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.

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).

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.

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.

Everyday wishes of older people living with dementia in care planning: a qualitative study.

BACKGROUND: The dementia care policy in Japan emphasizes the views of people living with dementia in care planning. An exploration of the everyday wishes of older people living with dementia can help clarify their priorities and assist in improving dementia care. This study aimed to explore the everyday wishes of older people living with dementia in Japan. METHODS: This qualitative study was conducted in Aichi prefecture in Japan. Older people with mild to moderate dementia were considered for inclusion. Participants were recruited from a dementia outpatient clinic. In-depth interviews were conducted with 36 participants in the same dementia outpatient clinic from January to October 2019. Audio-recorded interviews were transcribed verbatim. Inductive content analysis was carried out to analyze the data. FINDINGS: Participants expressed their everyday wishes within five themes (desire of being connected, freedom to decide, involvement in activities, status quo, and self-reliance). Older people living with dementia loved the connection with their family and wanted to have an enjoyable life by engaging in several activities without others' interference. They desired to maintain the status quo and not be a burden to others. CONCLUSIONS: This study provides evidence on the everyday wishes of people living with dementia. Identified wishes are mostly on emotional aspects of their daily lives. The findings of our study might help provide care for the people living with dementia considering their wishes. Further exploration, including people with severe dementia, is needed.

Global incidence of caesarean deliveries on maternal request: a systematic review and meta-regression.

BACKGROUND: Caesarean delivery on maternal request (CDMR) is considered a significant contributor to the unprecedented increase in caesarean deliveries (CDs) for nonclinical reasons. Current literature lacks a reliable assessment of the rate of CDMR, which hinders the planning and delivery of appropriate interventions for reducing CDMR rates. OBJECTIVES: To conduct a systematic review of the literature and meta-regression to explore the global incidence of CDMR. SEARCH STRATEGY: PubMed, Embase, CINAHL, Medline, Google scholar and grey literature were searched from January 1985 to May 2019. SELECTION CRITERIA: Observational studies that report CDMR data were included. We excluded non-English articles, case notes, editorial reviews and articles reporting elective CDs from pregnancy risk factors. DATA COLLECTION AND ANALYSIS: Two reviewers independently conducted the screening and quality appraisal using a validated tool. The weighted average of CDMR over total deliveries (absolute proportion) and by total CDs (relative proportion) were generated. Quality-effects meta-regression was used to explain the variability of the CDMR estimates by moderators, including study methodology and demography of study participants. MAIN RESULTS: We identified 31 articles from 14 countries that include 5 million total births. The absolute proportion of CDMR varies between 0.2 and 42.0%, with significant variations across studies and subgroups. The economic status of the country and study year together explained 84% of the absolute and 76% of the relative proportion of CDMR variation. CONCLUSIONS: An appropriate reporting of CDMR should be a key priority in maternal health policies and practices. TWEETABLE ABSTRACT: Globally, the proportion of maternal requested caesarean delivery has mostly been influenced by the economic status of the country.

Factors associated with the nutritional status of the older population in a selected area of Dhaka, Bangladesh.

BACKGROUND: Globally, older population (aged ≥60 years) comprise 11% of the total population, and 23% of them are malnourished. Lack of knowledge and education, adverse dietary habits, depression or psychological disorders, poor oral and dental health, disability, and diseases are the reported factors responsible for malnutrition among them. Geriatric people comprise 7.5% of the total population of Bangladesh, and almost a quarter are malnourished. But there is scarce data on the factors associated with the nutritional status of the older population in Bangladesh. METHODS: A cross-sectional study was conducted among 125 older individuals (male 59, female 66) living in three villages of Uttarkhan, Dhaka, Bangladesh, to identify the factors associated with their nutritional status. The Mini Nutritional Assessment scale, Geriatric Depression Scale-Short Form, and Geriatric Oral Health Assessment Index were used for assessing the nutritional status, mental health status, and oral health quality of the respondents, respectively. Information on socio-demographic characteristics, comorbidities and dietary factors, and food behaviors were gathered by a pretested semi-structured questionnaire. Ethical approval was obtained from the Institutional Review Board of Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh. RESULTS: The participants' mean age was 67.9 ± 7.1 years. Most of them (53.6%) had no formal education. Among the respondents, 22.0% male and 28.8% female were malnourished. The proportion of malnourished and at risk of malnutrition among the respondents living without a partner were 28.6 and 65.3%, respectively. A significantly (p < 0.05) higher odds of having depression (OR 15.6; 95% CI 3.1-78.1), poor oral health (OR 7.3; 95% CI 1.3-41.8), and no formal education (OR 6.5; 95% CI 1.3-32.1) was observed among the malnourished respondents. Though it was not statistically significant, among the malnourished, 31.3, 25.0 and 25.0% avoided highly oily food, beef/mutton, and sugary food, respectively. CONCLUSIONS: More than two-thirds of the older population were malnourished or at risk of malnutrition, where the female respondents were more vulnerable. Depression, inadequate oral health, and lack of education were negatively associated with the nutritional status of the older population.

Association of gestational diabetes mellitus and thyroid status during pregnancy: a cross-sectional study in a tertiary health care center of Bangladesh.

OBJECTIVE: To find out any association between gestational diabetes mellitus (GDM) and thyroid status (TS) throughout pregnancy in Bangladesh. METHODOLOGY: This study, designed as a cross-sectional study, was performed on randomly chosen 628 patients attending the Ad-Din Women's Medical College antenatal service from January 1 2019 to December 31 2019. After taking a detailed history, oral glucose tolerance test was done for all the participants. If eligible, then thyroid-stimulating hormone (TSH) and free thyroxine (F.T4) tests were done. t-test and Chi-square test were used to compare variables between various classes as necessary. RESULTS: The mean gestational age in GDM and non-GDM groups was 20.5 ± 9.1 years and 17.5 ± 9.2 years, which were significantly different (p<.001). There was a substantial (p<.001) high incidence of thyroid disorder (TD) in the non-GDM community. Mean F.T4 of the GDM group was lower in all three trimesters. The mean TSH of the GDM group was more deficient in the early stage of pregnancy but higher in the later stage (3rd trimester). Euthyroid cases were significantly higher (83.8%; p<.001) while subclinical hypothyroidism (9.5%; p<.001) and transient hyperthyroidism (2.4%; p<.001) cases were significantly lower in GDM group. CONCLUSIONS: Even though GDM and TD are the most prevalent endocrine disorders during pregnancy, neither TS during pregnancy nor any risk factors for TD have been associated with the development of GDM.

Discrimination against the elderly in health-care services: a systematic review.

Ageism in health-care services is a cardinal public health concern in geriatric health. It is important to know the types and extent of discrimination experienced by elderly individuals while seeking health care. This systematic review aimed to explore the available research to identify discrimination of elderly individuals in health-care services. MEDLINE through PubMed, Web of Science, PsycInfo, and Cochrane Database were searched by using a comprehensive search strategy in September 2020 with no limitation in the year of publication and types of publication. Articles published in English focusing on disparities in health-care service among the elderly were included. Two independent authors screened, extracted, and assessed the quality of data using the Joanna Briggs Institute Critical Appraisal Tool. A narrative synthesis was conducted followed by qualitative content analysis to identify themes from the extracted outcomes of the included studies. Of 3117 articles retrieved from the initial search, 21 articles were included. A total of 611 608 participants from 38 countries in four geographic regions were reported. Articles were published between 2003 and 2020. Most of the studies (n = 19) were cross-sectional in design, and the remaining two studies were qualitative. Major themes of discrimination were age-related discrimination, racial discrimination, gender discrimination, wealth-related discrimination, and technology-related discrimination. This systematic review identified the major perspectives on disparities faced by the elderly in accessing health services. There is a huge research gap on this issue. Specific strategies should be incorporated to address the varying types of discrimination experienced by elderly individuals.

Job satisfaction among physicians providing health care to the elderly in Japan: a qualitative study.

BACKGROUND: Physicians' job satisfaction plays an important role in service delivery. Japan is a country with a higher number of elderly people and their medical care is a crucial issue. To date, no study has been conducted on the job satisfaction of geriatricians serving the elderly in Japan. This study aims to explore the job satisfaction and motivation of physicians providing health care to the elderly working at different hospitals in Japan. METHODS: In-depth interview of 23 geriatric physicians was conducted and data were coded and analysed. Qualitative content analysis was conducted to identify the response themes. RESULTS: Three major themes emerged from the analysis and they are: satisfaction as a primary care provider, career development, and suitable communication with patients. Geriatric physicians enjoy their work with inter-professional collaboration and are satisfied to provide primary health care to elderly people. Geriatrics is a very promising career to them and they enjoy the communication and empathetic doctor-patient relationship in their service. CONCLUSIONS: Japanese physicians providing health care to the elderly are enjoying their work due to a suitable environment, multi-professional collaboration, work-life balance, and patient-doctor relationship.

Guillain-Barré syndrome associated with SARS-CoV-2 infection: A systematic review and individual participant data meta-analysis.

Several published reports have described a possible association between Guillain-Barré syndrome (GBS) and severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection. This systematic review aimed to summarize and meta-analyze the salient features and prognosis of SARS-CoV-2-associated GBS. We searched the PubMed (Medline), Web of Science and Cochrane databases for articles published between 01 January 2020 and 05 August 2020 using SARS-CoV-2 and GBS-related keywords. Data on sociodemographic characteristics, antecedent symptoms, clinical, serological and electrophysiological features, and hospital outcomes were recorded. We included 45 articles from 16 countries reporting 61 patients with SARS-CoV-2-associated GBS. Most (97.7%) articles were from high- and upper-middle-income countries. Forty-two (68.9%) of the patients were male; median (interquartile range) age was 57 (49-70) years. Reverse transcriptase polymerase chain reaction for SARS-CoV-2 was positive in 90.2% of patients. One report of SARS-CoV-2-associated familial GBS was found which affected a father and daughter of a family. Albuminocytological dissociation in cerebrospinal fluid was found in 80.8% of patients. The majority of patients (75.5%) had a demyelinating subtype of GBS. Intravenous immunoglobulin and plasmapheresis were given to 92.7% and 7.3% of patients, respectively. Around two-thirds (65.3%) of patients had a good outcome (GBS-disability score ≤ 2) on discharge from hospital. Two patients died in hospital. SARS-CoV-2-associated GBS mostly resembles the classical presentations of GBS that respond to standard treatments. Extensive surveillance is required in low- and lower-middle-income countries to identify and report similar cases/series. Further large-scale case-control studies are warranted to strengthen the current evidence. PROSPERO Registration Number CRD42020201673.

Physical activity and sedentary behaviour in Bangladesh: a systematic scoping review.

OBJECTIVES: Lack of physical activity (PA) contributes to increasing prevalence of non-communicable diseases (NCDs) globally. However, little is known about PA and sedentary behaviour (SB) among populations in low- and middle-income countries (LMICs). This systematic review examined prevalence of PA and SB in Bangladesh. STUDY DESIGN: Systematic review of the literature. METHODS: A systematic electronic search in eight databases and a manual search of retrieved articles' references were conducted. Original research conducted in Bangladesh with PA- and/or SB-related outcome(s) were included. RESULTS: Out of 1,162 retrieved titles, 33 articles (32 cross-sectional and one case-control study) met the inclusion criteria. Twenty-nine studies were with healthy populations: adults (n = 19); children and adolescents (n = 7); and children, adolescents and adults (n = 3). Five studies used nationally representative samples of adults and one of adolescents. Most studies (n = 26) assessed PA only; three only SB, and four both PA and SB. All studies used self-reported measures. Among healthy adults, prevalence of insufficient PA ranged from 5% to 83%. Occupational and transport-related PA contributed the most towards total PA with negligible contribution of recreational PA. Among children and adolescents, the prevalence of insufficient PA ranged between 20% and 67%. Females engaged in less PA compared to males. Limited evidence currently exists about the prevalence of SB, especially among adults. CONCLUSIONS: PA and SB research has received little attention in Bangladesh. Critical knowledge gaps identified in this review should be taken into account when designing new research and programmes in Bangladesh and other LMICs with similar socio-economic and cultural settings.

Government health expenditure, out-of-pocket payment and social inequality: A cross-national analysis of China and OECD countries.

This study aims to assess the association between Chinese out-of-pocket payments and government health spending, investigating their variation ratio in the context of OECD countries. Aggregated time-series data of 37 countries (from China and official OECD members) were collected from the World Bank Open Data source and analyzed using the multiple linear regression models. Benchmarking approach was applied to evaluate the causes of healthcare expenditure rise per capita. The results showed that China's government health expenditure was positively associated with out-of-pocket payment rise, with a higher variation score of 42.70%. The association was statistically significant at 5%. Likewise, the association between government expenditure and out-of-pocket payment in the OECD countries was positively significant at 1%, and their variation score was 2.41%. Health financing in OECD countries showed higher stability and equity than that in China. Policy implications for China is to reduce the distributional disparity of government health funds by tax adjustments in health services, universal health coverage, the removal of social health insurance disparities, and a single health payment method.

Prevalence and factors associated with tobacco use among men in India: findings from a nationally representative data.

BACKGROUND: Tobacco consumption causes almost 638,000 premature deaths per year in India. This study sought to examine the prevalence and determinants of tobacco use among men in India. METHODS: We analyzed data from the fourth round of the National Family Health Survey in India. These nationally representative cross-sectional sample data were collected from January 20, 2015, to December 4, 2016. A total of 112,122 men aged 15-54 years were included in this study. Primary outcomes were tobacco use categorized into smoking, smokeless, any tobacco, and both smoked and smokeless tobacco use. Complex survey design and sampling weights were applied in both the descriptive analyses and logistic regression models. We present the findings using odds ratios. RESULTS: The prevalence of tobacco use among men in India for the studied period was 45.5% (95% CI 44.9-46.1), smoking was 24.6% (95% CI 24.1-25.1), smokeless tobacco use was 29.1% (95% CI 28.6-29.6), and both smoked and smokeless tobacco use was 8.4% (95% CI 8.1-8.7). The prevalence of tobacco use among men was higher among the elderly, separated/divorced/widowed individuals, those with lower education and wealth status, alcohol consumers, manual workers, and residents of the northeast region. Multivariate analysis showed that age, lower education, occupation, region, alcohol consumption, separated/divorced/widowed status, and economic status were substantially associated with tobacco use among Indian men. CONCLUSIONS: Innovative and cost-effective strategies targeting high-risk groups are crucial to curbing the tobacco epidemic in India. Anti-smoking campaigns should also focus on mitigating alcohol abuse. Reducing tobacco marketing and implementing formal education about the dangers of tobacco use, progressive taxing, packaging, and labeling of tobacco products and price strategies should be harmonized in legal provisions.

Decoding the enigma of antiviral crisis: Does one target molecule regulate all?

Disease fatality associated with Ebola, SARS-CoV and dengue infections in humans is attributed to a cytokine storm that is triggered by excessive pro-inflammatory responses. Interleukin (IL)-6 acts as a mediator between pro- and anti-inflammatory reactivity by initiating trans- and classical-signaling, respectively. Hence, IL-6 is assumed to provide a target for a broad range of antiviral agents. Available immunosuppressive antivirals are directed to control an often exaggerated pro-inflammatory response that gives rise to complex clinical conditions such as lymphocytopenia. It is known that IL-6, via its soluble receptor (sIL-6R), initiates a pro-inflammatory response while an anti-inflammatory response is triggered by the membrane-bound IL-6 receptor (IL-6R). Future antivirals should thus aim to target the mechanism that regulates switching between IL-6 trans- and classical-signaling. In this review, we propose that the tumour necrosis factor-α converting enzyme ADAM-17 could be the master molecule involved in regulating IL-6 class switching and through this in controlling pro- and anti-inflammatory responses to viral antigenic stimuli. Therefore, ADAM-17 should be considered as a potential target molecule for novel antiviral drug discovery that would regulate host reactivity to infection and thereby limit or prevent fatal outcomes.

Association of biomass fuel smoke with respiratory symptoms among children under 5 years of age in urban areas: results from Bangladesh Urban Health Survey, 2013.

BACKGROUND: Little is known regarding the effect of exposure to biomass fuel smoke inhalation on respiratory symptoms in the Bangladeshi population which is a major health hazard in most of the developing countries. This study aims to explore the association between respiratory symptoms and biomass fuel smoke exposure among children under 5 years of age. METHODS: Data were extracted from the Bangladesh Urban Health Survey conducted in 2013. A total of 10,575 mothers with at least one surviving children were selected. Respiratory symptoms among children under 5 years of age were considered as the primary outcome. Sequential multiple logistic regression models were used to observe the association between respiratory symptoms and biomass fuel smoke exposure adjusting the effect of residential factors and mother and child characteristics. RESULTS: Around 40% of the mothers exclusively used biomass fuel irrespective of the kitchen location and 54% of them were habituated in indoor cooking. The prevalence of respiratory symptoms of under-five children among in-house and outdoor biomass fuel users was 23.0% and 21.9%, respectively. Results of fitted multiple logistic regression models showed that the odds of having respiratory symptoms among children under 5 years of age were increased due to in-house biomass fuel use [OR = 1.18; 95% CI, 1.04-1.36] compared with the non-biomass user. An increased risk of respiratory symptoms was also significantly associated with mother's birth complication [OR = 1.51; 95% CI, 1.36-1.67], non-government organization (NGO) membership of mothers [OR = 1.32; 95% CI, 1.16-1.51], age of the child (6-23m) [OR = 1.29; 95% CI, 1.10-1.52], and nutritional status (stunting) [OR = 1.18; 95% CI, 1.06-1.31]. CONCLUSION: This study found the use of in-house biomass fuel as a significant risk factor associated with respiratory symptoms of children under 5 years of age. More longitudinal studies should be designed to establish a causal relationship between HAP (household air pollution) and respiratory symptoms among children with more direct measures of HAP and clinical procedure.

Methylene-linked bis-phenylbenzimidazoles - a new scaffold to target telomeric DNA/RNA hybrid duplex.

We report a series of novel methylene-linked bis-phenylbenzimidazoles intercalators that stabilize telomeric DNA/RNA hybrid (tDRH) structures by up to 7.2 °C at a 1 µM ligand concentration while having negligible affinity for DNA/DNA duplexes, although with a low affinity for quadruplex DNA. We have used molecular modelling studies to rationalize this selectivity, concluding that the methylene spacer between the terminal benzimidazole and phenylene moieties plays a key role in facilitating the bis-intercalating process. This scaffold may be used to develop chemical tools or new therapeutics to selectively target the telomeric DNA/RNA duplex without affecting normal genomic DNA.

Genetic relatedness of Vibrio cholerae isolates within and between households during outbreaks in Dhaka, Bangladesh.

BACKGROUND: Household contacts of cholera patients have a 100 times higher risk of developing a cholera infection than the general population. To compare the genetic relatedness of clinical and water source Vibrio cholerae isolates from cholera patients' households across three outbreaks, we analyzed these isolates using whole-genome-sequencing (WGS) and multilocus variable-number tandem-repeat analysis (MLVA). RESULTS: The WGS analyses revealed that 80% of households had source water isolates that were more closely related to clinical isolates from the same household than to any other isolates. While in another 20% of households an isolate from a person was more closely related to clinical isolates from another household than to source water isolates from their own household. The mean pairwise differences in single nucleotide-variant (SNV) counts for isolates from the same household were significantly lower than those for different households (2.4 vs. 7.7 p < 0.0001), and isolates from the same outbreak had significantly fewer mean pairwise differences compared to isolates from different outbreaks (mean: 6.2 vs. 8.0, p < 0.0001). Based on MLVA in outbreak 1, we observed that the majority of households had clinical isolates with MLVA genotypes related to other clinical isolates and unrelated to water source isolates from the same household. While in outbreak 3, there were different MLVA genotypes between households, however within the majority of households, the clinical and water source isolates had the same MLVA genotypes. The beginning of outbreak 2 resembled outbreak 1 and the latter part resembled outbreak 3. We validated our use of MLVA by comparing it to WGS. Isolates with the identical MLVA genotype had significantly fewer mean pairwise SNV differences than those isolates with different MLVA genotypes (mean: 4.8 vs. 7.7, p < 0.0001). Furthermore, consistent with WGS results, the number of pairwise differences in the five MLVA loci for isolates within the same household was significantly lower than isolates from different households (mean: 1.6 vs. 3.0, p < 0.0001). CONCLUSION: These results suggest that transmission patterns for cholera are a combination of person-to-person and water-to-person cholera transmission with the proportions of the two modes varying within and between outbreaks.

Rapid dipstick detection of Vibrio cholerae in household stored and municipal water in Dhaka, Bangladesh: CHoBI7 trial.

OBJECTIVE: In urban Dhaka, Bangladesh, 30% of source water samples collected from the households of patients with cholera had detectable Vibrio cholerae. These findings indicate an urgent need for a public health intervention for this population. The Crystal VC® dipstick test is a rapid method for detecting V. cholerae in stool and water. However, to date no study has investigated the use of the rapid dipstick test for household surveillance of stored drinking water. METHODS: The efficacy of the Crystal VC® dipstick test for detecting V. cholerae in the Dhaka city municipal water supply and stored household drinking water sources after enrichment for 18 h in alkaline peptone water (APW) was compared to bacterial culture as the gold standard. RESULTS: A total of 1648 water samples (824 stored household drinking water samples and 824 municipal water supply samples) were collected from households of patients with cholera. The overall specificity and sensitivity of the dipstick test compared to bacterial culture was 99.6% (95% confidence interval (CI): 99.2%, 99.9%) and 65.6% (95% CI: 55.2%, 75%), respectively. The specificities for stored household drinking water and Dhaka city municipal supply water compared to bacterial culture were 99.8% (95% CI: 99.1%, 100%) and 99.5% (95% CI: 98.6%, 99.9%), respectively (P = 0.138), and the sensitivities were 66.7% (95% CI: 43.0%, 85.4%) and 65.3% (95% CI: 53.5%, 76.0%), respectively (P = 0.891). CONCLUSION: The Crystal VC® dipstick is a promising screening tool for cholera outbreak surveillance in resource-limited settings where elimination of false-positive results is critical. The lower than expected sensitivity should be further investigated in future studies.

Randomized Controlled Trial of Hospital-Based Hygiene and Water Treatment Intervention (CHoBI7) to Reduce Cholera.

The risk for cholera infection is >100 times higher for household contacts of cholera patients during the week after the index patient seeks hospital care than it is for the general population. To initiate a standard of care for this high-risk population, we developed Cholera-Hospital-Based-Intervention-for-7-Days (CHoBI7), which promotes hand washing with soap and treatment of water. To test CHoBI7, we conducted a randomized controlled trial among 219 intervention household contacts of 82 cholera patients and 220 control contacts of 83 cholera patients in Dhaka, Bangladesh, during 2013-2014. Intervention contacts had significantly fewer symptomatic Vibrio cholerae infections than did control contacts and 47% fewer overall V. cholerae infections. Intervention households had no stored drinking water with V. cholerae and 14 times higher odds of hand washing with soap at key events during structured observation on surveillance days 5, 6, or 7. CHoBI7 presents a promising approach for controlling cholera among highly susceptible household contacts of cholera patients.