Andexanet alfa versus PCC products for factor Xa inhibitor bleeding: A systematic review with meta-analysis.

Previous meta-analyses assessed andexanet alfa (AA) or prothrombin complex concentrate (PCC) products for the treatment of Factor Xa inhibitor (FXaI)-associated major bleeding. However, they did not include recent studies or assess the impact of the risk of bias. We conducted a systematic review with meta-analysis on the effectiveness of AA versus PCC products for FXaI-associated major bleeding, inclusive of the studies' risk of bias. PubMed and Embase were searched for comparative studies assessing major bleeding in patients using FXaI who received AA or PCC. We used the Methodological Index for NOn-Randomized Studies (MINORS) checklist and one question from the Joanna Briggs Institute (JBI) Critical Appraisal of Case Series tool to assess the risk of bias. Random-effects meta-analyses were performed to provide a pooled estimate for the effect of AA versus PCC products on hemostatic efficacy, in-hospital mortality, 30-day mortality, and thrombotic events. Low-moderate risk of bias studies were meta-analyzed separately, as well as combined with high risk of bias studies. Eighteen comparative evaluations of AA versus PCC were identified. Twenty-eight percent of the studies (n = 5) had low-moderate risk and 72% (n = 13) had a high risk of bias. Studies with low-moderate risk of bias suggested improvements in hemostatic efficacy [Odds Ratio (OR) 2.72 (95% Confidence Interval (CI): 1.15-6.44); one study], lower in-hospital mortality [OR 0.48 (95% CI: 0.38-0.61); three studies], and reduced 30-day mortality [OR 0.49 (95% CI: 0.30-0.80); two studies] when AA was used versus PCC products. When studies were included regardless of the risk of bias, pooled effects showed improvements in hemostatic efficacy [OR 1.36 (95% CI: 1.01-1.84); 12 studies] and reductions in 30-day mortality [OR 0.53 (95% CI: 0.37-0.76); six studies] for AA versus PCC. The difference in thrombotic events with AA versus PCC was not statistically significant in the low-moderate, high, or combined risk of bias groups. The evidence from low-moderate quality real-world studies suggests that AA is superior to PCC in enhancing hemostatic efficacy and reducing in-hospital and 30-day mortality. When studies are assessed regardless of the risk of bias, the pooled hemostatic efficacy and 30-day mortality risk remain significantly better with AA versus PCC.

Prediabetes and major adverse cardiac events after acute coronary syndrome: An overestimated concept.

BACKGROUND: Unlike diabetes, the effect of prediabetes on outcomes in patients with acute coronary syndrome (ACS) who underwent percutaneous coronary intervention (PCI) is not much investigated. We investigated the association between fasting glycemic status and major adverse cardiovascular and cerebrovascular events (MACCE) in patients with ACS undergoing PCI and had mid to long-term follow-up after coronary stenting. METHODS: Registry-based retrospective cohort study included ACS patients who underwent PCI at the Tehran Heart Center from 2015 to 2021 with a median follow-up of 378 days. Patients were allocated into normoglycemic, prediabetic, and diabetic groups. The primary and secondary outcomes were MACCE and its components, respectively. Unadjusted and adjusted Cox models were used to evaluate the association between glycemic status and outcomes. RESULTS: Among 13 682 patients, 3151 (23%) were prediabetic, and 5834 (42.6%) were diabetic. MACCE risk was significantly higher for diabetic versus normoglycemic (adjusted hazard ratio [aHR]: 1.22, 95% confidence interval [CI]: 1.06-1.41), but nonsignificantly higher for prediabetic versus normoglycemic (aHR: 0.95, 95% CI: 0.78-1.10). All-cause mortality risk was significantly higher in diabetic versus normoglycemic (aHR: 1.42, 95% CI: 1.08-1.86), but nonsignificantly higher for prediabetic versus normoglycemic (aHR: 1.15, 95% CI: 0.84-1.59). Among other components of MACCE, only coronary artery bypass grafting was significantly higher in diabetic patients, and not prediabetic, compared with normoglycemic. CONCLUSIONS: Prediabetic ACS patients undergoing PCI, unlike diabetics, are not at increased risk of MACCE and all-cause mortality. While prediabetic patients could be regarded as having the same risk as nondiabetics, careful consideration to provide more intensive pre- and post-PCI care in diabetic patients is mandatory.

Long-Term Neuropsychiatric, Neurocognitive, and Functional Outcomes of Patients Receiving ECMO: A Systematic Review and Meta-Analysis

BACKGROUND AND OBJECTIVES: Despite the common occurrence of neurologic complications during extracorporeal membrane oxygenation (ECMO) support, data on long-term neuropsychiatric, neurocognitive, and functional outcomes are sparse. We aimed to determine the prevalence of long-term neuropsychiatric symptoms, neurocognitive and functional impairment, and favorable neurologic outcomes in adult patients who receive ECMO. METHODS: PubMed, Embase, Cochrane, Web of Science, and Scopus were searched for text related to ECMO and neuropsychiatric, neurocognitive, and functional outcomes from inception to May 3, 2023. Our primary outcome was the prevalence of neuropsychiatric symptoms (pain/discomfort, anxiety, depression, posttraumatic stress disorder [PTSD], and sleep disturbance) at long-term (≥6 months) follow-up. Our secondary outcomes were the prevalence of neurocognitive impairment (memory, attention, and reasoning), functional impairment (daily activities, physical activity/mobility, and personal/self-care), and favorable neurologic outcomes (Cerebral Performance Category ≤2, modified Rankin scale ≤3, or Glasgow Outcome Scale ≥4). This study was registered in PROSPERO (CRD42023420565). RESULTS: We included 59 studies with 3,280 patients (median age 54 years, 69% male). The cohort consisted of 86% venoarterial (VA)-ECMO (n = 2,819) and 14% venovenous (VV)-ECMO (n = 461) patients. More than 10 tools were used to assess neuropsychiatric and neurocognitive outcomes, indicating a lack of standardization in assessment methodologies. The overall prevalence of neuropsychiatric symptoms was 41% (95% CI 33%-49%): pain/discomfort (52%, 95% CI 42%-63%), sleep disturbance (37%, 95% CI 0%-98%), anxiety (36%, 95% CI 27%-46%), depression (31%, 95% CI 22%-40%), and PTSD (18%, 95% CI 9%-29%). The prevalence of neurocognitive impairment was 38% (95% CI 13%-65%). The prevalence of functional impairment was 52% (95% CI 40%-64%): daily activities (54%, 95% CI 41%-66%), mobility (41%, 95% CI 28%-54%), and self-care (21%, 95% CI 13%-31%). The prevalence of neuropsychiatric symptoms in VV-ECMO patients was higher than that in VA-ECMO patients (55% [95% CI 34%-75%] vs 32% [95% CI 23%-41%], p = 0.01), though the prevalence of neurocognitive and functional impairment was not different between the groups. The prevalence of favorable neurologic outcomes was not different at various follow-ups: 3 months (23%, 95% CI 12%-36%), 6 months (25%, 95% CI 16%-35%), and ≥1 year (28%, 95% CI 21%-36%, p = 0.68). DISCUSSION: A substantial proportion of ECMO patients seemed to experience neuropsychiatric symptoms and neurocognitive and functional impairments at long-term follow-up. Considerable heterogeneity in methodology for gauging these outcomes exists, warranting the need for standardization. Multicenter prospective observational studies are indicated to further investigate risk factors for these outcomes in ECMO-supported patients.

The association between metabolic syndrome and major adverse cardiac and cerebrovascular events in patients with acute coronary syndrome undergoing percutaneous coronary intervention.

Metabolic syndrome (MetS) poses an additional risk for the development of coronary artery disease and major adverse cardiac and cerebrovascular events (MACCE). In this study, we investigated the association between MetS and its components and MACCE after percutaneous coronary intervention (PCI) in patients with acute coronary syndrome (ACS). The presence of MetS was calculated at baseline using the NCEP-ATP III criteria. The primary outcome was MACCE and its components were secondary outcomes. Unadjusted and adjusted Cox Regression models were used to calculate hazard ratios (HRs) and 95% confidence intervals (CI) of the association between MetS or its components and MACCE and its components. A total of 13,459 ACS patients who underwent PCI (MetS: 7939 and non-MetS: 5520) with a mean age of 62.7 ± 11.0 years (male: 72.5%) were included and median follow-up time was 378 days. Patients with MetS had significantly higher MACCE risk (adjusted HR [aHR] 1.22, 95% CI 1.08-1.39). The only component of MACCE that exhibited a significantly higher incidence in MetS patients was myocardial infarction (aHR 1.43, 95% CI 1.15-1.76). MetS components that were significantly associated with a higher incidence of MACCE were hypertension and impaired fasting glucose. Having three MetS components did not increase MACCE (aHR 1.12, 95% CI 0.96-1.30) while having four (aHR 1.32, 95% CI 1.13-1.55) or five (aHR 1.42, 95% CI 1.15-1.75) MetS components was associated with a higher incidence of MACCE. MetS was associated with a higher risk of MACCE in ACS patients undergoing PCI. Among MACCE components, myocardial infarction was significantly higher in patients with MetS. Impaired fasting glucose and hypertension were associated with a higher risk of MACCE. Identifying these patterns can guide clinicians in choosing appropriate preventive measures.

Impact of Berberine or Berberine Combination Products on Lipoprotein, Triglyceride and Biological Safety Marker Concentrations in Patients with Hyperlipidemia: A Systematic Review and Meta-Analysis.

Monoclonal antibody Proprotein Convertase Subtilisin/Kexin type 9 (PCSK9) inhibitors reduce total cholesterol (TC), low density lipoproteins (LDL), high density lipoproteins (HDL), and triglycerides (TG). We assessed the ability of berberine, a natural PCSK9 inhibitor, to reduce lipid concentrations either alone or combined with other nutraceuticals. We searched PubMed, Scopus and EMBASE from inception to September 30th, 2022 for randomized controlled trials (RCTs) assessing 8-18 wk of berberine therapy on. A total of 41 RCTs with 4,838 patients met our inclusion criteria. Berberine containing products significantly reduced TC (MD -17.42 mg/dL [95%CI: -22.91 to -11.93]), LDL (MD -14.98 mg/dL [95%CI: -20.67 to -9.28]), and TG (MD -18.67 mg/dL [95%CI: -25.82 to -11.51]) while raising HDL (MD 1.97 mg/dL [95%CI: 1.16 to 2.78]) versus control (I2 > 72% for all analyses). Products with berberine alone had less robust effects on TC (MD -12.08 mg/dL [95%CI: -21.79 to -2.37]), LDL (MD -9.26 mg/dL [95%CI: -20.31 to 1.78]), and HDL (MD 1.38 mg/dL [95%CI: -1.27 to 4.03]) but TG effects were similar (MD -17.40 mg/dL [95%CI: -32.57 to -2.23]). Berberine along with red yeast rice reduced TC (MD -19.62 mg/dL [95%CI: -28.56 to -10.68]) and LDL (MD -18.79 mg/dL [95%CI: -28.03 to -9.54]) as did combination therapy with Silybum maranium for TC (MD -31.81 mg/dL [95%CI: -59.88 to -3.73]) and LDL (MD -30.82 mg/dL [95%CI: -56.48 to -5.16]). Berberine, alone or with other nutraceuticals, can provide a modest positive impact on lipid concentrations.

Diagnostic prediction models to identify patients at risk for healthcare-facility-onset Clostridioides difficile: A systematic review of methodology and reporting.

OBJECTIVE: To systematically review the methodology, performance, and generalizability of diagnostic models for predicting the risk of healthcare-facility-onset (HO) Clostridioides difficile infection (CDI) in adult hospital inpatients (aged ≥18 years). BACKGROUND: CDI is the most common cause of healthcare-associated diarrhea. Prediction models that identify inpatients at risk of HO-CDI have been published; however, the quality and utility of these models remain uncertain. METHODS: Two independent reviewers evaluated articles describing the development and/or validation of multivariable HO-CDI diagnostic models in an inpatient setting. All publication dates, languages, and study designs were considered. Model details (eg, sample size and source, outcome, and performance) were extracted from the selected studies based on the CHARMS checklist. The risk of bias was further assessed using PROBAST. RESULTS: Of the 3,030 records evaluated, 11 were eligible for final analysis, which described 12 diagnostic models. Most studies clearly identified the predictors and outcomes but did not report how missing data were handled. The most frequent predictors across all models were advanced age, receipt of high-risk antibiotics, history of hospitalization, and history of CDI. All studies reported the area under the receiver operating characteristic curve (AUROC) as a measure of discriminatory ability. However, only 3 studies reported the model calibration results, and only 2 studies were externally validated. All of the studies had a high risk of bias. CONCLUSION: The studies varied in their ability to predict the risk of HO-CDI. Future models will benefit from the validation on a prospective external cohort to maximize external validity.

The impact of psychedelics on patients with alcohol use disorder: a systematic review with meta-analysis.

OBJECTIVES: Critique the available systematic review and de novo assessment of the role of psychedelics in the treatment of alcohol use disorder. METHODS: A systematic literature search of PubMed was completed from 1960 to 9/9/2023. We pooled randomized controlled trials comparing psychedelics to control therapy for the treatment of alcohol use disorder. RESULTS: At the first recorded follow-up, LSD [n = 3, Odds Ratio (OR) 1.99 (95% Confidence interval (CI): 1.10 to 3.61)] and any psychedelic [n = 4, OR 2.16 (95%CI: 1.26 to 3.69)] enhanced the odds of patients achieving abstinence or a substantial reduction in drinking alcohol versus placebo in randomized, double-blind, placebo-controlled trials. When the inclusion criteria were relaxed to include controlled trials without double-blinding or placebo control, LSD [n = 5, OR 1.79 (95%CI: 1.36 to 2.34)] and any psychedelic therapy [n = 6, OR 1.89 (95%CI: 1.42 to 2.50)] still enhanced the odds of patients achieving abstinence or a substantial reduction in drinking alcohol. Four of 6 trials had high risk of bias and other methodological issues. One trial found an instance of suicidal ideation as well as transient increases in blood pressure that requires further exploration before the balance of benefits to harms can be determined. CONCLUSIONS: The use of psychedelics to treat alcohol use disorder is promising, but the weaknesses in the literature base preclude making definitive statements about its value. Future trials with greater methodological rigor are needed.

Lysergic acid diethylamine (LSD) and psilocybin (hallucinogenic mushrooms) are psychedelics that have been studied in patients with alcohol use disorder (chronic issue with heavy or problem drinking). When all the studies are pooled together in a meta-analysis, the odds of being able to refrain from drinking alcohol or to substantially reduce the amount of alcohol consumed was enhanced by 89%. This is a promising finding that if bore out in additional studies, especially those with higher study quality, would be a major advance in patients with alcohol use disorder. We cannot make more definitive conclusions because all the LSD studies were published between 1966 and 1970 which may not reflect contemporary practice and most of the studies had methodological weaknesses that reduce confidence in the studies to prove the benefits. It is heartening that the single psilocybin trial from 2022 was of higher methodological quality, reflected contemporary practice, and still showed positive effects.

Severe cardiac events induced by combination immunotherapy in patients with cancer: a meta-analysis.

Introduction: The use of combined immunotherapy could increase non-severe and severe cardiac events in patients with cancer. To examine the occurrence of severe cardiac adverse events of combined immunotherapy compared to single immunotherapy, we analysed 4 electronic databases from inception to August 2021. Material and methods: We selected randomized controlled trials (RCTs) comparing combined versus single immunotherapy, for the treatment of melanoma, oesophagogastric cancer, renal cell carcinoma, and non-small cell lung cancer. Pre-defined combined immunotherapy included monoclonal antibodies against programmed cell death 1 (PD-1 inhibitors) plus against cytotoxic T lymphocyte antigen 4 (CTLA-4 inhibitors) or against programmed cell death ligand 1 (PD-L1 inhibitors) plus CTLA-4 inhibitors. The pooled risk ratios (RR) with their 95% confidence intervals (CI) were estimated using a random-effects model. Results: Four RCTs involving 1581 patients were included, with a follow-up time between 18 and 39 months. The use of combined immunotherapy in comparison with single immunotherapy was not associated with an increased risk of severe cardiac adverse events: acute coronary syndromes (RR = 1.76, 95% CI: 0.29-10.83, very low certainty of evidence (CoE)), myocardial infarction (RR = 3.93, 95% CI: 0.44-35.39, very low CoE), heart failure (RR = 2.99, 95% CI: 0.61-14.79, very low CoE), and atrial fibrillation (RR = 2.26, 95% CI: 0.62-8.16, very low CoE). Conclusions: Our meta-analysis shows that the risk of severe cardiac adverse events with combined immunotherapy seems similar to single immunotherapy, but the evidence is very uncertain. Therefore, more RCTs with longer follow-ups and adequately powered to assess cardiac adverse events are needed to confirm these findings.

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.

Echocardiographic Criteria to Differentiate Constrictive Pericarditis From Restrictive Cardiomyopathy: A Meta-analysis.

Background: To assess the diagnostic accuracy of the Mayo Clinic echocardiographic criteria for differentiating between constrictive pericarditis and restrictive cardiomyopathy. Methods: We searched electronic databases for the date range from their inception to July 1, 2022. The index tests were the Mayo Clinic echocardiographic criteria. We performed a bivariate random-effects model to estimate the pooled sensitivity and specificity, each with 95% confidence interval (CI). The area under the curve of the summary receiver operator characteristic curves, with 95% CI, was also calculated. Results: We included 17 case-control studies involving 889 patients. The pooled sensitivity and specificity (95% CI), respectively, were as follows: ventricular septal shift, 82% (60%-94%) and 78% (65%-87%); respiratory variation in mitral inflow ≥ 14.6%, 71% (51%-85%) and 82% (66%-91%); septal e' velocity ≥ 8 cm/s, 83% (80%-87%) and 90% (83%-95%); septal e' velocity/lateral e' velocity ≥ 0.88, 74% (64%-82%) and 81% (70%-88%); and hepatic vein ratio in expiration ≥ 0.79, 73% (65%-81%) and 71% (19%-96%). The area under the curve of the summary receiver operator characteristic curves varied from 0.75 to 0.85, with overlapping CIs across index tests. Conclusions: Our meta-analysis suggests that all echocardiographic parameters from the Mayo Clinic criteria have good diagnostic accuracy for differentiating between constrictive pericarditis and restrictive cardiomyopathy.

Contexte: Évaluation de l'exactitude diagnostique des critères échocardiographiques de la clinique Mayo visant à faire la distinction entre une péricardite constrictive et une cardiomyopathie restrictive. Méthodologie: Nous avons effectué une recherche dans des bases de données électroniques pour la période s'étendant de leur date de création au 1er juillet 2022. Les tests de concordance portaient sur les critères échocardiographiques de la clinique Mayo. Nous avons réalisé un modèle à effets aléatoires et à deux variables afin d'estimer la sensibilité et la spécificité en fonction des données regroupées, chacune avec un intervalle de confiance (IC) à 95 %. L'aire sous la courbe des courbes caractéristiques sommaires de la performance du test, avec un IC à 95 %, a également été calculée. Résultats: Nous avons inclus 17 études cas-témoins comptant 889 patients. Selon les données groupées, la sensibilité et la spécificité (IC à 95 %), respectivement, étaient les suivantes : déplacement du septum interventriculaire, 82 % (60 à 94 %) et 78 % (65 à 87 %); variation respiratoire lors du remplissage mitral ≥ 14,6 %, 71 % (51 à 85 %) et 82 % (66 à 91 %); vitesse eʹ mesurée en septal ≥ 8 cm/s, 83 % (80 à 87 %) et 90 % (83 à 95 %); rapport vitesse eʹ mesurée en septal/vitesse eʹ mesurée en latéral ≥ 0,88, 74 % (64 à 82 %) et 81 % (70 à 88 %); et rapport veineux hépatique lors de l'expiration ≥ 0,79, 73 % (65 à 81 %) et 71 % (19 à 96 %). L'aire sous la courbe des courbes caractéristiques sommaires de la performance du test variait de 0,75 à 0,85, avec des IC se chevauchant dans les tests de concordance. Conclusions: Notre méta-analyse laisse entendre que tous les paramètres échocardiographiques de la clinique Mayo ont une bonne exactitude diagnostique pour faire la distinction entre la péricardite constrictive et la cardiomyopathie restrictive.

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.

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.

Impact of Frailty on Clinical Outcomes in Patients With Atrial Fibrillation Who Underwent Cardiac Ablation Using a Nationwide Database.

This study aimed to assess the association between frailty and clinical outcomes in patients with atrial fibrillation (AF) who undergo catheter ablation. We conducted a retrospective cohort study using the National Inpatient Sample database from 2017 to 2019. Adult patients hospitalized with a primary diagnosis of AF who underwent catheter ablation were included. Frailty was assessed using the Hospital Frailty Risk Score. The primary outcome was the presence of any complication (vascular, cardiac, respiratory, neurologic, or infectious), and secondary outcomes were in-hospital mortality, length of hospital stay, and hospital charges. A total of 21,075 weighted hospitalizations were included, and 14% were classified as intermediate or great risk of frailty. Patients with intermediate (adjusted relative risk 2.86, 95% confidence interval 2.24 to 3.67) and great (adjusted relative risk 6.68, 95% confidence interval 3.77 to 11.84) risk of frailty were associated with a greater risk of any complication than that of the group at less risk. The in-hospital mortality rate was significantly higher among patients at intermediate risk than among those at less risk of frailty (2.6% vs 0.1%, p <0.001). Patients with great and intermediate risk had significantly longer hospital stays than did the group with less risk (median 14 vs 5 vs 2 days, p <0.001), in addition to greater total charges (median $189,072 vs $161,598 vs $130,672, p <0.001), respectively. In conclusion, frailty was associated with a greater risk of poor short-term outcomes in patients with AF who underwent catheter ablation. The Hospital Frailty Risk Score is a useful tool for identifying patients at increased risk of adverse events and could aid in preoperative optimization and postoperative management.

Nasogastric versus nasojejunal tube feeding for severe acutepancreatitis: 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.

La nutrición enteral temprana a través de una sonda de alimentación es esencial para el tratamiento de la pancreatitis aguda severa (PAS). Se ha preferido la nutrición por sonda nasoyeyunal, bajo el supuesto de que proporciona descanso pancreático en comparación con la sonda nasogástrica. Sin embargo, la colocación de la sonda nasoyeyunal es compleja, puede retrasar el inicio de la alimentación y aumentar los costos hospitalarios. Nuestro objetivo fue comparar la eficacia y seguridad de la alimentación enteral con sonda nasogástrica versus sonda nasoyeyunal en pacientes con PAS. Se realizaron búsquedas en cuatro bases de datos (PubMed, Web of Science, Scopus y Embase) hasta el 1 de diciembre de 2022. Se incluyeron ensayos controlados aleatorios (ECA) que compararon la alimentación enteral mediante sondas nasogástricas y nasoyeyunales en pacientes con PAS. El resultado primario fue la mortalidad por todas las causas. Los resultados secundarios fueron insuficiencia orgánica, infección, complicaciones, intervención quirúrgica, duración de la alimentación por sonda y duración de la estancia hospitalaria. Dos investigadores completaron de forma independiente la evaluación del riesgo de sesgo mediante la herramienta Cochrane RoB 2.0. Realizamos metanálisis de modelos de efectos aleatorios utilizando el método de varianza inversa. Las medidas del efecto se informaron como riesgos relativos (RR) y sus IC del 95% para resultados dicotómicos y diferencias de medias (DM) y sus IC del 95% para resultados continuos. Se incluyeron cuatro ECA con 192 pacientes con PAS. La edad media osciló entre 36 y 62 años. No hubo diferencias significativas en la mortalidad por todas las causas entre los brazos de alimentación nasogástrica y nasoyeyunal Cambiar lo resaltado por: (18/98 vs. 23/93; RR 1.34, 95%CI 0.77-2.30; p=0.30). No hubo diferencias significativas en todos los resultados secundarios entre los brazos de alimentación. Hubo tres ECA con algunas preocupaciones de sesgo en el proceso de asignación aleatorizado. En conclusión, en pacientes con PAS, la alimentación enteral administrada por sonda nasogástrica fue tan eficaz y segura como la sonda nasoyeyunal. Se necesitan más ensayos controlados aleatorios con más participantes y mejor diseño para confirmar estos hallazgos.

Weight and Metabolic Outcomes in Naïve HIV Patients Treated with Integrase Inhibitor-Based Antiretroviral Therapy: A Systematic Review and Meta-Analysis.

BACKGROUND: The use of integrase inhibitor-based antiretroviral therapy could be associated with worse weight and metabolic outcomes in patients with HIV infection. METHODS: PubMed, EMBASE, and Scopus were searched from inception to March 2022. We selected randomized controlled trials (RCTs) comparing integrase inhibitors with other antiretroviral classes (efavirenz-based or protease inhibitor-based therapies) in naïve HIV patients. Random effects meta-analysis was used to assess the effects of integrase inhibitors vs. controls on weight and lipid outcomes. Effects were described as mean differences (MD) and their 95% confidence intervals (CI). Certain pieces of evidence (CoE) were evaluated using the GRADE methodology. RESULTS: Six RCTs (n = 3521) were included, with patients followed up between 48 and 96 weeks. The use of integrase inhibitors in comparison with other antiretroviral classes was associated with an increase in weight (MD 2.15 kg, 95%CI 1.40 to 2.90, I2 = 0%, moderate CoE), and decreases in total cholesterol (MD -13.44 mg/dL, 95%CI -23.49 to -3.39, I2 = 96%, low CoE), LDL cholesterol (MD -1.37 mg/dL, 95%CI -19.24 to -3.50, I2 = 83%, low CoE), HDL cholesterol (MD -5.03 mg/dL, 95%CI -10.61 to 0.54, I2 = 95%, low CoE), and triglycerides (MD -20.70 mg/dL, 95%CI -37.25 to -4.15, I2 = 92%, low CoE). There was a high risk of bias in two RCTs and some concerns about bias in two RCTs. CONCLUSIONS: In HIV patients, the use of integrase inhibitor-based therapy in comparison with protease inhibitor- or NNRTI-based therapy was associated with a small increase in weight and small decreases in lipid serum levels.

The added value of hypertonic saline solution to furosemide monotherapy in patients with acute decompensated heart failure: A meta-analysis and trial sequential analysis.

We assessed the effects of hypertonic saline solution (HSS) plus furosemide versus furosemide alone in patients with acute decompensated heart failure (ADHF). We searched four electronic databases for randomized controlled trials (RCTs) until June 30, 2022. The quality of evidence (QoE) was assessed using the GRADE approach. All meta-analyses were performed using a random-effects model. A trial sequential analysis (TSA) was also conducted for intermediate and biomarker outcomes. Ten RCTs involving 3013 patients were included. HSS plus furosemide significantly reduced the length of hospital stay (mean difference [MD]: -3.60 days; 95% confidence interval [CI]: -4.56 to -2.64; QoE: moderate), weight (MD: -2.34 kg; 95% CI: -3.15 to -1.53; QoE: moderate), serum creatinine (MD: -0.41 mg/dL; 95% CI: -0.49 to -0.33; QoE: low), and type-B natriuretic peptide (MD: -124.26 pg/mL; 95% CI: -207.97 to -40.54; QoE: low) compared to furosemide alone. HSS plus furosemide significantly increased urine output (MD: 528.57 mL/24 h; 95% CI: 431.90 to 625.23; QoE: moderate), serum Na+ (MD: 6.80 mmol/L; 95% CI: 4.92 to 8.69; QoE: low), and urine Na+ (MD: 54.85 mmol/24 h; 95% CI: 46.31 to 63.38; QoE: moderate) compared to furosemide alone. TSA confirmed the benefit of HSS plus furosemide. Due to the heterogeneity in mortality and heart failure readmission, meta-analysis was not performed. Our study shows that HSS plus furosemide, compared to furosemide alone, improved surrogated outcomes in ADHF patients with low or intermediate QoE. Adequately powered RCTs are still needed to assess the benefit on heart failure readmission and mortality.

Efficacy and safety of sacubitril/valsartan in heart failure compared to renin-angiotensin-aldosterone system inhibitors: a systematic review and meta-analysis of randomised controlled trials.

Introduction: Heart failure (HF) is still a major cause of morbidity and mortality all over the world. Aim of the study was to assess the benefits and harms of sacubitril/valsartan (S/V) compared to angiotensin-converting enzyme inhibitors (ACEI) or angiotensin receptor blockers (ARB) in patients with HF. Material and methods: We systematically searched for randomised controlled trials (RCTs) evaluating S/V vs. ACEI or ARB in acute or chronic HF in August 2021. Primary outcomes were HF hospitalisations and cardiovascular (CV) mortality; secondary outcomes included all-cause mortality, biomarkers, and renal function. Results: We selected 11 RCTs (n = 18766) with 2-48 months follow-up. Five RCTs had ACEIs as control, 5 RCTs had ARBs as control, and one RCT had both ACEI and ARB as control. Compared to ACEI or ARB, S/V reduced HF hospitalisations by 20% (HR = 0.80, 95% CI: 0.68-0.94; 3 RCTs; I2 = 65%; high CoE), CV mortality by 14% (HR = 0.86, 95% CI: 0.73-1.01; 2 RCTs; I2 = 57%; high CoE), and all-cause mortality by 11% (HR = 0.89, 95% CI: 0.78-1.00; 3 RCTs; I2 = 36%; high CoE). S/V reduced NTproBNP (SMD = -0.34, 95% CI: -0.52 to -0.16; 3 RCTs; I2 = 62%) and hs-TNT (ratio of differences = 0.84, 95% CI: 0.79-0.88; 2 RCTs; I2 = 0%), and caused a decline in renal function by 33% (HR = 0.67, 95% CI: 0.39-1.14; 2 RCTs; I2 = 78%; high CoE). S/V increased hypotension (RR = 1.69, 95% CI: 1.33-2.15; 9 RCTs; I2 = 65%; high CoE). Hyperkalaemia and angioedema events were similar. Effects were in the same direction when stratified by type of control (ACEI vs. ARB). Conclusions: Sacubitril/valsartan had better clinical, intermediate, and renal outcomes in HF in comparison to ACEI or ARB. There was no difference in angioedema and hyperkalaemia events, but there were more hypotension events.

Effects of Probiotics on Intermediate Cardiovascular Outcomes in Patients with Overweight or Obesity: A Systematic Review and Meta-Analysis.

BACKGROUND: Clinical trials evaluating the effect of probiotics on cardiovascular intermediate outcomes have been scarce in recent years. We systematically evaluated the efficacy of probiotics on intermediate cardiovascular outcomes in patients with overweight or obesity. METHODS: We searched for randomized controlled trials (RCTs) in four databases (until August 2021) that evaluated the effects of probiotics versus controls on intermediate cardiovascular outcomes. The outcomes were body mass index (BMI), weight, systolic blood pressure (SBP), diastolic blood pressure (DBP), glucose, low-density lipoprotein (LDL), and high-density lipoprotein (HDL) levels. Inverse variance random effects meta-analyses were used. The effects were reported as mean difference (MD), with their 95% confidence intervals (95% CI). The quality of evidence (QoE) was assessed with GRADE (grading of recommendations, assessment, development and evaluations) methodology. RESULTS: A total of 25 RCTs were included (n = 2170), with a range of follow-up from two to six months. Probiotics likely reduced BMI (MD -0.27 kg/m2, 95%CI: -0.35 to -0.19; 17 RCTs; I2 = 26%, QoE: moderate), as well as likely reduced weight (MD -0.61 kg, 95%CI: -0.89 to -0.34; 15 RCTs; I2 = 0%, QoE: moderate), and may have slightly reduce LDL (MD -4.08 mg/dL; 95%CI: -6.99 to -1.17; 9 RCTs; I2 = 87%, QoE: low) in comparison to the controls. However, probiotics had no effect on SBP (MD -0.40 mmHg; 95%CI: -5.04 to 4.25; 7 RCTs; I2 = 100%, QoE: very low), DBP (MD -1.73 mmHg; 95%CI: -5.29 to 1.82; 5 RCTs; I2 = 98%, QoE: very low), glucose (MD -0.07 mg/dL; 95%CI -0.89 to 0.75; I2 = 96%, QoE: very low), HDL (MD -1.83 mg/dL; 95%CI: -4.14 to 2.47; 14 RCTs; I2 = 98%, QoE: very low), or triglycerides (MD -3.29 mg/dL, 95%CI -17.03 to 10.45; 14 RCTs, I2 = 95%, QoE: very low) compared to control arms, and the evidence was very uncertain. CONCLUSIONS: In obese or overweight patients, BMI, weight, and LDL were lower in patients who received probiotics compared to those who received controls. Other lipids, glucose, and blood pressure were not affected by the probiotics.

Efficacy of Tunnel Technique (TUN) versus Coronally Advanced Flap (CAF) in the Management of Multiple Gingival Recession Defects: A Meta-Analysis.

Objective: We systematically assessed the efficacy of tunnel technique (TUN) vs. coronally advanced flap (CAF) in the management of multiple gingival recession defects in adults. Methods: Five databases were searched until September 2021 for randomized controlled trials (RCTs) assessing TUN vs. CAF; grafts of interest were acellular dermal matrix (ADM) and connective tissue graft (CTG). Primary outcomes were root coverage (RC) and complete root coverage (CRC). Secondary outcomes were clinical attachment level (CAL), keratinized tissue width (KTW), probing depth (PD), and recession coverage (REC). Effect measures were risk ratio (RR) or mean difference (MD) with their confidence intervals (95% CI). Inverse variance methods and random-effects model meta-analyses were used. Subgroup analyses by the type of graft were performed. Quality of evidence was assessed using GRADE methodology. Results: Five RCTs (n = 173) were included, with a follow-up of 6 months for all outcomes. In comparison to CAF, TUN did not significantly reduce CRC (RR 0.65; 95% CI 0.002-176.7; p = 0.51) and did not increase RC (MD 0.99%; 95% CI -6.7 to 8.6; p = 0.80). In comparison to CAF, TUN showed no significant reduction of secondary outcomes. Subgroup analyses by type of graft showed no differences in comparison to primary analyses for primary and secondary outcomes. Three RCTs had a high risk of bias, and five RCTs had very low quality of evidence for all outcomes. Conclusions: In adults with gingival recessions, TUN had similar primary and secondary outcomes in comparison with CAF. Subgroup analyses by the type of graft did not affect main conclusions. More RCTs with better design are needed to further characterize the effects of TUN vs. CAF in the treatment of multiple gingival recession defects.

Short-term outcomes of endoscopic submucosal dissection for the treatment of superficial gastric neoplasms in non-Asian countries: a systematic review and meta-analysis.

Background: Endoscopic submucosal dissection (ESD) is now considered the standard treatment for early gastric cancer (EGC). However, the widespread adoption of ESD in western countries has been slow. We performed a systematic review to evaluate short-term outcomes of ESD for EGC in non-Asian countries. Methods: We searched 3 electronic databases from inception until October 26, 2022. Primary outcomes were en bloc, R0 and curative resections rate by region. Secondary outcomes were overall complications, bleeding, and perforation rate by region. The proportion of each outcome, with the 95% confidence interval (CI), was pooled using a random-effects model with the Freeman-Tukey double arcsine transformation. Results: Twenty-seven studies from Europe (n=14), South America (n=11) and North America (n=2) were included, involving 1875 gastric lesions. Overall, en bloc, R0, and curative resection rates were achieved in 96% (95%CI 94-98%), 85% (95%CI 81-89%), and 77% (95%CI 73-81%) of cases, respectively. Considering only information from lesions with adenocarcinoma, the overall curative resection was 75% (95CI 70-80%). Bleeding and perforation were observed in 5% (95%CI 4-7%) and 2% (95%CI 1-4%) of cases, respectively. Conclusion: Our results suggest that short-term outcomes of ESD for the treatment of EGC are acceptable in non-Asian countries.