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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.

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.

Background Perioperative administration of corticosteroid is common and variable. Guidelines for perioperative corticosteroid administration before non-cardiac non-transplant surgery in patients with current or previous corticosteroid use to reduce the risk of adrenal insufficiency are lacking. Perioperative use of corticosteroid may be associated with serious adverse events, namely hyperglycemia, infection, and poor wound healing. Objective To determine whether perioperative administration of corticosteroids, compared to placebo or no intervention, reduces the incidence of adrenal insufficiency in adult patients undergoing non-cardiac surgery who were or are exposed to corticosteroids. Methods We searched MEDLINE via Ovid and PubMed, EMBASE via Ovid, and the Cochrane Central Register of Controlled Trials, all from 1995 to January 2017. Selection criteria We included randomized controlled trials (RCTs), cohort studies, case-studies, and systematic reviews involving adults undergoing non-cardiac non-transplant surgery and reporting the incidence of postoperative adrenal insufficiency. Data collection and analysis Two authors independently assessed studies’ quality and extracted data. A descriptive and bias assessment analysis was performed. Results Two RCTs (total of 37 patients), five cohort studies (total of 462 patients), and four systematic reviews were included. Neither RCT showed a significant difference in the outcome. This result was like that of the five cohort studies. The quality of the evidence was low. Conclusion The current use of perioperative corticosteroid supplementation to prevent adrenal insufficiency is not supported by evidence. Given the significant studies’ limitations, it is not possible to conclude that perioperative administration of corticosteroids, compared to placebo, reduces the incidence of adrenal insufficiency. Electronic supplementary material The online version of this article (10.1186/s13741-018-0092-9) contains supplementary material, which is available to authorized users.

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.