Clinical features and outcomes of COVID-19 patients with concomitant herpesvirus co-infection or reactivation: A systematic review.

Background: Since the first case of COVID-19 was diagnosed in Wuhan, China in late 2019, concomitant infections with Herpesviridae were documented that were presented from simple skin manifestations to severe life-threatening conditions that may lead to mortality. In this systematic review, we have included studies conducted in different parts of the world to find out the association of clinical features and outcomes of COVID-19 infection and concomitant Herpesviridae infection. Methods: A comprehensive search was conducted in electronic databases including Medline through PubMed, Cochrane database, Scopus and Web of science (core collection). Two review authors independently screened the articles and extracted data. The Risk of bias assessment was done by using RoBANS tool. Results: A total of 919 studies were retrieved and 19 studies were included having data of 539 patients who were infected with both COVID-19 and Herpesviridae. Herpes Simplex-1, Varicella Zoster, Cytomegalovirus, Epstein-Barr virus and Human Herpes Virus-6 were the detected viruses in the included studies. Cytomegalovirus (CMV) reactivation was the most detected concomitant infection. In case of reactivation with more than one Herpes virus mortality among patients were detected along with single viral infection in some studies. Significant association was noted in dosage and usage of steroid and Herpesviridae reactivation in COVID-19 patients. Blood markers such as D-dimer, CRP along with length of stay in the ICU and usage of invasive mechanical ventilation were found to be the significantly associated markers. Conclusion: Findings from this study will aid clinicians to assess and treat COVID-19 cases with co-infections.

Association of HLA gene polymorphisms with Helicobacter pylori related gastric cancer-a systematic review.

The appropriate host cell immune responses for the progression of several diseases, including gastric or stomach cancer (GC), are significantly influenced by HLA polymorphisms. Our objective was to systematically review the evidence linking HLA polymorphisms with the risk of Helicobacter. pylori related GC. We conducted a comprehensive literature search to identify studies published between 2000 and April 2023 on the association of HLA polymorphisms with H. pylori related GC using databases such as Medline through PubMed, Embase, Web of Science (core collection), The Cochrane Library, and Scopus. Two authors independently screened articles, extracted data, and assessed the risk of bias using the Risk of Bias Assessment tool for Non-randomized Studies. From 7872 retrieved studies, 19 met inclusion criteria, encompassing 1656 cases and 16,787 controls across four World Health Organization regions, with Japan contributing the most studies. We explored HLA-A/B/C, HLA-DRB1/DQA1/DQB1, HLA-G, and MICA alleles. Of 29 significant HLA polymorphisms identified, 18 showed a positive association with GC, whereas 11 were negatively associated. HLA-DQB1*06 allele was most frequently associated to susceptibility, as reported in four studies, followed by HLA-DRB1*04 and HLA-DQA1*01, each reported in two studies. Conversely, HLA-G*01, HLA-DQA1*01, HLA-DQA1*05, and HLA-DQB1*03 were identified as protective in two studies each. Additionally, five genotypes and six haplotypes were reported as positive, whereas three genotypes and two haplotypes were negative factors for the disease incidence or mortality. Despite heterogeneity in the study population and types of HLA polymorphisms examined, our analysis indicates certain polymorphisms are associated with H. pylori related GC progression and mortality in specific populations.

A qualitative exploration of purchasing, stockpiling, and use of drugs during the COVID-19 pandemic in an urban city of Bangladesh.

Objectives: This research was conducted to explore the patterns and behavior of panic purchasing, stockpiling, and use of drugs during COVID-19 in the Sylhet city, Bangladesh. Study design: The study adopted qualitative exploratory research design. Methods: 25 in-depth interviews with drug sellers and clients and 7 key informant interviews were conducted with pharmacists and medical representatives of pharmaceutical companies in Sylhet city in Bangladesh from October 2020 to March 2021. Thematic analysis was used to evaluate the primary data. Results: The findings revealed that individuals sought out, purchased, and stockpiled prescription-only drugs for self-medication purposes during the COVID-19 pandemic. News and rumor spread by social media, television, and everyday interactions concerning the severity of infections and the number of deaths caused an increase in self-medication as a preventive measure. The reason for this panic buying of drugs was identified as a fear of drug shortages, price hikes, the rise of infection, and the availability of medicines and home delivery services during the pandemic. Conclusion: The purchasing, stockpiling and use of drugs by pharmacies varied based on the person dispensing the drugs, the customer, and the COVID-19 pandemic situation. Furthermore, the role of social media in spreading rumor and (dis) misinformation about drug use, a greater tendency to self-medicate, and poor regulation, influenced the individual's use of drugs. Therefore, the drug regulatory authorities and policymakers need to consider the real level of local drug use in order to encourage more rational use of drugs which will help to ensure that there is reliable access to safe, effective, and high-quality medicines and vaccines for all.

Monitoring and evaluation practices and operational research during public health emergencies in southeast Asia region (2012-2022) - a systematic review.

This systematic review aimed to explore the monitoring and evaluation (M&E) and operational research (OR) practices during public health emergencies (PHE) in the southeast Asian region (SEAR) over the last decade. We searched electronic databases and grey literature sources for studies published between 2012 and 2022. The studies written in English were included, and a narrative synthesis was undertaken. A total of 29 studies were included in this review. Among these 25 studies documented M&E and four studies documented OR practices. The majority of the studies were from India and Bangladesh, with no evidence found from Sri Lanka, Bhutan, Myanmar, and Timor-Leste. M&E of surveillance programs were identified among which PHE due to COVID-19 was most prevalent. M&E was conducted in response to COVID-19, cholera, Nipah, Ebola, Candida auris, and hepatitis A. OR practice was minimal and reported from India and Indonesia. India conducted OR on COVID-19 and malaria, whereas Indonesia focused on COVID-19 and influenza. While most SEAR countries have mechanisms for conducting M&E, there is a noticeable limitation in OR practices. There is a compelling need to develop a standard framework for M&E. Additionally, enhancing private sector engagement is crucial for strengthening preparedness against PHE. Furthermore, there is a necessity to increase awareness about the importance of conducting M&E and OR during PHE.

Oral killed cholera vaccines for preventing cholera.

BACKGROUND: Cholera causes acute watery diarrhoea and death if not properly treated. Outbreaks occur in areas with poor sanitation, including refugee camps. Several vaccines have been developed and tested over the last 50 years. This is an update of a Cochrane review, originally published in 1998, which explored the effects of all vaccines for preventing cholera. This review examines oral vaccines made from killed bacteria. OBJECTIVES: To assess the effectiveness and safety of the available World Health Organization (WHO)-prequalified oral killed cholera vaccines among children and adults. SEARCH METHODS: We searched the Cochrane Infectious Diseases Group Specialized Register; CENTRAL, MEDLINE; Embase; LILACS; and two trials registers (February 2023). SELECTION CRITERIA: We included randomized controlled trials (RCTs), including cluster-RCTs. There were no restrictions on the age and sex of the participants or the setting of the study. We considered any available WHO-prequalified oral killed cholera vaccine as an intervention. The control group was given a placebo, another vaccine, or no vaccine. The outcomes were related to vaccine effectiveness and safety. We included articles published in English only. DATA COLLECTION AND ANALYSIS: Two review authors independently applied the inclusion criteria and extracted data from included studies. We assessed the risk of bias using the Cochrane ROB 1 assessment tool. We used the generic inverse variance and a random-effects model meta-analysis to estimate the pooled effect of the interventions. We assessed the certainty of the evidence using the GRADE approach. For vaccine effectiveness (VE), we converted the overall risk ratio (RR) to vaccine effectiveness using the formula: VE = (1 - RR) x 100%. MAIN RESULTS: Five RCTs, reported in 12 records, with 462,754 participants, met the inclusion criteria. We identified trials on whole-cell plus recombinant vaccine (WC-rBS vaccine (Dukoral)) from Peru and trials on bivalent whole-cell vaccine (BivWC (Shanchol)) vaccine from India and Bangladesh. We did not identify any trials on other BivWC vaccines (Euvichol/Euvichol-Plus), or Hillchol. Two doses of Dukoral with or without a booster dose reduces cases of cholera at two-year follow-up in a general population of children and adults, and at five-month follow-up in an adult male population (overall VE 76%; RR 0.24, 95% confidence interval (CI) 0.08 to 0.65; 2 trials, 16,423 participants; high-certainty evidence). Two doses of Shanchol reduces cases of cholera at one-year follow-up (overall VE 37%; RR 0.63, 95% CI 0.47 to 0.85; 2 trials, 241,631 participants; high-certainty evidence), at two-year follow-up (overall VE 64%; RR 0.36, 95% CI 0.16 to 0.81; 2 trials, 168,540 participants; moderate-certainty evidence), and at five-year follow-up (overall VE 80%; RR 0.20, 95% CI 0.15 to 0.26; 1 trial, 54,519 participants; high-certainty evidence). A single dose of Shanchol reduces cases of cholera at six-month follow-up (overall VE 40%; RR 0.60, 95% CI 0.47 to 0.77; 1 trial, 204,700 participants; high-certainty evidence), and at two-year follow-up (overall VE 39%; RR 0.61, 95% CI 0.53 to 0.70; 1 trial, 204,700 participants; high-certainty evidence). A single dose of Shanchol also reduces cases of severe dehydrating cholera at six-month follow-up (overall VE 63%; RR 0.37, 95% CI 0.28 to 0.50; 1 trial, 204,700 participants; high-certainty evidence), and at two-year follow-up (overall VE 50%; RR 0.50, 95% CI 0.42 to 0.60; 1 trial, 204,700 participants; high-certainty evidence). We found no differences in the reporting of adverse events due to vaccination between the vaccine and control/placebo groups. AUTHORS' CONCLUSIONS: Two doses of Dukoral reduces cases of cholera at two-year follow-up. Two doses of Shanchol reduces cases of cholera at five-year follow-up, and a single dose of Shanchol reduces cases of cholera at two-year follow-up. Overall, the vaccines were safe and well-tolerated. We found no trials on other BivWC vaccines (Euvichol/Euvichol-Plus). However, BivWC products (Shanchol, Euvichol/Euvichol-Plus) are considered to produce comparable vibriocidal responses. Therefore, it is reasonable to apply the results from Shanchol trials to the other BivWC products (Euvichol/Euvichol-Plus).

Counter-on-chip for bacterial cell quantification, growth, and live-dead estimations.

Quantifying bacterial cell numbers is crucial for experimental assessment and reproducibility, but the current technologies have limitations. The commonly used colony forming units (CFU) method causes a time delay in determining the actual numbers. Manual microscope counts are often error-prone for submicron bacteria. Automated systems are costly, require specialized knowledge, and are erroneous when counting smaller bacteria. In this study, we took a different approach by constructing three sequential generations (G1, G2, and G3) of counter-on-chip that accurately and timely count small particles and/or bacterial cells. We employed 2-photon polymerization (2PP) fabrication technology; and optimized the printing and molding process to produce high-quality, reproducible, accurate, and efficient counters. Our straightforward and refined methodology has shown itself to be highly effective in fabricating structures, allowing for the rapid construction of polydimethylsiloxane (PDMS)-based microfluidic devices. The G1 comprises three counting chambers with a depth of 20 µm, which showed accurate counting of 1 µm and 5 µm microbeads. G2 and G3 have eight counting chambers with depths of 20 µm and 5 µm, respectively, and can quickly and precisely count Escherichia coli cells. These systems are reusable, accurate, and easy to use (compared to CFU/ml). The G3 device can give (1) accurate bacterial counts, (2) serve as a growth chamber for bacteria, and (3) allow for live/dead bacterial cell estimates using staining kits or growth assay activities (live imaging, cell tracking, and counting). We made these devices out of necessity; we know no device on the market that encompasses all these features.

Gut microbiota shifts favorably with delivery of handwashing with soap and water treatment intervention in a prospective cohort (CHoBI7 trial).

BACKGROUND: Cholera can result in the expulsion of important microbiota from the gut and result in death if left untreated. The disease transmits mainly via drinking water carrying Vibrio cholerae; and household contacts (HHC) of cholera patients are at elevated risk during the first week of infection. The gut microbiota profiles of HHC-children of cholera patients at Dhaka city slums were investigated before (day 0) and after (day 8) delivery of chlorinated water as part of the major study 'CHoBI7 trial (cholera-hospital-based intervention for 7 days)'. RESULT: Results of sequencing and analysis of bacterial community DNA revealed the predominance of two bacterial phyla: Bacteroidetes and Firmicutes at day 0 with a relative abundance of 62 ± 6 (mean ± SEM%) and 32 ± 7, respectively. The pattern reversed at day 8 with a decreased relative abundance of Bacteroidetes (39 ± 12; p = 0.034) and an increased abundance of Firmicutes (49 ± 12; p = 0.057). Of 65 bacterial families confirmed at day 0, six belonging to Proteobacteria including Vibrionaceae disappeared at day 8. Interestingly, the relative abundance of four Firmicutes families-Lachnospiraceae, Bifidobacteriaceae, Clostridiaceae, and Ruminococcaceae was increased in all five study children at day 8. CONCLUSION: The observed exclusion of pathogenic Proteobacteria and enhancement of beneficial Firmicutes in the gut of children delivered with chlorinated water as part of WASH intervention reflect a great promise of the CHoBI7 program in preventing cholera and improving child health.

Association of psychological factors with advanced-level functional competency: Findings from the Aichi workers' cohort study, 2002-2019.

Objective: This study examined the longitudinal association of perceived stress, ikigai, and having someone one can count on in middle age with the advanced-level functional competency in older age, which is crucial for the maintenance of independent life among older adults. The issue is especially relevant in super-aged countries like contemporary Japan, where more and more older people live in a household consisting only of older people. Methods: Data were collected in 2019 from a total of 1692 retirees of the Aichi Workers' Cohort Study participants in which baseline survey including psychological factors was conducted during their employment in 2002. Japan Science and Technology Agency Index of Competence (JST-IC) was used to measure the advanced-level functional competency. Multivariable-adjusted odds ratios (ORs) were obtained for having low JST-IC in later life by the degrees of psychological factors reported in the middle age adjusting for the presence of depressive mood in 2019. Results: Those who were not sure about ikigai (OR: 2.02, 95 % CI: 1.33 to 3.08) and who have no one to count on (OR: 2.19, 95 % CI: 1.52 to 3.16) in the middle age were significantly associated with low JST-IC after retirement. Having much stress was significantly inversely associated with a low JST-IC (OR: 0.69, 95 % CI: 0.50 to 0.97). Conclusion: Having ikigai and someone reliable, and stress during middle age might play a role in preventing impaired advanced-level functional competency. Improved ikigai and increased social interaction and support might improve functional competency. Further research might explore avenues for improving ikigai.

Good death for people living with dementia: a qualitative study.

BACKGROUND: Ensuring a good death is one of the primary objectives of palliative care and end-of-life care. There is insufficient evidence regarding what defines a good death for people living with dementia. Obtaining an understanding of what constitutes a good death could help improve dementia care. This study aimed to explore how multiple stakeholders perceive a good death for people living with dementia. METHODS: This qualitative study was carried out across six prefectures in Japan. Enrollment of participants took place within dementia outpatient clinics, hospitals, daycare centers, and community centers. A total of thirty-three in-depth interviews with people living with dementia, physicians, and nurses were conducted. Six focus group discussions were performed with family caregivers and care workers. Verbatim transcripts of the interviews were prepared, and inductive content analysis was used to examine the data. FINDINGS: Regarding the perception of a good death, the following themes were derived: (1) painless death; (2) dying in a preferred environment; (3) family's coping with loss; (4) maintaining regular life; (5) living with respect; and (6) preparation for death. All these themes are interrelated. Participants viewed a good death as a process rather than a single event. CONCLUSION: This study identifies crucial components of a good death for people living with dementia. The findings could be used to improve dementia care.

Effect of Milk Intake and Calcium-Vitamin D Supplementation on Serum Vitamin D Status.

Vitamin D is important for health and disease. Milk is a good natural source of it, and calcium-vitamin D supplements are widely available over-the-counter and prescribed in clinical practice. But the effect of milk intake and calcium-vitamin D supplementation on serum vitamin D status is not known. This cross-sectional study was done to see the relationship between vitamin D status and milk intake or oral calcium-vitamin D supplementation using a structured questionnaire and carried out in a private consultation centre of Dhaka city, the capital of Bangladesh from July 2017 to March 2018. Serum 25-hydroxyvitamin D [25(OH)D] level was measured by radioimmunoassay. Out of 259 patients, 64.1% had vitamin D deficiency defined as serum 25(OH)D level <20ng/mL. Sixty one percent of those who had serum 25(OH)D level <20ng/mL did not take milk or milk products, while 53.0% of those having 25(OH)D level ≥20ng/mL did not take milk. Approximately 89.0% of those who had serum 25(OH)D level <20ng/mL did not take oral calcium-vitamin D, whereas 72.0% of those having 25(OH)D level ≥20ng/mL did not take oral calcium-vitamin D (p=0.001). In the multiple logistic regression analysis, there were significantly increased odds of vitamin D deficiency for females as compared to males [odds ratio (OR) 2.48, 95% confidence interval (CI) 1.34-4.56] and not taking oral vitamin D as compared to taking oral vitamin D (OR 3.56, 95% CI 1.74-7.28). Vitamin D deficiency is widely prevalent. Lack of milk intake and calcium-vitamin D supplementation are more commonly associated with serum vitamin D deficiency, and calcium-vitamin D supplementation is specially important in females.

Artificial intelligence and digital health in improving primary health care service delivery in LMICs: A systematic review.

AIM: Technology including artificial intelligence (AI) may play a key role to strengthen primary health care services in resource-poor settings. This systematic review aims to explore the evidence on the use of AI and digital health in improving primary health care service delivery. METHODS: Three electronic databases were searched using a comprehensive search strategy without providing any restriction in June 2023. Retrieved articles were screened independently using the "Rayyan" software. Data extraction and quality assessment were conducted independently by two review authors. A narrative synthesis of the included interventions was conducted. RESULTS: A total of 4596 articles were screened, and finally, 48 articles were included from 21 different countries published between 2013 and 2021. The main focus of the included studies was noncommunicable diseases (n = 15), maternal and child health care (n = 11), primary care (n = 8), infectious diseases including tuberculosis, leprosy, and HIV (n = 7), and mental health (n = 6). Included studies considered interventions using AI, and digital health of which mobile-phone-based interventions were prominent. m-health interventions were well adopted and easy to use and improved the record-keeping, service deliver, and patient satisfaction. CONCLUSION: AI and the application of digital technologies improve primary health care service delivery in resource-poor settings in various ways. However, in most of the cases, the application of AI and digital health is implemented through m-health. There is a great scope to conduct further research exploring the interventions on a large scale.

Medication adherence and health-related quality of life among people with diabetes in Bangladesh: A cross-sectional study.

INTRODUCTION: Good adherence to anti-diabetic medications is an important protective factor for decreasing diabetes-related complications and disabilities but its association with health-related quality of life (HRQoL) is understudied. The current study aimed to assess an association between medication adherence to anti-diabetic drugs and HRQoL among people with diabetes in Dhaka city, Bangladesh. METHODS: We conducted a cross-sectional study among 480 people with diabetes aged between 50 and 70 years, who attended a tertiary-level hospital in Dhaka city. We used the EuroQol-5 Dimensions Questionnaire (EQ-5D-5L) to measure HRQoL and Morisky Medication Adherence Scale to assess the level of medication adherence to anti-diabetic drugs. Multivariable logistic regression was performed to assess the significance of relevant factors. RESULTS: The mean age of the participants was 59.0 (standard deviation [SD], 7.0) years. The majority of the participants (74%) had a lower level of medication adherence. The mean value of (EQ-5D-5L) was 2.0 (SD, 1.0). The percentage of severe disability in different domains were 6.7% for mobility, 3.5% for self-care, 11.9% for usual daily activities, 11.9% for pain/discomfort and 11.3% for anxiety. After adjusting for age, sex, years of education, household expenditure, hypertension, duration of diabetes, glycemic status and multi-morbidities; low adherence to anti-diabetic medication was inversely associated with pain (OR, 0.26; 95% CI, 0.08-0.80; p = .036), and positively associated with anxiety (OR, 7.18; 95% CI, 1.03-9.59; p = .043). CONCLUSIONS: Low medication adherence to anti-diabetic drugs was associated with anxiety and pain among the EQ-5D-5L indexes measured in people with diabetes in Dhaka, Bangladesh.

Effect of leisure-time physical activity on blood pressure in people with hypertension: a systematic review and meta-analysis.

High blood pressure is a major risk factor for premature death. Leisure-time physical activities have been recommended to control hypertension. Studies examining how leisure-time physical activity affects blood pressure have found mixed results. We aimed to conduct a systematic review examining the effect of leisure-time physical activity (LTPA) on lowering blood pressure among adults living with hypertension. We searched studies in Embase, Medline/PubMed, Web of Science, Physical Education Index, Scopus and CENTRAL (the Cochrane Library). The primary outcome variables were systolic blood pressure (SBP) and diastolic blood pressure (DBP). This systematic review is registered on PROSPERO (CRD42021260751). We included 17 studies out of 12,046 screened articles in this review. Moderate-intensity LTPA (all types) reduced SBP compared to the non-intervention control group (MD -5.35 mm Hg, 95% CI -8.06 to -2.65, nine trials, n = 531, low certainty of the evidence). Mean DBP was reduced by -4.76 mm Hg (95% CI -8.35 to -1.17, nine trials, n = 531, low certainty of the evidence) in all types of LTPA (moderate intensity) group compared to the non-intervention control group. Leisure-time walking reduced mean SBP by -8.36 mmHg, 95% CI -13.39 to -3.32, three trials, n = 128, low certainty of the evidence). Walking during leisure time reduced -5.03 mmHg mean DBP, 95% CI -8.23 to -1.84, three trials, n = 128, low certainty of the evidence). Performing physical activity during free time probably reduces SBP and DBP (low certainty of the evidence) among adults with hypertension.

Effective antimicrobial therapies of urinary tract infections among children in low- and middle-income countries: A systematic review.

Importance: Urinary tract infection (UTI) is one of the most common infections encountered in infancy and childhood. Despite the emerging problem of antibiotic resistance in recent years, the use of antibiotics for better management of UTIs is inevitable. Objective: This study aims to explore the efficacy and adverse effects of the available antimicrobial agents that are used in pediatric UTIs in low- and middle-income countries (LMICs). Methods: Five electronic databases were searched to identify relevant articles. Two reviewers independently performed screening, data extraction, and quality assessment of the available literature. Randomized controlled trials providing antimicrobial interventions in both male and female participants within the age range of 3 months to 17 years in LMICs were included. Results: Six randomized controlled trials from 13 LMICs were included in this review (four trials explored the efficacy). Due to high heterogeneity across the studies, a meta-analysis was not performed. Other than attrition and reporting bias, the risk of bias was moderate to high due to poor study designs. The differences in the efficacy and adverse events of different antimicrobials were not found to be statistically significant. Interpretation: This review indicates the necessity for additional clinical trials on children from LMICs with more significant sample numbers, adequate intervention periods, and study design.

Stool specimen for diagnosis of pulmonary tuberculosis in adults: a systematic review.

OBJECTIVE: To assess the diagnostic accuracy of stool specimens to diagnose pulmonary tuberculosis (PTB) in adults. DESIGN: Systematic review. DATA SOURCES: MEDLINE (Ovid), Embase (Ovid), Web of Science and the Cochrane database were searched from inception to 9 March 2023-10 March 2023 using a comprehensive search strategy; reference lists of selected articles and relevant review articles were manually searched. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: Studies in English reporting diagnostic performance of stool specimens against respiratory specimens using mycobacterial culture or smear microscopy or Xpert assay to diagnose PTB in adults were eligible for this systematic review. DATA EXTRACTION AND SYNTHESIS: Two reviewers independently screened the retrieved citations and extracted data. The risk of bias and applicability of results were assessed using the Quality Assessment of Diagnostic Accuracy Studies-2 tool. Narrative data synthesis was performed. RESULTS: A total of 1658 citations were screened, and 28 full-text articles were assessed. Nine studies met the inclusion criteria. The reported sensitivity and specificity of stool culture varied between 21.4% and 63.9%, and 61.5% and 100%, respectively. In stool smear microscopy, sensitivities and specificities ranged from 12.1% to 53.9%, and from 79.5% to 100%, respectively. The reported sensitivities of PCR assays, including Xpert assays, ranged from 69.7% to 100%, with specificities ranging from 69.8% to 100%. Most of the studies had a low risk of bias and a low applicability concern in all domains. CONCLUSION: This systematic review could not conclude on the diagnostic accuracy of stool specimens for PTB diagnosis in adults. Further studies are required to evaluate the accuracy of stool specimens in adults to enable meta-analyses in updates of this review as well as other systematic reviews. PROSPERO REGISTRATION NUMBER: CRD42021245203.

Aducanumab for the treatment of Alzheimer's disease: a systematic review.

Aducanumab is a novel disease-modifying anti-amyloid-beta (Aß) human monoclonal antibody specifically targeted to the pathophysiology of Alzheimer's disease (AD). It was granted for treating AD in June 2021 by the United States Food and Drug Administration. We systematically analyzed available trials to evaluate the efficacy and safety of aducanumab treating AD. We followed the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analysis) guidelines. We conducted an extensive literature search using the electronic databases MEDLINE through PubMed, EMBASE, Cochrane, Web of Science, and Scopus for suitable studies on aducanumab. We considered human clinical trials of aducanumab, assessing its efficacy and adverse effects in treating AD, excluding any experimental animal studies. We included three randomised controlled trials. Studies reported that aducanumab reduced brain amyloid-beta plaques in a time- and dose-dependent manner (dose-response, P < 0.05) and a slowed decline in cognition (22% reduction) in the high-dose treated group, difference of -0.39 versus placebo in Clinical Dementia Rating Scale Sum Boxes (95% CI, -0.69 to -0.09; P = 0.012) along with a reduced amyloid positron emission tomography standard uptake value ratio score (P < 0.001) and plasma p181-tau (phosphorylated tau) level. Amyloid-related imaging abnormality was reported as a serious adverse event and was profound in high-dose treated group (425/1029 in 10 mg/kg). Aducanumab has been reported to affect two main pathophysiologic hallmarks (Aß and tau) of AD. We suggest future studies addressing aducanumab's efficacy and safety to confirm that the benefit of this drug outweighs the risk.

Association of Low-Density Lipoprotein Cholesterol with Risk of Coronary Heart Disease and Stroke among Middle-Aged Japanese Workers: An Analysis using Inverse Probability Weighting.

AIMS: The associations between low-density lipoprotein cholesterol (LDL-C) and the risk of cardiovascular disease (CVD) subtypes are not well established among the Japanese population. This study used longitudinal data from the Aichi Workers' Cohort Study to explore the association between LDL-C levels and the risk of coronary heart disease (CHD) and stroke subtypes. METHODS: Pooled data of 8966 adults (7093men and 1903 women) who were recruited between (2002) and (2008) were used for the current analysis. Propensity scores for the LDL-C categories were generated using multinomial logistic regression. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated from the inverse probability weighted Cox proportional hazards model for LDL-C category associations with risks of CHD, stroke subtypes, and CVD. RESULTS: During a median follow-up of 12 years, 122 strokes (57 ischemic strokes, 25 intracerebral hemorrhage, and 40 unknown subtypes) and 82 cases of CHD were observed. LDL-C 160- mg/dL compared to LDL-C 100-119 mg/dL was positively and significantly associated with the risk of CHD (HR: 4.56; 95% CI: 1.91-10.9) but not with ischemic stroke (HR: 0.99; 95% CI: 0.44-2.22). LDL-C was inversely associated with the risk of intracerebral hemorrhage (P for trend=0.009). CONCLUSION: In middle-aged Japanese workers, LDL-C was significantly and positively associated with CHD, but not with ischemic stroke. LDL-C was inversely significantly associated with intracerebral hemorrhage.

Safety and immunogenicity of Zika virus vaccine: A systematic review of clinical trials.

Several phase-1 clinical trials have been performed to evaluate the safety and efficacy of candidate anti-Zika vaccines. In this systematic review, we systematically evaluated the safety and immunogenicity of candidate vaccines, which would aid researchers in formulating an effective vaccination strategy for phase-2 trials based on current evidence. A literature search was conducted using the electronic databases MEDLINE through Pubmed, Web of Science, and Cochrane Database for relevant studies on candidate anti-zika vaccines. Studies on animal models were excluded from our study. Healthy individuals who were administered candidate Zika vaccines to evaluate the immune response and adverse events (AEs) compared to placebo were considered. Data were extracted, tabulated, and analysed using Microsoft Excel, while the risk of bias plots were generated using tidyverse and Robvis packages in R-studio. A total of five phase-1 clinical trials were included in our analysis comprising of studies on inactivated, viral vector, and DNA vaccines. Immunogenicity ranged from 10% to 100% after vaccination with the lowest seroconversion rate (10%) and geometric mean titre (GMT) (6.3; 95% confidence interval (CI):3.7-10.8) observed among recipients of single-dose inactivated anti-zika vaccine (ZPIV). For DNA vaccines, the seroconversion rate ranged from 60% to 100% with the highest seroconversion rate (100%) and GMT (2871; 95% CI:705.3-11688) observed among recipients of three shots of high dose GLS-5700 vaccine. For viral vector vaccine (Ad26.ZIKV.001) seroconversion rate (100%) and GMT peaked after two shots with both low and high-dose vaccines. In all those studies AEs were mostly local including injection site pain, erythema, and itching. The most common systemic AEs included fever, myalgia, nausea, and fatigue. In phase-1 clinical trials, all candidate vaccines were found to be highly immunogenic and relatively safe, especially when administered in higher doses and with the help of needle-free devices.

Participatory approaches in primary health care related implementation research in low-and middle-income countries: A narrative review.

Objectives: Primary Health Care (PHC) oriented health systems are crucial to accelerate the achievement of Universal Health Coverage. Previous studies have suggested the importance of participatory approaches to improve PHC. This review aimed to identify the available published implementation research in PHC considering participatory approaches in Low and Middle-Income Countries (LMICs). Study design: A narrative review was conducted following the standard guidelines. Methods: Three electronic databases were searched where keywords were combined using Boolean operators. Studies were included considering the pre-specified inclusion and exclusion criteria through two-phase screening. The quality of the included studies was assessed using the Joanna Briggs Institution's critical appraisal tools. Data were presented using a narrative synthesis approach. Results: A total of 13 articles were included that focused on community-based approaches in PHC service, maternal and newborn care, family planning, tuberculosis, and mental health. Three studies focused on mental health and demonstrated the efficacy of community support groups, peer volunteers, and community-based mental education in promoting mental health services. Two studies described community participation to ensure patient safety and risk reduction. Other studies explored the effectiveness of community-based, directly observed treatment for tuberculosis; community health worker-based maternal and child health care; and a community-based package for family planning. Eleven studies were conducted in Africa and the rest were in South Asia. Conclusion: This review reveals the gap in implementation research incorporating participatory approaches in the field of PHC. Limited studies have been conducted which indicate the need and scope of implementation research with participatory approaches in the PHC field. Prospero registration: CRD42020150749.