Cholesteryl Ester Transfer Protein Inhibitors and Cardiovascular Outcomes: A Systematic Review and Meta-Analysis.

BACKGROUND: Atherosclerosis is a multi-factorial disease, and low-density lipoprotein cholesterol (LDL-C) is a critical risk factor in developing atherosclerotic cardiovascular disease (ASCVD). Cholesteryl-ester transfer-protein (CETP), synthesized by the liver, regulates LDL-C and high-density lipoprotein cholesterol (HDL-C) through the bidirectional transfer of lipids. The novelty of CETP inhibitors (CETPis) has granted new focus towards increasing HDL-C, besides lowering LDL-C strategies. To date, five CETPis that are projected to improve lipid profiles, torcetrapib, dalcetrapib, evacetrapib, anacetrapib, and obicetrapib, have reached late-stage clinical development for ASCVD risk reduction. Early trials failed to reduce atherosclerotic cardiovascular occurrences. Given the advent of some recent large-scale clinical trials (ACCELERATE, HPS3/TIMI55-REVEAL Collaborative Group), conducting a meta-analysis is essential to investigate CETPis' efficacy. METHODS: We conducted a thorough search of randomized controlled trials (RCTs) that commenced between 2003 and 2023; CETPi versus placebo studies with a ≥6-month follow-up and defined outcomes were eligible. PRIMARY OUTCOMES: major adverse cardiovascular events (MACEs), cardiovascular disease (CVD)-related mortality, all-cause mortality. SECONDARY OUTCOMES: stroke, revascularization, hospitalization due to acute coronary syndrome, myocardial infarction (MI). RESULTS: Nine RCTs revealed that the use of a CETPi significantly reduced CVD-related mortality (RR = 0.89; 95% CI: 0.81-0.98; p = 0.02; I2 = 0%); the same studies also reduced the risk of MI (RR = 0.92; 95% CI: 0.86-0.98; p = 0.01; I2 = 0%), which was primarily attributed to anacetrapib. The use of a CETPi did not reduce the likelihood any other outcomes. CONCLUSIONS: Our meta-analysis shows, for the first time, that CETPis are associated with reduced CVD-related mortality and MI.

Frequency of migraine according to the ICHD-3 criteria and its association with sociodemographic and triggering factors in Pakistan: A cross-sectional study.

Background: Migraine is a primary headache disorder marked by episodes of moderate to severe headache that is unilateral, throbbing in character, having a duration of 4 h to three days, and associated with nausea, vomiting, photophobia, and phonophobia. Aims: Our study aims to determine the frequency of migraine in Pakistan, its association with sociodemographic variables and triggering factors, and the coping mechanisms used. Methods: A cross-sectional study was conducted through an online survey from March 19, 2022, to June 15, 2022. The snowball sampling technique was used for data collection. The questions asked included those on sociodemographic information, screening questions, and questions on triggering factors and coping mechanisms. The screening was done using the ICHD-3 criteria and percentages were calculated using SPSS. Results: Of the 986 respondents, 393 suffered from migraine. The majority of them were female (78.1%), belonged to the age group 20-29 years (69.2%), and were students (76.1%). 32.8% of the migraineurs had a family history of migraine. Most frequent triggers included sleep disturbance (70.5%), stress (66.7%) and fatigue (64.4%). Of the female migraineurs, 31.8% had menstruation as a trigger. The coping mechanisms used included taking rest, medication, staying in a quiet and dark place, and doing massage. Conclusion: The findings suggest that young adults, especially females, with a stressful and sleep-deprived lifestyle are more vulnerable to migraine. However, further studies must focus on trigger synergy and interrelation of triggers that precipitate migraine so a better understanding can be developed for the prevention, diagnosis, and treatment of migraine.

Benvitimod for the treatment of psoriasis: A systematic review and meta-analysis of randomized controlled trials.

Benvitimod is a topical drug that has recently been approved for mild to moderate psoriasis and atopic dermatitis. The drug has just completed phase 3 trials for psoriasis, which calls for a systematic update of current evidence on the efficacy and safety of this drug. We searched MEDLINE (PubMed), EMBASE, Science Direct, International Clinical Trials Registry Platform (ICTRP), Cochrane Central Register of Controlled Trials, and Google Scholar for all available randomized controlled trials concerning the topic. We included six randomized controlled trials evaluating the efficacy of benvitimod 1.0% with a total of 1925 patients. Our meta-analysis demonstrated that more patients in the benvitimod group achieved physician global assessment score of 0 or 1 (RR 6.53, 95% CI 4.39-9.71), psoriasis area and severity index (PASI) 75 (RR 4.34, 95% CI 2.96-6.36), PASI 90 (RR 8.83, 95% CI 5.22-14.95) and body surface area reduction (MD -3.85, 95% CI -4.83, -2.88) than placebo at week 12. Patient-reported outcomes were also analyzed, yielding a significant benefit in the benvitimod group for peak pruritus numerical rating scale (PP-NRS) score (MD -1.20, 95% CI -1.98, -0.42), ≥4-point decrease in PP-NRS score (RR 1.58, 95% CI, 1.24-2.03) and dermatology life quality index score (MD -2.54, 95% CI -4.00, -1.07). There was a significantly higher incidence of adverse events in the benvitimod group compared to placebo (RR 1.98, 95% CI 1.73-2.27), while the risk was found to be non-significant for serious adverse events. Benvitimod is an effective treatment of psoriasis as compared to a placebo. However, more large-scale, high-quality trials are needed to comment on the safety of this drug.

Rarest of the rare: a case of pharyngeal-cervical-brachial variant of Guillain-Barré syndrome presenting with a demyelinating neuropathy.

BACKGROUND: Guillain-Barré syndrome (GBS) is a heterogeneous disease characterized by rapidly progressive, symmetrical limb weakness with hyporeflexia or areflexia. The rare pharyngeal-cervical-brachial (PCB) variant of GBS occurs in 3% of patients, presenting as rapidly progressive oropharyngeal and cervicobrachial weakness characterised by axonal, rather than a demyelinating neuropathy on nerve conduction studies. CASE DESCRIPTION: A 35 year old male presented with a 5-day history of dysphagia, dysarthria, slurred speech and upper limb weakness. Physical examination showed bilateral facial nerve weakness and an impaired gag reflex. Nerve conduction study was suggestive of sensory and motor polyneuropathy of predominantly demyelinating variety. As the condition of the patient worsened, respiratory support was required and plasmapharesis was started. There was significant improvement in his condition after completion of 5 sessions of plasmapharesis. CONCLUSION: The rare PCB variant may present with a predominantly demyelinating neuropathy. Early clinical recognition of this variant and prompt treatment with plasmapharesis is essential for preventing respiratory complications.

Adverse fetal and neonatal outcomes following in-utero exposure to oxcarbazepine: A systematic review and meta-analysis.

AIM: This systematic review aims to assess the safety profile of oxcarbazepine during pregnancy. METHODS: Observational studies that included women who took oxcarbazepine anytime during pregnancy were included in our systematic review. The review did not include non-English articles, reviews, meta-analyses, case reports and animal studies. Different online sources such as MEDLINE, Cochrane library, Virtual Health Library, etc., were searched for published and unpublished literature. Assessment of the risk of bias in observational studies was carried out using the Newcastle-Ottawa Scale. The meta-analyses were performed using a random-effect model. GRADE was used for the evaluation of the quality of evidence for the primary outcomes. RESULTS: We included 19 cohort studies with a total of 5 071 137 patients, of which 2450 were exposed to oxcarbazepine either as monotherapy or polytherapy. The summary odds ratio (OR) was 1.69 (95% CI, 0.95-2.98) for congenital malformations following in-utero exposure to oxcarbazepine as compared to the control group of unexposed patients (seven studies [n = 625]), and was 1.19 (95% CI, 0.67-2.12) when compared to those following lamotrigine (LTG) exposure during pregnancy (3 studies [n = 591]). In total, three studies (n = 770) reported the association between in-utero oxcarbazepine exposure and fetal/perinatal deaths. The meta-analysis yielded a summary OR of 3.33 (95% CI, 1.70-6.51). CONCLUSION: Our systematic review will help healthcare providers and guideline developers regarding the treatment of epilepsy and other neurological disorders during pregnancy. More cohort studies with a higher sample size concerning oxcarbazepine use in pregnant patients are required to truly assess the in-utero safety profile of the drug.

Probiotics for the Prevention of Ventilator-Associated Pneumonia: An Updated Systematic Review and Meta-Analysis of Randomised Controlled Trials.

BACKGROUND: Presently, there is conflicting evidence regarding the efficacy of probiotics in the prevention of ventilator-associated pneumonia (VAP). This meta-analysis was conducted to update current clinical evidence and evaluate the efficacy and safety of probiotics for the prevention of VAP. METHODS: We searched three databases and two trial registers to retrieve randomised controlled trials (RCTs) comparing probiotics or synbiotics with placebo or standard treatment for the prevention of VAP in adult patients receiving mechanical ventilation in the intensive care unit (ICU). RESULTS: Our meta-analysis included 18 RCTs involving 4893 patients. Our results showed that probiotics may reduce the incidence of VAP (RR 0.68, 95% CI: 0.55-0.84; low certainty). However, in our subgroup and sensitivity analyses, the effect was not significant in double-blind studies, and in studies with a low risk of bias in the randomisation process. Probiotics reduced the length of ICU stay (MD -2.22 days, 95% CI: -4.17 to -0.28; moderate certainty) and the duration of antibiotic use (MD -1.25 days, 95% CI -1.86 to -0.64; moderate certainty). CONCLUSIONS: Probiotics may reduce the incidence of VAP but due to the low quality of pooled evidence, the use of probiotics warrants caution. Further, large-scale, high-quality RCTs need to be conducted to provide conclusive evidence.