Clinical decision support systems to optimize adherence to anticoagulant guidelines in patients with atrial fibrillation: a systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Clinical decision support systems (CDSS) have been utilized as a low-cost intervention to improve healthcare process measures. Thus, we aim to estimate CDSS efficacy to optimize adherence to oral anticoagulant guidelines in eligible patients with atrial fibrillation (AF). METHODS: A systematic review and meta-analysis of randomized controlled trials (RCTs) retrieved from PubMed, WOS, SCOPUS, EMBASE, and CENTRAL through August 2023. We used RevMan V. 5.4 to pool dichotomous data using risk ratio (RR) with a 95% confidence interval (CI). PROSPERO ID: CRD42023471806. RESULTS: We included nine RCTs with a total of 25,573 patients. There was no significant difference, with the use of CDSS compared to routine care, in the number of patients prescribed anticoagulants (RR: 1.06, 95% CI [0.98, 1.14], P = 0.16), the number of patients prescribed antiplatelets (RR: 1.01 with 95% CI [0.97, 1.06], P = 0.59), all-cause mortality (RR: 1.19, 95% CI [0.31, 4.50], P = 0.80), major bleeding (RR: 0.84, 95% CI [0.21, 3.45], P = 0.81), and clinically relevant non-major bleeding (RR: 1.05, 95% CI [0.52, 2.16], P = 0.88). However, CDSS was significantly associated with reduced incidence of myocardial infarction (RR: 0.18, 95% CI [0.06, 0.54], P = 0.002) and cerebral or systemic embolic event (RR: 0.11, 95% CI [0.01, 0.83], P = 0.03). CONCLUSION: We report no significant difference with the use of CDSS compared to routine care in anticoagulant or antiplatelet prescription in eligible patients with AF. CDSS was associated with a reduced incidence of myocardial infarction and cerebral or systemic embolic events.

Effect of methotrexate hold on COVID-19 vaccine response in the patients with autoimmune inflammatory disorders: a systematic review and meta-analysis.

Immunosuppressants, such as methotrexate (MTX), can suppress the COVID-19 vaccine response in patients with autoimmune diseases. Thus, this study aims to evaluate the effects of MTX hold following COVID-19 vaccination on vaccine efficacy response. A systematic review and meta-analysis of relevant studies retrieved from Web of Science, SCOPUS, PubMed, and CENTRAL from inception until Oct 1, 2023, was conducted. Covidence was used to screen the eligible articles, and all relevant outcomes data were synthesized using risk ratios (RRs) or standardized mean differences (SMDs) with 95% confidence intervals (CIs) in meta-analysis models within RevMan 5.4. PROSPERO ID: CRD42024511628. Four studies with a total of 762 patients with autoimmune inflammatory disorders were included. Holding MTX following the COVID-19 vaccination for approximately 2 weeks was associated with significantly higher antibody titer (SMD: 0.70, 95% CI [0.54, 0.87], P < 0.00001). However, the flare rate was significantly higher in the MTX hold group based on CDAI > 10 or DAS28-CRP > 1.2 either after 1st dose (RR: 2.49 with 95% CI [1.39, 4.47], P = 0.002) or 2nd dose (RR: 2.16 with 95% CI [1.37, 3.41], P = 0.0009) and self-reported disease flare (RR: 1.71 with 95% CI [1.35, 2.17], P < 0.00001). Holding MTX for 2 weeks after the COVID-19 vaccination resulted in significantly higher antibody titer but also had a higher disease flare rate, necessitating cautious clinical monitoring during this period. There is still a need to investigate safer MTX hold duration, considering patients' vulnerability to COVID-19, disease status, and demographics while adopting this strategy.

Etrolizumab as an induction and maintenance therapy for ulcerative colitis: A systematic review and meta-analysis of randomized controlled trials.

Background and Aim: Etrolizumab is a gut-targeted anti-ß7 integrin monoclonal antibody. However, the evidence of etrolizumab efficacy and safety in ulcerative colitis remains inconclusive. Therefore, we aim to evaluate the safety and efficacy of etrolizumab as an induction and maintenance therapy for active moderate to severe ulcerative colitis. Methods: We synthesized randomized controlled studies (RCTs) from MEDLINE, Scopus, EMBASE, PubMed, Web of Science, and Cochrane Library until April 2023. The risk ratio (RR) for dichotomous outcomes with the corresponding 95% confidence interval (CI) was used. The study protocol was registered in PROSPERO with ID: CRD42023437040. Results: Five RCTs with 1849 participants were included. The etrolizumab group had a significant clinical response (RR: 1.28 with 95% CI [1.08, 1.51], P = 0.005), clinical remission rates during the induction phase (RR: 2.47 with 95% CI [1.48, 4.11], P = 0.0005), compared with the placebo group in ulcerative colitis; however, there was no statistically significant difference between the two groups, regarding the corticosteroids-free remission rate (RR: 1.92 with 95% CI [0.94, 3.92], P = 0.07). Moreover, endoscopic improvement, endoscopic remission, and histologic remission rates were observed more in the etrolizumab group during both the induction and maintenance phases. For safety outcomes, etrolizumab was significantly safer, but any adverse event was higher in the etrolizumab group than in the placebo. Conclusion: Etrolizumab shows its effectiveness as both an induction and maintenance therapy for moderate or severe UC. The findings demonstrate its positive impact on clinical, endoscopic, and histologic remission rates. Regarding safety, other than any side effects, etrolizumab showed a good safety than a placebo.

Efficacy and safety of high-power short-duration ablation for atrial fibrillation: a systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: High-power short-duration (HPSD) ablation has emerged as an alternative to conventional standard-power long-duration (SPLD) ablation. We aim to assess the efficacy and safety of HPSD versus SPLD for atrial fibrillation (AF) ablation. METHODS: A systematic review and meta-analysis of randomized controlled trials (RCTs) retrieved from PubMed, WOS, SCOPUS, EMBASE, and CENTRAL were performed through August 2023. We used RevMan V. 5.4 to pool dichotomous data using risk ratio (RR) and continuous data using mean difference (MD) with a 95% confidence interval (CI). PROSPERO ID: CRD42023471797. RESULTS: We included six RCTs with a total of 694 patients. HPSD was significantly associated with a decreased total procedure time (MD: -22.88 with 95% CI [-36.13, -9.63], P = 0.0007), pulmonary vein isolation (PVI) time (MD: -19.73 with 95% CI [-23.93, -15.53], P < 0.00001), radiofrequency time (MD: -10.53 with 95% CI [-12.87, -8.19], P < 0.00001). However, there was no significant difference between HPSD and SPLD ablation with respect to the fluoroscopy time (MD: -0.69 with 95% CI [-2.00, 0.62], P = 0.30), the incidence of esophageal lesions (RR: 1.15 with 95% CI [0.43, 3.07], P = 0.77), and the incidence of first pass isolation (RR: 0.98 with 95% CI [0.88, 1.08], P = 0.65). CONCLUSION: HPSD ablation was significantly associated with decreased total procedure time, PVI time, and radiofrequency time compared with SPLD ablation. On the contrary, SPLD ablation was significantly associated with low maximum temperature.

Intensive Blood Pressure Control After Endovascular Thrombectomy for Acute Ischemic Stroke: a Systematic Review and Meta-Analysis.

BACKGROUND AND PURPOSE: Optimal clinical outcome with successful recanalization from endovascular thrombectomy (EVT) requires optimal blood pressure (BP) management. We aimed to evaluate the efficacy and safety of the intensive BP target (< 140 mm Hg) versus the standard BP target (< 180 mm Hg) after EVT for acute ischemic stroke. METHODS: We conducted a systematic review and meta-analysis synthesizing evidence from randomized controlled trials (RCTs) obtained from PubMed, Embase Cochrane, Scopus, and WOS until September 7th, 2023. We used the fixed-effect model to report dichotomous outcomes using risk ratio (RR) and continuous outcomes using mean difference (MD), with a 95% confidence interval (CI). PROSPERO ID: CRD42023463206. RESULTS: We included four RCTs with 1559 patients. There was no difference between intensive BP and standard BP targets regarding the National Institutes of Health Stroke Scale (NIHSS) change after 24 h [MD: 0.44 with 95% CI (0.0, 0.87), P = 0.05]. However, the intensive BP target was significantly associated with a decreased risk of excellent neurological recovery (mRS ≤ 1) [RR: 0.87 with 95% CI (0.76, 0.99), P = 0.03], functional independence (mRS ≤ 2) [RR: 0.81 with 95% CI (0.73, 0.90), P = 0.0001] and independent ambulation (mRS ≤ 3) [RR: 0.85 with 95% CI (0.79, 0.92), P < 0.0001]. CONCLUSIONS: An intensive BP target after EVT is associated with worse neurological recovery and significantly decreased rates of functional independence and independent ambulation compared to the standard BP target. Therefore, the intensive BP target should be avoided after EVT for acute ischemic stroke.

Intermittent fasting regimens for metabolic dysfunction-associated steatotic liver disease: a systematic review and network meta-analysis of randomized controlled trials.

Metabolic dysfunction-associated steatotic liver disease (MASLD) is a prevalent metabolic disorder characterized by excessive hepatic fat accumulation. Intermittent fasting (IF) has emerged as a potential therapeutic strategy with the ability to induce weight loss, improve insulin sensitivity and reduce hepatic steatosis. We aim to compare the efficacy of different IF regimens for MASLD management. A systematic review and network meta-analysis of randomized controlled trials investigating different IF regimens for MASLD. PubMed , EMBASE , WOS , SCOPUS and Cochrane Central Register of Controlled Trials were searched until 10 April 2023. Analysis was performed using R software with the meta and netmeta packages. Mean difference (MD) was used to pool continuous outcomes with 95% confidence intervals (CIs). Our meta-analysis was registered in PROSPERO (CRD42023418467). Our meta-analysis included eight randomized controlled trials with a total of 635 participants. The 5 : 2 diet significantly improved liver stiffness (MD, -0.32; 95% CI, -0.55 to -0.09; P  < 0.01). Time-restricted feeding significantly improved liver steatosis (controlled attenuation parameter score) (MD, -39.83; 95% CI, -64.78 to -14.87; P  < 0.01). No significant changes were observed in asparate aminotransferase, gamma-glutamyl transpeptidase, low-density lipoproteins cholesterol, total cholesterol, triglyceride levels, basal metabolic index, blood pressure, Homeostatic Model Assessment of Insulin Resistance, fasting blood sugar, lean body mass or waist circumference across all IF regimens. However, alternate-day fasting showed positive results in anthropometric measures, including significant improvements in lean body mass, waist circumference, fat mass and weight reduction ( P  < 0.05). IF regimens showed various positive effects on clinical outcomes in MASLD patients; however, these effects were not consistent. Therefore, a patient-tailored IF regimen should be considered.

Efficacy and safety of restrictive versus liberal blood transfusion strategies in acute myocardial infarction and anemia: a systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Blood transfusion strategies in patients with acute myocardial infarction (AMI) and anemia are yet to be conclusively identified. Thus, we aim to assess the efficacy and safety of restrictive versus liberal blood transfusion strategies for AMI and anemia. METHODS: A systematic review and meta-analysis of randomized controlled trials (RCTs) retrieved from PubMed, web of science, SCOPUS, EMBASE, and Cochrane Central Register of Controlled Trials were performed through November 2023. We used RevMan V. 5.4 to pool dichotomous data using risk ratio (RR) and continuous data using mean difference (MD) with a 95% confidence interval (CI). (PROSPERO): ID: CRD42023490692. RESULTS: We included four RCTs with 4.325 patients. There was no significant difference between both groups regarding MACE whether at 30 days (RR: 0.93 with 95% CI [0.57-1.51], P  = 0.76) or ≥ six months (RR: 1.17 with 95% CI [0.95-1.45], P  = 0.14), all-cause mortality at 30 days (RR: 1.16 with 95% CI [0.95-1.40], P  = 0.14) or ≥ six months (RR: 1.16 with 95% CI [0.88-1.53], P  = 0.28). However, the liberal strategy was significantly associated with increased hemoglobin level change (MD: -1.44 with 95% CI [-1.68 to -1.20], P  < 0.00001). However, the restrictive strategy was significantly associated with a lower incidence of acute lung injury (RR: 0.11 with 95% CI [0.02-0.60], P  = 0.01). CONCLUSION: There was no significant difference between the restrictive blood transfusion strategy and the liberal blood transfusion strategy regarding the clinical outcomes. However, restrictive blood transfusion strategy was significantly associated with a lower incidence of acute lung injury than liberal blood transfusion strategy.

The efficacy and safety of pre-hospital plasma in patients at risk for hemorrhagic shock: an updated systematic review and meta-analysis of randomized controlled trials.

BACKGROUND AND OBJECTIVE: Plasma is a critical element in hemostatic resuscitation post-injury, and its prompt administration within the prehospital setting may reduce the complications resulting from hemorrhage and shock. Our objective is to assess the efficacy and safety of prehospital plasma infusion in patients susceptible to hemorrhagic shock. METHODS: We conducted our study by aggregating randomized controlled trials (RCTs) sourced from PubMed, EMBASE, Scopus, Web of Science, and Cochrane CENTRAL up to January 29, 2023. Quality assessment was implemented using the Cochrane RoB 2 tool. Our study protocol is registered in PROSPERO under ID: CRD42023397325. RESULTS: Three RCTs with 760 individuals were included. There was no difference between plasma infusion and standard care groups in 24-h mortality (P = 0.11), 30-day mortality (P = 0.12), and multiple organ failure incidences (P = 0.20). Plasma infusion was significantly better in the total 24-h volume of PRBC units (P = 0.03) and INR on arrival (P = 0.009). For all other secondary outcomes evaluated (total 24-h volume of packed FFP units, total 24-h volume of platelets units, massive transfusion, vasopressor need during the first 24 h, any adverse event, acute lung injury, transfusion reaction, and sepsis), no significant differences were observed between the two groups. CONCLUSION: Plasma infusion in trauma patients at risk of hemorrhagic shock does not significantly affect mortality or the incidence of multiple organ failure. However, it may lead to reduced packed red blood cell transfusions and increased INR at hospital arrival.

Protective efficacy and safety of radiation-attenuated and chemo-attenuated Plasmodium Falciparum sporozoite vaccines against controlled and natural malaria infection: a systematic review and meta-analysis of randomized controlled trials.

BACKGROUND AND OBJECTIVE: Despite the significant burden of Plasmodium falciparum (Pf) malaria and the licensure of two vaccines for use in infants and young children that are partially effective in preventing clinical malaria caused by Pf, a highly effective vaccine against Pf infection is still lacking. Live attenuated vaccines using Pf sporozoites as the immunogen (PfSPZ Vaccines) hold promise for addressing this gap. Here we review the safety and efficacy of two of the most promising PfSPZ approaches: PfSPZ Vaccine (radiation attenuated PfSPZ) and PfSPZ-CVac (chemo-attenuated PfSPZ). METHODS: We conducted a systematic review and meta-analysis by searching PubMed, EMBASE, SCOPUS, CENTRAL, and WOS until 22nd December 2021. We included randomized controlled trials (RCTs) of these two vaccine approaches that measured protection against parasitaemia following controlled human malaria infection (CHMI) in malaria-naive and malaria-exposed adults or following exposure to naturally transmitted Pf malaria in African adults and children (primary outcome) and that also measured the incidence of solicited and unsolicited adverse events as indicators of safety and tolerability after vaccination (secondary outcome). We included randomized controlled trials (RCTs) that measured the detected parasitaemia after vaccination (primary outcome) and the incidence of various solicited and unsolicited adverse events (secondary outcome). The quality of the included RCTs using the Cochrane ROB 1 tool and the quality of evidence using the GRADE system were evaluated. We pooled dichotomous data using the risk ratio (RR) for development of parasitemia in vaccinees relative to controls as a measure of vaccine efficacy (VE), including the corresponding confidence interval (CI). This study was registered with PROSPERO (CRD42022308057). RESULTS: We included 19 RCTs. Pooled RR favoured PfSPZ Vaccine (RR: 0.65 with 95% CI [0.53, 0.79], P = 0.0001) and PfSPZ-table (RR: 0.42 with 95% CI [0.27, 0.67], P = 0.0002) for preventing parasitaemia, relative to normal saline placebo. Pooled RR showed no difference between PfSPZ Vaccine and the control in the occurrence of any solicited adverse event (RR: 1.00 with 95% CI [0.82, 1.23], P = 0.98), any local solicited adverse events (RR: 0.73 with 95% CI [0.49, 1.08], P = 0.11), any systemic solicited adverse events (RR: 0.94 with 95% CI [0.75, 1.17], P = 0.58), and any unsolicited adverse event (RR: 0.93 with 95% CI [0.78, 1.10], P = 0.37). CONCLUSION: PfSPZ and PfSPZ-CVacs showed comparable efficacy. Therefore, they can introduce a promising strategy for malaria prophylaxis, but more large-scale field trials are required to sustain efficacy and yield clinically applicable findings.

The efficacy and safety of exercise regimens to mitigate chemotherapy cardiotoxicity: a systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Cardiotoxicity is one of the most common adverse events of the chemotherapy. Physical exercise was shown to be cardioprotective. We aim to estimate the efficacy and safety of exercise in cancer patients receiving cardiotoxic chemotherapy. METHODS: We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs), which were retrieved by systematically searching PubMed, Web of Science, SCOPUS, Cochrane, Clinical Trials.gov, and MedRxiv through July 17th, 2023. We used RevMan V. 5.4 to pool dichotomous data using risk ratio (RR) and continuous data using mean difference (MD), with a 95% confidence interval (CI). PROSPERO ID: CRD42023460902. RESULTS: We included thirteen RCTs with a total of 952 patients. Exercise significantly increased VO2 peak (MD: 1.95 with 95% CI [0.59, 3.32], P = 0.005). However, there was no significant effect regarding left ventricular ejection fraction, global longitudinal strain, cardiac output, stroke volume, left ventricular end-diastolic volume, left ventricular end-systolic volume, E/A ratio, resting heart rate, peak heart rate, resting systolic blood pressure, and resting diastolic blood pressure. Also, there was no significant difference regarding any adverse events (AEs) (RR: 4.44 with 95% CI [0.47, 41.56], P = 0.19), AEs leading to withdrawal (RR: 2.87 with 95% CI [0.79, 10.43], P = 0.11), serious AEs (RR: 3.00 with 95% CI [0.14, 65.90], P = 0.49), or all-cause mortality (RR: 0.25 with 95% CI [0.03, 2.22], P = 0.21). CONCLUSION: Exercise is associated with increased VO2 peak in cancer patients receiving cardiotoxic chemotherapy. However, there was no significant difference between exercise and usual care regarding the echocardiographic and safety outcomes.

The efficacy and safety of botulinum toxin epicardial fat injection to prevent postoperative atrial fibrillation in patients undergoing cardiac surgery: a meta-analysis of randomized controlled trials.

Background: Postoperative atrial fibrillation (POAF) is prevalent in about 30% to 60% of patients undergoing cardiac surgery, leading to worse outcomes. Botulinum toxin type A (BTX) epicardial injection has been proposed to prevent POAF by impairing cholinergic signaling. Methods: A systematic review and meta-analysis synthesized randomized controlled trials, which were retrieved by searching PubMed, EMBASE, Web of Science, SCOPUS, and Cochrane through November 23, 2022. RevMan version 5.4 was used to pool dichotomous outcomes using risk ratio (RR) and continuous outcomes using mean differences (MD) presented with the corresponding confidence interval (CI). Results: Three randomized controlled trials with 509 patients (308 in the BTX group and 205 in the placebo group) were included in the analysis. There was no difference between BTX and placebo regarding POAF incidence (RR 0.81 with 95% CI [0.65, 1.00], P = 0.05), postoperative hospital length of stay in days (MD -0.03 with 95% CI [-0.54, 0.49], P = 0.91), all-cause mortality (RR 1.64 with 95% CI [0.22, 12.17], P = 0.63), any adverse event (RR 1.03 with 95% CI [0.94, 1.12], P = 0.51), or any serious adverse event (RR 0.89 with 95% CI [0.68, 1.15], P = 0.36). Conclusion: There was no difference between the epicardial fat injection of BTX versus placebo for preventing POAF.

Perioperative balanced crystalloids versus normal saline during kidney transplantation: a systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: In kidney transplant (KT) surgery, the perioperative administration of intravenous (IV) fluids plays a crucial role, with potential effects on graft function. Our meta-analysis aims to assess the post-KT outcomes of perioperative balanced crystalloids (BC) versus normal saline (NS). METHODS: We conducted a comprehensive search across five databases to identify relevant randomized controlled trials (RCTs). The search results were imported into Covidence for article eligibility screening, and all relevant outcome data were synthesized using risk ratios (RR) or mean differences (MD) with 95% confidence intervals (CIs) in meta-analysis models within RevMan 5.4. PROSPERO ID: CRD42023448457. RESULTS: Pooled data from 15 RCTs with 2,008 participants showed that the rate of delayed graft function (DGF) was significantly lower with BC (RR: 0.78, 95% CI [0.68, 0.91], P = 0.0009). Also, BC was associated with significantly higher post-op blood pH (MD: 0.05, 95% CI [0.03, 0.07], P < 0.01), lower serum chloride (MD: - 7.31, 95% CI [- 10.58, - 3.77], P < 0.01), and sodium (MD: - 1.94, 95% CI [- 3.32, - 0.55], P = 0.006) as compared to NS. However, serum potassium, serum creatinine, and urine output at POD 1 to 7 did not differ between the two groups. CONCLUSION: BC significantly reduced the incidence of DGF, resulting in more stable post-operative acid-base parameters, and lower chloride levels compared to NS. Hence, substituting NS with BC offers a strategy to protect grafts from acidotic and hyperchloremic insults, optimizing KT outcomes.

Once-weekly Insulin Icodec Versus Once-daily Long-acting Insulin for Type II Diabetes: A Meta-analysis of Randomized Controlled Trials.

Background: Insulin icodec is a novel basal insulin analog with once-weekly subcutaneous administration. We aim to estimate the efficacy and safety of insulin icodec vs long-acting insulin (insulin glargine and degludec) in type II diabetic patients. Methods: We conducted a systematic review and meta-analysis synthesizing randomized controlled trials (RCTs), which were retrieved by systematically searching PubMed, Web of Science, SCOPUS, and Cochrane through May 29, 2023. We used RevMan V. 5.4 to pool dichotomous data using risk ratio (RR) and continuous data using mean difference (MD) with a 95% confidence interval (CI). Our primary outcome was glycated hemoglobin (HbA1C) change. Results: We included 7 RCTs with a total of 3183 patients. Insulin icodec was associated with significantly decreased HbA1C (MD: -0.15 with 95% CI [-0.24, -0.06], P = .002) and increased percentage of time with glucose in range (TIR) (MD: 4.06 with 95% CI [2.06, 6.06], P = .0001). However, insulin icodec was associated with increased body weight (MD: 0.57 with 95% CI [0.45, 0.70], P = .00001). Also, there was no difference regarding any serious adverse events (AEs) (RR: 0.96 with 95% CI [0.76, 1.20], P = .7) or AEs leading to withdrawal (RR: 1.54 with 95% CI [0.84, 2.82], P = .16). However, insulin icodec was associated with increased any AEs incidence (RR: 1.06 with 95% CI [1.01, 1.12], P = .02). Conclusion: Insulin icodec was associated with decreased HbA1C, increased TIR, with similar hypoglycemic and serious AEs. However, it was also associated with increased body weight and the incidence of any AEs.

Soluble guanylate cyclase stimulators for heart failure: a network meta-analysis and subgroup analyses of reduced and preserved ejection fraction.

BACKGROUND: Soluble guanylate cyclase (sGC) stimulators have been investigated for heart failure (HF) in several randomized controlled trials (RCTs). However, its place in the management guidelines of either HFrEF or HfpEF is still inconclusive. METHODS: We conducted a network meta-analysis synthesizing RCTs investigating sGC for HF management, which were retrieved by systematically searching five databases until January 24th, 2023. Dichotomous outcomes were pooled using risk ratio (RR) along with confidence interval (CI). RESULTS: Eight RCTs with a total of 7307 patients were included. Vericiguat 10 mg significantly reduced the composite cardiovascular (CVS) mortality and HF hospitalization in HF (RR: 0.88, 95% CI [0.79; 0.98]) and in HFrEF (RR: 0.87, 95% CI [0.78; 0.97]); however, it was not effective in HFpEF (RR: 0.69, 95% CI [0.15; 3.05]). Also, vericiguat 10 mg showed no difference compared to placebo regarding the incidence of all-cause mortality (RR: 0.96, 95% CI [0.84; 1.10]), any adverse events (AEs) (RR: 0.94, 95% CI [0.83; 1.07]), any serious AEs (RR: 0.91, 95% CI [0.81; 1.01]), and any AEs leading to drug discontinuation (RR: 1.14, 95% CI [0.92; 1.40]). CONCLUSION: Vericiguat 10 mg was effective in reducing the composite CVS mortality and HF hospitalization, with an acceptable safety profile. This was only observed in HFrEF patients, but not in HFpEF patients. However, our data regarding other agents (riociguat and praliciguat) and HFpEF can be underpowered, warranting further RCTs to clarify vericiguat 10 mg place in HFrEF management guidelines and to investigate sGC stimulators for HFpEF in large-scale trials.

The efficacy and safety of new potassium binders on renin-angiotensin-aldosterone system inhibitor optimization in heart failure patients: a systematic review and meta-analysis.

Guideline-directed medical therapy (GDMT) has improved outcomes in patients with heart failure, including the use of renin-angiotensin-aldosterone system inhibitors, which can hinder the excretion of potassium, resulting in hyperkalaemia. New potassium binders (NPBs) can prevent this adverse effect; however, the efficacy and safety of NPB for this indication have not been fully established. We conducted a systematic review and meta-analysis synthesizing randomized controlled trials (RCTs), which were retrieved by systematically searching PubMed, Web of Science, Scopus, and Cochrane through 26 April 2023. The risk of bias assessment was conducted, following Cochrane's updated Risk of Bias 2 assessment tool. We used the fixed-effects model to pool dichotomous data using risk ratio (RR) and continuous data using mean difference (MD), with a 95% confidence interval (CI) (PROSPERO ID: CRD42023426113). We included six RCTs with a total of 1432 patients. NPB was significantly associated with successful mineralocorticoid receptor antagonist (MRA) optimization [RR: 1.13 with 95% CI (1.02-1.25), P = 0.02], decreased patients with MRA at less than the target dose [RR: 0.72 with 95% CI (0.57-0.90), P = 0.004], and decreased hyperkalaemic episodes [RR: 0.42 with 95% CI (0.24-0.72), P = 0.002]. However, there was no difference between NPB and placebo regarding angiotensin-converting enzyme inhibitor (ACEi)/angiotensin receptor blocker (ARB)/angiotensin receptor/neprilysin inhibitor (ANRi) optimization [RR: 1.02 with 95% CI (0.89-1.17), P = 0.76] and serum potassium change [MD: -0.31 with 95% CI (-0.61 to 0.00), P = 0.05], with an acceptable safety profile except for the increased incidence of hypokalaemia with NPB [RR: 1.57 with 95% CI (1.12-2.21), P = 0.009]. NPB has been shown to improve GDMT outcomes by enhancing MRA optimization and reducing hyperkalaemic episodes. However, there are limited data on the effects of NPB on ACEi/ARB/ANRi optimization. Future RCTs should investigate ACEi/ARB/ANRi optimization and conduct head-to-head comparisons of NPB (patiromer and sodium zirconium cyclosilicate).

Intravenous fluid rate of 250 mL/h versus 125 mL/h in nulliparous women: A systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Evidence regarding the type and rate of intravenous (IV) fluid administration during labor is still inconclusive and the studies assessing the impact of IV fluids had mixed results. OBJECTIVES: To evaluate the effects of IV fluids at an infusion rate of 250 mL/h as compared with 125 mL/h on labor outcomes in nulliparous women. SEARCH STRATEGY: We searched six databases for relevant studies through a search strategy containing the relevant keywords "IV hydration", "IV fluids", and "labor" from the inception of these databases to May 1, 2023, without any applied restrictions. SELECTION CRITERIA: Search results were imported to Covidence for screening of eligible articles for this review. Randomized controlled trials (RCTs) assessing the impact of IV fluids at 250 mL/h on the outcomes of labor in nulliparous women at term (>37 weeks) as compared with 125 mL/h were included only. DATA COLLECTION AND ANALYSIS: Data regarding the characteristics of included studies, participant's baseline characteristics, and concerned outcomes were collected in an Excel spreadsheet and all the concerned outcomes were pooled as risk ratios (RR) or mean difference (MD) with 95% confidence interval (CI) in the meta-analysis models using RevMan 5.4. MAIN RESULTS: Pooled data from 11 RCTs with 1815 patients showed that 250 mL/h infusion rate had a significant reduction in cesarean section rate (RR 0.70, 95% CI 0.56-0.88, P = 0.002), the first stage of labor duration (MD -46.97, 95% CI -81.79 to -12.14, P = 0.008), the second stage of labor duration (MD -2.69, 95% CI -4.34 to -1.05, P = 0.001), prolonged labor incidence (RR 0.72, 95% CI 0.58-0.89, P = 0.003), as compared with 125 mL/h. Also, the vaginal delivery rate (RR 1.07, 95% CI 1.02-1.12, P = 0.009) was higher with a 250 mL/h infusion rate. CONCLUSION: IV fluids at an infusion rate of 250 mL/h during labor in nulliparous women decreased the cesarean delivery rate, increased the vaginal delivery rate, shortened the first and second-stage labor duration, decreased the incidence of prolonged labor as compared with 125 mL/h. These findings suggest enhanced labor progression and a lower risk of labor complications with higher infusion rates. However, future research involving a more diverse population and exploring the potential benefits of combining IV infusion rates with other interventions, such as adding dextrose or less restrictive oral intake during labor, is needed.

Sphingosine 1-phosphate (S1P) receptor modulators as an induction and maintenance therapy for ulcerative colitis: a systematic review and meta-analysis of randomized controlled trials.

BACKGROUND AND OBJECTIVE: One sphingosine-1-phosphate (S1P) receptor modulator is approved (ozanimod) and another (etrasimod) is under investigation for the induction and maintenance of remission of ulcerative colitis (UC). We aim to evaluate the efficacy and safety of S1P modulators in patients with active UC. METHODS: We conducted a systematic review and meta-analysis synthesizing randomized controlled trials (RCTs), which were retrieved by systematically searching: PubMed, Web of Science, SCOPUS, and Cochrane through May 13th, 2023. We used the fixed-effect model to pool dichotomous data using risk ratio (RR) with a 95% confidence interval (CI). RESULTS: Five RCTs with a total of 1990 patients were included. S1P receptor modulators were significantly associated with increased clinical response during both the induction (RR 1.71 with 95% CI [1.50, 1.94], P = 0.00001) and maintenance phases (RR 1.89 with 95% CI [1.33, 2.69], P = 0.0004); clinical remission rates during both induction (RR 2.76 with 95% CI [1.88, 4.05], P = 0.00001) and maintenance phases (RR 3.34 with 95% CI [1.41, 7.94], P = 0.006); endoscopic improvement during both induction (RR 2.15 with 95% CI [1.71, 2.70], P = 0.00001) and maintenance phases (RR 2.41 with 95% CI [1.15, 5.05], P = 0.02); and histologic remission during both induction (RR 2.60 with 95% CI [1.89, 3.57] [1.17, 2.10], P = 0.00001) and maintenance phases (RR 2.52 with 95% CI [1.89, 3.37], P = 0.00001). Finally, there was no difference regarding safety outcomes as compared to placebo in both the induction and maintenance phases. CONCLUSION: S1P receptor modulators are effective in inducing and maintaining remission in patients with moderate to severe UC.

Istaroxime for Patients with Acute Heart Failure: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Istaroxime, an intravenous inotropic agent with a dual mechanism-increasing both cardiomyocyte contractility and relaxation-is a novel treatment for acute heart failure (AHF), the leading cause of morbidity and mortality in heart failure. We conducted a systematic review and meta-analysis that synthesized randomized controlled trials (RCTs), which were retrieved by systematically searching PubMed, Web of Science, SCOPUS, and Cochrane until 24 April 2023. We used a fixed-effect or random-effect model-according to heterogeneity-to pool dichotomous data using the risk ratio (RR) and continuous data using the mean difference (MD), with a 95% confidence interval (CI). We included three RCTs with a total of 300 patients. Istaroxime was significantly associated with an increased left ventricular ejection fraction (mL) (MD: 1.06, 95% CI: 0.29, 1.82; p = 0.007), stroke volume index (MD: 3.04, 95% CI: 2.41, 3.67; p = 0.00001), and cardiac index (L/min/m2) (MD: 0.18, 95% CI: 0.11, 025; p = 0.00001). Also, istaroxime was significantly associated with a decreased E/A ratio (MD: -0.39, 95% CI: -0.58, -0.19; p = 0.0001) and pulmonary artery systolic pressure (mmHg) (MD: 2.30, 95% CI: 3.20, 1.40; p = 0.00001). Istaroxime was significantly associated with increased systolic blood pressure (mmHg) (MD: 5.32, 95% CI: 2.28, 8.37; p = 0.0006) and decreased heart rate (bpm) (MD: -3.05, 95% CI: -5.27, -0.82; p = 0.007). Since istaroxime improved hemodynamic and echocardiographic parameters, it constitutes a promising strategy for AHF management. However, the current literature is limited to a small number of RCTs, warranting further large-scale phase III trials before clinical endorsement.

Low-Value Surgical Procedures in Low- and Middle-Income Countries: A Systematic Scoping Review.

Importance: Overuse of surgical procedures is increasing around the world and harms both individuals and health care systems by using resources that could otherwise be allocated to addressing the underuse of effective health care interventions. In low- and middle-income countries (LMICs), there is some limited country-specific evidence showing that overuse of surgical procedures is increasing, at least for certain procedures. Objectives: To assess factors associated with, extent and consequences of, and potential solutions for low-value surgical procedures in LMICs. Evidence Review: We searched 4 electronic databases (PubMed, Embase, PsycINFO, and Global Index Medicus) for studies published from database inception until April 27, 2022, with no restrictions on date or language. A combination of MeSH terms and free-text words about the overuse of surgical procedures was used. Studies examining the problem of overuse of surgical procedures in LMICs were included and categorized by major focus: the extent of overuse, associated factors, consequences, and solutions. Findings: Of 4276 unique records identified, 133 studies across 63 countries were included, reporting on more than 9.1 million surgical procedures (median per study, 894 [IQR, 97-4259]) and with more than 11.4 million participants (median per study, 989 [IQR, 257-6857]). Fourteen studies (10.5%) were multinational. Of the 119 studies (89.5%) originating from single countries, 69 (58.0%) were from upper-middle-income countries and 30 (25.2%) were from East Asia and the Pacific. Of the 42 studies (31.6%) reporting extent of overuse of surgical procedures, most (36 [85.7%]) reported on unnecessary cesarean delivery, with estimated rates in LMICs ranging from 12% to 81%. Evidence on other surgical procedures was limited and included abdominal and percutaneous cardiovascular surgical procedures. Consequences of low-value surgical procedures included harms and costs, such as an estimated US $3.29 billion annual cost of unnecessary cesarean deliveries in China. Associated factors included private financing, and solutions included social media campaigns and multifaceted interventions such as audits, feedback, and reminders. Conclusions and Relevance: This systematic review found growing evidence of overuse of surgical procedures in LMICs, which may generate significant harm and waste of limited resources; the majority of studies reporting overuse were about unnecessary cesarean delivery. Therefore, a better understanding of the problems in other surgical procedures and a robust evaluation of solutions are needed.