Evaluation of Apixaban standard dosing in underweight patients with non-valvular atrial fibrillation: a retrospective cohort study.

BACKGROUND: Recent guidelines recommend using direct oral anticoagulants (DOACs) as first-line agents in patients with non-valvular atrial fibrillation (NVAF). Research is currently investigating the use of Apixaban in underweight patients, with some results suggesting altered pharmacokinetics, decreased drug absorption, and potential overdosing in this population. This study examined the effectiveness and safety of standard Apixaban dosing in adult patients with atrial NVAF weighing less than 50 kg. METHODS: This is a retrospective cohort study conducted at King Abdulaziz Medical City (KAMC); adult patients with a body mass index (BMI) below 25 who received a standard dose of Apixaban (5 mg twice daily) were categorized into two sub-cohorts based on their weight at the time of Apixaban initiation. Underweight was defined as patients weighing ≤ 50 kg, while the control group (Normal weight) comprised patients weighing > 50 kg. We followed the patients for at least one year after Apixaban initiation. The study's primary outcome was the incidence of stroke events, while secondary outcomes included bleeding (major or minor), thrombosis, and venous thromboembolism (VTE). Propensity score (PS) matching with a 1:1 ratio was used based on predefined criteria and regression model was utilized as appropriate. RESULTS: A total of 1,433 patients were screened; of those, 277 were included according to the eligibility criteria. The incidence of stroke events was lower in the underweight than in the normal weight group at crude analysis (0% vs. 9.1%) p-value = 0.06), as well in regression analysis (OR (95%CI): 0.08 (0.001, 0.76), p-value = 0.002). On the other hand, there were no statistically significant differences between the two groups in the odds of major and minor bleeding (OR (95%CI): 0.39 (0.07, 2.03), p-value = 0.26 and OR (95%CI): 1.27 (0.56, 2.84), p-value = 0.40, respectively). CONCLUSION: This exploratory study revealed that underweight patients with NVAF who received standard doses of Apixaban had fewer stroke events compared to normal-weight patients, without statistically significant differences in bleeding events. To confirm these findings, further randomized controlled trials with larger sample sizes and longer observation durations are required.

Efficacy and Safety of Preoperative Melatonin for Women Undergoing Cesarean Section: A Systematic Review and Meta-Analysis of Randomized Placebo-Controlled Trials.

Background: Cesarean section (CS) has been linked to a number of negative effects, such as pain, anxiety, and sleeping problems. The aim of this systematic review and meta-analysis was to investigate the safety and efficacy of preoperative melatonin on postoperative outcomes in pregnant women who were scheduled for elective CS. Methods: We systemically searched 4 electronic databases (PubMed, Scopus, Web of Science, and Cochrane Library) from inception until 10 March 2023. We included randomized controlled trials (RCTs) comparing melatonin and placebo for postoperative outcomes in CS patients. For risk of bias assessment, we used the Cochrane Risk of Bias 2 tool. Continuous variables were pooled as mean difference (MD), and categorical variables were pooled as a risk ratio (RR) with a 95% confidence interval (CI). Results: We included 7 studies with a total of 754 pregnant women scheduled for CS. The melatonin group had a lower pain score (MD = -1.23, 95% CI [-1.94, -0.51], p < 0.001) and longer time to first analgesic request (MD = 60.41 min, 95% CI [45.47, 75.36], p < 0.001) than the placebo group. No difference was found regarding hemoglobin levels, heart rate, mean arterial pressure, total blood loss, or adverse events. Conclusions: Preoperative melatonin may reduce postoperative pain in CS patients without side effects. This research offers a safe and affordable pain management method for this population, which has clinical consequences. Further research is needed to validate these findings and determine the best melatonin dosage and timing.

Safety and tolerability of Empagliflozin use during the holy month of Ramadan by fasting patients with type 2 diabetes: A prospective cohort study.

Background: Type 2 Diabetes Mellitus (T2DM) patients are exposed to a 7.5 times higher risk of hypoglycemia while fasting during Ramadan. Relevant diabetes guidelines prioritize the use of SGLT2 inhibitors over other classes. There is a great need to enrich data on their safe and effective use by fasting patients at greater risk of hypoglycemia. Therefore, this study aims to assess the safety and tolerability of Empagliflozin in T2DM Muslim patients during Ramadan. Methodology: A prospective cohort study was conducted for adult Muslim T2DM patients. Patients who met the inclusion criteria were categorized into two sub-cohorts based on Empagliflozin use during Ramadan (Control versus Empagliflozin). The primary outcomes were the incidence of hypoglycemia symptoms and confirmed hypoglycemia. Other outcomes were secondary. All patients were followed up to eight weeks post-Ramadan. A propensity score (PS) matching and Risk Ratio (RR) were used to report the outcomes. Results: Among 1104 patients with T2DM who were screened, 220 patients were included, and Empagliflozin was given to 89 patients as an add-on to OHDs. After matching with PS (1:1 ratio), the two groups were comparable. The use of other OHDs, such as sulfonylurea, DPP4 inhibitors, and Biguanides, was not statistically different between the two groups. The risk of hypoglycemia symptoms during Ramadan was lower in patients who received Empagliflozin than in the control group (RR 0.48 CI 0.26, 0.89; p-value = 0.02). Additionally, the risk of confirmed hypoglycemia was not statistically significant between the two groups (RR 1.09 CI 0.37, 3.22; p-value = 0.89). Conclusion: Empagliflozin use during Ramadan fasting was associated with a lower risk of hypoglycemia symptoms and higher tolerability. Further randomized control trials are required to confirm these findings.

Efficacy of stem cell therapy in patients with chronic liver disease: an umbrella review of systematic reviews.

BACKGROUND: Stem cell therapy offers promising benefits like modulating immune responses, reducing inflammation, and aiding liver regeneration. This umbrella review seeks to compile evidence from systematic reviews to assess the efficacy of stem cell therapy for improving liver function and survival rates in chronic liver disease patients. METHODS: We searched electronic databases up to February 15, 2024. The selection process focused on systematic reviews comparing stem cell therapy with standard care or a placebo. The primary outcomes evaluated were changes in liver enzymes, the MELD score, and survival rates. Nested Knowledge software was utilized for screening and data extraction. All statistical analyses were performed using R software, version 4.3. RESULTS: Our umbrella review included 28 systematic reviews. The meta-analysis showcased a notable improvement in survival rates with a pooled RR of 1.487 (95% CI: 1.281 to 1.727). In non-randomized studies, albumin levels exhibited an SMD of 0.786 (95% CI: 0.368 to 1.204), indicating positive therapeutic effects. For ALT, the meta-analysis revealed a decrease in levels with an SMD of -0.499 (95% CI: -0.834 to -0.164), and for AST, an overall SMD of -0.362 (95% CI: -0.659 to -0.066) was observed, suggesting hepatoprotective effects. No significant changes were observed in total bilirubin levels and MELD scores in RCTs. CONCLUSION: Stem cell therapy exhibits potential as a novel treatment for chronic liver diseases, as it has demonstrated improvements in survival rates and certain liver function markers. More high-quality RCTs are needed in the future to fully ascertain the efficacy of stem cell therapy in this patient population.

Azelaic Acid Versus Hydroquinone for Managing Patients With Melasma: Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Melasma, a commonly acquired hyperpigmentation skin condition, is usually treated with topical agents as the first line of management. This systematic review and meta-analysis aimed to assess the efficacy and safety of azelaic acid versus hydroquinone in treating melasma patients. We conducted a comprehensive search across four online databases (PubMed, Scopus, Web of Science, and Cochrane Library) from the time of their creation until May 28, 2023. We considered randomized controlled studies comparing hydroquinone with azelaic acid for the treatment of melasma patients. We used the Cochrane Risk of Bias tool 2 to evaluate the risk of bias. The mean difference (MD) for continuous variables and the risk ratio (RR) for categorical variables, with a 95% confidence interval (CI) were pooled. Six studies were included, with a total of 673 patients with melasma. The azelaic acid had a lower mean change in melasma area severity index (MASI) than the hydroquinone group [MD= -1.23, 95% CI (-2.05, -0.40), P=0.004]. No difference was observed regarding the improvement via the objective response scale, the reduction in pigmentation, or the adverse events reported. However, despite not being statistically significantly different, there was a trend towards having more good responses in the azelaic acid group. Azelaic acid may be better than hydroquinone in reducing melasma severity (measured by MASI). However, larger studies with long-term follow-up are needed to validate these findings.

Dexmedetomidine in Patients Undergoing Transsphenoidal Resection of Pituitary Adenoma: An Updated Systematic Review and Meta-Analysis of Randomized Placebo-Controlled Trials.

Dexmedetomidine has been widely studied in many surgical settings, with possible benefits in lowering anesthetic requirements, improving perioperative hemodynamic stability, and improving postoperative outcomes. This systematic review aims to evaluate the effects of dexmedetomidine in patients undergoing transsphenoidal resection of pituitary adenoma, shedding light on its potential as an adjunctive agent in anesthesia for this specific surgical population. In this review, we searched PubMed, Cochrane Library, Scopus, Web of Science, and Google Scholar from inception to July 20, 2023. A total of six randomized clinical trials (RCTs) investigating the effects of dexmedetomidine versus placebo in patients undergoing transsphenoidal resection of pituitary adenoma were included in this review. The outcomes of interest were extracted from the included studies as mean difference (MD) and standard deviation (SD), then analyzed using the Review Manager (RevMan, RevMan International Inc., New York, USA) software. Our literature search process retrieved 274 records. Of them, six studies were included in the meta-analysis. There was a significant difference between the dexmedetomidine group compared to the placebo group in terms of heart rate at the end of the surgery (MD = -16.5; CI = [-25.36 to -7.64]; P value = 0.0003) and after extubation (MD = -16.81; CI = [-23.18 to -10.43]; P values < 0.00001). Furthermore, dexmedetomidine significantly reduced the mean arterial blood pressure (MAP) at after both intubation and extubation (MD = -9.11 and -21.5; CI = [-13.56 to -4.65] and [-30.93 to -12.06]; P values < 0.00001). This systematic review and meta-analysis demonstrated that dexmedetomidine appears to have several potential benefits in patients undergoing transsphenoidal resection of pituitary adenoma. The use of dexmedetomidine was associated with reductions in heart rate, mean arterial blood pressure, blood loss, and duration of surgery, while showing no significant difference in propofol dose or time to extubation of the trachea.

Analgesic Efficacy of Pre-operative Pregabalin in Dacryocystorhinostomy Surgery: A Systematic Review and Meta-Analysis of Randomized Placebo-Controlled Trials.

Dacryocystorhinostomy (DCR) is an effective surgical procedure for addressing lacrimal drainage problems. However, it can be a painful operation that involves incisions both inside and outside the eye, often leading to a high incidence of postoperative nausea and vomiting. Preemptive analgesics can be employed to alleviate this unrelieved pain. Nonetheless, many of the drugs used can induce a wide range of adverse effects. Therefore, the aim of this systematic review and meta-analysis is to assess the current evidence regarding the efficacy of pregabalin in managing postoperative pain following DCR surgery. We conducted a thorough search of five electronic databases, namely, PubMed, Web of Science, Scopus, Cochrane, and Google Scholar, to identify relevant randomized controlled trials (RCTs) published before September 2023. The quality of the included studies was assessed using the Cochrane Risk of Bias tool for RCTs. The outcomes we evaluated included postoperative pain, surgery duration, time to first analgesia, total pethidine consumption, and postoperative nausea and vomiting (PONV). Continues data reported as mean difference (MD), and dichotomous data reported as risk ratio (RR), with 95% confidence interval (CI). A pooled meta-analysis of three RCTs, including 240 patients in both the pregabalin and placebo groups, was conducted. The results revealed that the pooled MD in pain scores was significantly lower in patients treated with pregabalin compared to those receiving a placebo ((MD = -1.35 (95% CI: -1.83 to -0.87, p < 0.00001)). Additionally, the pooled MD of pethidine consumption was significantly lower in patients treated with pregabalin compared to those receiving a placebo (MD = -54.13 (95% CI: -103.77 to -4.50, p = 0.03)). However, there was no statistical significance between both groups in terms of time to first analgesia and duration of surgery (p > 0.05). On the other hand, the pooled RR of PONV was significantly lower in patients treated with pregabalin compared to those receiving a placebo (RR = 0.37 (95% CI: 0.24-0.57, p < 0.001)). This meta-analysis demonstrates that pregabalin is an effective and well-tolerated intervention for reducing postoperative pain and PONV following DCR surgery, without significantly affecting surgery duration or time to first analgesia. These findings support the use of pregabalin in improving patient comfort and outcomes in this surgical context.

When antivirals backfire: An evaluation of favipiravir's clinical outcomes in critically ill patients with COVID-19: A multicenter cohort study.

BACKGROUND: Favipiravir is an oral antiviral, that might treat COVID-19 by enhancing viral eradication, particularly in patients with mild-to-moderate disease. Yet, the findings on the use of favipiravir in critically ill patients with COVID-19 are inconsistent. Therefore, this study aimed to assess the effectiveness and safety of favipiravir in critically ill patients with COVID-19. METHOD: A multicenter retrospective cohort study includes critically ill adult patients with COVID-19 admitted to the intensive care units (ICUs) was conducted from March 2020 to July 2021. Patients were categorized based on favipiravir use (control vs. favipiravir). The primary outcome was in-hospital mortality. Secondary outcomes included mechanical ventilation (MV) duration, 30-day mortality, ICU length of stay (LOS), hospital LOS, and complications during the stay. RESULTS: After propensity score (PS) matching (1:1 ratio), 146 patients were included in the final analysis. A higher in-hospital and 30-day mortality were observed in patients receiving favipiravir compared to the control group at crude analysis (65.3% vs. 43.8%; P-value=0.009 and 56.3% vs. 40.3; P-value=0.06, respectively); however, no differences were observed using multivariable Cox proportional hazards regression analysis (HR 1.17; 95% CI 0.73, 1.87; P-value =0.51 and HR 0.86; 95% CI 0.53, 1.39; P-value=0.53, respectively). Conversely, the MV duration and ICU LOS were longer in patients who received favipiravir than the control group (ß coefficient 0.51; CI 0.09, 0.92; P-value = 0.02, ß coefficient 0.41; CI 0.17, 0.64; P-value = 0.0006, respectively). Complications during the stay were comparable between the two groups. CONCLUSION: The use of favipiravir in critically ill patients with COVID-19 did not demonstrate a reduction in mortality; instead, it was linked with longer MV duration and ICU stay. This finding suggests limiting favipiravir use to infections where it is more effective, other than COVID-19. Further randomized clinical trials are needed to confirm these findings.