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.

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.

Adjunctive left atrial posterior wall isolation for atrial fibrillation: An updated systematic review and meta-analysis.

OBJECTIVE: Posterior left atrial wall isolation (PWI) plus traditional pulmonary vein isolation (PVI) has been proposed as a promising intervention to decrease atrial fibrillation (AF) recurrence. We aim to investigate the efficacy and safety of adding PWI to the traditional PVI in patients with AF. METHODS: A systematic review and meta-analysis was conducted using synthesizing randomized controlled trials (RCTs) retrieved by systematically searching PubMed, Web of Science, SCOPUS, EMBASE, and Cochrane through June 14, 2023. We used Stata version 17 to pool dichotomous data using risk ratio (RR) and continuous data using mean difference (MD), with a 95% confidence interval (CI) (PROSPERO ID: CRD42023446227). RESULTS: We included 11 RCTs with a total number of 1534 patients. Combined ablation with PWI + PVI was not associated with any significant difference over PVI only regarding the recurrence of clinical AF (RR: 0.86 with 95% CI [0.70-1.06]), all atrial arrhythmia (RR: 0.93 with 95% CI [0.82-1.07]), nonatrial fibrillation arrhythmia (RR: 1.22 with 95% CI [0.97-1.53]), early AF (RR: 0.89 with 95% CI [0.62-1.27]), and antiarrhythmic drugs at discharge (RR: 0.83 with 95% CI [0.67-1.04]). However, it was associated with increased total ablation duration (minutes) (MD: 12.58 with 95% CI [6.80-18.37]) and total procedure duration (minutes) (MD: 16.77 with 95% CI [9.63-23.91]), without any significant difference regarding adverse events (RR: 1.05 with 95% CI [0.63-1.74]). CONCLUSION: While the pooled data from PWI + PVI using point-by-point radiofrequency did not suggest a benefit in the recurrence of various atrial arrhythmias compared to PVI alone, PWI+PVI using direct posterior wall ablation, especially with cryoballoon, demonstrated a significant reduction in recurrence of AF/atrial arrhythmias. Also, PWI + PVI significantly increased the ablation and total procedure durations.

Postoperative Spinal Cord Ischemia Monitoring: A Review of Techniques Available After Endovascular Aortic Repair.

BACKGROUND: Spinal cord ischemia is one of the complications that can occur after open and endovascular thoracoabdominal aortic repair. This occurs despite various perioperative approaches, including distal aortic perfusion, hybrid procedures with extra anatomical bypasses, motor-evoked potential, and cerebrospinal fluid drainage. The inability to recognize spinal ischemia in a timely manner remains a devastating complication after thoracoabdominal aortic repair. OBJECTIVES: This review aims to look at novel technologies that are designed for continuous monitoring to detect early changes that signal the development of spinal cord ischemia and to discuss their benefits and limitations. METHODS: We conducted a systematic review of the technologies available for continuous monitoring in the intensive care unit (ICU) for early detection of spinal cord ischemia. Studies were eligible for inclusion if they used different technologies for monitoring spinal ischemia during the postoperative period. All articles that were not available in English were excluded. To ensure that all relevant articles were included, no other significant restrictions were imposed. RESULTS: We identified 59 studies from outset to December 2022 to be included in our study. New techniques have been studied as potentially useful monitoring tools that could provide simple and effective monitoring of the spinal cord. These include Near-infrared spectroscopy, Contrast-enhanced ultrasound, Magnetic Resonance Imaging, fiber optic monitoring of the spinal cord, and CSF biomarkers. CONCLUSION: Despite the development of new techniques to monitor for postoperative spinal cord ischemia, their use remains limited. We recommend more future research to ensure rapid intervention for our patients.

Monkeypox viral detection in semen specimens of confirmed cases: A systematic review and meta-analysis.

The current literature shows increasing concerns about potential seminal transmission of monkeypox virus (MPXV). Accordingly, we aimed to understand better the potential presence of MPXV in the seminal fluids and others specimens obtained from MPX cases. On June 26, 2022, a systematic search of the literature was conducted to find articles that examine the presence of MPXV in the seminal fluid of confirmed cases. The search was updated once on August 12 and another on October 12, 2022, to include newly published articles. The prevalence of MPXV DNA presence in the seminal fluid and other specimens was pooled in a meta-analysis (from studies with sample size > 5 to reduce overestimation) and results were presented as effect sizes (ES) and their corresponding 95% confidence intervals (CI). Nine articles were included. Only five studies were eligible for a meta-analysis, and the pooled prevalence of MPXV DNA in semen specimens was 72.4% (95% CI: 55.7%-84.5%) among 115 patients. The positive rate of MPXV viral polymerase chain reaction (PCR) was higher among skin samples (89%; 95% CI: 78.2%-94.8%; N = 62; studies = 2), followed by anogenital/rectal samples (74.3%; 95% CI: 60.4%-84.5%; N = 54; studies = 2). On the other hand, the positivity rate was lower in nasopharyngeal (62.4%; 95% CI: 20.4%-91.5%; N = 587; studies = 3), urine (21.1%; 95% CI: 4.3%-61.1%; N = 617; studies = 4), and blood/plasma (14.3%; 95% CI: 11.3%-18.1%; N = 609; studies = 3) samples. Besides, MPXV can be detected in semen early from Day 1 and up to 19 days after symptoms onset. Finally, two articles investigated the infectivity of MPXV particles detected in seminal specimens by testing their replication competence. Culturing MPXV was successful in two out of four patients included in these studies. MPXV is highly prevalent in seminal specimens of MPX cases, further corroborating the role of sexual transmission of the disease. However, further evidence is still needed to shed more light on the replication competence of these particles.

Cold Versus Hot Snare Polypectomy for Colorectal Polyps: An Updated Systematic Review and Meta-analysis of Randomized Controlled Trials.

BACKGROUND AND OBJECTIVE: Endoscopic polypectomy is an excellent tool for colon cancer prevention. With the innovation of novel resection techniques, the best method is still being investigated. Hence, we aim to evaluate the efficacy and safety of cold snare polypectomy (CSP) versus hot snare polypectomy (HSP) for colorectal polyp resection. METHODS: A systematic review and meta-analysis synthesizing evidence from randomized controlled trials retrieved from PubMed, EMBASE, WOS, SCOPUS, and CENTRAL until July 16, 2022. We pooled dichotomous outcomes using risk ratio (RR) with the corresponding CI. This review's protocol was prospectively registered in PROSPERO with ID: CRD42022347496. RESULTS: We included 18 randomized controlled trials with a total of 4317 patients and 7509 polyps. Pooled RR favored HSP regarding the complete resection rate (RR: 0.96 with 95% CI: 0.95, 1, P = 0.03) and local recurrence incidence (RR: 5.74 with 95% CI: 1.27, 25.8, P = 0.02). Pooled RR favored CSP regarding the colonoscopy time (mean difference: -6.50 with 95% CI: -7.55, -5.44, P = 0.00001) and polypectomy time (mean difference: -57.36 with 95% CI: -81.74, -32.98, P = 0.00001). There was no difference regarding the incidence of immediate bleeding ( P = 0.06) and perforation ( P = 0.39); however, HSP was associated with more incidence of delayed bleeding ( P = 0.01), abdominal pain ( P = 0.007), and postresection syndrome ( P = 0.02). DISCUSSION: HSP is associated with a higher complete resection and lower recurrence rates; however, HSP is also associated with a higher incidence of adverse events. Therefore, improving the complete resection rate with CSP still warrants more innovation, giving the technique safety and shorter procedure duration.

The efficacy of vitamin D supplementation for irritable bowel syndrome: narrow scope and GRADE miss-interpretation.

We read the article by Haung et al. that pooled the effects of vitamin D on irritable bowel syndrome symptoms and associated quality of life. However, the current review suffers from some methodological errors: inadequate search strategy; the grading of recommendations assessment, development, and evaluation (GRADE) miss-assessment; and miss-interpretation. Accordingly, addressing the emphasized limitations will lead to more robust findings and conclusions.

The efficacy and safety of tenecteplase versus alteplase for acute ischemic stroke: an updated systematic review, pairwise, and network meta-analysis of randomized controlled trials.

Tenecteplase (TNK) is a promising candidate to replace alteplase as the standard of care for acute ischemic stroke (AIS); however, the optimal dosage is still to be investigated. Therefore, we aim to evaluate the safety and efficacy of TNK versus alteplase and to investigate the optimal TNK dosage. A systematic review, pairwise, and network meta-analysis synthesizing randomized controlled trials (RCTs) from WOS, SCOPUS, EMBASE, and PubMed until July 26th, 2022. We used the risk ratio (RR) for dichotomous outcomes presented with the corresponding 95% confidence interval (CI). We registered our protocol in PROSPERO with ID: CRD42022352038. Nine RCTs with a total of 3,707 patients were included. TNK significantly led to complete recanalization (RR: 1.27 with 95% CI [1.02, 1.57], P = 0.03); however, we found no difference regarding early neurological improvement (RR: 1.07 with 95% CI [0.94, 1.21], P = 0.33) and excellent neurological recovery (RR: 1.03 with 95% CI [0.96, 1.10], P = 0.42). Also, TNK was similar to alteplase regarding mortality (RR: 0.99 with 95% CI [0.82, 1.18], P = 0.88), intracranial haemorrhage (RR: 1.00 with 95% CI [0.85, 1.18], P = 0.99), and parenchymal hematoma (RR: 1.13 with 95% CI [0.83, 1.54], P = 0.44). TNK in the dose of 0.25 mg is a viable candidate to displace alteplase as the standard of care in patients with an AIS within 4.5 h of presentation due to its better rate of early neurological recovery and non-inferiority in terms of safety outcomes. However, the evidence regarding TNK's role in AIS presenting after 4.5 h from symptoms onset, wake-up stroke, and minor stroke/TIA is still lacking, necessitating further double-blinded pragmatic RCTs in this regard.

Physical therapy interventions for the management of hand tremors in patients with Parkinson's disease: a systematic review.

BACKGROUND: Several physical therapy modalities have been used to improve hand tremors in patients with Parkinson's disease (PD). However, little is known about the efficacy of these techniques. Therefore, we conducted this study to synthesize evidence from published studies on the efficacy of physical therapy techniques for hand tremors in PD patients. METHODS: We followed the PRISMA statement and Cochrane handbook guidelines when conducting this study. We conducted an electronic literature search of PubMed, Cochrane Central Register of Clinical Trials, Web of Science, Ovid, and Embase, and then we selected clinical trials assessing the efficacy of any physical therapy intervention for hand tremors in patients with PD. Study outcomes were extracted, and evidence was synthesized narratively. RESULTS: A total of six modalities described in six studies were included in this systematic review. Out of the six interventions, the tremor's glove and electrical stimulation showed significant improvements in root mean square angular velocity (59% and 43.8%, respectively) and UPDRS tremor score (P < 0.05 for both). Also, eccentric exercises were associated with significant reductions in the mean resting tremor amplitude (P < 0.05). These data were dependent on single studies; therefore, a meta-analysis was not feasible. CONCLUSION: Several physical therapy interventions, such as electrical stimulation, exercises, transcranial low voltage pulsed electromagnetic fields, weights, and virtual reality showed promising results in reducing hand tremors. However, this evidence was based on a limited number of included studies, and more RCTs with larger sample sizes are required to confirm the efficacy of these interventions.

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.

Does ramadan fasting affect the therapeutic and clinical outcomes of warfarin? a systematic review and meta-analysis.

BACKGROUND: Warfarin's therapeutic effect is affected by many factors, including diet modifications. The impact of Ramadan fasting on warfarin is controversial. The aim of this systematic review and meta-analysis was to investigate the effect of Ramadan fasting on patients taking warfarin. METHODS: A literature search was done in PubMed, WOS, Scopus, and Embase from inception to May 24, 2021. All relevant studies measuring the international normalized ratio (INR), time in therapeutic range (TTR), or the number of patients within therapeutic range before, during, and after Ramadan were assessed by full-text screening for achieving all of the inclusion criteria. We used the Newcastle-Ottawa Scale for quality assessment and RevMan 5.4 software for meta-analysis. RESULTS: A total of five studies with 446 patients were included in the meta-analysis. The patients served as their own control. Our pooled analyses showed no significant difference during Ramadan compared to pre-Ramadan (MD: 0.08; 95% CI: - 0.00, 0.15; P = 0.06) and post-Ramadan (MD: - 0.00; 95% CI: - 0.14, 0.14; P = 1.00, respectively). There was only a significant increase in the risk ratio of supratherapeutic INR when comparing post-Ramadan vs. pre-Ramadan (RR: 1.69; 95% CI: 1.22, 2.33; P = 0.001). However, there was no significant risk for supratherapeutic INR during Ramadan compared to pre-Ramadan or post-Ramadan; the number of patients within the therapeutic range of INR during Ramadan compared to pre-Ramadan; and TTR during Ramadan, pre-Ramadan, and post-Ramadan. CONCLUSION: Ramadan fasting did not affect INR level, TTR, or the number of patients within the therapeutic range before, during, and after Ramadan. However, there was a possibility of achieving a supratherapeutic INR post-Ramadan compared to pre-Ramadan. Therefore, INR monitoring and warfarin dose adjustments accordingly are recommended after Ramadan.

The effects of curcumin as dietary supplement for patients with polycystic ovary syndrome: An updated systematic review and meta-analysis of randomized clinical trials.

This review aims to evaluate if there are clinical benefits of curcumin (CUR) in patients with polycystic ovary syndrome (PCOS). Electronic databases (PubMed, EMBASE, Scopus, Web of Science, Cochrane Central, and Google Scholar) were systematically searched to identify only randomized clinical trials (RCTs) that assessed CUR in patients with PCOS from inception to May 5, 2021. Five RCTs were included with a total of 296 patients, with 148 among the CUR groups and 148 patients among the control group. Revised Cochrane risk-of-bias tool for randomized trials was used to assess the risk of bias, three RCTs provided a low risk of bias and two provided a high risk of bias. Compared with the control group, CUR was associated with a statistically significant improvement in the glycemic control including fasting blood glucose (MD = -3.67; 95% CI = [-5.25, -2.08], p < .00001), insulin level (MD = -1.91; 95% CI = [-2.97, -0.84], p = .0005), homeostasis model assessment of insulin resistance (MD = -0.55; 95% CI = [-0.83, -0.27], p = .0001), and quantitative insulin sensitivity check index (MD = 0.01; 95% CI = [0.00, 0.02], p = .0005). The mean difference in total cholesterol was also statistically significant (MD = -15.55; 95% CI = [-30.33, -0.76], p < .04). The rest of the secondary outcomes, including LDL, HDL, sex hormone, body weight, and CRP, were not statistically significant. This review concluded that among patients with PCOS, the use of CUR demonstrated a significant difference from the control group for glycemic control. Those findings suggest that CUR confers clinical benefits in patients with PCOS. However, due to the limited number of the included studies, further high-quality studies are needed to establish the clinical efficacy of the CUR.

Reply to Aljabali et al. Comment on "Abbas et al. The Safety and Efficacy of Nusinersen in the Treatment of Spinal Muscular Atrophy: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. Medicina 2022, 58, 213".

We appreciate Ahmed Sami Aljabali and his colleagues for their interest and comments [...].

The Safety and Efficacy of Nusinersen in the Treatment of Spinal Muscular Atrophy: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Background and objectives: Spinal muscular atrophy (SMA) is a neurodegenerative disease that leads to progressive proximal muscle weakness and muscle atrophy. To assess the beneficial and adverse effects of nusinersen, a promising intervention for SMA, we conducted a systematic search and meta-analysis of the published randomized control trials (RCTs) of nusinersen for SMA. Materials and methods: Utilizing the Preferred Reporting for Systematic Review and Meta-Analysis (PRISMA), we searched PubMed, Scopus, Web of Science, Cochrane Central, and Clinicaltrials.gov from inception to 22 July 2021. Results: Three RCTs satisfying the inclusion and exclusion criteria covered 274 patients: 178 patients in the nusinersen group. Our results show a significant risk difference (RD) in the motor milestone response (RD: 0.51; 95% CI: 0.39, 0.62; p < 0.00001) and improvement in the HINE-2 score (RD: 0.26; 95% CI: 0.12, 0.40; p < 0.0003) in the nusinersen group compared to the control group. Moreover, a significant decrease in the risk ratio (RR) for severe adverse events (RR: 0.72; 95% CI: 0.57, 0.92; p = 0.007) and any adverse event leading to treatment discontinuation (RR: 0.40; 95% CI: 0.22, 0.74; p = 0.004) was observed. An insignificant result was found for any adverse effects (RR: 0.93; 95% CI: 0.97, 1.01; p = 0.14) and for serious adverse effects (RR: 0.81; 95% CI: 0.60, 1.07; p = 0.14). Conclusions: This review provides evidence that nusinersen treatment was effective in treatment for infants with SMA and was associated with fewer severe adverse events; however, more RCTs are needed to establish evidence.

Ischemic heart disease in Africa: An overnight epidemiological transition.

Ischemic heart disease (IHD) falls among the leading causes of death, representing a major burden, ranking first in all regions of the world and eighth in Africa as a leading killer. Recent evidence suggests that Africa is having an epidemiological transition with higher rates of non-communicable diseases (NCDs). IHD contributed to 361 thousand deaths in the African region in 2005, and this number is expected to be more than double by 2030. IHD currently ranks as the leading cause of death for men and the second leading cause of death for women in the African region in patients older than 60 years. There are multiple risk factors related to lifestyle associated with IHD. Thus, strict measures are the key in terms of health promotion and disease prevention. Hurdles impeding the prevention and control of IHD in Africa include poor health care services, low income, and rising costs of cardiac interventions..

The effect of intensive blood pressure lowering on left ventricular hypertrophy in patients with hypertension: a systematic review and meta-analysis of randomized controlled trials.

Background: We conducted a comprehensive systematic review to examine the efficacy of intensive blood pressure lowering on the risk of left ventricular hypertrophy (LVH). Methods: We searched PubMed, Scopus, Web of Science, Cochrane Central, and EMBASE for all relevant randomized controlled trials. The primary outcome was the incidence of left ventricular hypertrophy. We used the risk ratio (RR) and hazard ratio (HR) with a 95% confidence interval as our effect sizes. Results: Four studies, comprising 20,747 patients, were included. Intensive blood pressure lowering was linked with a diminished LVH incidence (RR: 0.66, 95% CI [0.56-0.77]). We also found that intensive blood pressure lowering increased the risk of LVH regression in patients with baseline LVH (RR: 1.21, 95% CI [1.11-1.32]). Finally, intensive blood pressure lowering was linked with a reduced risk of cardiovascular disease (HR: 0.71, 95% CI [0.60-0.85]). No significant heterogeneity was seen in either outcome. Conclusion: Our study suggests that intensive blood pressure lowering effectively reduces the risk of LVH and cardiovascular disease. An interactive version of our analysis can be accessed here: https://databoard.shinyapps.io/lvh_hypertophy/.