Efficacy and safety of bedaquiline and delamanid in the treatment of drug-resistant tuberculosis in adults: A systematic review and meta-analysis.

Multi and extensively drug-resistant tuberculosis is a grave cause of global public health concern due to its high mortality and limited treatment options. We conducted this systemic review and meta-analysis to evaluate the efficacy and safety of bedaquiline and delamanid, which have been added to the WHO-recommended regimen for treating drug-resistant tuberculosis. Electronic databases were searched from their inception until December 1st, 2021, for eligible studies assessing the efficacy and safety of bedaquiline and delamanid for treating drug-resistant tuberculosis. Binary outcomes were pooled using a DerSimonian-Laird random-effects model and arcsine transformation and reported on a log scale with a 95% confidence interval (CIs). Twenty-one studies were shortlisted in which bedaquiline, delamanid, and a combination of both were administered in 2477, 937, and 169 patients. Pooled culture conversion at 6 months was 0.801 (p < 0.001), 0.849 (p = 0.059) for bedaquiline and delamanid, respectively, and 0.823 (p = 0.017), concomitantly. In the bedaquiline cohort, the pooled proportion of all-cause mortality at 6 months was reported as 0.074 (p < 0.001), 0.031 (p = 0.372) in the delamanid cohort, and 0.172 in the combined cohort. The incidence of adverse events in the bedaquiline cohort ranged from 11.1% to 95.2%, from 13.2% to 86.2% in the delamanid cohort, and 92.5% in a study in the combined cohort. The incidence of QTC prolongation reported in each cohort is as follows: bedaquiline 0.163 (p < 0.001), delamanid 0.344 (p = 0.272) and combined 0.340 (p < 0.001). Our review establishes the efficacy of delamanid, bedaquiline, and their combined use in treating drug-resistant tuberculosis with reasonable rates of culture conversion, low mortality rates, and safety of co-administration, as seen with their effect on the QTc interval.

Virology and safety profile of Molnupiravir at three different doses for treatment of SARS-CoV-2: a systematic review and meta-analysis.

Molnupiravir is incorporated into the viral genome, thereby increasing errors, mismatching, and misdirecting the viral polymerase thereby, halting viral RNA replication of SARS-CoV-2. Following PRISMA guidelines, a thorough literature search was performed on electronic and medical databases from December 2022 till January 2023. Molnupiravir 800 mg showed significance in creating viral RNA error rate at Day 5 (WMD: 4.91; 95% CI; [1.19, 8.63] p = 0.01; I2 = 0%). Similarly, at 400 mg, Molnupiravir creates an RNA error rate (WMD: 2.27; 95% CI; 2.27 [0.50, 4.65] p = 0.02; I2 = 0%). Furthermore, exhibit a significant outcome for mean change in SARS-CoV-2 RNA viral load from baseline in nasopharyngeal sample at 800 mg Molnupiravir on Day 3 (WMD: -0.22; 95% CI; [-0.35, -0.08] p = 0.002; I2 = 0%), Day 5 (WMD: -0.32; 95% CI; [-0.53, -0.11] p = 0.003; I2 = 24%) and overall pooled analysis (WMD: -0.17; 95% CI; [-0.29, 0.33] p = 0.003; I2 = 32%). Moreover, Molnupiravir 400 mg significantly reduced the incidence of death compared to the placebo group (RR: 0.17; 95% CI; [0.07, 0.43] p = 0.0002; I2 = 0%). Molnupiravir effectively treats SARS-CoV-2 patients by eliminating the virus from the host.

Workplace violence against healthcare workers in Pakistan; call for action, if not now, then when? A systematic review.

BACKGROUND: Workplace violence (WPV) is a global problem that affects healthcare workers' physical and mental health and impairs work performance. Pakistan's healthcare system is not immune to WPV, which the World Health Organization recognises as an occupational hazard. OBJECTIVES: The primary objective of this systematic review is to determine the prevalence of physical, verbal, or other forms of WPV in healthcare workers in Pakistan. Secondary objectives include identifying the associated risk factors and perpetrators of WPV. METHODS: A systematic review of six electronic databases was conducted through August 2022. Studies were included if they met the following criteria: 1) healthcare workers (HCWs), including physicians, nurses, and paramedic staff working in the private or public sector of Pakistan; 2) exposure to physical, verbal, or any type of violence. Data were extracted and analysed for the prevalence of WPV, types of violence, associated risk factors, and perpetrators of violence. RESULTS: Twenty-four studies including 16,070 HCWs were included in this review. Verbal violence was the most common form of violence levied, with its highest prevalence (100%) reported in Islamabad and lowest verbal violence prevalence (25%) in Karachi. Verbal abuse was preponderant against female HCWs, while physical abuse was directed more towards males. The most common perpetrators were patient attendants, followed by the patients. CONCLUSION: Our review determines a 25-100% prevalence of WPV against HCWs in Pakistani medical setups. This occupational hazard needs the attention of relevant authorities in the country to put protective enforcement policies in place. Large-scale surveys should be conducted to better gauge the current plight of HCWs in the nation.

Association of adverse childhood experiences with adulthood multiple sclerosis: A systematic review of observational studies.

INTRODUCTION: Adverse childhood experiences (ACEs) are proposed to increase the risk of developing multiple sclerosis (MS) later in life. This systematic review aimed to explore the correlation between ACEs and MS development, age of onset, quality of life in MS patients and MS relapse rates. METHODS: We searched a total of six databases in June 2022 and retrieved the relevant studies. The population included adult (18+) individuals who either had been diagnosed or were at risk for developing MS and also had exposure to ACEs. Our primary outcomes include the risks of MS development, age of MS onset, and MS relapse rate in patients who were exposed to different types of ACEs. RESULTS: A total of 11 studies were included in our review. A study reported that among 300 women diagnosed with MS, 71 (24%) reported a history of childhood abuse; moreover, with further research, it was concluded that ACEs were associated with the development of MS. Abuse that occurred 2-3 times per week was associated with an 18.81-fold increased risk of having MS when compared to the unexposed sample. The relapse rate of MS was found to be substantially greater in severe cases of ACEs compared to individuals who did not report any ACEs. CONCLUSIONS: Results support a significant association between ACEs and the development of MS; individuals with a positive history of ACEs develop MS symptoms earlier. Moreover, the severity of ACEs is also linked with increased relapse rates of MS.

No difference in myocardial iron concentration and serum ferritin with deferasirox and deferiprone in pediatric patients with hemoglobinopathies: A systematic review and meta-analysis.

OBJECTIVES: Iron overload is a common complication experienced by transfusion-dependent children with hemoglobin disorders. Chelators such as deferasirox (DFX) and deferiprone (DFP) are effective in overcoming this problem. We conducted this systematic review and meta-analysis to evaluate the effectiveness of DFX compared to DFP in treating iron overload amongst pediatric patients with hemoglobin disorders. MATERIAL AND METHODS: PubMed and Cochrane Central were searched from their inception until Dec 21 2021, for randomized clinical trials (RCTs) and observational studies, which assessed the efficacy of DFX compared to DFP in the treatment of inherited hemoglobin disorders. The outcomes of interest included myocardial iron concentration (MRI T2*) at the end of the trial and change in mean serum ferritin (SF) levels at the 6 and 12 months mark. Weighted mean differences (WMDs) with their corresponding 95% confidence intervals (CIs) were calculated for continuous outcomes using random effects model. RESULTS: A total of 5 studies comprising 607 children were included. The results of our analysis revealed no significant difference between DFX and DFP in MRI T2* at the end of treatment (WMD: -0.92; 95% CI [-3.35, 1.52]; p = 0.46; I2 = 0). Moreover, there has been no significant difference noted in SF levels at both 6 months (WMD: 97.31; 95% CI [-236.16, 430.77]; p = 0.57; I2 = 0) and 12 months (WMD: 46.99; 95% CI [-191.42, 285.40]; p = 0.70; I2 = 0) respectively. CONCLUSION: Our analysis shows no significant difference between the efficacy of DFX and DFP in the management of iron overload in children with inherited blood disorders. Future large-scale clinical trials are required to further validate our results.

Two-way association between alopecia areata and sleep disorders: A systematic review of observational studies.

Background: Alopecia Areata (AA) is found to be the most prevalent autoimmune disorder amongst the general population. It was observed that AA patients are at a significantly higher risk of developing obstructive sleep apnea and non-apneic insomnia than patients without AA. On the contrary, patients with identified sleep disorders were found to be more prone to developing AA as compared to the patients without sleep disorders. This study, therefore, validated the hypothesis of a bidirectional association between AA and sleep disorders. Aims: In this systematic review, our primary aim is to assess the prevalence of sleep disorders in Alopecia Areata patients while also assessing the inverse relationship between the two disorders. Methods: A literature search of MEDLINE, Google Scholar and Cochrane CENTRAL was performed from their inception to April 2022. Articles were selected for inclusion if they met the following eligibility criteria: (a) Studies enrolling patients having alopecia areata to assess the sleep quality. (b) Studies assessing the risks of alopecia areata in individuals with sleep disorder (c) Studies evaluating the bidirectional association between alopecia areata and sleep quality. Case reports, commentaries, and editorials were excluded. The outcomes of recruited studies were qualitatively synthesised and study findings are summarized in the results section and tabulated in summary tables. Results: Our search on electronic databases yielded 1562 articles. After abstract screening and full text review, 5 cross sectional and 3 cohort studies are included in this systematic review. Cases with PSQI scores higher than 5 and 6 were found to be in greater numbers amongst the AA patient population when compared to the control population (p < 0.001). Moreover, studies showed that patients with sleep disorders were greatly predisposed to develop subsequent AA as compared to patients without sleep disorders (aHR 4.70; 95% CI 3.99-5.54) (P < 0.0001). Conclusion: The findings from our results display a significant bi-directional cause-effect relation between AA and sleep disorders. However, more large-scale observational studies on this subject are required to further validate our findings.

Efficacy of statins in treatment and development of non-alcoholic fatty liver disease and steatohepatitis: A systematic review and meta-analysis.

BACKGROUND: Non-Alcoholic Fatty Liver Disease (NAFLD) is one of the most common causes of chronic liver disease worldwide. There is no universally accepted effective treatment for NAFLD. Although various studies propose statins effective in lowering liver enzymes and in improving liver histology, their potency in the treatment and development of NAFLD remains unknown. PURPOSE: We conducted this meta-analysis to evaluate the efficacy of statins in the treatment and the development of NAFLD. METHODS: Electronic databases (MEDLINE and Cochrane CENTRAL) were searched from their inception until May 2021 for observational studies and randomized controlled trials (RCTs) that assessed the efficacy of statins for the treatment of NAFLD and its development. Studies were included irrespective of the dosage or duration, and their risk of bias was assessed. The outcomes of interest for our study were the effect of statins on liver histology (steatosis, fibrosis and necroinflammation, NAFLD activity score [NAS]) and liver enzymes (Alanine transaminase [ALT], Aspartate transaminase [AST], and Gamma-glutamyl transferase [GGT] levels). To pool continuous outcomes, a random-effects model was used to derive weighted mean difference (WMD) or standardized mean difference (SMD) and their corresponding 95% confidence intervals (CIs). Generic inverse variance was then used for different measurement units reported by the studies. For studies investigating the effects of statins on the development of NAFLD, generic inverse variance along with random effects model was used to derive odds ratio (ORs) and its corresponding 95% confidence interval (CI). RESULTS: A total of 14 studies including 1,247,503 participants were short-listed for our analysis. All the studies included in our analysis had a low to moderate risk of bias. The results of our analysis suggest that statins may significantly reduce the risk of developing NAFLD (OR:0.69, 95% CI [0.57,0.84]; p = 0.0002; I² =36%). Statin use significantly reduced ALT levels (WMD: -27.28, 95% CI [-43.06, -11.51]; p = 0.0007; I² =90%), AST levels (WMD: -10.99, 95% CI [-18.17, -3.81]; p = 0.003; I² =79%) and GGT levels (WMD: -23.40, 95% CI [-31.82, -14.98]; p < 0.00001; I² = 21%) in patients presenting with NAFLD at baseline. In liver histology outcomes, steatosis grade (SMD: -2.59, 95% CI [-4.61, -0.56]; p = 0.01; I² = 95%), NAS (WMD: -1.03, 95% CI [-1.33, -0.74]; p < 0.00001; I² = 33%), necro-inflammatory stage (WMD: -0.19, 95% CI [-0.26, -0.13]; p < 0.00001; I² = 0%) and significant fibrosis (OR:0.20, 95% CI [0.04, 0.95]; p = 0.04; I² = 97%) underwent notable reduction. However, fibrosis stage outcome (WMD: 0.07, 95% CI [-0.05, 0.20]; p = 0.27; I² = 0%) was non-significant. CONCLUSION: There was a significant decrease in transaminase and transferase levels. Marked improvement in liver histology of NAFLD patients was observed. Statin use also remarkably reduced the risk of developing NAFLD. Future large-scale trials can further aid in identifying the positive impact of statins in treatment for NAFLD and those at risk of developing it.