeries not listed in Food and Drug Administration labels (ie, total abdominal hysterectomy and retroperitoneal lymph node dissection). Similar effects were observed in traditional and enhanced recovery pathway settings, but enhanced recovery pathway elements varied across studies. There is very low certainty of evidence supporting alvimopan for patients undergoing minimally invasive surgery. Conclusion Evidence supports that alvimopan improves outcomes after open bowel resection and open radical cystectomy. Benefits for patients undergoing minimally invasive surgery and treated in contemporary enhanced recovery pathway settings remain uncertain. These findings contribute important new knowledge to inform evidence-based alvimopan prescribing.

BackgroundPneumocystis jirovecii pneumonia (PJP) remains a common and highly morbid infection for immunocompromised patients. Trimethoprim-sulfamethoxazole (TMP-SMX) is the antimicrobial treatment of choice. However, treatment with TMP-SMX can lead to significant dose-dependent renal and hematologic adverse events. Although TMP-SMX is conventionally dosed at 15–20 mg/kg/d of trimethoprim for the treatment of PJP, reduced doses may be effective and carry an improved safety profile.MethodsWe conducted a systematic search in the Medline, Embase, and Cochrane Library databases from inception through March 2019 for peer-reviewed studies reporting on reduced doses of TMP-SMX (15 mg/kg/d of trimethoprim or less) for the treatment of PJP. PRISMA, MOOSE, and Cochrane guidelines were followed. Gray literature was excluded.ResultsTen studies were identified, and 6 were included in the meta-analysis. When comparing standard doses with reduced doses of TMP-SMX, there was no statistically significant difference in mortality (absolute risk difference, –9% in favor of reduced dose; 95% confidence interval [CI], –27% to 8%). When compared with standard doses, reduced doses of TMP-SMX were associated with an 18% (95% CI, –31% to –5%) absolute risk reduction of grade ≥3 adverse events.ConclusionsIn this systematic review, treatment of PJP with doses of ≤10 mg/kg/d of trimethoprim was associated with similar rates of mortality when compared with standard doses and with significantly fewer treatment-emergent severe adverse events. Although limited by the observational nature of the studies included, this review provides the most current available evidence for the optimal dosing of TMP-SMX in the treatment of PJP.

Background Pneumocystis jirovecii pneumonia (PJP) remains a common and highly morbid infection for immunocompromised patients. Trimethoprim-sulfamethoxazole (TMP-SMX) is the antimicrobial treatment of choice. However, treatment with TMP-SMX can lead to significant dose-dependent renal and hematologic adverse events. Although TMP-SMX is conventionally dosed at 15–20 mg/kg/d of trimethoprim for the treatment of PJP, reduced doses may be effective and carry an improved safety profile. Methods We conducted a systematic search in the Medline, Embase, and Cochrane Library databases from inception through March 2019 for peer-reviewed studies reporting on reduced doses of TMP-SMX (15 mg/kg/d of trimethoprim or less) for the treatment of PJP. PRISMA, MOOSE, and Cochrane guidelines were followed. Gray literature was excluded. Results Ten studies were identified, and 6 were included in the meta-analysis. When comparing standard doses with reduced doses of TMP-SMX, there was no statistically significant difference in mortality (absolute risk difference, –9% in favor of reduced dose; 95% confidence interval [CI], –27% to 8%). When compared with standard doses, reduced doses of TMP-SMX were associated with an 18% (95% CI, –31% to –5%) absolute risk reduction of grade ≥3 adverse events. Conclusions In this systematic review, treatment of PJP with doses of ≤10 mg/kg/d of trimethoprim was associated with similar rates of mortality when compared with standard doses and with significantly fewer treatment-emergent severe adverse events. Although limited by the observational nature of the studies included, this review provides the most current available evidence for the optimal dosing of TMP-SMX in the treatment of PJP.

IntroductionExcessive prescribing after surgery has contributed to a public health crisis of opioid addiction and overdose in North America. However, the value of prescribing opioids to manage postoperative pain after surgical discharge remains unclear. We propose a systematic review and meta-analysis to assess the extent to which opioid analgesia impact postoperative pain intensity and adverse events in comparison to opioid-free analgesia in patients discharged after surgery.Methods and analysisMajor electronic databases (MEDLINE, Embase, Cochrane Library, Scopus, AMED, BIOSIS, CINAHL and PsycINFO) will be searched for multi-dose randomised-trials examining the comparative effectiveness of opioid versus opioid-free analgesia after surgical discharge. Studies published from January 1990 to July 2019 will be targeted, with no language restrictions. The search will be re-run before manuscript submission to include most recent literature. We will consider studies involving patients undergoing minor and major surgery. Teams of reviewers will, independently and in duplicate, assess eligibility, extract data and evaluate risk of bias. Our main outcomes of interest are pain intensity and postoperative vomiting. Study results will be pooled using random effects models. When trials report outcomes for a common domain (eg, pain intensity) using different scales, we will convert effect sizes to a common standard metric (eg, Visual Analogue Scale). Minimally important clinical differences reported in previous literature will be considered when interpreting results. Subgroup analyses defined a priori will be conducted to explore heterogeneity. Risk of bias will be assessed according to the Cochrane Collaboration's Risk of Bias Tool 2.0. The quality of evidence for all outcomes will be evaluated using the GRADE rating system.Ethics and disseminationEthical approval is not required since this is a systematic review of published studies. Our results will be published in a peer-reviewed journal and presented at relevant conferences. Further knowledge dissemination will be sought via public and patient organisations focussed on pain and opioid-related harms.

While the root causes for individual neurodegenerative diseases are distinct, many shared pathological features and mechanisms contribute to neurodegeneration across diseases. Altered levels of microRNAs, small non-coding RNAs involved in post transcriptional regulation of gene expression, are reported for numerous neurodegenerative diseases. Yet, comparison between diseases to uncover commonly dysregulated microRNAs during neurodegeneration in general is lagging. We performed a systematic review of peer-reviewed publications describing differential microRNA expression in neurodegenerative diseases and related animal models. We compiled the results from studies covering the prevalent neurodegenerative diseases in the literature: Alzheimer’s disease, amyotrophic lateral sclerosis, age-related macular degeneration, ataxia, dementia, myotonic dystrophy, epilepsy, glaucoma, Huntington’s disease, multiple sclerosis, Parkinson’s disease, and prion disorders. MicroRNAs which were dysregulated most often in these diseases and their models included miR-9-5p, miR-21-5p, the miR-29 family, miR-132-3p, miR-124-3p, miR-146a-5p, miR-155-5p, and miR-223-3p. Common pathways targeted by these predominant miRNAs were identified and revealed great functional overlap across diseases. We also identified a strong role for each microRNA in both the neural and immune components of diseases. microRNAs regulate broad networks of genes and identifying microRNAs commonly dysregulated across neurodegenerative diseases could cultivate novel hypotheses related to common molecular mechanisms underlying neurodegeneration.

Pre-operative hyperglycemia is associated with post-operative adverse outcomes in diabetic and non-diabetic patients. Current pre-operative screening includes random plasma glucose, yet plasma glycated hemoglobin (HbA1c) is a better measure of long-term glycemic control. It is not clear whether pre-operative HbA1c can identify non-diabetic patients at risk of post-operative complications. The systematic review summarizes the evidence pertaining to the association of suboptimal pre-operative HbA1c on post-operative outcomes in adult surgical patients with no history of diabetes mellitus. A detailed search strategy was developed by a librarian to identify all the relevant studies to date from the major online databases. Six observational studies met all the eligibility criteria and were included in the review. Four studies reported a significant association between pre-operative HbA1c levels and post-operative complications in non-diabetic patients. Two studies reported increased post-operative infection rates, and two reported no difference. Of four studies assessing the length of stay, three did not observe any association with HbA1c level and only one study observed a significant impact. Only one study found higher mortality rates in patients with suboptimal HbA1c. Based on the limited available evidence, suboptimal pre-operative HbA1c levels in patients with no prior history of diabetes predict post-operative complications and represent a potentially modifiable risk factor.