Quantifying the Cost of Shigella Diarrhea in the Enterics for Global Health (EFGH) Shigella Surveillance Study.

Background: Comparative costs of public health interventions provide valuable data for decision making. However, the availability of comprehensive and context-specific costs is often limited. The Enterics for Global Health (EFGH) Shigella surveillance study-a facility-based diarrhea surveillance study across 7 countries-aims to generate evidence on health system and household costs associated with medically attended Shigella diarrhea in children. Methods: EFGH working groups comprising representatives from each country (Bangladesh, Kenya, Malawi, Mali, Pakistan, Peru, and The Gambia) developed the study methods. Over a 24-month surveillance period, facility-based surveys will collect data on resource use for the medical treatment of an estimated 9800 children aged 6-35 months with diarrhea. Through these surveys, we will describe and quantify medical resources used in the treatment of diarrhea (eg, medication, supplies, and provider salaries), nonmedical resources (eg, travel costs to the facility), and the amount of caregiver time lost from work to care for their sick child. To assign costs to each identified resource, we will use a combination of caregiver interviews, national medical price lists, and databases from the World Health Organization and the International Labor Organization. Our primary outcome will be the estimated cost per inpatient and outpatient episode of medically attended Shigella diarrhea treatment across countries, levels of care, and illness severity. We will conduct sensitivity and scenario analysis to determine how unit costs vary across scenarios. Conclusions: Results from this study will contribute to the existing body of literature on diarrhea costing and inform future policy decisions related to investments in preventive strategies for Shigella.

Assessment of vaccine herd protection in a cluster-randomised trial of Vi conjugate vaccine against typhoid fever: results of further analysis.

Background: A cluster-randomised trial of Vi-tetanus toxoid (Vi-TT) conjugate vaccine conducted in urban Bangladeshi children found a high level of direct protection by Vi-TT but no significant vaccine herd protection. We reassessed the trial using a "fried egg" analysis to evaluate whether herd protection might have been obscured by transmission of typhoid into the clusters from the outside. Methods: A participant- and observer-blind, cluster-randomised trial was conducted between February 14, 2018 and August 12, 2019 in three wards of Mirpur, a densely populated urban area of Dhaka, Bangladesh. Children 9 months to under 16 years of age in 150 geographic clusters, which had a total of 311,289 persons present at baseline or entering during follow-up, were randomised by cluster to a single-dose of Vi-TT or Japanese encephalitis (JE) vaccine. Vi-TT protection against typhoid fever, detected at 8 treatment centres serving the study population, was compared in the original clusters for the trial, and for progressively more central subclusters ("yolks" of the "fried egg") of the cluster residents. If transmission of typhoid into the clusters had diluted observed vaccine herd protection, we hypothesised that analysis of the innermost "yolks" would reveal vaccine herd protection that was not evident in analysis of the entire clusters. The trial is registered at www.isrctn.com as ISRCTN11643110. Findings: At ≤18 months of follow-up, total vaccine effectiveness (protection of Vi-TT recipients relative to JE vaccine recipients) was 85% (95% CI: 76%, 90%); indirect effectiveness (protection of non-Vi-TT recipients in Vi-TT clusters relative to non-JE vaccine recipients in JE vaccine clusters) was 17% (95% CI: -13%, 40%); and overall effectiveness (protection of all residents in the Vi-TT clusters relative to all residents of the JE vaccine clusters) was 57% (95% CI: 44%, 66%). Analyses of subpopulations in inner 75%, 50% and 25% "yolks" of the clusters failed to reveal significant changes in any of these estimates. Interpretation: Our analysis did not reveal Vi-TT herd protection in the trial. Consideration should be given to exploring whether targeting adults as well as children with Vi-TT yields appreciable levels of vaccine herd protection. Funding: Bill & Melinda Gates Foundation (OPP1151153, INV-025388).

Assessment of the management of carcinomatous meningitis from breast cancer globally: a study by the Breast International Group Brain Metastasis Task Force.

BACKGROUND: Carcinomatous meningitis (CM) is a severe complication of breast cancer. The Breast International Group (BIG) carried out a survey to describe the approach to CM internationally. PATIENTS AND METHODS: A questionnaire on the management of CM was developed by the Brain Metastases Task Force of BIG and distributed to its groups, requesting one answer per group site. RESULTS: A total of 241 sites responded, 119 from Europe, 9 from North America, 39 from Central/South America, 58 from Asia, and 16 in Australia/New Zealand, with 24.5% being general hospitals with oncology units, 44.4% university hospitals, 22.4% oncology centers, and 8.7% private hospitals. About 56.0% of sites reported seeing <5 cases annually with 60.6% reporting no increase in the number of cases of CM recently. Nearly 63.1% of sites investigate for CM when a patient has symptoms or radiological evidence, while 33.2% investigate only for symptoms. For diagnosis, 71.8% of sites required a positive cerebrospinal fluid cytology, while magnetic resonance imaging findings were sufficient in 23.7% of sites. Roughly 97.1% of sites treat CM and 51.9% also refer patients to palliative care. Intrathecal therapy is used in 41.9% of sites, mainly with methotrexate (74.3%). As many as 20 centers have a national registry for patients with breast cancer with central nervous system metastases and of those 5 have one for CM. Most (90.9%) centers would be interested in participating in a registry as well as in studies for CM, the latter preferably (62.1%) breast cancer subtype specific. CONCLUSIONS: This is the first study to map out the approach to CM from breast cancer globally. Although guidelines with level 1 evidence are lacking, there is a high degree of homogeneity in the approach to CM globally and great interest for conducting studies in this area.

Effectiveness of a killed whole-cell oral cholera vaccine in Bangladesh: further follow-up of a cluster-randomised trial.

BACKGROUND: Killed whole-cell oral cholera vaccines (OCVs) are widely used for prevention of cholera in developing countries. However, few studies have evaluated the protection conferred by internationally recommended OCVs for durations beyond 2 years of follow-up. METHODS: In this study, we followed up the participants of a cluster-randomised controlled trial for 2 years after the end of the original trial. Originally, we had randomised 90 geographical clusters in Dhaka slums in Bangladesh in equal numbers (1:1:1) to a two-dose regimen of OCV alone (targeted to people aged 1 year or older), a two-dose regimen of OCV plus a water-sanitation-hygiene (WASH) intervention, or no intervention. There was no masking of group assignment. The WASH intervention conferred little additional protection to OCV and was discontinued at 2 years of follow-up. Surveillance for severe cholera was continued for 4 years. Because of the short duration and effect of the WASH intervention, we combined the two OCV intervention groups. The primary outcomes were OCV overall protection (protection of all members of the intervention clusters) and total protection (protection of individuals who got vaccinated in the intervention clusters) against severe cholera, which we assessed by multivariable survival models appropriate for cluster-randomised trials. This trial is registered on ClinicalTrials.gov, NCT01339845. FINDINGS: The study was done between April 17, 2011, and Nov 1, 2015. 268 896 participants were present at the time of the first dose, with 188 206 in the intervention group and 80 690 in the control group. OCV coverage of the two groups receiving OCV was 66% (123 659 of 187 214 participants). During 4 years of follow-up, 441 first episodes of severe cholera were detected (243 episodes in the vaccinated groups and as 198 episodes in the unvaccinated group). Overall OCV protection was 36% (95% CI 19 to 49%) and total OCV protection was 46% (95% CI 32 to 58). Cumulative total vaccine protection was notably lower for people vaccinated before the age of 5 years (24%; -30 to 56) than for people vaccinated at age 5 years or older (49%; 35 to 60), although the differences in protection for the two age groups were not significant (p=0·3308). Total vaccine protection dropped notably (p=0·0115) after 3 years in children vaccinated at 1-4 years of age. INTERPRETATION: These findings provide further evidence of long-term effectiveness of killed whole-cell OCV, and therefore further support for the use of killed whole-cell OCVs to control endemic cholera, but indicate that protection is shorter-lived in children vaccinated before the age of 5 years than in people vaccinated at the age of 5 years or older. FUNDING: Bill & Melinda Gates Foundation. TRANSLATION: For the Bengali translation of the abstract see Supplementary Materials section.

Integrated control of COVID-19 in resource-poor countries.

Low- and middle-income countries (LMICs) face many challenges in controlling COVID-19. Healthcare resources are limited and so are ICU beds. RT-PCR testing is conducted on a limited scale and treatment options are few. There is no vaccine. Therefore, what low-cost solutions remain for the prevention, diagnosis, and treatment of SARS-CoV-2? How should these essential health services be delivered in order to reach the most vulnerable in our societies? In this editorial we discuss several important strategies for controlling COVID-19 including: vaccination, molecular and serological diagnostics, hygiene and WaSH interventions, and low-cost therapeutics. We also discuss the delivery of such services in order to reach the most in need. The proposed integrated control strategy requires immediate action and political will in order to reduce the widening health inequalities caused by the pandemic.

Epidemiology of childhood intussusception in Bangladesh: Findings from an active national hospital based surveillance system, 2012-2016.

INTRODUCTION: Rotavirus vaccines have significantly decreased the burden of diarrheal diseases in countries that have introduced them into their immunization programs. In some studies, there has been a small association between rotavirus vaccines and intussusception in post-marketing surveillance, highlighting the importance of tracking incidence before and after vaccine introduction. The objective of this study was to describe the epidemiology of intussusception among Bangladeshi children pre-vaccine introduction. METHODS: We conducted active, hospital-based surveillance for intussusception at 7 tertiary care hospitals with pediatric surgical facilities during July 2012 to September 2016. Hospitalized children under 2years of age were identified according to Brighton Collaboration level 1 criteria for intussusception. The frequency and proportion of intussusception among overall surgical admissions, as well as the demographic and clinical information of the cases is described. RESULTS: Overall 153 cases of intussusception among children <2years-old were identified at participating sites over the enrolment period, confirmed by Level 1 Brighton criteria. These cases represented 2% of all surgical admissions under 2years of age. One hundred twelve cases (73%) were male; the median age was 7months; and the median duration of hospitalization was 7days. One hundred forty-six (95%) children with intussusception required surgery, and 11 (7%) died. CONCLUSIONS: Confirmed cases of intussusception represented nearly 2% of pediatric surgical admissions at tertiary referral centers in Bangladesh during the study period and 7% of children with intussusception died. Given the high burden of rotavirus disease in Bangladesh, vaccine introduction is warranted, however, further studies after introduction of rotavirus vaccine are necessary to determine any association between vaccine and intussusception in this setting.

The STRATAA study protocol: a programme to assess the burden of enteric fever in Bangladesh, Malawi and Nepal using prospective population census, passive surveillance, serological studies and healthcare utilisation surveys.

INTRODUCTION: Invasive infections caused by Salmonella enterica serovar Typhi and Paratyphi A are estimated to account for 12-27 million febrile illness episodes worldwide annually. Determining the true burden of typhoidal Salmonellae infections is hindered by lack of population-based studies and adequate laboratory diagnostics.The Strategic Typhoid alliance across Africa and Asia study takes a systematic approach to measuring the age-stratified burden of clinical and subclinical disease caused by typhoidal Salmonellae infections at three high-incidence urban sites in Africa and Asia. We aim to explore the natural history of Salmonella transmission in endemic settings, addressing key uncertainties relating to the epidemiology of enteric fever identified through mathematical models, and enabling optimisation of vaccine strategies. METHODS/DESIGN: Using census-defined denominator populations of ≥100 000 individuals at sites in Malawi, Bangladesh and Nepal, the primary outcome is to characterise the burden of enteric fever in these populations over a 24-month period. During passive surveillance, clinical and household data, and laboratory samples will be collected from febrile individuals. In parallel, healthcare utilisation and water, sanitation and hygiene surveys will be performed to characterise healthcare-seeking behaviour and assess potential routes of transmission. The rates of both undiagnosed and subclinical exposure to typhoidal Salmonellae (seroincidence), identification of chronic carriage and population seroprevalence of typhoid infection will be assessed through age-stratified serosurveys performed at each site. Secondary attack rates will be estimated among household contacts of acute enteric fever cases and possible chronic carriers. ETHICS AND DISSEMINATION: This protocol has been ethically approved by the Oxford Tropical Research Ethics Committee, the icddr,b Institutional Review Board, the Malawian National Health Sciences Research Committee and College of Medicine Research Ethics Committee and Nepal Health Research Council. The study is being conducted in accordance with the principles of the Declaration of Helsinki and Good Clinical Practice. Informed consent was obtained before study enrolment. Results will be submitted to international peer-reviewed journals and presented at international conferences. TRIAL REGISTRATION NUMBER: ISRCTN 12131979. ETHICS REFERENCES: Oxford (Oxford Tropical Research Ethics Committee 39-15).Bangladesh (icddr,b Institutional Review Board PR-15119).Malawi (National Health Sciences Research Committee 15/5/1599).Nepal (Nepal Health Research Council 306/2015).

Assessment of needs, health-related quality of life, and satisfaction with care in breast cancer patients to better target supportive care.

BACKGROUND: This study assessed whether breast cancer (BC) patients express similar levels of needs for equivalent severity of symptoms, functioning difficulties, or degrees of satisfaction with care aspects. BC patients who did (or not) report needs in spite of similar difficulties were identified among their sociodemographic or clinical characteristics. PATIENTS AND METHODS: Three hundred and eighty-four (73% response rate) BC patients recruited in ambulatory or surgery hospital services completed the European Organisation for Research and Treatment of Cancer Quality of Life questionnaire (EORTC QLQ)-C30 quality of life [health-related quality of life (HRQOL)], the EORTC IN-PATSAT32 (in-patient) or OUT-PATSAT35 (out-patient) satisfaction with care, and the supportive care needs survey short form 34-item (SCNS-SF34) measures. RESULTS: HRQOL or satisfaction with care scale scores explained 41%, 45%, 40% and 22% of variance in, respectively, psychological, physical/daily living needs, information/health system, and care/support needs (P < 0.001). BC patients' education level, having children, hospital service attendance, and anxiety/depression levels significantly predicted differences in psychological needs relative to corresponding difficulties (adjusted R² = 0.11). Medical history and anxiety/depression levels significantly predicted differences in information/health system needs relative to degrees of satisfaction with doctors, nurses, or radiotherapy technicians and general satisfaction (adjusted R² = 0.12). Unmet needs were most prevalent in the psychological domains across hospital services. CONCLUSIONS: Assessment of needs, HRQOL, and satisfaction with care highlights the subgroups of BC patients requiring better supportive care targeting.

Maternal depressive symptoms and infant growth in rural Bangladesh.

BACKGROUND: Depressive disorders are a major source of disability among low-income mothers in developing countries. OBJECTIVES: The objectives were to examine the association of maternal depressive symptoms and infant growth among infants in rural Bangladesh and to examine how the relation is affected by infant irritability and caregiving practices. DESIGN: Infant growth was measured among 221 infants at 6 and 12 mo. Mothers reported their depressive symptoms and perceptions of their infant's temperament, and a home observation of caregiving was conducted. RESULTS: At 6 mo, 18% of infants were stunted (length-for-age < -2 z scores). At 12 mo, 36.9% of infants were stunted; infants of mothers with depressive symptoms had a 2.17 higher odds of being stunted (95% CI: 1.24, 3.81; P = 0.007) than did infants of mothers with few symptoms (45.3% compared with 27.6%). In a multivariate regression analysis, maternal depressive symptoms were associated with 12-mo length-for-age, adjusted for 6-mo length-for-age, maternal education, infant sex, birth order, receipt of iron and zinc, months breastfed, maternal perception of infant temperament, and caregiving observations. Maternal depressive symptoms were not related to 12-mo weight-for-length. The relation between depressive symptoms and infant growth was not moderated by maternal perceptions of infant temperament, but was partially mediated by caregiving. CONCLUSIONS: The finding that infants of mothers with depressive symptoms in Bangladesh experience poor linear growth may extend to other low-income countries with high rates of food insecurity. Interventions to promote growth in infants should include prevention or treatment of maternal depressive disorders and strategies to ensure adequate food security.

The effect of social franchising on access to and quality of health services in low- and middle-income countries.

BACKGROUND: Social franchising has developed as a possible means of improving provision of health services through engaging the non-state sector in low- and middle-income countries. OBJECTIVES: To examine the evidence that social franchising has on access to and quality of health services in low- and middle-income countries. SEARCH STRATEGY: We searched the Cochrane Effective Practice and Organisation of Care (EPOC) Group Specialised Register (up to October 2007), Cochrane Central Register of Controlled Trials (The Cochrane Library 2007, Issue 3), MEDLINE, Ovid (1950 to September Week 3 2007), EMBASE, Ovid (1980 to 2007 Week 38), CINAHL, Ovid (1982 to September Week 3 2007), EconLit, WebSPIRS (1969 to Sept 2007), LILACS, Science Citation Index Expanded and Social Sciences Citation Index (1975 to March 2008), Sociological Abstracts, CSA Illumnia (1952 September 2007), WHOLIS (1948 November 2007). SELECTION CRITERIA: Randomized controlled trials, non-randomized controlled trials, controlled before and after studies and interrupted time series comparing social franchising models with other models of health service delivery, other social franchising models or absence of health services. DATA COLLECTION AND ANALYSIS: Two review authors independently applied the criteria for inclusion and exclusion of studies to scan titles and abstracts. The same two review authors independently screened full reports of selected citations . At each stage, results were compared and discrepancies settled through discussion. MAIN RESULTS: No studies were found which were eligible for inclusion in this review. AUTHORS' CONCLUSIONS: There is a need to develop rigorous studies to evaluate the effects of social franchising on access to and quality of health services in low- and middle-income countries. Such studies should be informed by the wider literature to identify models of social franchising that have a sound theoretical basis and empirical research addressing their reach, acceptability, feasibility, maintenance and measurability.

Association between experience of stressful life events and muscle-related temporomandibular disorders in patients seeking free treatment in a dental hospital.

OBJECTIVES: Psychological factors are known to play an important role in the etiology and maintenance of temporomandibular disorders. Since there have been very few studies on this issue in Asian countries, the study was aimed to investigate the relationship between various stressful life events and temporomandibular disorders in patients seeking free treatment in a Dental Hospital, Bangladesh. MATERIALS AND METHODS: Five hundred and twenty Bangladeshi adults (370 males and 150 females; mean age, 30.9 +/- 8.2 years) participated in this study. The subjects were given a questionnaire to evaluate their stress status in the last 12 months. The Research Diagnostic Criteria for TMD (RDC/TMD) was used as TMD diagnostic system by three standardized examiners. Two hundred and thirty-six patients were RDC/TMD-defined TMD-positive and were subsequently classified into 7 groups: group I, myofacial pain only; group II, disk displacement only; group III, joint pain only; group IV, myofacial pain and disc displacement; group V, myofacial pain and joint pain; group VI, disc displacement and joint pain; and group VII, myofacial pain, disk displacement and joint pain. Two hundred and eighty-four subjects were RDC/TMD-defined TMD-negative subjects (controls). Adjusted odds ratios were calculated by multiple logistic regression analysis. RESULTS: Logistic regression analysis revealed that patients diagnosed with myofacial pain (group I) and a combination of myofacial and joint pain (group V) had significantly higher levels of financial and job stress than did the controls. Self-health-related stress and stress related to a spouse or deaths of a relative were also identified as predisposing factors for myofacial pain (group I). CONCLUSION: This study suggests that myofacial pain is more common in individuals with various types of psychological stress. When treating patients with facial pain, dentists should consider the possible presence of psychological factors.

Perception and practice of rest during pregnancy among mothers and family decision-makers.

The incidence of low birthweight (LBW) in Bangladesh is one of the highest in the world. Inadequate rest of the mothers during pregnancy is a contributing factor to LBW. To assess the perception and practice of rest during pregnancy, 136 mothers and family members who make important decisions on family matter (FDM) were studied in rural Bangladesh. Eighty per cent of mothers perceived the importance of rest during pregnancy, whereas only 29 per cent practised rest (p < 0.003). Of the mothers who lacked perception, none practised. Eighty-five per cent of FDM perceived rest as important, yet only 27 per cent practised rest. Mothers' education and socioeconomic status were significantly associated with perception (p < 0.028,p < 0.001) and practice (p < 0.008,p < 0.006) of rest. The mother's education was also significantly (p < 0.000) associated with the socioeconomic status of the family. Our study suggests that the inability to take rest was due to workload at home, illiteracy, low socioeconomic status and failure of family members to share the workload.