Remimazolam versus propofol for sedation in gastrointestinal endoscopy and colonoscopy within elderly patients: a meta-analysis of randomized controlled trials.

PURPOSE: Propofol has become the sedative of choice for endoscopy and colonoscopy. However, it has shown associations with various adverse effects, specifically in the geriatric population. In contrast, remimazolam is a novel benzodiazepine, demonstrating a superior clinical safety profile. Hence, this systematic review and meta-analysis aims to clarify the efficacy and safety of remimazolam versus propofol in elderly patients (≥ 60 years) undergoing gastrointestinal endoscopic and colonoscopy procedures. METHODS: Electronic databases including PubMed, Cochrane Library, ScienceDirect, and Google Scholar were explored from inception till January 7, 2024. The Cochrane Risk of Bias Tool for Randomized Controlled Trials (RoB-2) was utilized to evaluate the quality of each included study reported in this meta-analysis. RESULTS: Seven randomized control trials were included, resulting in the pooling of 1,466 patients (remimazolam: 731 patients; propofol: 735 patients). Propofol demonstrated a significantly lower time to loss of consciousness (P < 0.00001, 4 studies, 784 patients) and a greater sedation success after first dose (P = 0.05, 5 studies, 1,271 patients). Remimazolam reported a significantly lower risk of bradycardia (P = 0.02, 5 studies, 1,323 patients), hypoxemia (P < 0.00001, 6 studies, 1,389 patients), and pain on injection site (P < 0.00001, 5 studies, 1,184 patients). No statistically significant differences in sedation time, number of supplemental doses, procedural parameters, and other adverse outcomes were reported. CONCLUSION: As per the results of our analyses, propofol demonstrated comparatively superior efficacy, however, remimazolam demonstrated comparatively superior safety. The debatable evidence generated from this meta-analysis may not currently be powerful enough to advocate for the use of remimazolam in elderly patients undergoing gastrointestinal procedures; hence, further comprehensive studies are necessary in order to arrive at a robust conclusion.

Menstrual hygiene management in flood-affected Pakistan: Addressing challenges and ensuring women's health and dignity.

Pakistan's recent floods have worsened women's and girls' menstrual hygiene problems, compromising their health, dignity, and well-being. Supply chain issues, poor facilities, and cultural stigma limit menstrual products and hygiene management. Gender-sensitive disaster management and menstrual health education programmes can help. The Minimum Initial Service Package (MISP) can provide emergency reproductive health services. Involving men, working with religious leaders, and pre-disaster planning for menstrual hygiene management can help break the taboo and increase access to resources. Meeting ongoing needs requires timely menstrual hygiene product distribution, restocking, and renewal. By addressing these issues, Pakistan can empower post-flood women and girls through economic opportunities and legal protection.

Role of soluble urokinase type plasminogen activator receptor (suPAR) in predicting mortality, readmission, length of stay and discharge in emergency patients: A systematic review and meta analysis.

BACKGROUND: Soluble urokinase plasminogen activator receptor (suPAR) is an inflammatory biomarker that is used to predict mortality, readmission, early discharge, and LOS, thus, serves as a useful tool for ED physicians. Our study aims to analyze the efficacy of suPAR in predicting these prognostic markers in ED. METHODS: We performed a comprehensive search on 6 databases from the inception to 30th November 2022, to select the following eligibility criteria; a) observation or triage trial studies investigating the role of suPAR levels in predicting: 30 day and 90-day mortality, 30-day readmission, early discharge (within 24hr), and LOS in patients coming to AMU. RESULTS: A total of 13 studies were included, with a population size of 35,178, of which 52.9% were female with a mean age of 62.93 years. Increased risk of 30-day mortality (RR = 10.52; 95% CI = 4.82-22.95; I2 = 38%; P < .00001), and risk of 90-day mortality (RR = 5.76; 95% CI = 3.35-9.91; I2 = 36%; P < .00001) was observed in high suPAR patients. However, a slightly increased risk was observed for 30-day readmission (RR = 1.50; 95% CI = 1.16-1.94; I2 = 54%; P = .002). More people were discharged within 24hr in the low suPAR level group compared to high suPAR group (RR = 0.46; 95% CI = 0.40-0.53; I2 = 41%; P < .00001). LOS was thrice as long in high suPAR level patients than in patients with low suPAR (WMD = 3.20; 95% CI = 1.84-4.56; I2 = 99%; P < .00001). CONCLUSION: suPAR is proven to be a significant marker in predicting 30-day and 90-day mortality in ED patients.

Efficacy and safety of fezolinetant, a neurokinin-3 antagonist, in treating vasomotor symptoms in postmenopausal women: A systematic review and meta-analysis.

BACKGROUND: Menopause causes a variety of symptoms such as hot flashes and night sweats. While menopausal hormonal therapy has been used for managing postmenopausal vasomotor symptoms (VMS) for quite a while, it has a considerably poor safety profile. OBJECTIVE: To review and analyze existing data to evaluate the efficacy of the neurokinin-3 antagonist, fezolinetant, in treating postmenopausal VMS and to assess its safety profile. METHODS: A thorough literature search was performed on PubMed, Cochrane Library, and Google Scholar in compliance with Preferred Reporting Items for Systematic Reviews and Meta-Analysis 2020, to find publications on the efficacy of fezolinetant for postmenopausal VMS. Changes in the frequency and severity scores of moderate/severe VMS and changes in the Hot Flash-Related Daily Interference Scale (HFRDIS), Greene Climacteric Scale (GCS), and Menopause-Specific Quality of Life (MENQoL) were the efficacy outcomes. Adverse events, drug-related treatment-emergent adverse effects (TEAEs), drug-related dropouts, hepatotoxicity, endometrial hyperplasia or tumor, and uterine bleeding were all safety outcomes. We used Review Manager 5.4 for pooling risk ratios (RRs) and mean differences (MDs) for dichotomous and continuous outcomes, respectively. A P value of < .05 was considered significant. RESULTS: There was a significant reduction in mean daily VMS frequency at weeks 4 and 12 (MD, -2.36; 95% confidence interval [CI], -2.85 to -1.87; P < .00001, for week 12) and also a significant decrease in VMS severity scores in the treatment group. Furthermore, improvements in MENQoL, HFRDIS, and GCS scores were observed. There was no significant difference in adverse events while drug-related TEAEs (RR, 1.21; 95% CI, 0.90-1.63; P = .21) showed a slight increase with fezolinetant. Drug-related dropouts were again similar across the 2 groups. Uterine bleeding had a lower incidence while endometrial events and hepatotoxicity showed a statistically insignificant, increasing trend in the fezolinetant group. DISCUSSION AND IMPLICATIONS: Fezolinetant can be a treatment option for postmenopausal VMS but warns of a risk increase in endometrial hyperplasia or tumors. The heterogeneity in the data being analyzed, short follow-up period, and small sample size in most of the included randomized controlled trials were the greatest limitations, which must be considered in further research and safety profile exploration.

Effect of COVID-19 on air pollution related illnesses in India.

Ambient air pollution level not only causes respiratory diseases but also cardiovascular diseases, besides, increased visits to the emergency department for asthma, chronic obstructive pulmonary disease (COPD), bronchitis, allergic rhinitis, attention deficit hyperactivity disorder (ADHD) in children and premature deaths in infants. The occurrence of Coronavirus-19 (COVID-19) pandemic is both, a boon and bane. Despite the deplorable situation aroused by the pandemic, strict lockdown measures implemented to curb the drastic spread of the disease, also culminated into astonishing outcomes that were not prioritized. This article illustrates the effects of the ongoing pandemic on air pollution and provides recommendations aimed at limiting it.

Novel drug delivery systems for inflammatory bowel disease.

Inflammatory bowel disease (IBD) is a chronic illness characterized by relapsing inflammation of the intestines. The disorder is stratified according to the severity and is marked by its two main phenotypical representations: Ulcerative colitis and Crohn's disease. Pathogenesis of the disease is ambiguous and is expected to have interactivity between genetic disposition, environmental factors such as bacterial agents, and dysregulated immune response. Treatment for IBD aims to reduce symptom extent and severity and halt disease progression. The mainstay drugs have been 5-aminosalicylates (5-ASAs), corticosteroids, and immunosuppressive agents. Parenteral, oral and rectal routes are the conventional methods of drug delivery, and among all, oral administration is most widely adopted. However, problems of systematic drug reactions and low specificity in delivering drugs to the inflamed sites have emerged with these regular routes of delivery. Novel drug delivery systems have been introduced to overcome several therapeutic obstacles and for localized drug delivery to target tissues. Enteric-coated microneedle pills, various nano-drug delivery techniques, prodrug systems, lipid-based vesicular systems, hybrid drug delivery systems, and biologic drug delivery systems constitute some of these novel methods. Microneedles are painless, they dislodge their content at the affected site, and their release can be prolonged. Recombinant bacteria such as genetically engineered Lactococcus Lactis and eukaryotic cells, including GM immune cells and red blood cells as nanoparticle carriers, can be plausible delivery methods when evaluating biologic systems. Nano-particle drug delivery systems consisting of various techniques are also employed as nanoparticles can penetrate through inflamed regions and adhere to the thick mucus of the diseased site. Prodrug systems such as 5-ASAs formulations or their derivatives are effective in reducing colonic damage. Liposomes can be modified with both hydrophilic and lipophilic particles and act as lipid-based vesicular systems, while hybrid drug delivery systems containing an internal nanoparticle section for loading drugs are potential routes too. Leukosomes are also considered as possible carrier systems, and results from mouse models have revealed that they control anti- and pro-inflammatory molecules.

Association of Motoric Cognitive Risk Syndrome with Cardiovascular and Noncardiovascular Factors: A Systematic Review and Meta-Analysis.

OBJECTIVES: Motoric cognitive risk syndrome (MCR) is a recently proposed predementia syndrome characterized by subjective cognitive impairment and slow gait. We aim to assess the cardiovascular and noncardiovascular factors associated with MCR. DESIGN: Systematic review and meta-analysis. SETTING AND PARTICIPANTS: Studies comparing patients with MCR to those without MCR, and identifying the factors associated with MCR. METHODS: We used databases, including PubMed, Cochrane CENTRAL, and Embase, to identify studies evaluating the factors associated with MCR. Mean differences, odds ratios (ORs), risk ratios (RRs), and hazard ratios (HRs) with 95% CIs were calculated using Review Manager. RESULTS: Meta-analysis revealed that all cardiovascular factors, including diabetes (21 studies; OR 1.50, 95% CI 1.37, 1.64), hypertension (21 studies; OR 1.20, 95% CI 1.08, 1.33), stroke (16 studies; OR 2.03, 95% CI 1.70, 2.42), heart disease (7 studies; OR 1.45, 95% CI 1.13, 1.86), coronary artery disease (5 studies; OR 1.49, 95% CI 1.16, 1.91), smoking (13 studies; OR 1.28, 95% CI 1.04, 1.58), and obesity (12 studies; OR 1.34, 95% CI 1.13, 1.59) were significantly higher in the MCR than the non-MCR group. Noncardiovascular factors, including age (22 studies; MD = 1.08, 95% CI 0.55, 1.61), education (8 studies; OR 2.04, 95% CI 1.28, 3.25), depression (17 studies; OR 2.19, 95% CI 1.65, 2.91), prior falls (9 studies; OR 1.45, 95% CI 1.17, 1.80), arthritis (6 studies; OR 1.35, 95% CI 1.07, 1.70), polypharmacy (5 studies; OR 1.65, 95% CI 1.07, 2.54), and sedentary lifestyle (11 studies; OR 2.00, 95% CI 1.59, 2.52), were significantly higher in the MCR than in the non-MCR group. Alcohol consumption (6 studies; OR 0.84, 95% CI 0.72, 0.98), however, favored the MCR over the non-MCR group. Additionally, there was no significant association of MCR with gender (22 studies; OR 1.04, 95% CI 0.94, 1.15) and cancer (3 studies; OR 2.39, 95% CI 0.69, 8.28). MCR was also significantly associated with an increased likelihood of incident dementia (5 studies; HR 2.84, 95% CI 1.77, 4.56; P < .001), incident cognitive impairment [2 studies; adjusted hazard ratio (aHR) 1.76, 95% CI 1.44, 2.15], incident falls (4 studies; RR 1.37, 95% CI 1.17, 1.60), and mortality (2 studies; aHR 1.58, 95% CI 1.35, 1.85). CONCLUSIONS AND IMPLICATIONS: MCR syndrome was significantly associated with diabetes, hypertension, stroke, obesity, smoking, low education, sedentary lifestyle, and depression. Moreover, MCR significantly increased the risk of incident dementia, cognitive impairment, falls, and mortality.

Incidence, predictors, and outcomes of early hospital readmissions after kidney transplantation: Systemic review and meta-analysis.

Background: Early hospital readmission (EHR) within 30 days after kidney transplantation is a significant quality indicator of transplant centers and patient care. This meta-analysis aims to evaluate the incidence, predictors, and outcomes of EHR after kidney transplantation. Methods: We comprehensively searched the databases, including PubMed, Cochrane CENTRAL, and Embase, from inception until December 2021 to identify studies that assessed incidence, risk factors, and outcome of EHR. The outcomes included death-censored graft failure and mortality. Data from each study were combined using the random effect to calculate the pooled incidence, mean difference (MD), odds ratio (OR), and hazard ratio (HR) with 95% confidence interval (CI). Results: A total of 17 studies were included. The pooled EHR incidence after kidney transplant was 24.4% (95% CI 21.7-27.3). Meta-analysis showed that recipient characteristics, including older recipient age (MD 2.05; 95% CI 0.90-3.20), Black race (OR 1.31; 95% CI 1.11, 1.55), diabetes (OR 1.32; 95% CI 1.22-1.43), and longer dialysis duration (MD 0.85; 95% CI 0.41, 1.29), donor characteristics, including older donor age (MD 2.02; 95% CI 0.93-3.11), and transplant characteristics, including delayed graft function (OR 1.75; 95% CI 1.42-2.16) and longer length of hospital stay during transplantation (MD 1.93; 95% CI 0.59-3.27), were significantly associated with the increased risk of EHR. EHR was significantly associated with the increased risk of death-censored graft failure (HR 1.70; 95% CI 1.43-2.02) and mortality (HR 1.46; 95% CI 1.27-1.67) within the first year after transplantation. Conclusion: Almost one-fourth of kidney transplant recipients had EHR within 30 days after transplant, and they had worse post-transplant outcomes. Several risk factors for EHR were identified. This calls for future research to develop and implement for management strategies to reduce EHR in high-risk patients.

Risk factors for blood transfusion in Cesarean section: A systematic review and meta-analysis.

OBJECTIVE: The current study has been conducted to identify the risk factors associated with blood transfusion in women undergoing cesarean section (C-section). A detailed account of the risk factors associated withblood transfusion will ultimately prevent unnecessary crossmatching in hospitals , leading to the conservation of declining blood supplies and resources without subjugating the quality of care. MATERIAL AND METHODS: We performed a rigorous literature search using electronic databases, including PubMed, Cochrane CENTRAL, and Embase, for studies evaluating the risk factors for blood transfusion in C-section published until March 31, 2021. The Newcastle-Ottawa Quality Assessment Scale was deployed to assess the methodologic quality of the included studies. Mean differences (MD) and odds ratios (OR) with 95% confidence intervals were calculated using Review Manager version 5.3. RESULTS: The search yielded 1563 records, 22 of which were eligible for inclusion, representing 426,094 women (10,959 in the transfused group and 415,135 in the non-transfused group). Participants in the transfused group had lower mean preoperative hematocrit (MD=-3.71 [-4.46, -2.96]; p<0.00001; I2=88%). Placenta previa (OR=9.54 [7.23, 12.59]; p<0.00001; I2=88%), placental abruption (OR=6.77 [5.25, 8.73]; p<0.00001; I2=72%), emergency C-section (OR=1.92 [1.42, 2.60]; p<0.0001; I2=75%), general anesthesia (OR=8.43 [7.90, 9.00]; p<0.00001; I2=72%), multiple gestations (OR=1.60 [1.24, 2.06]; p=0.0003; I2=85%), preterm labor (OR=3.34 [2.75, 4.06]; p<0.00001; I2=85%), prolonged labor (OR=1.68 [1.44, 1.96]; p<0.00001; I2=78%), unbooked cases (OR=2.42 [1.22, 4.80]; p=0.01; I2=80%), hypertensive disorders of pregnancy (OR=1.81 [1.72, 1.90]; p<0.00001; I2=71%), and fibroids (OR=2.32 [1.55, 3.47]; p<0.0001; I2=72%) were significantly higher in the transfused group compared to the non-transfused group. Chronic hypertension (OR=0.67 [0.29, 1.55]; p=0.36; I2=90%), maternal age (MD=0.09 [-0.27, 0.45]; p=0.62; I2=50%), maternal body mass index (MD=-0.14 [-0.81, 0.53]; p=0.67, I2=86%), diabetes (OR=0.93 [0.75, 1.15]; p=0.51; I2=52%), and malpresentation (OR=0.65 [0.38, 1.11]; p=0.13; I2=64%) were not significantly associated with an increased risk of blood transfusion in C-section in the two groups. CONCLUSION: Placenta previa, placental abruption, emergency C-section, booking status, multiple gestations, and preoperative hematocrit were the risk factors most significantly associated with blood transfusion, while a prior C-section did not increase the risk of transfusion.

Efficacy and Safety of Dotinurad in Hyperuricemic Patients With or Without Gout: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Introduction A systematic review and meta-analysis of the available randomized controlled trials (RCTs) were conducted to investigate the efficacy and safety of dotinurad in hyperuricemic patients with or without gout. Dotinurad is a novel selective urate reabsorption inhibitor (SURI) that increases uric acid excretion by selectively inhibiting urate transporter 1 (URAT1). To the best of our knowledge, this is the first meta-analysis conducted to gauge the efficacy and safety of dotinurad.  Methods Electronic databases (PubMed, the Cochrane Library, and ClinicalTrials.gov) were searched from inception till March 2, 2021, according to the Preferred Reporting Items for Systematic Review and Meta-Analysis statement. Randomized controlled trials comparing the efficacy and safety of dotinurad with placebo- or active (febuxostat or benzbromarone) control were included. The eligible studies were analyzed with RevMan 5.3 Software (The Nordic Cochrane Centre, Cochrane Collaboration, Copenhagen). Results Four eligible studies, consisting of 684 hyperuricemic patients were included. The number of patients who achieved serum uric acid (sUA) levels ≤ 6.0 mg/dl favoured dotinurad 1 mg group as compared to placebo group (risk ratio {RR} = 39.27, 95% onfidence interval {CI}, 5.59 to 275.65; p = 0.0002), dotinurad 2 mg group compared with placebo group (RR = 45.36, 95% CI, 6.48 to 317.38; p= 0.0001), and dotinurad 4 mg group compared with placebo group (RR = 54.16, 95% CI, 7.76 to 377.77; p < 0.0001). Conversely, there was no significant difference in the number of patients who achieved the target sUA levels between dotinurad 2 mg and active control (RR = 1.00, 95% CI, 0.92 to 1.08; p = 0.91). Moreover, the percentage change in sUA levels from baseline to final visit favoured dotinurad 1 mg vs. placebo ((RR = 36.51, 95% CI, 33.00 to 40.02; p < 0.00001), dotinurad 2 mg vs. placebo (RR = 46.70, 95% CI, 42.53 to 50.87; p < 0.00001), and dotinurad 4 mg vs. placebo (RR = 63.84, 95% CI, 60.51 to 67.16; p < 0.00001), while no significant difference was seen in dotinurad 2 mg vs. active control (RR = -0.08, 95% CI, -4.27 to 4.11; p= 0.97). Compared with active or placebo control, dotinurad 2 mg showed no significant difference in the number of events of gouty arthritis (RR= 1.31, 95% CI, 0.47 to 3.71; p = 0.60), the number patients with adverse events (RR = 1.09, 95% CI, 0.91 to 1.30; p = 0.36), and the number of patients who experienced adverse drug reactions (RR = 1.00, 95% CI, 0.68 to 1.47; p = 0.99). Conclusion Dotinurad shows significant improvement in serum uric acid levels in hyperuricemic individuals with or without gout. Its urate-lowering effect is comparable to the commonly available anti-hyperuricemic agents. Moreover, it is effective at doses 1 mg, 2 mg, and 4 mg and well-tolerated at a dose of 2 mg.