Disease State Transition Probabilities Across the Spectrum of NAFLD: A Systematic Review and Meta-Analysis of Paired Biopsy or Imaging Studies.

BACKGROUND & AIMS: We conducted a meta-analysis to summarize the rates of progression to and regression of nonalcoholic fatty liver (NAFL), nonalcoholic steatohepatitis (NASH), and fibrosis in adults with nonalcoholic fatty liver disease (NAFLD). METHODS: We searched PubMed/Medline and 4 other databases from 1985 through 2020. We included observational studies and randomized controlled trials in any language that used liver biopsy or imaging to diagnose NAFLD in adults with a follow-up period ≥48 weeks. Rates were calculated as incident cases per 100 person-years and pooled using the random-effects Poisson distribution model. Heterogeneity was assessed using the I2 statistic. RESULTS: We screened 9744 articles and included 54 studies involving 26,738 patients. Among observational studies, 20% of healthy adults developed NAFL (incidence rate, 4.8/100 person-years) while 21% of people with fatty liver had resolution of NAFL (incidence rate, 2.4/100 person-years) after a median of approximately 4.5 years. In addition, 31% of patients developed NASH after 4.7 years (incidence rate, 7.4/100 person-years), whereas in 29% of those with NASH, resolution occurred after a median of 3.5 years (incidence rate, 5.1/100 person-years). Time to progress by 1 fibrosis stage was 9.9, 10.3, 13.3, and 22.2 years for F0, F1, F2, and F3, respectively. Time to regress by 1 stage was 21.3, 12.5, 20.4, and 40.0 years for F4, F3, F2, and F1, respectively. Rates estimated from randomized controlled trials were higher than those from observational studies. CONCLUSIONS: In our meta-analysis, progression to NASH was more common than regression from NASH. Rates of fibrosis progression were similar across baseline stage, but patients with advanced fibrosis were more likely to regress than those with mild fibrosis.

Vegetarian diets on anthropometric, metabolic and blood pressure outcomes in people with overweight and obesity: a systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: It is unknown whether vegetarian diets (VDs) may improve outcomes in people with overweight and obesity. OBJECTIVE: To systematically assess the effects of VDs vs. omnivore diets on anthropometric, metabolic, and blood pressure outcomes in people with overweight and obesity. METHODS: We searched for randomized controlled trials (RCTs) in EMBASE, PubMed, Web of Science, and Scopus until February 2, 2022. Primary outcomes were anthropometric risk factors (weight, body mass index [BMI], waist circumference [WC], hip circumference [HC], and body fat percentage). Secondary outcomes were metabolic risk factors (fasting serum glucose, HbA1c, insulin levels) and blood pressure (systolic blood pressure [SBP], diastolic blood pressure [DBP]). Random-effects meta-analyses were performed and effects were expressed as mean difference (MD) and their 95% confidence intervals (CI). The quality of evidence was assessed using GRADE methods. RESULTS: Nine RCTs (n = 1628) were included. VDs decreased weight (MD -3.60 kg, 95%CI -4.75 to -2.46) and glucose (MD -10.64 mg/dL, 95%CI -15.77 to -5.51), but did not decrease WC (MD -3.00 cm, 95%CI -6.20 to 0.20), BMI (MD -0.87 kg/m2, 95%CI -1.80 to 0.06), or HC (MD: -0.86 cm, 95%CI -3.46 to 1.74). VDs did not decrease HbA1c (MD -0.40%, 95%CI -0.89 to 0.10), insulin (MD -3.83 mU/L, 95%CI -8.06 to 0.40), SBP (MD -0.25 mmHg, 95%CI -2.58 to 2.07), or DBP (MD -1.57 mmHg, 95%CI -3.93 to 0.78). Subgroup analyses by type of VD (four RCTs evaluated lacto-ovo-vegetarian diets and five RCTs vegan diets) showed similar results to the main analyses. QoE was very low for most of the outcomes. CONCLUSIONS: In comparison to an omnivorous diet, VDs may reduce weight and glucose, but not blood pressure or other metabolic or anthropometric outcomes. However, the QoE was mostly very low. Larger RCTs are still needed to evaluate the effects of VD on anthropometric, metabolic factors, and blood pressure in people with overweight and obesity.

The Impact of Ketamine for Treatment of Post-Traumatic Stress Disorder: A Systematic Review With Meta-Analyses.

BACKGROUND: Ketamine has been used in anesthesia, pain management, and major depressive disorder. It has recently been studied in patients with post-traumatic stress disorder (PTSD). OBJECTIVE: To determine the impact of ketamine on PTSD symptomatology and depression scores. METHODS: We conducted a literature search of Medline 1960 to May 20, 2023, and found 6 randomized controlled trials that met our inclusion criteria. We extracted data on the Clinician-Administered PTSD (CAPS), PTSD Checklist (PCL), or Montgomery-Asberg Depression Rating (MADRS) scales. RESULTS: The use of ketamine significantly reduced CAPS scores (n = 5, MD: -10.63 [95% CI -14.95 to -6.32]), PCL scores (n = 3, MD: -6.13 [95% CI -8.61 to -3.64]), and MADRS scores (n = 3, MD: -6.33 [95% CI -8.97 to -3.69]) at the maximal follow-up times versus control. Significant benefits were found at day 1 and weeks 1, 2, and 4 for CAPS and PCL scores as well as MADRS scores at day 1, week 1, and week 4 for ketamine versus control. The time to PTSD relapse was prolonged in the patients receiving ketamine versus control (n = 2, 15.74 days [95% CI 3.57 to 29.91 days]). More dry mouth (n = 2, OR 5.85 [95% CI 1.32 to 25.95]), dizziness (n = 2, OR 3.83 [95% CI 1.28 to 11.41]), and blurred vision (n = 2, OR 7.57 [1.00 to 57.10]) occurred with ketamine than control therapy. CONCLUSIONS AND RELEVANCE: Ketamine modestly reduced PTSD and depression scores as early as 1 day of therapy, but the longevity of effect needs to be determined. Given similar magnitude of benefit with SSRIs and venlafaxine, ketamine would not supplant these traditional options for chronic use.

Prevalence of statin intolerance: a meta-analysis.

AIMS: Statin intolerance (SI) represents a significant public health problem for which precise estimates of prevalence are needed. Statin intolerance remains an important clinical challenge, and it is associated with an increased risk of cardiovascular events. This meta-analysis estimates the overall prevalence of SI, the prevalence according to different diagnostic criteria and in different disease settings, and identifies possible risk factors/conditions that might increase the risk of SI. METHODS AND RESULTS: We searched several databases up to 31 May 2021, for studies that reported the prevalence of SI. The primary endpoint was overall prevalence and prevalence according to a range of diagnostic criteria [National Lipid Association (NLA), International Lipid Expert Panel (ILEP), and European Atherosclerosis Society (EAS)] and in different disease settings. The secondary endpoint was to identify possible risk factors for SI. A random-effects model was applied to estimate the overall pooled prevalence. A total of 176 studies [112 randomized controlled trials (RCTs); 64 cohort studies] with 4 143 517 patients were ultimately included in the analysis. The overall prevalence of SI was 9.1% (95% confidence interval 8.0-10%). The prevalence was similar when defined using NLA, ILEP, and EAS criteria [7.0% (6.0-8.0%), 6.7% (5.0-8.0%), 5.9% (4.0-7.0%), respectively]. The prevalence of SI in RCTs was significantly lower compared with cohort studies [4.9% (4.0-6.0%) vs. 17% (14-19%)]. The prevalence of SI in studies including both primary and secondary prevention patients was much higher than when primary or secondary prevention patients were analysed separately [18% (14-21%), 8.2% (6.0-10%), 9.1% (6.0-11%), respectively]. Statin lipid solubility did not affect the prevalence of SI [4.0% (2.0-5.0%) vs. 5.0% (4.0-6.0%)]. Age [odds ratio (OR) 1.33, P = 0.04], female gender (OR 1.47, P = 0.007), Asian and Black race (P < 0.05 for both), obesity (OR 1.30, P = 0.02), diabetes mellitus (OR 1.26, P = 0.02), hypothyroidism (OR 1.37, P = 0.01), chronic liver, and renal failure (P < 0.05 for both) were significantly associated with SI in the meta-regression model. Antiarrhythmic agents, calcium channel blockers, alcohol use, and increased statin dose were also associated with a higher risk of SI. CONCLUSION: Based on the present analysis of >4 million patients, the prevalence of SI is low when diagnosed according to international definitions. These results support the concept that the prevalence of complete SI might often be overestimated and highlight the need for the careful assessment of patients with potential symptoms related to SI.

A systematic review of primary care-focused, self-reported medication adherence tools.

BACKGROUND: Clinician recognition of nonadherence is generally low. Tools that clinicians have used to assess medication adherence are self-reported adherence instruments that ask patients questions about their medication use experience. There is a need for more structured reviews that help clinicians comprehensively distinguish which tool might be most useful and valuable for their clinical setting and patient populations. OBJECTIVES: This systematic review aimed to (1) identify validated, self-reported medication adherence tools that are applicable to the primary care setting and (2) summarize selected features of the tools as an assessment of clinical feasibility and applicability. METHODS: The investigators systematically reviewed MEDLINE via Ovid, Embase via Ovid, International Pharmaceutical Abstracts, and CINAHL from inception to December 1, 2020. Investigators independently screened 3394 citations, identifying 43 articles describing validation parameters for 25 unique adherence tools. After screening each tool, 17 tools met the inclusion criteria and were qualitatively summarized. RESULTS: Findings highlight 25 various tool characteristics (i.e., descriptions, parameters and diseases, measures and validity comparators, and other information), which clinicians might consider when selecting a self-reported adherence tool with strong measurement validity that is practical to administer to patients. There was much variability about the nature and extent of adherence measurement. Considerable variation was noted in the objective measures used to correlate to the self-reported tools' measurements. There were wide ranges of correlation between self-reported and objective measures. Several included tools had relatively low to moderate criterion validities. Many manuscripts did not describe whether tools were associated with costs, had copyrights, and were available in other languages; how much time was required for patients to complete self-report tools; and whether patient input informed tool development. CONCLUSION: There is a critical need to ensure that adherence tool developers establish a key list of tool characteristics to report to help clinicians and researchers make practical comparisons among tools.

Nasogastric versus nasojejunal tube feeding for severe acute pancreatitis: A systematic review of randomized controlled trials.

Early enteral nutrition through a feeding tube is essential for the management of severe acute pancreatitis (SAP). Nasojejunal tube nutrition has been preferred on the assumption that it provided pancreatic rest in comparison to the nasogastric tube. However, nasojejunal tube placement is complex, may delay feeding initiation and can increase hospital costs. Our aim was to compare the efficacy and safety of enteral feeding with a nasogastric tube versus nasojejunal tube in patients with SAP. We searched four databases (PubMed, Web of Science, Scopus, and Embase) until December 1, 2022. We included randomized controlled trials (RCTs) comparing enteral feeding by nasogastric and nasojejunal tubes in patients with SAP. Primary outcome was all-cause mortality. Secondary outcomes were organ failure, infection, complications, surgical intervention, duration of tube feeding and length of hospital stay. Risk of bias assessment was completed independently by two investigators using the Cochrane RoB 2.0 tool. We performed random effects model meta-analyses using the inverse variance method. Effect measures were reported as relative risks (RR) and their 95% CIs for dichotomous outcomes and mean differences (MD) and their 95% CIs for continuous outcomes. We included four RCTs involving 192 patients with SAP. The mean ages ranged between 36 and 62 years old. There was no significant difference in all-cause mortality between the nasogastric and nasojejunal feeding arms (18/98 vs. 23/93; RR 1.34, 95%CI 0.77-2.30; p=0.30). There were no significant differences in all secondary outcomes between feeding arms. There were three RCTs with some concerns of bias, in the randomization process. In conclusion, in patients with SAP, enteral feeding delivered by nasogastric tube was as efficacious and safe as nasojejunal tube. Further randomized controlled trials with more participants and better design are needed to confirm these findings.

Ivermectin for the Treatment of Coronavirus Disease 2019: A Systematic Review and Meta-analysis of Randomized Controlled Trials.

BACKGROUND: We systematically assessed benefits and harms of the use of ivermectin (IVM) in patients with coronavirus disease 2019 (COVID-19). METHODS: Published and preprint randomized controlled trials (RCTs) assessing the effects of IVM on adult patients with COVID-19 were searched until 22 March 2021 in 5 engines. Primary outcomes were all-cause mortality rate, length of hospital stay (LOS), and adverse events (AEs). Secondary outcomes included viral clearance and severe AEs (SAEs). The risk of bias (RoB) was evaluated using the Cochrane Risk of Bias 2.0 tool. Inverse variance random effect meta-analyses were performed, with quality of evidence (QoE) evaluated using GRADE methods. RESULTS: Ten RCTs (n = 1173) were included. The controls were the standard of care in 5 RCTs and placebo in 5. COVID-19 disease severity was mild in 8 RCTs, moderate in 1, and mild and moderate in 1. IVM did not reduce all-cause mortality rates compared with controls (relative risk [RR], 0.37 [95% confidence interval, .12-1.13]; very low QoE) or LOS compared with controls (mean difference, 0.72 days [95% confidence interval, -.86 to 2.29 days]; very low QoE). AEs, SAEs, and viral clearance were similar between IVM and control groups (low QoE for all outcomes). Subgroups by severity of COVID-19 or RoB were mostly consistent with main analyses; all-cause mortality rates in 3 RCTs at high RoB were reduced with IVM. CONCLUSIONS: Compared with the standard of care or placebo, IVM did not reduce all-cause mortality, LOS, or viral clearance in RCTs in patients with mostly mild COVID-19. IVM did not have an effect on AEs or SAEs and is not a viable option to treat patients with COVID-19.

Does Targeted Temperature Management Improve Neurological Outcome in Extracorporeal Cardiopulmonary Resuscitation (ECPR)?

PURPOSE: Targeted temperature management (TTM) is a standard of care in patients after cardiac arrest for neuroprotection. Currently, the effectiveness and efficacy of TTM after extracorporeal cardiopulmonary resuscitation (ECPR) is unknown. We aimed to compare neurological and survival outcomes between TTM vs non-TTM in patients undergoing ECPR for refractory cardiac arrest. METHODS: We searched PubMed and 5 other databases for randomized controlled trials and observational studies reporting neurological outcomes or survival in adult patients undergoing ECPR with or without TTM. Good neurological outcome was defined as cerebral performance category <3. Two independent reviewers extracted the data. Random-effects meta-analyses were used to pool data. RESULTS: We included 35 studies (n = 2,643) with the median age of 56 years (interquartile range [IQR]: 52-59). The median time from collapse to ECMO cannulation was 58 minutes (IQR: 49-82) and the median ECMO duration was 3 days (IQR: 2.0-4.1). Of 2,643, 1,329 (50.3%) patients received TTM and 1,314 (49.7%) did not. There was no difference in the frequency of good neurological outcome at any time between TTM (29%, 95% confidence interval [CI]: 23%-36%) vs. without TTM (19%, 95% CI: 9%-31%) in patients with ECPR (P = 0.09). Similarly, there was no difference in overall survival between patients with TTM (30%, 95% CI: 22%-39%) vs. without TTM (24%, 95% CI: 14%-34%) (P = 0.31). A cumulative meta-analysis by publication year showed improved neurological and survival outcomes over time. CONCLUSIONS: Among ECPR patients, survival and neurological outcome were not different between those with TTM vs. without TTM. Our study suggests that neurological and survival outcome are improving over time as ECPR therapy is more widely used. Our results were limited by the heterogeneity of included studies and further research with granular temperature data is necessary to assess the benefit and risk of TTM in ECPR population.

Association between Lipid Profile and Apolipoproteins with Risk of Diabetic Foot Ulcer: A Systematic Review and Meta-Analysis.

Background and Aims: Biomarkers are necessary to stratify the risk of diabetic foot ulcers (DFUs). This systematic review and meta-analysis aimed to evaluate the association between the lipid profile and apolipoproteins with the risk of DFU. Methods: A systematic search was conducted in PubMed, Scopus, Cochrane Library, and Web of Science among adult patients. Cohort and case-control studies were included. Random-effects models were used for meta-analyses, and the effects were expressed as odds ratio (OR) and their 95% confidence intervals (CIs). We evaluated publication bias through Egger's test and funnel plot. Results: A total of 12 cohort studies and 26 case-control studies were included, with 17076 patients. We found that the higher values of total cholesterol (TC), low-density lipoprotein (LDL), triglycerides, and lipoprotein(a) (Lp(a)) were associated with a higher risk of developing DFU (OR: 1.47, OR: 1.47, OR: 1.5, OR: 1.85, respectively). Otherwise, the lower values of HDL were associated with a higher risk of developing DFU (OR: 0.49). Publication bias was not found for associations between TC, HDL, LDL, or TG and the risk of DFU. Conclusions: The high values of LDL, TC, TG, and Lp(a) and low values of HDL are associated with a higher risk of developing DFU. Furthermore, we did not find a significant association for VLDL, ApoA1, ApoB, and ApoB/ApoA1 ratio.

Effect of exercise on epicardial adipose tissue in adults: a systematic review and meta-analyses.

According to previous epidemiological studies, we can reduce the thickness of epicardial fat and improve cardiovascular risk factors through exercise, and the changes may depend on the form of exercise. We systemically reviewed published studies that evaluated exercise intervention on epicardial adipose tissue (EAT) levels. We included randomized controlled trials (RCTs) comparing one exercise with another exercise or diet for the treatment to reduce EAT. We used fixed effects models for meta-analyses; effects of exercise on outcomes were described as mean differences (MD) or standardized difference of means (SMD) was used, their 95% confidence intervals (CI). Five RCTs were included (n = 299), 156 in exercise group and 143 in the control. In comparison to the control group, exercise significantly reduced EAT (SMD - 0.57, 95%CI - 0.97 to - 0.18) and waist circumference (MD - 2.95 cm, 95%CI - 4.93 to - 0.97). Exercise did not have an effect on BMI (MD - 0.23 kg/m2, 95%CI - 0.73 to 0.27), weight (MD - 0.06 kg, 95%CI - 1.46 to 1.34), or HDL (SMD 0.26, 95%CI - 0.06 to 0.57).VO2 was significantly increased by exercise (SMD 1.58, 95%CI 1.17 to 1.99). Risk of bias was high for 3 studies, and GRADE quality of evidence was very low to moderate. Exercise reduced epicardial adipose tissue and waist circumference, and did not have effect on weight, BMI, or HDL. Newer trials with better design and methods are necessary to improve the quality of the evidence. PROSPERO registration number (CRD42018096581).

Making Narrative Statements to Describe Treatment Effects.

Accurately describing treatment effects using plain language and narrative statements is a critical step in communicating research findings to end users. However, the process of developing these narratives has not been historically guided by a specific framework. The Agency for Healthcare Research and Quality Evidence-based Practice Center Program developed guidance for narrative summaries of treatment effects that identifies five constructs. We explicitly identify these constructs to facilitate developing narrative statements: (1) direction of effect, (2) size of effect, (3) clinical importance, (4) statistical significance, and (5) strength or certainty of evidence. These constructs clearly overlap. It may not always be feasible to address all five constructs. Based on context and intended audience, investigators can determine which constructs will be most important to address in narrative statements.

Efficacy of psychological interventions on psychological outcomes in coronary artery disease: systematic review and meta-analysis.

BACKGROUND: The benefits of cognitive-behavioral treatment (CBT) and positive psychology therapy (PPT) in patients with cardiovascular disease are still not well defined. We assessed the efficacy of CBT and PPT on psychological outcomes in coronary artery disease (CAD) patients. METHODS: Randomized controlled trials evaluating CBT or PPT in CAD patients published until May 2018 were systematically analyzed. Primary outcomes were depression, stress, anxiety, anger, happiness, and vital satisfaction. Random effects meta-analyses using the inverse variance method were performed. Effects were expressed as standardized mean difference (SMD) or mean differences (MD) with their 95% confidence intervals (CIs); risk of bias was assessed with the Cochrane tool. RESULTS: Nineteen trials were included (n = 1956); sixteen evaluated CBT (n = 1732), and three PPT (n = 224). Compared with control groups, depressive symptoms (13 trials; SMD -0.80; 95% CI -1.33 to -0.26), and anxiety (11 trials; SMD -1.26; 95% CI -2.11 to -0.41) improved after the PI, and depression (6 trials; SMD -2.08; 95% CI -3.22 to -0.94), anxiety (5 trials; SMD -1.33; 95% CI -2.38 to -0.29), and stress (3 trials; SMD -3.72; 95% CI -5.91 to -1.52) improved at the end of follow-up. Vital satisfaction was significantly increased at follow-up (MD 1.30, 0.27, 2.33). Non-significant effects on secondary outcomes were found. Subgroup analyses were consistent with overall analyses. CONCLUSION: CBT and PPT improve several psychological outcomes in CAD patients. Depression and anxiety improved immediately after the intervention while stress and vital satisfaction improve in the mid-term. Future research should assess the individual role of CBT and PPT in CAD populations.

Diagnostic accuracy of Xpert MTB/RIF for tuberculous meningitis: systematic review and meta-analysis.

OBJECTIVE: This systematic review evaluated the diagnostic accuracy of Xpert MTB/RIF to detect tuberculous meningitis (TBM). METHODS: PubMed and five other databases were systematically searched through March 2019. All studies evaluating diagnostic accuracy of Xpert MTB/RIF on cerebrospinal fluid (CSF) samples were included. Reference standards were definitive or definite plus probable TBM. The quality of studies was assessed by the QUADAS-2 tool. We performed bivariate random-effects meta-analysis and calculated summary diagnostic statistics. RESULTS: We identified 30 studies (n = 3972 participants), including 5 cohort studies and 25 cross-sectional studies. Reference standards were definite TB (n = 28 studies) or definite plus probable TBM (n = 6 studies). The pooled Xpert MTB/RIF sensitivity was 85% (95% CI, 70-93%), and specificity was 98% (95% CI, 97-99%) with a negative likelihood ratio of 0.15 (95% CI, 0.04-0.27) for definite TBM. For probable TBM cases, pooled sensitivity was 81% (95% CI, 66-90%), and specificity was 99% (95% CI, 97-99%). For both reference standard types, meta-analyses showed a C-statistic area under the curve of 0.98. The QUADAS-2 tool revealed low risk of bias as well as low concerns regarding applicability. Methodological heterogeneity was high among studies. CONCLUSIONS: Xpert MTB/RIF showed high accuracy for TBM diagnosis, but a negative Xpert MTB/RIF test does not rule out TBM. Repeat Xpert testing may be necessary. In clinical practice, Xpert MTB/RIF adds speed and sensitivity when compared to classic TBM diagnostic methods or previous commercial nucleic acid amplification techniques. More studies and better strategies for rapidly confirming a diagnosis of TBM in children are urgently needed.

OBJECTIF: Cette revue systématique a évalué la précision diagnostique de Xpert MTB/RIF pour détecter la méningite tuberculeuse (MTB). MÉTHODES: PubMed et cinq autres bases de données ont fait l'objet d'une recherche systématique jusqu'en mars 2019. Toutes les études évaluant la précision du diagnostic de Xpert MTB/RIF sur des échantillons de liquide céphalo-rachidien (LCR) ont été incluses. Les étalons de référence étaient des MTB définitives ou définitives et probables. La qualité des études a été évaluée par l'outil QUADAS-2. Nous avons effectué une méta-analyse des effets aléatoires bivariés et calculé des statistiques de résumés diagnostiques. RÉSULTATS: Nous avons identifié 30 études (n = 3.972 participants), dont 5 études de cohorte et 25 études transversales. Les étalons de référence étaient la TB définitive (n = 28 études) ou la MTB définitive et probable (n = 6 études). La sensibilité poolée Xpert MTB/RIF était de 85% (IC95%: 70-93%) et la spécificité était de 98% (IC95%: 97-99%) avec un rapport de vraisemblance négatif de 0,15 (IC95%: 0,04-0,27) pour la MTB définitive. Pour les cas probables de la MTB, la sensibilité poolée était de 81% (IC95%: 66-90%) et la spécificité était de 99% (IC95%: 97-99%). Pour les deux types d'étalons de référence, les méta-analyses ont montré une aire statistique C sous la courbe de 0,98. L'outil QUADAS-2 a révélé un faible risque de biais ainsi que de faibles préoccupations concernant l'applicabilité. L'hétérogénéité méthodologique était élevée parmi les études. CONCLUSIONS: Xpert MTB/RIF a montré une grande précision pour le diagnostic de la MTB, mais un test Xpert MTB/RIF négatif n'exclut pas la MTB. La répétition du tests Xpert peut être nécessaire. Dans la pratique clinique, Xpert MTB/RIF ajoute vitesse et sensibilité par rapport aux méthodes de diagnostic classiques de la MTB ou aux précédentes techniques d'amplification d'acide nucléique commerciales. Des études supplémentaires et de meilleures stratégies pour confirmer rapidement un diagnostic de MTB chez les enfants sont nécessaires d'urgence.

Short-term efficacy of umbilical cord milking in preterm infants: systematic review and meta-analysis.

BACKGROUND: To systematically evaluate short-term efficacy of UCM versus other interventions in preterm infants. METHODS: Six engines were searched until February 2020 for randomized controlled trials (RCTs) assessing UCM versus immediate cord clamping (ICC), delayed cord clamping (DCC), or no intervention. Primary outcomes were overall mortality, intraventricular hemorrhage (IVH), and patent ductus arteriosus (PDA); secondary outcomes were need for blood transfusion, mean blood pressure (MBP), serum hemoglobin (Hb), and ferritin levels. Random-effects meta-analyses were used. RESULTS: Fourteen RCTs (n = 1708) were included. In comparison to ICC, UCM did not decrease mortality (RR 0.5, 95% CI 0.2-1.1), IVH (RR 0.7, 95% CI 0.5-1.0), or PDA (RR 1.0, 95% CI 0.7-1.5). However, UCM reduced need of blood transfusion (RR 0.5, 95% CI 0.3-0.9) and increased MBP (MD 2.5 mm Hg, 95% CI 0.5-4.5), Hb (MD 1.2 g/dL, 95% CI 0.8-1.6), and ferritin (MD 151.4 ng/dL, 95% CI 59.5-243.3). In comparison to DCC, UCM did not reduce mortality, IVH, PDA, or need of blood transfusion but increased MBP (MD 3.7, 95% CI 0.6-6.9) and Hb (MD 0.3, 95% CI -0.2-0.8). Only two RCTs had high risk of bias. CONCLUSIONS: UCM did not decrease short-term clinical outcomes in comparison to ICC or DCC in preterm infants. Intermediate outcomes improved significantly with UCM. IMPACT: In 14 randomized controlled trials (RCTs), umbilical cord milking (UCM) did not reduce mortality, intraventricular hemorrhage, or patent ductus arteriosus compared to immediate (ICC) or delayed cord clamping (DCC). UCM improved mean blood pressure and hemoglobin levels compared to ICC or DCC. In comparison to ICC, UCM reduced the need for blood transfusion. We updated searches until February 2020, stratified by type of control, and performed subgroup analyses. There was low quality of evidence about clinical efficacy of UCM. Most of RCTs had low risk of bias. UCM cannot be recommended as standard of care for preterm infants.

QTc prolongation in COVID-19 patients treated with hydroxychloroquine, chloroquine, azithromycin, or lopinavir/ritonavir: A systematic review and meta-analysis.

PURPOSE: Hydroxychloroquine, chloroquine, azithromycin, and lopinavir/ritonavir are drugs that were used for the treatment of coronavirus disease 2019 (COVID-19) during the early pandemic period. It is well-known that these agents can prolong the QTc interval and potentially induce Torsades de Pointes (TdP). We aim to assess the prevalence and risk of QTc prolongation and arrhythmic events in COVID-19 patients treated with these drugs. METHODS: We searched electronic databases from inception to September 30, 2020 for studies reporting peak QTc ≥500 ms, peak QTc change ≥60 ms, peak QTc interval, peak change of QTc interval, ventricular arrhythmias, TdP, sudden cardiac death, or atrioventricular block (AVB). All meta-analyses were conducted using a random-effects model. RESULTS: Forty-seven studies (three case series, 35 cohorts, and nine randomized controlled trials [RCTs]) involving 13 087 patients were included. The pooled prevalence of peak QTc ≥500 ms was 9% (95% confidence interval [95%CI], 3%-18%) and 8% (95%CI, 3%-14%) in patients who received hydroxychloroquine/chloroquine alone or in combination with azithromycin, respectively. Likewise, the use of hydroxychloroquine (risk ratio [RR], 2.68; 95%CI, 1.56-4.60) and hydroxychloroquine + azithromycin (RR, 3.28; 95%CI, 1.16-9.30) was associated with an increased risk of QTc prolongation compared to no treatment. Ventricular arrhythmias, TdP, sudden cardiac death, and AVB were reported in <1% of patients across treatment groups. The only two studies that reported individual data of lopinavir/ritonavir found no cases of QTc prolongation. CONCLUSIONS: COVID-19 patients treated with hydroxychloroquine/chloroquine with or without azithromycin had a relatively high prevalence and risk of QTc prolongation. However, the prevalence of arrhythmic events was very low, probably due to underreporting. The limited information about lopinavir/ritonavir showed that it does not prolong the QTc interval.

Prevalence and Outcome of Acute Respiratory Distress Syndrome in Traumatic Brain Injury: A Systematic Review and Meta-Analysis.

OBJECTIVES: Acute respiratory distress syndrome (ARDS) in patients with traumatic brain injury (TBI) is associated with increased mortality. Information on the prevalence of ARDS and its neurological outcome after TBI is sparse. We aimed to systematically review the prevalence, risk factors, and outcome of ARDS in TBI population. DATA SOURCES: PubMed and four other databases (Embase, Cochrane Library, Web of Science Core Collection, and Scopus) from inception to July 6, 2020. STUDY SELECTION: Randomized controlled trials (RCTs) and observational studies in patients older than 18 years old. DATA EXTRACTION: Two independent reviewers extracted the data. Study quality was assessed by the Cochrane Risk of Bias tool for RCTs, the Newcastle-Ottawa Scale for cohort and case-control studies. Good neurological outcome was defined as Glasgow Outcome Scale ≥ 4. Random-effects meta-analyses were conducted to estimate pooled outcome prevalence and their 95% confidence intervals (CI). DATA SYNTHESIS: We included 20 studies (n = 2830) with median age of 44 years (interquartile range [IQR] = 35-47, 64% male) and 79% (n = 2237) suffered severe TBI. In meta-analysis, 19% patients (95% CI = 0.13-0.27, I2 = 93%) had ARDS after TBI. The median time from TBI to ARDS was 3 days (IQR = 2-5). Overall survival at discharge for the TBI cohort was 70% (95% CI = 0.64-0.75; I2 = 85%) and good neurological outcome at any time was achieved in 31% of TBI patients (95% CI = 0.23-0.40; I2 = 88%). TBI cohort without ARDS had higher survival (67% vs. 57%, p = 0.01) and good neurological outcomes (34% vs. 23%, p = 0.02) compared to those with ARDS. We did not find any specific risk factors for developing ARDS. CONCLUSION: In this meta-analysis, approximately one in five patients had ARDS shortly after TBI with the median time of 3 days. The presence of ARDS was associated with worse neurological outcome and mortality in TBI. Further research on prevention and intervention strategy of TBI-associated ARDS is warranted.

Prognostic value of neutrophil-to-lymphocyte ratio in COVID-19 patients: A systematic review and meta-analysis.

BACKGROUND: Neutrophil-to-lymphocyte ratio (NLR) is an accessible and widely used biomarker. NLR may be used as an early marker of poor prognosis in patients with COVID-19. OBJECTIVE: To evaluate the prognostic value of the NLR in patients diagnosed with COVID-19. METHODS: We conducted a systematic review and meta-analysis. Observational studies that reported the association between baseline NLR values (ie, at hospital admission) and severity or all-cause mortality in COVID-19 patients were included. The quality of the studies was assessed using the Newcastle-Ottawa Scale (NOS). Random effects models and inverse variance method were used for meta-analyses. The effects were expressed as odds ratios (ORs) and their 95% confidence intervals (CIs). Small study effects were assessed with the Egger's test. RESULTS: We analysed 61 studies (n = 15 522 patients), 58 cohorts, and 3 case-control studies. An increase of one unit of NLR was associated with higher odds of severity (OR 6.22; 95%CI 4.93 to 7.84; P < .001) and higher odds of all-cause mortality (OR 12.6; 95%CI 6.88 to 23.06; P < .001). In our sensitivity analysis, we found that 41 studies with low risk of bias and moderate heterogeneity (I2  = 53% and 58%) maintained strong association between NLR values and both outcomes (severity: OR 5.36; 95% CI 4.45 to 6.45; P < .001; mortality: OR 10.42 95% CI 7.73 to 14.06; P = .005). CONCLUSIONS: Higher values of NLR were associated with severity and all-cause mortality in hospitalised COVID-19 patients.

Hydroxychloroquine or Chloroquine for Treatment or Prophylaxis of COVID-19: A Living Systematic Review.

BACKGROUND: Hydroxychloroquine and chloroquine have antiviral effects in vitro against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). PURPOSE: To summarize evidence about the benefits and harms of hydroxychloroquine or chloroquine for the treatment or prophylaxis of coronavirus disease 2019 (COVID-19). DATA SOURCES: PubMed (via MEDLINE), EMBASE (via Ovid), Scopus, Web of Science, Cochrane Library, bioRxiv, Preprints, ClinicalTrials.gov, World Health Organization International Clinical Trials Registry Platform, and the Chinese Clinical Trials Registry from 1 December 2019 until 8 May 2020. STUDY SELECTION: Studies in any language reporting efficacy or safety outcomes from hydroxychloroquine or chloroquine use in any setting in adults or children with suspected COVID-19 or at risk for SARS-CoV-2 infection. DATA EXTRACTION: Independent, dually performed data extraction and quality assessments. DATA SYNTHESIS: Four randomized controlled trials, 10 cohort studies, and 9 case series assessed treatment effects of the medications, but no studies evaluated prophylaxis. Evidence was conflicting and insufficient regarding the effect of hydroxychloroquine on such outcomes as all-cause mortality, progression to severe disease, clinical symptoms, and upper respiratory virologic clearance with antigen testing. Several studies found that patients receiving hydroxychloroquine developed a QTc interval of 500 ms or greater, but the proportion of patients with this finding varied among the studies. Two studies assessed the efficacy of chloroquine; 1 trial, which compared higher-dose (600 mg twice daily for 10 days) with lower-dose (450 mg twice daily on day 1 and once daily for 4 days) therapy, was stopped owing to concern that the higher dose therapy increased lethality and QTc interval prolongation. An observational study that compared adults with COVID-19 receiving chloroquine phosphate, 500 mg once or twice daily, with patients not receiving chloroquine found minor fever resolution and virologic clearance benefits with chloroquine. LIMITATION: There were few controlled studies, and control for confounding was inadequate in observational studies. CONCLUSION: Evidence on the benefits and harms of using hydroxychloroquine or chloroquine to treat COVID-19 is very weak and conflicting. PRIMARY FUNDING SOURCE: Agency for Healthcare Research and Quality.

[Clinical practice guidelines for the diagnosis and management chronic infection of hepatitis viral C of the Peruvian Health Social Security (EsSalud)]. / Guía de práctica clínica para el diagnóstico y tratamiento de la infección crónica por el virus de hepatitis C en el Seguro Social de Salud del Perú (EsSalud).

INTRODUCTION: This article summarizes the clinical practice guidelines (CPG) for the diagnosis and treatment of chronic infection of hepatitis viral C of the Peruvian Health Social Security (EsSalud). OBJECTIVE: To provide clinical recommendations based on evidence for the diagnosis and treatment of chronic infection of hepatitis viral C in EsSalud. METHODS: A guideline development group (GDG) was established, including medical specialists and methodologists. The GDG formulated 4 clinical questions to be answered in this CPG. Systematic searches of systematic reviews and primary studies (when pertinent) were conducted in PubMed, and Central (Cochrane) during 2019. The evidence was selected to answer each of the clinical questions. The accuracy of the evidence was evaluated using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) methodology. In periodic work meetings, the GEG used the GRADE methodology to review the evidence and formulate the recommendations, the points of good clinical practice and the treatment flowchart. Finally, the CPG was approved with Resolution No. 151-IETSIESSALUD-2019. RESULTS: The present CPG addressed 4 clinical questions of four topics: screening, diagnosis, staging and treatment. Based on these questions, 13 recommendations (8 strong recommendations and 5 weak recommendations), 27 points of good clinical practice, and 1 flowchart were formulated. CONCLUSION: This paper summarizes the methodology and evidencebased conclusions from the CPG for for the diagnosis and treatment of chronic infection of hepatitis viral C of the EsSalud.

Efficacy and safety of bempedoic acid for the treatment of hypercholesterolemia: A systematic review and meta-analysis.

BACKGROUND: Bempedoic acid is a first-in-class lipid-lowering drug recommended by guidelines for the treatment of hypercholesterolemia. Our objective was to estimate its average effect on plasma lipids in humans and its safety profile. METHODS AND FINDINGS: We carried out a systematic review and meta-analysis of phase II and III randomized controlled trials on bempedoic acid (PROSPERO: CRD42019129687). PubMed (Medline), Scopus, Google Scholar, and Web of Science databases were searched, with no language restriction, from inception to 5 August 2019. We included 10 RCTs (n = 3,788) comprising 26 arms (active arm [n = 2,460]; control arm [n = 1,328]). Effect sizes for changes in lipids and high-sensitivity C-reactive protein (hsCRP) serum concentration were expressed as mean differences (MDs) and 95% confidence intervals (CIs). For safety analyses, odds ratios (ORs) and 95% CIs were calculated using the Mantel-Haenszel method. Bempedoic acid significantly reduced total cholesterol (MD -14.94%; 95% CI -17.31%, -12.57%; p < 0.001), non-high-density lipoprotein cholesterol (MD -18.17%; 95% CI -21.14%, -15.19%; p < 0.001), low-density lipoprotein cholesterol (MD -22.94%; 95% CI -26.63%, -19.25%; p < 0.001), low-density lipoprotein particle number (MD -20.67%; 95% CI -23.84%, -17.48%; p < 0.001), apolipoprotein B (MD -15.18%; 95% CI -17.41%, -12.95%; p < 0.001), high-density lipoprotein cholesterol (MD -5.83%; 95% CI -6.14%, -5.52%; p < 0.001), high-density lipoprotein particle number (MD -3.21%; 95% CI -6.40%, -0.02%; p = 0.049), and hsCRP (MD -27.03%; 95% CI -31.42%, -22.64%; p < 0.001). Bempedoic acid did not significantly modify triglyceride level (MD -1.51%; 95% CI -3.75%, 0.74%; p = 0.189), very-low-density lipoprotein particle number (MD 3.79%; 95% CI -9.81%, 17.39%; p = 0.585), and apolipoprotein A-1 (MD -1.83%; 95% CI -5.23%, 1.56%; p = 0.290). Treatment with bempedoic acid was positively associated with an increased risk of discontinuation of treatment (OR 1.37; 95% CI 1.06, 1.76; p = 0.015), elevated serum uric acid (OR 3.55; 95% CI 1.03, 12.27; p = 0.045), elevated liver enzymes (OR 4.28; 95% CI 1.34, 13.71; p = 0.014), and elevated creatine kinase (OR 3.79; 95% CI 1.06, 13.51; p = 0.04), though it was strongly associated with a decreased risk of new onset or worsening diabetes (OR 0.59; 95% CI 0.39, 0.90; p = 0.01). The main limitation of this meta-analysis is related to the relatively small number of individuals involved in the studies, which were often short or middle term in length. CONCLUSIONS: Our results show that bempedoic acid has favorable effects on lipid profile and hsCRP levels and an acceptable safety profile. Further well-designed studies are needed to explore its longer-term safety.