Search

Abstract Although the existing literature on environmental sustainability (ES) emphasizes its importance, yet few empirical studies look at the major contributing variables to ES. Therefore, we examine how the use of renewable energy, globalization, and technological innovation (TI) contribute to ES, with the moderating influence of foreign aid, spanning the period from 1996 to 2019 in BRICS economies. For data analysis, we apply the ARDL methodology, revealing an adverse and substantial link among globalization, TI, and the consumption of renewable energy with ES. Additionally, we discover that foreign aid has a beneficial moderating effect on the association between ES, globalization, and TI. On the other hand, it is found that foreign aid has an adverse moderating impact on the link between renewable energy sources and ES. This research also yields crucial practical implications, offering in-depth insights for the design of more effective policies to foster economic growth.

Introduction Semaglutide is increasingly used for the treatment of type 2 diabetes mellitus, overweight and other conditions. It is well known that semaglutide lowers blood glucose levels and leads to significant weight loss. Still, a systematic review has yet to investigate the adverse effects with semaglutide for all patient groups.Methods and analysis We will conduct a systematic review and search major medical databases (Cochrane Central Register of Controlled Trials, Medline, Embase, Latin American and Caribbean Health Sciences Literature, Science Citation Index Expanded, Conference Proceedings Citation Index—Science) and clinical trial registries from their inception and onwards to identify relevant randomised clinical trials. We expect to conduct the literature search in July 2024. Two review authors will independently extract data and perform risk-of-bias assessments. We will include randomised clinical trials comparing oral or subcutaneous semaglutide versus placebo. Primary outcomes will be all-cause mortality and serious adverse events. Secondary outcomes will be myocardial infarction, stroke, all-cause hospitalisation and non-serious adverse events. Data will be synthesised by meta-analyses and trial sequential analysis; risk of bias will be assessed with Cochrane Risk of Bias tool—version 2, an eight-step procedure will be used to assess if the thresholds for statistical and clinical significance are crossed, and the certainty of the evidence will be assessed by Grading of Recommendations, Assessment, Development and Evaluations.Ethics and dissemination This protocol does not present any results. Findings of this systematic review will be published in international peer-reviewed scientific journals.PROSPERO registration number CRD42024499511.

BACKGROUND &OBJECTIVE: Gaining admission to medical school is highly competitive, requiring rigorous selection criteria by educational institutions. They carefully assess entry qualifications and eligibility tests to identify suitable applicants for their medical programs. The objective is to evaluate how well these criteria predict student's overall academic performance in medical colleges across Pakistan. METHODOLOGY: The descriptive, observational study was conducted at a private medical and dental College, in Karachi. A multiple linear regression analysis was conducted to predict the final year score based on factors such as HSC score, entry test score, and scores from the first, second, third, and fourth years. RESULTS: The study shows that the pre-medical scores of HSC and A levels have a moderate positive correlation with the first-year MBBS (r=0.403) and a strong correlation with the final-year scores (r=0.603). The entry test (MDCAT) has a moderately positive correlation with the first, third (r=0.348), and fourth-year (r=0.367) scores. On comparing pre-clinical year scores with clinical years, a strong positive correlation was seen between 1st year and 3rd year (r=0.721), 1st year and 4th year (r=0.570), 1st year and final year (r=0.619), 3rd year and 4th year (r=0.711), 3rd year and 5th-year scores (r=0.602), 4th year, and 5th-year scores (r=0.651). CONCLUSION: This study shows that the pre-medical scores and medical college entry tests can predict student’s overall future academic performance in professional examinations. Also, provides insight to medical educationists to identify weak students in their early medical college years.

Question Tricyclic antidepressants are used to treat depression worldwide, but the adverse effects have not been systematically assessed. Our objective was to assess the beneficial and harmful effects of all tricyclic antidepressants for adults with major depressive disorder.Study selection and analysis We conducted a systematic review with meta-analysis and trial sequential analysis. We searched CENTRAL, MEDLINE, Embase, LILACS and other sources from inception to January 2023 for randomised clinical trials comparing tricyclic antidepressants versus placebo or ‘active placebo’ for adults with major depressive disorder. The primary outcomes were depressive symptoms measured on the 17-item Hamilton Depression Rating Scale (HDRS-17), serious adverse events and quality of life. The minimal important difference was defined as three points on the HDRS-17.Findings We included 103 trials randomising 10 590 participants. All results were at high risk of bias, and the certainty of the evidence was very low or low. All trials only assessed outcomes at the end of the treatment period at a maximum of 12 weeks after randomisation. Meta-analysis and trial sequential analysis showed evidence of a beneficial effect of tricyclic antidepressants compared with placebo (mean difference −3.77 HDRS-17 points; 95% CI −5.91 to −1.63; 17 trials). Meta-analysis showed evidence of a harmful effect of tricyclic antidepressants compared with placebo on serious adverse events (OR 2.78; 95% CI 2.18 to 3.55; 35 trials), but the required information size was not reached. Only 2 out of 103 trials reported on quality of life and t-tests showed no evidence of a difference.Conclusions The long-term effects of tricyclic antidepressants and the effects on quality of life are unknown. Short-term results suggest that tricyclic antidepressants may reduce depressive symptoms while also increasing the risks of serious adverse events, but these results were based on low and very low certainty evidence.PROSPERO registration number CRD42021226161.

Purpose: This article establishes a connection between entrepreneurial orientation (EO) and firm performance, exploring the mediating effects of knowledge-based capabilities (KBC), social media use capabilities (SMUCs) and customer relationship management capabilities (CRMCs), with moderation by environmental dynamism (ED). Utilising the resource-based view (RBV) framework and a mediation moderation model, the research empirically explores these connections. Design/methodology/approach: Data were gathered via a survey from 900 listed firms in Ethiopia and China, spanning manufacturing and service industries. The questionnaire underwent translation into Chinese and Amharic from English. A quantitative approach, utilising convenience sampling for survey distribution, was employed. SPSS 24 software facilitated mediation analysis, revealing no concerns related to discriminant validity. Findings/results: The findings affirm the positive impacts of EO on KBC, SMUC and CRMC in China, while only on SMUC in Ethiopia. In addition, a positive mediation of KBC, SMUC and CRMC between EO and firm performance. Additionally, ED moderated the link between SMUC, CRMC and firm performance. Practical implications: Our study recommends that policymakers and managers should invest in training programmes and information technology, organising workshops to educate staff on the effective use of social media tools. This investment holds substantial potential for dynamically transforming business models, processes and customer trends. Originality/value: This study adds to the current body of knowledge by exploring EO-firm performance correlation, incorporating the mediating effects of KBC, SMUC and CRMC while considering the moderating influence of ED.

Abstract Background Major depressive disorder causes a great burden on patients and societies. Venlafaxine and mirtazapine are commonly prescribed as second-line treatment for patients with major depressive disorder worldwide. Previous systematic reviews have concluded that venlafaxine and mirtazapine reduce depressive symptoms, but the effects seem small and may not be important to the average patient. Moreover, previous reviews have not systematically assessed the occurrence of adverse events. Therefore, we aim to investigate the risks of adverse events with venlafaxine or mirtazapine versus ‘active placebo’, placebo, or no intervention for adults with major depressive disorder in two separate systematic reviews. Methods This is a protocol for two systematic reviews with meta-analysis and Trial Sequential Analysis. The assessments of the effects of venlafaxine or mirtazapine will be reported in two separate reviews. The protocol is reported as recommended by Preferred Reporting Items for Systematic Reviews and Meta-Analysis Protocols, risk of bias will be assessed with the Cochrane risk-of-bias tool version 2, clinical significance will be assessed using our eight-step procedure, and the certainty of the evidence will be assessed with the Grading of Recommendations Assessment, Development and Evaluation approach. We will search for published and unpublished trials in major medical databases and trial registers. Two review authors will independently screen the results from the literature searches, extract data, and assess risk of bias. We will include published or unpublished randomised clinical trial comparing venlafaxine or mirtazapine with ‘active placebo’, placebo, or no intervention for adults with major depressive disorder. The primary outcomes will be suicides or suicide attempts, serious adverse events, and non-serious adverse events. Exploratory outcomes will include depressive symptoms, quality of life, and individual adverse events. If feasible, we will assess the intervention effects using random-effects and fixed-effect meta-analyses. Discussion Venlafaxine and mirtazapine are frequently used as second-line treatment of major depressive disorder worldwide. There is a need for a thorough systematic review to provide the necessary background for weighing the benefits against the harms. This review will ultimately inform best practice in the treatment of major depressive disorder. Systematic review registration PROSPERO CRD42022315395.

ABSTRACT The implementation of artemisinin (ART) combination therapies (ACTs) has greatly decreased deaths caused by Plasmodium falciparum malaria, but increasing ACT resistance in Southeast Asia and Africa could reverse this progress. Parasite population genetic studies have identified numerous genes, single-nucleotide polymorphisms (SNPs), and transcriptional signatures associated with altered artemisinin activity with SNPs in the Kelch13 (K13) gene being the most well-characterized artemisinin resistance marker. However, there is an increasing evidence that resistance to artemisinin in P. falciparum is not related only to K13 SNPs, prompting the need to characterize other novel genes that can alter ART responses in P. falciparum. In our previous analyses of P. falciparum piggyBac mutants, several genes of unknown function exhibited increased sensitivity to artemisinin that was similar to a mutant of K13. Further analysis of these genes and their gene co-expression networks indicated that the ART sensitivity cluster was functionally linked to DNA replication and repair, stress responses, and maintenance of homeostatic nuclear activity. In this study, we have characterized PF3D7_1136600, another member of the ART sensitivity cluster. Previously annotated as a conserved Plasmodium gene of unknown function, we now provide putative annotation of this gene as a Modulator of Ring Stage Translation (MRST). Our findings reveal that the mutagenesis of MRST affects gene expression of multiple translation-associated pathways during the early ring stage of asexual development via putative ribosome assembly and maturation activity, suggesting an essential role of MRST in protein biosynthesis and another novel mechanism of altering the parasite’s ART drug response. IMPORTANCE Plasmodium falciparum malaria killed more than 600,000 people in 2021, though ACTs have been critical in reducing malaria mortality as a first-line treatment for infection. However, ACT resistance in Southeast Asia and emerging resistance in Africa are detrimental to this progress. Mutations to Kelch13 (K13) have been identified to confer increased artemisinin tolerance in field isolates, however, genes other than K13 are implicated in altering how the parasite responds to artemisinin prompts additional analysis. Therefore, in this study we have characterized a P. falciparum mutant clone with altered sensitivity to artemisinin and identified a novel gene (PF3D7_1136600) that is associated with alterations to parasite translational metabolism during critical timepoints for artemisinin drug response. Many genes of the P. falciparum genome remain unannotated, posing a challenge for drug–gene characterizations in the parasite. Therefore, through this study, we have putatively annotated PF3D7_1136600 as a novel MRST gene and have identified a potential link between MRST and parasite stress response mechanisms.

Objectives To assess the effects of interventions authorised by the European Medicines Agency (EMA) or the US Food and Drug Administration (FDA) for prevention of COVID-19 progression to severe disease in outpatients.Setting Outpatient treatment.Participants Participants with a diagnosis of COVID-19 and the associated SARS-CoV-2 virus irrespective of age, sex and comorbidities.Interventions Drug interventions authorised by EMA or FDA.Primary outcome measures Primary outcomes were all-cause mortality and serious adverse events.Results We included 17 clinical trials randomising 16 257 participants to 8 different interventions authorised by EMA or FDA. 15/17 of the included trials (88.2%) were assessed at high risk of bias. Only molnupiravir and ritonavir-boosted nirmatrelvir seemed to improve both our primary outcomes. Meta-analyses showed that molnupiravir reduced the risk of death (relative risk (RR) 0.11, 95% CI 0.02 to 0.64; p=0.0145, 2 trials; very low certainty of evidence) and serious adverse events (RR 0.63, 95% CI 0.47 to 0.84; p=0.0018, 5 trials; very low certainty of evidence). Fisher’s exact test showed that ritonavir-boosted nirmatrelvir reduced the risk of death (p=0.0002, 1 trial; very low certainty of evidence) and serious adverse events (p

Purpose – The purpose of this study was to assess the knowledge of head and neck cancers (HNCs), their risk factors, signs and symptoms among the general public of Karachi, Pakistan. Design/methodology/approach – Initially, 503 individuals were approached for data collection, out of which 404 fit the inclusion criteria (response rate = 80.03%). Nonprobability convenience sampling was utilized to select participants who fell under the age group of 15–60 years, barring the fields of Bachelor of Medicine and Bachelors of Surgery (MBBS) and Bachelors of Dentistry (BDS). Knowledge was evaluated by a 9-item questionnaire, the scores of which yielded the following interpretations: No (0), low (1–3), moderate (4–6) and high (7–9) knowledge. Findings – Of the 404 participants who completed the questionnaire, 357 (88.4%) participants claimed to be aware of HNC. The HNC knowledge scores had a statistical relevance with socioeconomic status (p =

This aim of this research is to examine the role of Corporate Governance and Corporate Reputation (CR) in the disclosure of Corporate Social Responsibility (CSRD) and firm performance. A moderating – mediation model addresses this research objective based on 3588 observations from 833 firms from 31 countries between 2005 and 2011. Significant effect of CSRD on CR was observed, especially contributing to firm performance. The results verified a moderate effect of “corporate governance” on “CSRD” and CR. The study also demonstrated how CEO integrity, ownership concentration, and CR contribute to fostering CSRD and firm performance. This paper also discusses about the theoretical contributions and practical implications of the study.

Introduction: Telepathology (TP) allows for remote slide review with performance comparable to traditional light microscopy. Use of TP in the intraoperative setting allows for faster turnaround and greater user convenience by obviating the physical presence of the attending pathologist. We sought to perform a practical validation of an intraoperative TP system using the Leica Aperio LV1 scanner in tandem with Zoom teleconferencing software. Methods: A validation was performed in accordance with recommendations from CAP/ASCP, using a retrospectively identified sample of surgical pathology cases with a 1 year washout period. Only cases with frozen-final concordance were included. Validators underwent training in the operation of the instrument and conferencing interface, then reviewed the blinded slide set annotated with clinical information. Validator diagnoses were compared to original diagnoses for concordance. Results: 60 slides were chosen for inclusion. 8 validators completed the slide review, each requiring 2 h. The validation was completed in 2 weeks. Overall concordance was 96.4%. Intraobserver concordance was 97.3%. No major technical hurdles were encountered. Conclusion: Validation of the intraoperative TP system was completed rapidly and with high concordance, comparable to traditional light microscopy. Institutional teleconferencing implementation driven by the COVID pandemic facilitated ease of adoption.

Background: Pneumonia remains one of the main causes of childhood mortality despite the availability of simple, safe, effective and inexpensive interventions to curb its mortality. This could result from sub-optimal care seeking practices and child rearing, supplemented by lack of access to healthcare.We conducted a studyto identify the association of malnutrition and initiation of breastfeeding variables with severe pneumonia and pneumonia/no pneumonia Objective: To determine association of malnutrition and colostrums intake among children aged 2-24 months admitted in tertiary care hospital for severe pneumonia. Methods: A total of 288 patients with severe pneumonia were included in this case-control study. Patients were divided into 2 groups with 144 patients in each group selected through non-probability consecutive sampling. Sample size was calculated using WHO sample size calculator keeping power of test at 80%, P1= 1% and P2=7.8%. Data was analyzed through SPSS version 19 and p-value < 0.05 considered as significant. Association between study variables and severe pneumonia was computed using Chi Square Test. Results: Mean age for group A (67 males and 77 females) was 13.00±6.40 months and group B (78 males, 66 females) 12.83±6.90 months. Malnutrition was seen in 41% of group A and 17.4% of group B patients. Colostrum intake (Initiation of breast feeding with 72 hours) was reported in 78.5% of group A and 79.2% of group B. There was a significant association of malnutrition with severe pneumonia (p=0.000) whereas, no significant relation was found with colostrum intake (p=0.885). Conclusion: Malnutrition was significantly associated with severe pneumonia. Colostrum was the most prevalent factor in both groups but the difference was insignificant.

Abstract Background Major depressive disorder is a common psychiatric disorder causing great burden on patients and societies. Tricyclic antidepressants are frequently used worldwide to treat patients with major depressive disorder. It has repeatedly been shown that tricyclic antidepressants reduce depressive symptoms with a statistically significant effect, but the effect is small and of questionable clinical importance. Moreover, the beneficial and harmful effects of all types of tricyclic antidepressants have not previously been systematically assessed. Therefore, we aim to investigate the beneficial and harmful effects of tricyclic antidepressants versus ‘active placebo’, placebo or no intervention for adults with major depressive disorder. Methods This is a protocol for a systematic review with meta-analysis that will be reported as recommended by Preferred Reporting Items for Systematic Reviews and Meta-Analysis Protocols, bias will be assessed with the Cochrane Risk of Bias tool—version 2, our eight-step procedure will be used to assess if the thresholds for clinical significance are crossed, Trial Sequential Analysis will be conducted to control random errors and the certainty of the evidence will be assessed with the Grading of Recommendations Assessment, Development and Evaluation approach. To identify relevant trials, we will search both for published and unpublished trials in major medical databases and trial registers, such as CENTRAL, MEDLINE, EMBASE and ClinicalTrials.gov from their inception to 12 May 2021. Clinical study reports will be applied for from regulatory authorities and pharmaceutical companies. Two review authors will independently screen the results from the literature searches, extract data and perform risk of bias assessment. We will include any published or unpublished randomised clinical trial comparing tricyclic antidepressants with ‘active placebo’, placebo or no intervention for adults with major depressive disorder. The following interventions will be assessed: amineptine, amitriptyline, amoxapine, butriptyline, cianopramine, clomipramine, desipramine, demexiptiline, dibenzepin, dosulepin, dothiepin, doxepin, imipramine, iprindole, lofepramine, maprotiline, melitracen, metapramine, nortriptyline, noxiptiline, opipramol, protriptyline, tianeptine, trimipramine and quinupramine. Primary outcomes will be depressive symptoms, serious adverse events and quality of life. Secondary outcomes will be suicide or suicide-attempts and non-serious adverse events. If feasible, we will assess the intervention effects using random-effects and fixed-effect meta-analyses. Discussion Tricyclic antidepressants are recommended by clinical guidelines and frequently used worldwide in the treatment of major depressive disorder. There is a need for a thorough systematic review to provide the necessary background for weighing the benefits against the harms. This review will ultimately inform best practice in the treatment of major depressive disorder. Systematic review registration PROSPERO CRD42021226161 .

Abstract Background Major depression significantly impairs quality of life, increases the risk of suicide, and poses tremendous economic burden on individuals and societies. Duloxetine, a serotonin norepinephrine reuptake inhibitor, is a widely prescribed antidepressant. The effects of duloxetine have, however, not been sufficiently assessed in earlier systematic reviews and meta-analyses. Methods/design A systematic review will be performed including randomised clinical trials comparing duloxetine with ‘active’ placebo, placebo or no intervention for adults with major depressive disorder. Bias domains will be assessed, an eight-step procedure will be used to assess if the thresholds for clinical significance are crossed. We will conduct meta-analyses. Trial sequential analysis will be conducted to control random errors, and the certainty of the evidence will be assessed using GRADE. To identify relevant trials, we will search Cochrane Central Register of Controlled Trials, Medical Literature Analysis and Retrieval System Online, Excerpta Medica database, PsycINFO, Science Citation Index Expanded, Social Sciences Citation Index, Conference Proceedings Citation Index—Science and Conference Proceedings Citation Index—Social Science & Humanities. We will also search Chinese databases and Google Scholar. We will search all databases from their inception to the present. Two review authors will independently extract data and perform risk of bias assessment. Primary outcomes will be the difference in mean depression scores on Hamilton Depression Rating Scale between the intervention and control groups and serious adverse events. Secondary outcomes will be suicide, suicide-attempts, suicidal ideation, quality of life and non-serious adverse events. Discussion No former systematic review has systematically assessed the beneficial and harmful effects of duloxetine taking into account both the risks of random errors and the risks of systematic errors. Our review will help clinicians weigh the benefits of prescribing duloxetine against its adverse effects and make informed decisions. Systematic review registration PROSPERO 2016 CRD42016053931

Background: Diverse strategies are employed globally to integrate medical curricula. Nevertheless, a gap exists in assessing the role of medical instructors in meaningful integration. We developed and used a tool to explore the current level of integration, score medical instructors’ individual practices for integration, and investigate contextual elements minimizing integration. Methodology: This cross-sectional study, conducted in September-November-2020, used convenience-sampling. The study participants were basic-sciences and clinical instructors at two private-sector medical colleges in Karachi-Pakistan (with a response rate of 53.5%, n = 107). We validated a paper-based questionnaire through a pilot study on five participants. This tool with 11 close-ended questions on a 5-point Likert scale generated instructors’ integration scores, and six open-ended questions probed instructors’ perspectives. Results: The mean integration score was 37.4±6.7. Participants’ perspectives indicated a need for participation of clinical faculty in teaching initial undergraduate years, involving lecturers in curriculum meetings, and integration of assessment. The questionnaire Cronbach-alpha was 0.732 with satisfactory principal-component-analysis. Conclusion: Medical instructors facilitated integration mainly through concurrent timetabling of similar topics. Moreover, formal consultation through committee meetings, with discipline-based and integrated approaches complementing each other, were in practice to achieve curricular goals.

Background: Various anticoagulant therapies are prescribed to patients under physicians’ discretion and recently Direct Oral Anticoagulants(DOAC) have been under trials to evaluate their safety and efficacy. In addition to this, the regimen of DOACs and Aspirin is of keen interest as researchers continue to find an optimal regimen to treat blood clots in patients. This study is a systematic review and meta-analysis of randomized controlled trials and observational studies that asses the safety and efficacy of DOAC with and without Aspirin. Methods: We queried MEDLINE and Cochrane CENTRAL from their inception to April 2021, for published and randomized controlled trials and observational studies in any language that compared dual (DOAC + ASA) therapy or mono (DOAC alone) therapy in patients with AF. The results from the studies were presented as risk ratios (RRs) with 95% confidence intervals (CIs) and were pooled using a random-effects model. Endpoints of interest included major bleeding, myocardial infarction (MI), major adverse cardiovascular events (MACEs), hospitalizations, all-cause mortality, and stroke. Results: The risk of major bleeding was significantly lower in the DOAC alone group compared with DOAC plus aspirin group. Non-significant results were obtained (P value greater than 0.05) for other outcomes establishing that DOAC monotherapy was not superior to the combined regimen in reducing the risk of MACE, Stroke, Hospitalization, Death. Conclusion: Among patients with NVAF (Non valvular Atrial Fibrillation) and VTE (Venous thromboembolism) receiving anticoagulation prophylaxis, in terms of safety profile our comparisons showed a statistically significant reduction in Major Bleeding in DOAC Alone group compared with DOAC Plus Aspirin.

Abstract Background Major depressive disorder is one of the most common, burdensome, and costly psychiatric disorders worldwide. Antidepressants are frequently used to treat major depressive disorder. It has been shown repeatedly that antidepressants seem to reduce depressive symptoms with a statistically significant effect, but the clinical importance of the effect sizes seems questionable. Both beneficial and harmful effects of antidepressants have not previously been sufficiently assessed. The main objective of this review will be to evaluate the beneficial and harmful effects of antidepressants versus placebo, ‘active placebo’, or no intervention for adults with major depressive disorder. Methods/design A systematic review with meta-analysis will be reported as recommended by Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA), bias will be assessed with the Cochrane Risk of Bias tool-version 2 (ROB2), our eight-step procedure will be used to assess if the thresholds for clinical significance are crossed, Trial Sequential Analysis will be conducted to control for random errors, and the certainty of the evidence will be assessed with the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. To identify relevant trials, we will search both for published and unpublished trials in major medical databases from their inception to the present. Clinical study reports will be obtained from regulatory authorities and pharmaceutical companies. Two review authors will independently screen the results of the literature searches, extract data, and perform risk of bias assessment. We will include any published or unpublished randomised clinical trial comparing one or more antidepressants with placebo, ‘active placebo’, or no intervention for adults with major depressive disorder. The following active agents will be included: agomelatine, amineptine, amitriptyline, bupropion, butriptyline, cianopramine, citalopram, clomipramine, dapoxetine, demexiptiline, desipramine, desvenlafaxine, dibenzepin, dosulepin, dothiepin, doxepin, duloxetine, escitalopram, fluoxetine, fluvoxamine, imipramine, iprindole, levomilnacipran, lofepramine, maprotiline, melitracen, metapramine, milnacipran, mirtazapine, nefazodone, nortriptyline, noxiptiline, opipramol, paroxetine, protriptyline, quinupramine, reboxetine, sertraline, trazodone, tianeptine, trimipramine, venlafaxine, vilazodone, and vortioxetine. Primary outcomes will be depressive symptoms, serious adverse events, and quality of life. Secondary outcomes will be suicide or suicide attempt, suicidal ideation, and non-serious adverse events. Discussion As antidepressants are commonly used to treat major depressive disorder in adults, a systematic review evaluating their beneficial and harmful effects is urgently needed. This review will inform best practice in treatment and clinical research of this highly prevalent and burdensome disorder. Systematic review registration PROSPERO CRD42020220279

Abstract Background Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes coronavirus disease 2019 (COVID-19) which has rapidly spread worldwide. Several human randomized clinical trials assessing potential vaccines are currently underway. There is an urgent need for a living systematic review that continuously assesses the beneficial and harmful effects of all available vaccines for COVID-19. Methods/design We will conduct a living systematic review based on searches of major medical databases (e.g., MEDLINE, EMBASE, CENTRAL) and clinical trial registries from their inception onwards to identify relevant randomized clinical trials. We will update the literature search once a week to continuously assess if new evidence is available. Two review authors will independently extract data and conduct risk of bias assessments. We will include randomized clinical trials comparing any vaccine aiming to prevent COVID-19 (including but not limited to messenger RNA; DNA; non-replicating viral vector; replicating viral vector; inactivated virus; protein subunit; dendritic cell; other vaccines) with any comparator (placebo; “active placebo;” no intervention; standard care; an “active” intervention; another vaccine for COVID-19) for participants in all age groups. Primary outcomes will be all-cause mortality; a diagnosis of COVID-19; and serious adverse events. Secondary outcomes will be quality of life and non-serious adverse events. The living systematic review will include aggregate data meta-analyses, trial sequential analyses, network meta-analyses, and individual patient data meta-analyses. Within-study bias will be assessed using Cochrane risk of bias tool. The Grading of Recommendations, Assessment, Development and Evaluations (GRADE) and Confidence in Network Meta-Analysis (CINeMA) approaches will be used to assess certainty of evidence. Observational studies describing harms identified during the search for trials will also be included and described and analyzed separately. Discussion COVID-19 has become a pandemic with substantial mortality. A living systematic review assessing the beneficial and harmful effects of different vaccines is urgently needed. This living systematic review will regularly inform best practice in vaccine prevention and clinical research of this highly prevalent disease. Systematic review registration PROSPERO CRD42020196492

Background COVID-19 is rapidly spreading causing extensive burdens across the world. Effective vaccines to prevent COVID-19 are urgently needed. Methods and findings Our objective was to assess the effectiveness and safety of COVID-19 vaccines through analyses of all currently available randomized clinical trials. We searched the databases CENTRAL, MEDLINE, Embase, and other sources from inception to June 17, 2021 for randomized clinical trials assessing vaccines for COVID-19. At least two independent reviewers screened studies, extracted data, and assessed risks of bias. We conducted meta-analyses, network meta-analyses, and Trial Sequential Analyses (TSA). Our primary outcomes included all-cause mortality, vaccine efficacy, and serious adverse events. We assessed the certainty of evidence with GRADE. We identified 46 trials; 35 trials randomizing 219 864 participants could be included in our analyses. Our meta-analyses showed that mRNA vaccines (efficacy, 95% [95% confidence interval (CI), 92% to 97%]; 71 514 participants; 3 trials; moderate certainty); inactivated vaccines (efficacy, 61% [95% CI, 52% to 68%]; 48 029 participants; 3 trials; moderate certainty); protein subunit vaccines (efficacy, 77% [95% CI, −5% to 95%]; 17 737 participants; 2 trials; low certainty); and viral vector vaccines (efficacy 68% [95% CI, 61% to 74%]; 71 401 participants; 5 trials; low certainty) prevented COVID-19. Viral vector vaccines decreased mortality (risk ratio, 0.25 [95% CI 0.09 to 0.67]; 67 563 participants; 3 trials, low certainty), but comparable data on inactivated, mRNA, and protein subunit vaccines were imprecise. None of the vaccines showed evidence of a difference on serious adverse events, but observational evidence suggested rare serious adverse events. All the vaccines increased the risk of non-serious adverse events. Conclusions The evidence suggests that all the included vaccines are effective in preventing COVID-19. The mRNA vaccines seem most effective in preventing COVID-19, but viral vector vaccines seem most effective in reducing mortality. Further trials and longer follow-up are necessary to provide better insight into the safety profile of these vaccines.

The current study empirically tests a financial well-being (FWB) model built on financial socialization (FS) and early childhood consumer experience (ECCE). The current study was conducted based on primary data obtained through structured questionnaires. By using a convenient sampling technique, data were collected from 1,500 respondents from Pakistan. Results advocated that childhood experiences directly affect the FWB in adults. In addition, FS agents, such as parents, have direct and indirect effects on the FWB in adults. Findings revealed that financial coping behaviors mediate the relationship among FS agents, such as parents, students, and the FWB. Surprisingly, FS agent peers do not impact adult FWBs. The study concluded that FWB could be improved by socializing with parents and teachers and using childhood experiences. Considering the importance of the role of parents and teachers, they should discuss financial issues with children. Policymakers should work to provide some opportunities for children so that they can practice and gain experience.

This study explores the nexus between foreign direct investment, financial development, energy consumption, economic growth and globalization for a selected panel of Belt and Road Initiative (BRI) countries over the period 1990–2016. After employing appropriate panel unit root tests, the Westerlund co-integration test, the DSUR long-run panel estimation approach and the Dumitrescu-Hurlin panel causality test, the results reveal a significant long-run relationship among the analyzed variables. The DSUR results show that energy consumption is boosted by 0.023 and 0.790% when a 1% rise occurs in foreign direct investment and economic growth. A 1% increase in financial development and globalization reduces energy consumption by 0.049 and 0.621%, respectively. We also found bidirectional relationships of energy consumption with financial development and foreign direct investment with globalization for the selected sample of our study. A unidirectional causal relationship exists, moving from energy consumption towards both financial development and foreign direct investment. An increase in FDI, the introduction of energy-efficient technology, and development of the financial sector lead to sustainable economic growth. The findings reveal the need to formulate policies that promote energy efficiency among Belt and Road (BR) countries. The policy implications of this study are presented in the Conclusion.

AbstractIntroduction:There are few longitudinal studies about South Asians (SAs) and little information about recruitment and retention approaches for this ethnic group.Methods:We followed 906 SAs enrolled in the Mediators of Atherosclerosis in South Asians Living in America (MASALA) cohort for 5 years. Surviving participants were invited for a second clinical exam from 2015 to 2018. A new wave of participants was recruited during 2017–2018. We assessed the yields from different methods of recruitment and retention.Results:A total of 759 (83%) completed the second clinical exam, and 258 new participants were enrolled. Providing a nearby community hospital location for the study exam, offering cab/shared ride reimbursement, and conducting home visits were the most effective methods for enhancing retention. New participant recruitment targeted women and individuals with lower socioeconomic status, and we found that participant referrals and active community engagement were most effective. Mailing invitational letters to those identified by electronic health records had very low yield.Conclusion:Recruitment and retention strategies that address transportation barriers and increase community engagement will help increase the representation of SAs in health research.

BackgroundCOVID-19 is a rapidly spreading disease that has caused extensive burden to individuals, families, countries, and the world. Effective treatments of COVID-19 are urgently needed. This is the second edition of a living systematic review of randomized clinical trials assessing the effects of all treatment interventions for participants in all age groups with COVID-19.Methods and findingsWe planned to conduct aggregate data meta-analyses, trial sequential analyses, network meta-analysis, and individual patient data meta-analyses. Our systematic review was based on PRISMA and Cochrane guidelines, and our eight-step procedure for better validation of clinical significance of meta-analysis results. We performed both fixed-effect and random-effects meta-analyses. Primary outcomes were all-cause mortality and serious adverse events. Secondary outcomes were admission to intensive care, mechanical ventilation, renal replacement therapy, quality of life, and non-serious adverse events. According to the number of outcome comparisons, we adjusted our threshold for significance to p = 0.033. We used GRADE to assess the certainty of evidence. We searched relevant databases and websites for published and unpublished trials until November 2, 2020. Two reviewers independently extracted data and assessed trial methodology. We included 82 randomized clinical trials enrolling a total of 40,249 participants. 81 out of 82 trials were at overall high risk of bias. Meta-analyses showed no evidence of a difference between corticosteroids versus control on all-cause mortality (risk ratio [RR] 0.89; 95% confidence interval [CI] 0.79 to 1.00; p = 0.05; I2 = 23.1%; eight trials; very low certainty), on serious adverse events (RR 0.89; 95% CI 0.80 to 0.99; p = 0.04; I2 = 39.1%; eight trials; very low certainty), and on mechanical ventilation (RR 0.86; 95% CI 0.55 to 1.33; p = 0.49; I2 = 55.3%; two trials; very low certainty). The fixed-effect meta-analyses showed indications of beneficial effects. Trial sequential analyses showed that the required information size for all three analyses was not reached. Meta-analysis (RR 0.93; 95% CI 0.82 to 1.07; p = 0.31; I2 = 0%; four trials; moderate certainty) and trial sequential analysis (boundary for futility crossed) showed that we could reject that remdesivir versus control reduced the risk of death by 20%. Meta-analysis (RR 0.82; 95% CI 0.68 to 1.00; p = 0.05; I2 = 38.9%; four trials; very low certainty) and trial sequential analysis (required information size not reached) showed no evidence of difference between remdesivir versus control on serious adverse events. Fixed-effect meta-analysis showed indications of a beneficial effect of remdesivir on serious adverse events. Meta-analysis (RR 0.40; 95% CI 0.19 to 0.87; p = 0.02; I2 = 0%; two trials; very low certainty) showed evidence of a beneficial effect of intravenous immunoglobulin versus control on all-cause mortality, but trial sequential analysis (required information size not reached) showed that the result was severely underpowered to confirm or reject realistic intervention effects. Meta-analysis (RR 0.63; 95% CI 0.35 to 1.14; p = 0.12; I2 = 77.4%; five trials; very low certainty) and trial sequential analysis (required information size not reached) showed no evidence of a difference between tocilizumab versus control on serious adverse events. Fixed-effect meta-analysis showed indications of a beneficial effect of tocilizumab on serious adverse events. Meta-analysis (RR 0.70; 95% CI 0.51 to 0.96; p = 0.02; I2 = 0%; three trials; very low certainty) showed evidence of a beneficial effect of tocilizumab versus control on mechanical ventilation, but trial sequential analysis (required information size not reached) showed that the result was severely underpowered to confirm of reject realistic intervention effects. Meta-analysis (RR 0.32; 95% CI 0.15 to 0.69; p < 0.00; I2 = 0%; two trials; very low certainty) showed evidence of a beneficial effect of bromhexine versus standard care on non-serious adverse events, but trial sequential analysis (required information size not reached) showed that the result was severely underpowered to confirm or reject realistic intervention effects. Meta-analyses and trial sequential analyses (boundary for futility crossed) showed that we could reject that hydroxychloroquine versus control reduced the risk of death and serious adverse events by 20%. Meta-analyses and trial sequential analyses (boundary for futility crossed) showed that we could reject that lopinavir-ritonavir versus control reduced the risk of death, serious adverse events, and mechanical ventilation by 20%. All remaining outcome comparisons showed that we did not have enough information to confirm or reject realistic intervention effects. Nine single trials showed statistically significant results on our outcomes, but were underpowered to confirm or reject realistic intervention effects. Due to lack of data, it was not relevant to perform network meta-analysis or possible to perform individual patient data meta-analyses.ConclusionsNo evidence-based treatment for COVID-19 currently exists. Very low certainty evidence indicates that corticosteroids might reduce the risk of death, serious adverse events, and mechanical ventilation; that remdesivir might reduce the risk of serious adverse events; that intravenous immunoglobin might reduce the risk of death and serious adverse events; that tocilizumab might reduce the risk of serious adverse events and mechanical ventilation; and that bromhexine might reduce the risk of non-serious adverse events. More trials with low risks of bias and random errors are urgently needed. This review will continuously inform best practice in treatment and clinical research of COVID-19.Systematic review registrationPROSPERO CRD42020178787.

BackgroundCoronavirus disease 2019 (COVID-19) is a rapidly spreading disease that has caused extensive burden to individuals, families, countries, and the world. Effective treatments of COVID-19 are urgently needed.Methods and findingsThis is the first edition of a living systematic review of randomized clinical trials comparing the effects of all treatment interventions for participants in all age groups with COVID-19. We planned to conduct aggregate data meta-analyses, trial sequential analyses, network meta-analysis, and individual patient data meta-analyses. Our systematic review is based on Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) and Cochrane guidelines, and our 8-step procedure for better validation of clinical significance of meta-analysis results. We performed both fixed-effect and random-effects meta-analyses. Primary outcomes were all-cause mortality and serious adverse events. Secondary outcomes were admission to intensive care, mechanical ventilation, renal replacement therapy, quality of life, and nonserious adverse events. We used Grading of Recommendations Assessment, Development and Evaluation (GRADE) to assess the certainty of evidence. We searched relevant databases and websites for published and unpublished trials until August 7, 2020. Two reviewers independently extracted data and assessed trial methodology. We included 33 randomized clinical trials enrolling a total of 13,312 participants. All trials were at overall high risk of bias. We identified one trial randomizing 6,425 participants to dexamethasone versus standard care. This trial showed evidence of a beneficial effect of dexamethasone on all-cause mortality (rate ratio 0.83; 95% confidence interval [CI] 0.75-0.93; p < 0.001; low certainty) and on mechanical ventilation (risk ratio [RR] 0.77; 95% CI 0.62-0.95; p = 0.021; low certainty). It was possible to perform meta-analysis of 10 comparisons. Meta-analysis showed no evidence of a difference between remdesivir versus placebo on all-cause mortality (RR 0.74; 95% CI 0.40-1.37; p = 0.34, I2 = 58%; 2 trials; very low certainty) or nonserious adverse events (RR 0.94; 95% CI 0.80-1.11; p = 0.48, I2 = 29%; 2 trials; low certainty). Meta-analysis showed evidence of a beneficial effect of remdesivir versus placebo on serious adverse events (RR 0.77; 95% CI 0.63-0.94; p = 0.009, I2 = 0%; 2 trials; very low certainty) mainly driven by respiratory failure in one trial. Meta-analyses and trial sequential analyses showed that we could exclude the possibility that hydroxychloroquine versus standard care reduced the risk of all-cause mortality (RR 1.07; 95% CI 0.97-1.19; p = 0.17; I2 = 0%; 7 trials; low certainty) and serious adverse events (RR 1.07; 95% CI 0.96-1.18; p = 0.21; I2 = 0%; 7 trials; low certainty) by 20% or more, and meta-analysis showed evidence of a harmful effect on nonserious adverse events (RR 2.40; 95% CI 2.01-2.87; p < 0.00001; I2 = 90%; 6 trials; very low certainty). Meta-analysis showed no evidence of a difference between lopinavir-ritonavir versus standard care on serious adverse events (RR 0.64; 95% CI 0.39-1.04; p = 0.07, I2 = 0%; 2 trials; very low certainty) or nonserious adverse events (RR 1.14; 95% CI 0.85-1.53; p = 0.38, I2 = 75%; 2 trials; very low certainty). Meta-analysis showed no evidence of a difference between convalescent plasma versus standard care on all-cause mortality (RR 0.60; 95% CI 0.33-1.10; p = 0.10, I2 = 0%; 2 trials; very low certainty). Five single trials showed statistically significant results but were underpowered to confirm or reject realistic intervention effects. None of the remaining trials showed evidence of a difference on our predefined outcomes. Because of the lack of relevant data, it was not possible to perform other meta-analyses, network meta-analysis, or individual patient data meta-analyses. The main limitation of this living review is the paucity of data currently available. Furthermore, the included trials were all at risks of systematic errors and random errors.ConclusionsOur results show that dexamethasone and remdesivir might be beneficial for COVID-19 patients, but the certainty of the evidence was low to very low, so more trials are needed. We can exclude the possibility of hydroxychloroquine versus standard care reducing the risk of death and serious adverse events by 20% or more. Otherwise, no evidence-based treatment for COVID-19 currently exists. This review will continuously inform best practice in treatment and clinical research of COVID-19.

Background: To evaluate the effects and safety profile of Paroxetine on hot - flashes in post - menopausal women. Methods: It was prospective open label control clinical trial. This study is conducted in the Department of pharmacology & Therapeutics in collaboration with the Department of Obstetrics & Gynecology JPMC. The patients were selected from outpatients department (OPD) of Obstetrics & Gynecology. Duration of the study was 12 month from January 2014 to January 2015. Enrolling 180 outpatients who had menopause with hot flushes divided into three groups. The Greene Climacteric Score Scaling was applied to observe the effects of 12.5mg, 20mg Paroxetine on frequency of hot flashes as compared to Placebo. Results: Mean GCS scoring frequency in 12.5mg Paroxetine group at 12 week was 1.97±0.31 and the baseline 2.64±0.29. In 20mg Paroxetine mean GCS at baseline was 2.76±0.23 and 12 week 2.04±0.12. Where as in Placebo mean GCS scoring frequency at 12 week was 2.80±0.24 and at baseline 2.76±0.24. Conclusion: The frequency of hot flashes with Paroxetine 20mg and 12.5mg, is significantly reduced in post menopauseal women as compared to Placebo.