Characteristics and clinical outcomes of patients with pre-delta, delta and omicron SARS-CoV-2 infection in Indonesia (2020-2023): a multicentre prospective cohort study.

Background: Limited data exist from southeast Asia on the impact of SARS-CoV-2 variants and inactivated vaccines on disease severity and death among patients hospitalised with COVID-19. Methods: A multicentre hospital-based prospective cohort was enrolled from September 2020 through January 2023, spanning pre-delta, delta, and omicron periods. The participant hospitals were conveniently sampled based on existing collaborations, site willingness and available study resources, and included six urban and two rural general hospitals from East Nusa Tenggara, Jakarta, and North Sumatra provinces. Factors associated with severe disease and day-28 mortality were examined using logistic and Cox regression. Findings: Among 822 participants, the age-adjusted percentage of severe disease was 26.8% (95% CI 22.7-30.9) for pre-delta, 50.1% (44.0-56.2) for delta, and 15.2% (9.7-20.7) for omicron. The odds of severe disease were 64% (18-84%) lower for omicron than delta (p < 0.001). One or more vaccine doses reduced the odds of severe disease by 89% (65-97%) for delta and 98% (91-100%) for omicron. Age-adjusted mortality was 11.9% (8.8-15.0) for pre-delta, 24.4% (18.8-29.9) for delta and 9.6% (5.2-14.0) for omicron. The day-28 cumulative incidence of death was lower for omicron (9.2% [5.6-13.9%]) than delta (28.6% [22.0-35.5%]) (p < 0.001). Severe disease on admission was the predominant prognostic factor for death (aHR34.0 [16.6-69.9] vs mild-or-moderate; p < 0.001). After controlling for disease severity on admission as an intermediate, the risk of death was 48% (32-60%) lower for omicron than delta (p < 0.001); and 51% (38-61%; p < 0.001) lower for vaccinated participants than unvaccinated participants overall, and 56% (37-69%; p < 0.001) for omicron, 46% (-5 to 73%; p = 0.070) for pre-delta (not estimable for delta). Interpretation: Infections by omicron variant resulted in less severe and fatal outcomes than delta in hospitalised patients in Indonesia. However, older, and unvaccinated individuals remained at greater risk of adverse outcomes. Funding: University of Oxford and Wellcome Trust.

Efficacy of telemedicine-based antimicrobial stewardship program to combat antimicrobial resistance: A systematic review and meta-analysis.

INTRODUCTION: Antimicrobial resistance (AMR) is a major public health threat. Improving antimicrobial use is the main strategy against AMR, but it is challenging to implement especially in low-resource settings. Thus, this review aims to explore the efficacy of telehealth-based antimicrobial stewardship programs (ASP), which is more accessible. METHODS: Registered to PROSPERO and following PRISMA guidelines, literature search was performed in databases including PubMed, Scopus, Cochrane, Science Direct, EBSCOhost, EMBASE, and Google Scholar, searching for studies implementing telehealth ASP. Critical appraisal of studies was performed using Newcastle-Ottawa Scale for Cohort Studies (NOS), Cochrane Risk-of-Bias tool (RoB) 2.0, and Risk Of Bias In Non-randomised Studies-of Interventions (ROBINS-I). We utilized inverse variance, random effects model to obtain the pooled odds ratio (OR) and mean difference (MD) estimates, as well as sensitivity and subgroup analysis. RESULTS AND DISCUSSION: The search yielded 14 studies. Telehealth-based ASP was associated with better adherence to guidelines (pooled OR: 2.78 [95%CI:1.29-5.99], p = 0.009; I2 = 93%), within which streamlining yielded better odds (pooled OR: 30.54 [95%CI:10.42-89.52], p < 0.001) more than the compliance with policy subgroup (pooled OR: 1.60 [95%CI:1.02-2.51], p = 0.04). The odds of antimicrobial prescription rate reduced significantly (pooled OR: 0.60 [95%CI:0.42-0.85], p = 0.005; I2 = 94%), especially for the lower respiratory infection subgroup (pooled OR: 0.37 [95%CI:0.28-0.49], p < 0.001). Days of therapy decreased (pooled MD: -47.12 [95%CI: -85.78- -8.46], p = 0.02; I2 = 100%), with the greatest effect in acute care settings (pooled MD: -97.73 [95%CI:-147.48-47.97], p = 0.0001). Mortality did not change significantly (pooled OR: 1.20 [95%CI:0.69-2.10], p = 0.52; I2 = 63%). CONCLUSION: Telehealth-based ASP was proven beneficial to increase adherence to guideline and reduce prescription rates, without significantly affecting patient clinical outcome. After further studies, we recommend more widespread use of telemedicine to combat AMR.

Global knowledge gaps on antimicrobial resistance in the human health sector: A scoping review.

OBJECTIVES: To identify and summarize existing global knowledge gaps on antimicrobial resistance (AMR) in human health, focusing on the World Health Organization (WHO) bacterial priority pathogens, Mycobacterium tuberculosis, and selected fungi. METHODS: We conducted a scoping review of gray and peer-reviewed literature, published in English from January 2012 through December 2021, that reported on the prevention, diagnosis, treatment, and care of drug-resistant infections. We extracted relevant knowledge gaps and, through an iterative process, consolidated those into thematic research questions. RESULTS: Of 8409 publications screened, 1156 were included, including 225 (19.5%) from low- and middle-income countries. A total of 2340 knowledge gaps were extracted, in the following areas: antimicrobial research and development, AMR burden and drivers, resistant tuberculosis, antimicrobial stewardship, diagnostics, infection prevention and control, antimicrobial consumption and use data, immunization, sexually transmitted infections, AMR awareness and education, policies and regulations, fungi, water sanitation and hygiene, and foodborne diseases. The knowledge gaps were consolidated into 177 research questions, including 78 (44.1%) specifically relevant to low- and middle-income countries and 65 (36.7%) targeting vulnerable populations. CONCLUSION: This scoping review presents the most comprehensive compilation of AMR-related knowledge gaps to date, informing a priority-setting exercise to develop the WHO Global AMR Research Agenda for the human health sector.

Knowledge, attitude, and practice related to the COVID-19 pandemic among undergraduate medical students in Indonesia: A nationwide cross-sectional study.

INTRODUCTION: The potential role of medical students in raising awareness during public health emergencies has been acknowledged. To further explore their potentials as public educators and role models for the communities during the coronavirus disease 2019 (COVID-19) pandemic, this study aims to assess the knowledge, attitude, and practice of these students toward COVID-19. METHODS: An online cross-sectional survey was conducted among undergraduate medical students in Indonesia. Socio-demographics characteristics, social interaction history, information-seeking behavior, as well as knowledge, attitude, and practice toward COVID-19 were collected through a self-reported questionnaire. A p-value of <0.05 indicated statistical significance. RESULTS: Out of 4870 respondents, 64.9% had positive attitude and 51.5% had positive practice toward COVID-19, while only 29.8% had adequate knowledge. Knowledge was slightly positively correlated with attitude and practice (ρ = 0.074 and ρ = 0.054, respectively; both p<0.001), while attitude was weakly correlated with practice (ρ = 0.234, p<0.001). Several factors including age, sex, place of residence, institution type, academic level, family income, history of chronic illness, prior volunteering experience, and perceptual awareness on COVID-19 were significantly associated with either knowledge, attitude, and/or practice toward COVID-19. Furthermore, health institution's and the government's press releases, as well as health expert opinions were deemed as the most reliable sources of COVID-19-related information-yet trivially none of these sources were associated with knowledge, attitude, and practice in the study population. CONCLUSION: Many undergraduate medical students in Indonesia had positive attitude and practice against COVID-19, yet only a few had adequate knowledge. This warrants further interventions to keep them updated with COVID-19 evidence to maximize their potentials in raising public awareness on COVID-19.

Detection of gestational diabetes mellitus by circulating plasma and serum microRNAs: A systematic review and meta-analysis.

BACKGROUND AND AIMS: The diagnostic performance of microRNAs (miRNAs), which have recently emerged as a potential early diagnostic tool capable of detecting gestational diabetes mellitus (GDM) in its early stages, has yet to be systematically investigated. This meta-analysis aims to investigate the diagnostic utility of circulating plasma or serum miRNAs in detecting GDM patients. METHODS: Eligible studies were included and assessed for risk of bias with the Quality Assessment of Diagnostic Accuracy Studies 2 tool. A bivariate meta-analysis using the hierarchical summary receiver operating characteristic model was performed to estimate the pooled diagnostic value of miRNAs. RESULTS: Twelve studies (32 index tests) cumulating a total of 1768 patients were included in the present study. The pooled sensitivity of miRNAs was 74.5% (95% confidence interval [CI]: 63.7-82.9) and the pooled specificity was 84.1% (95% CI: 76.8-89.3). The overall area under the curve was 0.869 (95% CI: 0.818-0.907) with a relatively narrow 95% confidence region and a wide 95% prediction region. CONCLUSION: miRNAs may emerge as a promising diagnostic tool in detecting GDM. Further cross-sectional cohort studies with larger sample sizes and more heterogeneous populations, and studies evaluating the accuracy of multiple miRNAs in diagnosing GDM are required to confirm our findings.

Optimizing antibiotic use in Indonesia: A systematic review and evidence synthesis to inform opportunities for intervention.

Background: A major driver of antimicrobial resistance (AMR) and poor clinical outcomes is suboptimal antibiotic use, although data are lacking in low-resource settings. We reviewed studies on systemic antibiotic use (WHO ATC/DDD category J01) for human health in Indonesia, and synthesized available evidence to identify opportunities for intervention. Methods: We systematically searched five international and national databases for eligible peer-reviewed articles, in English and Indonesian, published between 1 January 2000 and 1 June 2021 including: (1) antibiotic consumption; (2) prescribing appropriateness; (3) antimicrobial stewardship (AMS); (4) consumers' and providers' perceptions. Two independent reviewers included studies and extracted data. Study-level data were summarized using random-effects model meta-analysis for consumption and prescribing appropriateness, effect direction analysis for antimicrobial stewardship (AMS) interventions, and qualitative synthesis for perception surveys. (PROSPERO: CRD42019134641). Findings: Of 9323 search hits, we included 100 reports on antibiotic consumption (20), prescribing appropriateness (49), AMS interventions (13), and/or perception (25) (8 categorized in >1 domain). The pooled estimate of overall antibiotic consumption was 134.8 DDD per 100 bed-days (95%CI 82.5-187.0) for inpatients and 121.1 DDD per 1000 inhabitants per day (10.4-231.8) for outpatients. Ceftriaxone, levofloxacin, and ampicillin were the most consumed antibiotics in inpatients, and amoxicillin, ciprofloxacin, and cefadroxil in outpatients. Pooled estimates for overall appropriate prescribing (according to Gyssens method) were 33.5% (18.1-53.4) in hospitals and 49.4% (23.7-75.4) in primary care. Pooled estimates for appropriate prescribing (according to reference guidelines) were, in hospitals, 99.7% (97.4-100) for indication, 84.9% (38.5-98.0) for drug choice, and 6.1% (0.2-63.2) for overall appropriateness, and, in primary care, 98.9% (60.9-100) for indication, 82.6% (50.5-95.7) for drug choice and 10.5% (0.8-62.6) for overall appropriateness. Studies to date evaluating bundled AMS interventions, although sparse and heterogeneous, suggested favourable effects on antibiotic consumption, prescribing appropriateness, guideline compliance, and patient outcomes. Key themes identified in perception surveys were lack of community antibiotic knowledge, and common non-prescription antibiotic self-medication. Interpretation: Context-specific intervention strategies are urgently needed to improve appropriate antibiotic use in Indonesian hospitals and communities, with critical evidence gaps concerning the private and informal healthcare sectors. Funding: Wellcome Africa Asia Programme Vietnam.

Prehospital tele-electrocardiographic triage improves the management of acute coronary syndrome in rural populations: A systematic review and meta-analysis.

INTRODUCTION: Acute coronary syndrome (ACS) patients residing in rural areas are predisposed to higher risk of poor outcomes due to substantial delays in disease management, emphasising the importance of emerging telecardiology technologies in delivering emergency services in such settings. This meta-analysis aimed to investigate the impacts of prehospital telecardiology strategies on the clinical outcomes of rural ACS patients. METHODS: A literature search was performed of articles published up to April 2020 through six databases. Included studies were assessed for bias risk using the ROBINS-I tool, and a random-effects model was utilised to estimate effect sizes. Certainty of evidence was assessed using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE). RESULTS: Twelve studies with a total of 3989 patients were included in this review. Prehospital telecardiology in the form of tele-electrocardiography (tele-ECG) enabled prompt diagnosis and triage, resulting in a decreased door-to-balloon (DTB) time (mean difference = -25.53 minutes, 95% confidence interval (CI) -36.08 to -14.97 minutes; I2 = 98%), as well as lower in-hospital mortality (odds ratio (OR) = 0.57, 95% CI 0.36-0.92) and long-term mortality (OR = 0.52, 95% CI 0.39-0.69) rates, both with negligible heterogeneity (I2 = 0%). GRADE assessment yielded very low to moderate certainty of evidence.Conclusion Prehospital tele-ECG appeared to be an effective and worthwhile approach in the management of rural ACS patients, as shown by moderate quality evidence on lower long-term mortality. Given the uncertainties of the evidence quality on DTB time and in-hospital mortality, future studies with a higher quality of evidence are required to confirm our findings.

Does immune checkpoint inhibitor increase the risks of poor outcomes in COVID-19-infected cancer patients? A systematic review and meta-analysis.

BACKGROUND: The association between immune checkpoint inhibitor (ICI) and outcomes of cancer patients with coronavirus disease 2019 (COVID-19) infection has yet to be systematically evaluated. This meta-analysis aims to investigate the effects of ICI treatment on COVID-19 prognosis, including mortality, severity, and any other prognosis-related outcomes. METHODS: Eligible studies published up to 27 February 2021 were included and assessed for risk of bias using the Quality in Prognosis Studies tool. A random-effects meta-analysis was conducted to estimate the pooled effect size along with its 95% confidence intervals. The quality of body evidence was evaluated using the modified Grading of Recommendations Assessment, Development, and Evaluation framework. RESULTS: Eleven studies involving a total of 2826 COVID-19-infected cancer patients were included in the systematic review. We discovered a moderate-to-high quality of evidence that ICI was not associated with a higher mortality risk, while the other outcomes yielded a very low-to-low-evidence quality. Although our findings indicated that ICI did not result in a higher risk of severity and hospitalization, further evidence is required to confirm our findings. In addition, we discovered that prior exposure to chemoimmunotherapy may be linked with a higher risk of COVID-19 severity (OR 8.19 [95% CI: 2.67-25.08]; I2 = 0%), albeit with small sample size. CONCLUSION: Our findings indicated that ICI treatment should not be adjourned nor terminated during the current pandemic. Rather, COVID-19 vigilance should be increased in such patients. Further studies with larger cohorts and higher quality of evidence are required to substantiate our findings. TRIAL REGISTRATION NUMBER: This project has been prospectively registered at PROSPERO (registration ID: CRD42020202142) on 4 August 2020.

Indonesian medical frontliners during the coronavirus disease 2019 pandemic: Have we been protecting them enough?

BACKGROUND AND AIM: The coronavirus disease 2019 pandemic has brought deteriorating physical and mental burdens to health care workers (HCWs) in Indonesia, mainly attributed to the lack of protection and screening among HCWs, patients' concealment of their travel and medical history, and perceived social stigma and discrimination. Hence, we deliver our perspectives and recommendations based on the current situation in Indonesia to enforce their safeties. We encourage stakeholders to implement a systematic approach by employing stringent prevention strategies, ensuring adequate personal protective equipment (PPE) provision and equitable PPE distribution, and routine HCWs screening to prevent nosocomial clusters, in addition to the provision of psychosocial support to HCWs by offering social aids and psychological sessions. Furthermore, social stigma and discrimination toward HCWs and patients should also be addressed and mitigated, thus preventing concealments of patients' history and alleviating emotional burdens. We believe that providing continuous support to HCWs would lead to key benefits in ensuring a winning battle against the COVID-19 pandemic. RELEVANCE FOR PATIENTS: HCWs are pivotal players in winning the battle against the COVID- 19 pandemic. Ensuring their safety and well-being will enable them to deliver better healthcare services, thus resulting in mutual benefit for themselves, the patients, and the nation's recovery.

Safety and Pharmacokinetic Profiles of Long-Acting Injectable Antiretroviral Drugs for HIV-1 Pre-Exposure Prophylaxis: A Systematic Review and Meta-analysis of Randomized Trials.

Objectives: To investigate the safety and pharmacokinetic profiles of long-acting injectable pre-exposure prophylaxis (LAI PrEP), notably cabotegravir (CAB-LA) and rilpivirine (RPV-LA), for the prevention of human immunodeficiency virus-1 (HIV-1) infection. Methods: Eligible randomized trials of LAI PrEP in HIV-uninfected and/or healthy patients were included and assessed with the Revised Cochrane risk-of-bias tool for randomized trials. Where feasible, a meta-analysis was performed for safety outcomes by using a random-effects model with risk ratios and their 95% confidence intervals as the common effect measure. The protocol was registered with PROSPERO CRD42020154772. Results: Eight studies cumulating a total of 666 participants were included in this systematic review, including five (362 intervention-arm volunteers) and four trials (194 intervention-arm volunteers) that investigated CAB-LA and RPV-LA, respectively. We found that both CAB-LA and RPV-LA were generally well-tolerated as their safety profiles were similar to placebo in terms of any adverse event (AE), serious AE, and AE-related withdrawals. Furthermore, pharmacokinetic analyses revealed favorable prospects in viral inhibitory activity of CAB-LA and RPV-LA. Intramuscular (IM) injection of CAB-LA 600 mg Q8W was superior to CAB-LA 800 mg Q12W in male participants, while the same was true for RPV-LA 1200 mg IM Q8W over other dosing regimens. Although these results are promising, further research is required to confirm the findings on RPV-LA as current evidence is limited. Conclusion: CAB-LA and RPV-LA have promising safety and pharmacokinetic profiles. The preventive efficacy of these agents is being evaluated in Phase 3 trials.

Soil-transmitted helminth infection, anemia, and malnutrition among preschool-age children in Nangapanda subdistrict, Indonesia.

BACKGROUND: Soil-transmitted helminth (STH) infections are still prevalent in Indonesia, with roughly one-third of infected population being preschool-age children (PSC), which are generally at higher risk of morbidity such as malnutrition and anemia. This study aimed to investigate the association of STH infections with nutritional status and anemia among PSC in Nangapanda subdistrict, Ende, East Nusa Tenggara. METHODS: A cross-sectional survey involving PSC ranging from 12 to 59 months old from Nangapanda subdistrict, Ende district, East Nusa Tenggara was performed. Socio-demographic, breastfeeding, and complementary feeding information was obtained from structured questionnaires, while nutritional and anemia status was determined from anthropometry and hemoglobin measurements, respectively. Anthropometric z-scores were calculated based on the World Health Organization 2006 standards and stool samples were examined using Kato-Katz method. RESULTS: A total of 393 PSC randomly selected from 22 villages were examined. The prevalence of underweight, stunting, wasting, and anemia were 33.1%, 40.2%, 17.1%, and 60.3%, respectively. STH infection, predominated by Ascaris lumbricoides, was found in 160 (58.8%) PSC. Single STH infection, but not multiple infection, was independently associated with a lower risk of anemia (odds ratio [OR] 0.320, 95% confidence interval [CI]: 0.126-0.809, p = 0.016). Similar association with anemia was also found on mild STH infection (OR 0.318 [95% CI: 0.114-0.887], p = 0.029). On the other hand, younger children were found to have a higher risk of anemia and stunting. None of the examined variables were independently associated with underweight and wasting. CONCLUSION: STH infection as well as anemia and malnutrition were prevalent in this region. However in this study, current STH infections seemed to have minimal negative impact on children's nutritional status.

Is there a need to reconsider the use of metformin in COVID-19 patients with type 2 diabetes mellitus?

Introduction: Diabetes has been linked with poorer outcomes in coronavirus disease (COVID-19) patients. However, the question to whether continue or withdraw metformin therapy in COVID-19 patients with type 2 diabetes mellitus remains contentious. This study aims to investigate the association between metformin and poor COVID-19 outcomes. Methods: Eligible studies published up to 21 October 2020 were included and appraised for validity, importance, and applicability. The included studies were further ranked according to the level of evidence (LOE). Results: Nine studies were included for further assessments, of which seven studies stated that metformin was not associated with poor COVID-19 outcomes (LOE II-V), while the other two with poorer designs stated otherwise (LOE V). Although metformin may increase the risk of developing acidosis and lactic acidosis (LOE IV), the observed risks were more accentuated in patients with severe COVID-19 disease or kidney impairment and in patients with > 2 daily metformin doses. Interestingly, one study revealed that metformin may even yield therapeutic role in reducing the risk of COVID-19 mortality (LOE II), although further studies are required to confirm these findings. Conclusions: Our findings indicated that metformin may be safely continued in COVID-19 patients. The benefit of metformin therapy with simultaneous continuous monitoring of COVID-19 severity and kidney function may outweigh the risks of lactic acidosis, of which incidence is relatively rare. Supplementary Information: The online version contains supplementary material available at 10.1007/s13410-021-00924-w.

Willingness to volunteer and readiness to practice of undergraduate medical students during the COVID-19 pandemic: a cross-sectional survey in Indonesia.

BACKGROUND: The question to involve or restrict medical students' involvement in the coronavirus disease 2019 (COVID-19) pandemic response remains contentious. As their state of preparation and perceptions in volunteering during this pandemic have yet to be investigated, this study aims to evaluate Indonesian medical students' willingness to volunteer and readiness to practice during the COVID-19 pandemic. METHODS: A web-based survey was conducted among undergraduate medical students throughout Indonesia. Socio-demographic and social interaction information, in addition to willingness to volunteer and readiness to practice, were obtained using a self-reported questionnaire. The significance level was set at 5%. RESULTS: Among 4870 participants, 2374 (48.7%) expressed their willingness to volunteer, while only 906 (18.6%) had adequate readiness to practice. Male students, students with prior volunteering experience in health or non-health sectors, and students from public universities or living in Central Indonesia (vs Java) had higher scores of willingness and readiness to volunteer. Students from Sumatra also had better preparedness (odds ratio [OR] 1.56, 95% confidence interval [CI] 1.15-2.12, p = 0.004), while the opposite occurred for students from Eastern Indonesia (OR 0.63, 95% CI: 0.44-0.89, p = 0.002)-when compared to students from Java. In addition, compared to students with high family income, students from lower-middle income families were less willing to volunteer (OR 0.76, 95% CI: 0.59-0.98, p = 0.034), though those with low family income had better readiness (OR 1.51, 95% CI: 1.10-2.08, p = 0.011). Shortage of medical personnel, sense of duty, and solicitation by stakeholders were the main reasons increasing the students' willingness to volunteer; whereas contrarily fear for own's health, absence of a cure, and fear of harming patients were the primary factors diminishing their willingness to volunteer. CONCLUSION: Our findings indicated that many Indonesian medical students are willing to volunteer, yet only few of them were ready to practice, indicating that further preparations are required to maximize their potentials and minimize their exposure to hazards. We suggest that their potentials as a firm support system during the pandemic should not be overlooked, and that the integration of relevant courses to the medical curricula are imperative to prepare for future public health emergencies.

The effect of human immunodeficiency virus infection on adverse events during treatment of drug-resistant tuberculosis: A systematic review and meta-analysis.

BACKGROUND: Adverse events (AEs) during drug-resistant tuberculosis (DR-TB) treatment, especially with human immunodeficiency virus (HIV) co-infection, remains a major threat to poor DR-TB treatment adherence and outcomes. This meta-analysis aims to investigate the effect of HIV infection on the development of AEs during DR-TB treatment. METHODS: Eligible studies evaluating the association between HIV seropositivity and risks of AE occurrence in DR-TB patients were included in this systematic review. Interventional and observational studies were assessed for risk of bias using the Risk of Bias in Nonrandomized Studies of Intervention and Newcastle-Ottawa Scale tool, respectively. Random-effects meta-analysis was performed to estimate the pooled risk ratio (RR) along with their 95% confidence intervals (CIs). RESULTS: A total of 37 studies involving 8657 patients were included in this systematic review. We discovered that HIV infection independently increased the risk of developing AEs in DR-TB patients by 12% (RR 1.12 [95% CI: 1.02-1.22]; I2 = 0%, p = 0.75). In particular, the risks were more accentuated in the development of hearing loss (RR 1.44 [95% CI: 1.18-1.75]; I2 = 60%), nephrotoxicity (RR 2.45 [95% CI: 1.20-4.98], I2 = 0%), and depression (RR 3.53 [95% CI: 1.38-9.03]; I2 = 0%). Although our findings indicated that the augmented risk was primarily driven by antiretroviral drug usage rather than HIV-related immunosuppression, further studies investigating their independent effects are required to confirm our findings. CONCLUSION: HIV co-infection independently increased the risk of developing AEs during DR-TB treatment. Increased pharmacovigilance through routine assessments of audiological, renal, and mental functions are strongly encouraged to enable prompt diagnosis and treatment in patients experiencing AEs during concomitant DR-TB and HIV treatment.

Proximal fibular osteotomy for the management of medial compartment knee osteoarthritis: A systematic review and meta-analysis.

BACKGROUND: The promising prospects of proximal fibular osteotomy (PFO) as an alternative treatment of knee osteoarthritis (KOA), which has gained popularity in recent years, has yet to be systematically evaluated. Hence, this meta-analysis aims to critically assess the clinical and radiological outcome of PFO in the management of medial compartment KOA. METHODS: Literature searches through PubMed, Scopus, CENTRAL, CINAHL, Google Scholar, and ProQuest databases were conducted, searching for eligible studies published from inception up to April 2020. Risk of bias assessments of randomized trials were performed via Cochrane RoB 2, while those of non-randomized studies with ROBINS-I tool. Random-effects model was utilized to estimate effect sizes. RESULTS: A total of 907 patients and 1012 knees were included in this meta-analysis. PFO successfully ameliorated patients' knee function (Hedges' g 1.90; 95% confidence interval (CI) 1.62-2.18; I2 = 67%) and pain (visual analog scale: mean difference (MD) -4.13; 95% CI: -5.29 to -2.97), and also resulted in minimal complication rates, with peroneal nerve paresthesia being the most prevalent adverse event (5.93%; 95% CI: 2.15-11.25%), followed by peroneal nerve palsy (2.25%; 95% CI: 0.14-6.14%), fracture (0.56%; 95% CI: 0-1.74%), and recurrent deformity (0.54%; 95% CI: 0-1.74%). Furthermore, PFO was also associated with improved medial/lateral joint space ratio (MD 0.17; 95% CI: 0.15-0.19). CONCLUSION: PFO yielded promising prospects in the management of medial compartment KOA, as shown by substantial improvements in clinical and radiological outcomes. However, considering the low quality of evidence, further studies with more diverse populations and higher quality of body evidence are required to confirm these findings.

High admission blood glucose independently predicts poor prognosis in COVID-19 patients: A systematic review and dose-response meta-analysis.

AIMS: To investigate the prognostic value of admission blood glucose (BG) in predicting COVID-19 outcomes, including poor composite outcomes (mortality/severity), mortality, and severity. METHODS: Eligible studies evaluating the association between admission fasting BG (FBG) and random BG (RBG) levels with COVID-19 outcomes were included and assessed for risk of bias with the Quality in Prognosis Studies tool. Random-effects dose-response meta-analysis was conducted to investigate potential linear or non-linear exposure-response gradient. RESULTS: The search yielded 35 studies involving a total of 14,502 patients. We discovered independent association between admission FBG and poor COVID-19 prognosis. Furthermore, we demonstrated non-linear relationship between admission FBG and severity (Pnon-linearity < 0.001), where each 1 mmol/L increase augmented the risk of severity by 33% (risk ratio 1.33 [95% CI: 1.26-1.40]). Albeit exhibiting similar trends, study scarcity limited the evidence strength on the independent prognostic value of admission RBG. GRADE assessment yielded high-quality evidence for the association between admission FBG and COVID-19 severity, and moderate-quality evidence for its association with mortality and poor outcomes. CONCLUSION: High admission FBG level independently predicted poor COVID-19 prognosis. Further research to confirm the prognostic value of admission RBG and to ascertain the estimated dose-response risk between admission FBG and COVID-19 severity are required.

Telestroke strategies to enhance acute stroke management in rural settings: A systematic review and meta-analysis.

BACKGROUND: The potential of telestroke implementation in resource-limited areas has yet to be systematically evaluated. This study aims to investigate the implementation of telestroke on acute stroke care in rural areas. METHODS: Eligible studies published up to November 2019 were included in this study. Randomized trials were further evaluated for risk of bias with Cochrane RoB 2, while nonrandomized studies with ROBINS-I tool. Random effects model was utilized to estimate effect sizes, and the certainty of evidence was assessed using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) tool. RESULTS: The search yielded 19 studies involving a total of 28,496 subjects, comprising of prehospital and in-hospital telestroke interventions in the form of mobile stroke units and hub-and-spoke hospitals network, respectively. Telestroke successfully increased the proportion of patients treated ≤3 hr (OR 2.15; 95% CI 1.37-3.40; I2  = 0%) and better three-month functional outcome (OR 1.29; 95% CI 1.01-1.63; I2  = 44%) without increasing symptomatic intracranial hemorrhage rate (OR 1.27; 0.65-2.49; I2  = 0%). Furthermore, telestroke was also associated with shorter onset-to-treatment time (mean difference -27.97 min; 95% CI -35.51, -20.42; I2  = 63%) and lower in-hospital mortality rate (OR 0.67; 95% CI 0.52-0.87; I2  = 0%). GRADE assessments yielded low-to-moderate certainty of body evidences. CONCLUSION: Telestroke implementation in rural areas was associated with better clinical outcomes as compared to usual care. Its integration in both prehospital and in-hospital settings could help optimize emergency stroke approach. Further studies with higher-level evidence are needed to confirm these findings.

Alpha-Mangostin Improves Cardiac Hypertrophy and Fibrosis and Associated Biochemical Parameters in High-Fat/High-Glucose Diet and Low-Dose Streptozotocin Injection-Induced Type 2 Diabetic Rats.

PURPOSE: The aim of present study was to analyze the effect of alpha-mangostin on cardiac hypertrophy and fibrosis and biochemical parameters in high-fat/high-glucose diet and low-dose streptozotocin injection (HF/HG/STZ)-induced type 2 diabetic rats. METHODS: Diabetes was induced in male Wistar rats by giving a combination of high-fat/high-glucose (HF/HG) diet for 3 weeks and followed by low-dose streptozotocin intraperitoneal injection (STZ; 35 mg/kg) at Week-3 and the HF/HG diet was continued until 8 weeks. The diabetic rats were then divided into four groups (each, n=6): untreated diabetic group (HF/HG/STZ); diabetic group treated with metformin 200 mg/kg/day (HF/HG/STZ+Metformin); diabetic group treated with alpha-mangostin 100 mg/kg/day (HF/HG/STZ+AM100); and diabetic group treated with alpha-mangostin 200 mg/kg/day (HF/HG/STZ+AM200) and all were given by oral gavage for 8 weeks. We also included a control group (C) treated with AM200 (C+AM200). The role of alpha-mangostin was assessed through its effect on blood glucose levels, HOMA-IR, blood pressure, body weight, pro-inflammatory cytokines in cardiac tissue, serum aminotransferases (ALT and AST), lipid profiles (cholesterol and triglyceride), blood urea nitrogen (BUN), uric acid, cardiac hypertrophy and fibrosis. RESULTS: Diabetic rats treated with alpha-mangostin in both doses for 8 weeks showed decrease in blood glucose levels, HOMA-IR, and blood pressure. Alpha-mangostin treatment also prevented HF/HG/STZ-induced changes in the activities of ALT, AST, BUN, uric acid, lipid profiles, and pro-inflammatory cytokines, which were comparable with the standard drug metformin, while alpha-mangostin did not show any significant effects on control rats (p>0.05). The cardiac hypertrophy and fibrosis were also attenuated in diabetic rats treated with alpha-mangostin in both doses. CONCLUSION: These data suggest that administration of alpha-mangostin can effectively attenuate diabetes-induced alteration in cardiac hypertrophy and fibrosis as well as biochemical parameters in HF/HG/STZ rats.