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.

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.

Defibrillation strategies for refractory ventricular fibrillation out-of-hospital cardiac arrest: A systematic review and network meta-analysis.

BACKGROUND AND OBJECTIVE: Double sequential external defibrillation (DSED) and vector-change defibrillation (VCD) have been suggested to enhance clinical outcomes for patients with ventricular fibrillation (VF) refractory of standard defibrillation (SD). Therefore, this network meta-analysis aims to evaluate the comparative efficacy of DSED, VCD, and SD for refractory VF. METHODS: A systematic review and network meta-analysis synthesizing randomized controlled trials (RCTs) and comparative observational studies retrieved from PubMed, EMBASE, WOS, SCOPUS, and Cochrane through November 15th, 2022. R software netmeta and netrank package (R version 4.2.0) and meta-insight software were used to pool dichotomous outcomes using odds ratio (OR) presented with the corresponding confidence interval (CI). Our protocol was prospectively published in PROSPERO with ID: CRD42022378533. RESULTS: We included seven studies with a total of 1632 participants. DSED was similar to SD in survival to hospital discharge (OR: 1.14 with 95% CI [0.55, 2.83]), favorable neurological outcome (modified Rankin scale ≤2 or cerebral performance category ≤2) (OR: 1.35 with 95% CI [0.46, 3.99]), and return of spontaneous circulation (ROSC) (OR: 0.81 with 95% CI [0.43; 1.5]). In addition, VCD was similar to SD in survival to hospital discharge (OR: 1.12 with 95% CI [0.27, 4.57]), favorable neurological outcome (OR: 1.01 with 95% CI [0.18, 5.75]), and ROSC (OR: 0.88 with 95% CI [0.24; 3.15]). CONCLUSION: Double sequential external defibrillation and VCD were not associated with enhanced outcomes in patients with refractory VF out-of-hospital cardiac arrest, compared to SD. However, the current evidence is still inconclusive, warranting further large-scale RCTs.

Efficacy and safety of triple therapy versus dual therapy for lymphatic filariasis: A systematic review and meta-analysis.

OBJECTIVE: Lymphatic filariasis is a serious public health issue. Recent studies showed that a single dosage of triple therapy (Ivermectin, Diethylcarbamazepine, and Albendazole) is more effective than dual therapy (Ivermectin plus Albendazole or Diethylcarbamazepine plus Albendazole) for clearing microfilaria from the blood. We aimed to evaluate the efficacy and safety of triple therapy versus dual therapy in patients infected with microfilaria and communities endemic to lymphatic filariasis. METHODS: For this systematic review and meta-analysis, we searched MEDLINE, EMBASE, SCOPUS, Cochrane Central Register of Controlled Trials, and Web of Science until 24th June 2021. We included randomized control trials that compared triple with dual therapy given to patients with lymphatic filariasis or endemic communities. This study was registered with PROSPERO (CRD42021266724). RESULTS: We included eight articles after the screening process. Triple therapy caused more clearance of microfilaria in the blood (RR: 1.52; 95% CI: 1.15, 2.02; p = 0.003), while dual therapy caused more clearance of the circulating filariae antigen in the blood (RR: 0.76; 95% CI: 0.65, 0.88; p = 0.0003), both 12 months after drug administration. The triple therapy had a similar adverse effect compared with the dual therapy group. CONCLUSION: Based on the greater efficacy in the clearance of microfilaria and the safety of triple therapy, it constitutes a better strategy for the eradication programs of lymphatic filariasis in endemic regions. However, further studies are needed to confirm our results.

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.

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.

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 pulsed-field versus conventional thermal ablation for atrial fibrillation: A systematic review and meta-analysis.

Background: Pulsed-field ablation (PFA) has emerged as an innovative alternative to radiofrequency (RF) and cryoablation because it selectively targets myocardial tissue. Thus, we aim to estimate the efficacy and safety of PFA versus thermal ablation for atrial fibrillation (AF) ablation. Methods: A systematic review and meta-analysis were retrieved from PubMed, WOS, SCOPUS, EMBASE, and CENTRAL through September 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: CRD42023480321. Results: We included 17 studies with a total of 2255 patients. PFA was significantly associated with a decreased incidence of AF recurrence (RR: 0.66 with 95% CI [0.51, 0.87], p = .003). However, there was no significant difference between PFA and thermal ablation in arrhythmia recurrence (RR: 0.92 with 95% CI [0.74, 1.46], p = .42). PFA was significantly associated with decreased total procedure time (MD: -15.15 with 95% CI [-20.23, -10.07], p < .00001), decreased heart rate change (MD: -7.39 with 95% CI [-12.16, -2.62], p = .002), decreased phrenic nerve palsy (RR: 0.38 with 95% CI [0.15, 0.98], p = .05), and reduced esophageal lesions (RR: 0.09 with 95% CI [0.01, 0.69], p = .02). On the contrary, PFA was significantly associated with increased pericardial tamponade (RR: 6.14 with 95% CI [1.43, 26.33], p = .01). Conclusion: PFA was significantly associated with decreased AF recurrence, total procedure time, heart rate change, phrenic nerve palsy, esophageal lesion, and increased incidence of pericardial tamponade compared with thermal ablation.

The impact of abdominal compression devices on colonoscopy outcomes: a systematic review and meta-analysis of randomized controlled trials.

OBJECTIVE: Colonoscopy is the gold standard method for colorectal cancer screening. Looping occurs in 91% of cases undergoing colonoscopy and can cause patient discomfort, prolonged cecal intubation time (CIT), and colon perforation. This meta-analysis investigates the impact of abdominal compression devices (ACD) on colonoscopy outcomes. METHODS: A systematic review and meta-analysis synthesizing randomized controlled trials (RCTs), retrieved by systematically searching: PubMed, EMBASE, WOS, SCOPUS, and Cochrane through February 2nd, 2023. Continuous and dichotomous outcomes were pooled using mean difference (MD) and risk ratio (RR) along with confidence interval (CI) using Revman. Our review protocol was prospectively published on PROSPERO with ID: CRD42023397344. RESULTS: We included eight RCTs with a total of 1,889 patients. ACD was effective to decrease CIT (MD: -2.15 with a 95% CI [-3.49, -0.80], p = .002), postural change (RR: 0.57 with 95% CI [0.49, 0.66], p = .00001), and VAS pain score (MD: -1.49 with 95% CI [-1.81, -1.17], p = .0001). However, there was no difference between ACD and control groups regarding manual compression (RR: 0.65 with 95% CI [0.42, 1.00], p = .05), complete colonoscopy rate (CCR) (RR: 1.01 with 95% CI [0.99, 1.04], p = .31), and cecal intubation length (CIL) (MD: -2.25 with 95% CI [-7.64, 3.14], p = .41). CONCLUSION: ACD during colonoscopy may enhance patient comfort by reducing CIT, pain, and postural changes. Nevertheless, additional RCTs are necessary to validate these results and determine the most suitable approach to utilize ACD for colonoscopy.

The efficacy and safety of vibrating capsules for functional constipation: a systematic review and meta-analysis of randomized controlled trials.

OBJECTIVE: Chronic constipation is a challenging functional gastrointestinal disorder that remains a global burden. Pharmacologic therapy, including laxatives and dietary fibers, are suggested as lines of treatment. Recent trials introduced an orally ingested vibrating capsule (VC) as an eligible option for chronic constipation management. METHODS: We conducted a literature search in English on electronic databases CENTRAL, PubMed, EMBASE, Scopus, and WOS until February 27th, 2023. RevMan was used to perform the meta-analysis. The results were reported as risk ratios (RRs), mean differences (MDs), and 95% confidence intervals (CIs). The study protocol was registered in PROSPERO with ID: (CRD42023409422). RESULTS: Three RCTs with a total of 601 patients were included in our analysis. There was no difference between the VC and placebo in responder rate (RR: 1.37 with 95% CI [0.82, 2.28], p = .22), CSBM change from baseline (MD: 0.21 with 95% CI [-0.26, 0.69], p = .38), SBM change from baseline (MD: 0.14 with 95% CI [-0.22, 0.49], p = .46), and the incidence of any adverse event (RR: 1.45 with a 95% CI of [0.79, 2.63], p = .23). However, VC was associated with increased vibration sensation (RR: 17.23, 95% CI [3.29, 90.20], p = .0008). CONCLUSIONS: VC was not effective to improve bowel movement in patients with functional constipation with no difference in response rate. However, evidence is still uncertain, with only three small RCTs that yielded heterogenous findings, mainly due to the different vibration protocols. Also, our findings suggest that VC is safe and well-tolerated, with no significant harmful effects observed. Therefore, more large-scale RCTs are needed to confirm the efficacy and safety of VC in patients with functional constipation, determining the most effective dose, frequency, and duration of treatment.

Reno-protective effects of perioperative dexmedetomidine in kidney transplantation: a systematic review and meta-analysis of randomized controlled trials.

BACKGROUND AND OBJECTIVE: There is currently no FDA-approved medical therapy for delayed graft function (DGF). Dexmedetomidine (DEX) has multiple reno-protective effects preventing ischemic reperfusion injury, DGF, and acute kidney injury. Therefore, we aimed to evaluate the reno-protective effects of perioperative DEX during renal transplantation. METHODS: A systematic review and meta-analysis synthesizing randomized controlled trials (RCTs) from WOS, SCOPUS, EMBASE, PubMed, and CENTRAL until June 8th, 2022. We used the risk ratio (RR) for dichotomous outcomes and the mean difference for continuous outcomes; both presented with the corresponding 95% confidence interval (CI). We registered our protocol in PROSPERO with ID: CRD42022338898. RESULTS: We included four RCTs with 339 patients. Pooled risk ratio found no difference between DEX and placebo in reducing DGF (RR: 0.58 with 95% CI [0.34, 1.01], p = 0.05) and acute rejection (RR: 0.88 with 95% CI [0.52, 1.49], p = 0.63). However, DEX improved short-term creatinine on day 1 (MD: - 0.76 with 95% CI [- 1.23, - 0.3], p = 0.001) and day 2 (MD: - 0.28 with 95% CI [- 0.5, - 0.07], p = 0.01); and blood urea nitrogen on day 2 (MD: - 10.16 with 95% CI [- 17.21, - 3.10], p = 0.005) and day 3 (MD: - 6.72 with 95% CI [- 12.85, - 0.58], p = 0.03). CONCLUSION: Although there is no difference between DEX and placebo regarding reducing DGF and acute rejection after kidney transplantation, there may be some evidence that it has reno-protective benefits because we found statistically significant improvement in the short-term serum creatinine and blood urea nitrogen levels. More trials are required to investigate the long-term reno-protective effects of DEX.

Transjugular intrahepatic portosystemic shunt with or without variceal embolization to prevent variceal rebleeding: an updated meta-analysis.

BACKGROUND: Transjugular intrahepatic portosystemic shunt (TIPS) is an established treatment for portal hypertension complications. Still, the role of adjuvant variceal embolization is a matter of debate. Thus, we aim to evaluate the efficacy and safety of TIPS with variceal embolization versus TIPS alone to prevent variceal rebleeding. RESEARCH DESIGN AND METHODS: We used PubMed, CENTRAL, and OVID to search for all randomized controlled trials (RCTs) and comparative observational studies up to 17 June 20221117 June 2022. We pooled binary outcomes using risk ratios (RRs) presented with 95% confidence intervals (CIs) using RevMan 5.4. RESULTS: We included 11 studies (two RCTs and nine observational studies) with 1024 patients. Pooled RR favored TIPS with embolization in preventing variceal rebleeding (RR 0.58, 95% CI: 0.44, 0.76); however, there was no difference between the two groups regarding shunt dysfunction (RR 0.92, 95% CI: 0.68, 1.23), encephalopathy (RR 0.88, 95% CI: 0.70, 1.11), and death (RR 0.97, 95% CI: 0.77, 1.22). CONCLUSIONS: TIPS with embolization can be an effective strategy for preventing variceal rebleeding; however, our results should be interpreted cautiously as most data were observational and the technical quality of the embolization is questionable. Further RCTs are required using the proper techniques of embolization and comparing TIPS with embolization with other treatment modalities such as endoscopic ligation, and balloon-occluded retrograde transvenous obliteration.

The efficacy of nitroglycerin to prevent radial artery spasm and occlusion during and after transradial catheterization: A systematic review and meta-analysis of randomized controlled trials.

Radial artery spasm (RAS) is the most common cause of transradial access site crossover and is a common intra-procedural complication. RAS incidence can lead to radial artery occlusion (RAO) postprocedure, preventing the radial artery as a future access site. We evaluated the efficacy of nitroglycerin preventing RAS and RAO during transradial catheterization discussing the different routes of administration, including topical, subcutaneous, and intra-arterial. A systematic review and meta-analysis included all relevant articles until April 23, 2022. We searched six databases Google Scholar, Web of Science, SCOPUS, EMBASE, PubMed (MEDLINE), and CENTRAL. We registered our review protocol in PROSPERO with ID: CRD42022330356. We included 11 trials with 5814 patients. Compared to placebo, the pooled analysis favored subcutaneous nitroglycerin in preventing RAS (risk ratio [RR]: 0.57 with 95% confidence interval [CI] [0.43-0.77], p = .0003) and RAO (RR: 0.39 with 95% CI [0.16-0.98], p = .05). In contrast to the intra-arterial nitroglycerin that showed nonstatistically significant results in preventing RAS and RAO (RR: 0.8 with 95% CI [0.63-1.02], p = .07)- (RR: 0.78 with 95% CI [0.6-1.01], p = .06)), respectively. Also, topical nitroglycerin did not prevent RAS (RR: 0.73 with 95% CI [0.42-1.24], p = .24). Compared with placebo, subcutaneous nitroglycerin during transradial catheterization reduced the incidence of RAS and RAO. Meanwhile, Intra-arterial and topical nitroglycerin did not show statistically significant outcomes. Subcutaneous nitroglycerin may be a practical and cost-effective technique to facilitate transradial catheterization; however, more RCTs are needed to evaluate the subcutaneous versus intra-arterial nitroglycerin administration.