Multi-country Prospective Cohort Study Research Articles

Economic burden and health-related quality-of-life among infants with respiratory syncytial virus infection: A multi-country prospective cohort study in Europe.

Respiratory syncytial virus (RSV) causes a considerable disease burden in young children globally, but reliable estimates of RSV-related costs and health-related quality-of-life (HRQoL) are scarce. This study aimed to evaluate the RSV-associated costs and HRQoL effects in infants and their caregivers in four European countries. Healthy term-born infants were recruited at birth and actively followed up in four European countries. Symptomatic infants were systematically tested for RSV. Caregivers recorded the daily HRQoL of their child and themselves, measured by a modified EQ-5D with Visual Analogue Scale, for 14 consecutive days or until symptoms resolved. At the end of each RSV episode, caregivers reported healthcare resource use and work absenteeism. Direct medical costs per RSV episode were estimated from a healthcare payer's perspective and indirect costs were estimated from a societal perspective. Means and 95% confidence intervals (CI) of direct medical costs, total costs (direct costs+productivity loss) and quality-adjusted life-day (QALD) loss per RSV episode were estimated per RSV episode, as well as per subgroup (medical attendance, country). Our cohort of 1041 infants experienced 265 RSV episodes with a mean symptom duration of 12.5days. The mean (95% CI) cost per RSV episode was €399.5 (242.3, 584.2) and €494.3 (317.7, 696.1) from the healthcare payer's and societal perspective, respectively. The mean QALD loss per RSV episode of 1.9 (1.7, 2.1) was independent of medical attendance (in contrast to costs, which also differed by country). Caregiver and infant HRQoL evolved similarly. This study fills essential gaps for future economic evaluations by prospectively estimating direct and indirect costs and HRQoL effects on healthy term infants and caregivers separately, for both medically attended (MA) and non-MA laboratory-confirmed RSV episodes. We generally observed greater HRQoL losses than in previous studies which used non-community and/or non-prospective designs.

Treatment-seeking and recovery among young undernourished children post-hospital discharge in Bangladesh: A qualitative study.

IntroductionPost-hospital discharge mortality is high among undernourished children in many low and middle-income countries. Although a number of quantitative studies have highlighted a range of potential socio-cultural, economic and health system factors influencing paediatric post-discharge treatment-seeking and recovery, few studies have explored family and provider perspectives of the post-discharge period in-depth.MethodsThis work was part of a large, multi-country prospective cohort study, the Childhood Acute Illness and Nutrition (CHAIN) Network. We conducted a qualitative sub-study to understand the post-discharge treatment-seeking and recovery experiences of families of undernourished children aged 2–23 months admitted in a rural and urban icddr,b (International Centre for Diarrhoeal Disease Research, Bangladesh) hospital. Methods included repeat in-depth interviews (73 interviews in total) with 29 family members of 17 purposively selected children. These data were supplemented by interviews with 33 health workers, and by observations in hospitals and homes.ResultsImportant drivers of treatment-seeking perceived to support recovery included advice provided to family members while in hospital, media campaigns on hygiene practice, availability of free treatment, and social and financial support from family members, relatives and neighbours. Key perceived challenges included low household incomes, mothers having to juggle multiple responsibilities in addition to caring for the sick child, lack of support (sometimes violence) from the child’s father, and family members’ preference for relatively accessible drug shops, physicians or healers over hospital admission.ConclusionDevelopment of interventions that address the challenges that families face is essential to support post-discharge adherence to medical advice and recovery. Potential interventions include strengthening information giving during hospitalization on what post-discharge care is needed and why, reducing direct and indirect costs associated with hospital visits, engaging fathers and other ‘significant others’ in post-discharge advice, and building mobile phone-based support for follow-up care.

A multi-country, prospective cohort study to measure rate and risk of relapse among children recovered from severe acute malnutrition in Mali, Somalia, and South Sudan: a study protocol

BackgroundThe Community-Based Management of Acute Malnutrition (CMAM) model transformed the treatment of severe acute malnutrition (SAM) by shifting treatment from inpatient facilities to the community. Evidence shows that while CMAM programs are effective in the initial recovery from SAM, recovery is not sustained for some children requiring them to receive treatment repeatedly. This indicates a potential gap in the model, yet little evidence is available on the incidence of relapse, the determinants of the phenomena, or its financial implications on program delivery.MethodsThis study is a multi-country prospective cohort study following “post-SAM” children (defined as children following anthropometric recovery from SAM through treatment in CMAM) and matched community controls (defined as children not previously experiencing acute malnutrition (AM)) monthly for six months. The aim is to assess the burden and determinants of relapse to SAM. This study design enables the quantification of relapse among post-SAM children, but also to determine the relative risk for, and excess burden of, AM between post-SAM children and their matched community controls. Individual -, household-, and community-level information will be analyzed to identify potential risk-factors for relapse, with a focus on associations between water, sanitation, and hygiene (WASH) related exposures, and post-discharge outcomes. The study combines a microbiological assessment of post-SAM children’s drinking water, food, stool via rectal swabs, dried blood spots (DBS), and assess for indicators of enteric pathogens and immune function, to explore different exposures and potential associations with treatment and post-treatment outcomes.DiscussionThis study is the first of its kind to systematically track children after recovery from SAM in CMAM programs using uniform methods across multiple countries. The design allows the use of results to: 1) facilitate understandings of the burden of relapse; 2) identify risk factors for relapse and 3) elucidate financial costs associated with relapse in CMAM programs. This protocol’s publication aims to support similar studies and evaluations of CMAM programs and provides opportunities for comparability of an evidence-based set of indicators for relapse to SAM.

Population-based rates, risk factors and consequences of preterm births in South-Asia and sub-Saharan Africa: A multi-country prospective cohort study.

BackgroundPreterm birth is the leading cause of neonatal deaths in low middle-income countries (LMICs), yet there exists a paucity of high-quality data from these countries. Most modelling estimates are based on studies using inaccurate methods of gestational age assessment. We aimed to fill this gap by measuring the population-based burden of preterm birth using early ultrasound dating in five countries in South-Asian and sub-Saharan Africa.MethodsWe identified women early in pregnancy (<20 weeks based on last menstrual period) by home visits every 2-3 months (except in Zambia where they were identified at antenatal care clinics) in 5 research sites in South-Asia and sub-Saharan Africa between July 2012 and September 2016. Trained sonographers performed an ultrasound scan for gestational age dating. Women were enrolled if they were 8-19 weeks pregnant on ultrasound. Women <8 weeks were rescheduled for repeat scans after 4 weeks, and identified women were followed through pregnancy until 6 weeks postpartum. Site-specific rates and proportions were calculated and a logistic regression model was used to predict the risk factors of preterm birth.ResultsPreterm birth rates ranged from 3.2% in Ghana to 15.7% in Pakistan. About 46% of all neonatal deaths occurred among preterm infants, 49% in South Asia and 40% in sub-Saharan Africa. Fourteen percent of all preterm infants died during the neonatal period. The mortality was 37.6% for early preterm babies (<34 weeks), 5.9% for late preterm babies (34 to <37 weeks), and 1.7% for term babies (37 to <42 weeks). Factors associated lower gestation at birth included South-Asian region (adjusted mean difference (Adj MD) = -6.2 days, 95% confidence interval (CI) = -5.5, -6.9), maternal morbidities (Adj MD = -3.4 days, 95% CI = -4.6, -2.2), multiple pregnancies (Adj MD = -17.8 days, 95% CI = -19.9,-15.8), adolescent pregnancy (Adj MD = –2.7 days, 95% CI = -3.7, -1.6) and lowest wealth quintile (Adj MD = -1.3 days, 95% CI = -2.4, -0.3).ConclusionsPreterm birth rates are higher in South Asia than in sub-Saharan Africa and contribute to 49% and 40% of all neonatal deaths in the two regions, respectively. Adolescent pregnancy and maternal morbidities are modifiable risk factors associated with preterm birth.

Access to HIV Viral Load Testing and Antiretroviral Therapy Switch Practices: A Multicountry Prospective Cohort Study in Sub-Saharan Africa.

Poor access to HIV viral load (VL) testing prevents the timely monitoring of HIV treatment adherence and efficacy. Factors enabling clinical benefits of VL testing when added to local standards of care, can inform the development of more cost-effective routine VL scale-up plans. We compared antiretroviral therapy (ART) switch practices in 13 clinics across 6 countries, with full (N = 8), phasing-in (N = 3) or no onsite access (N = 2) to VL. The analysis used data from the Pan-African Studies to Evaluate Resistance (PASER), observing virological and drug resistance outcomes among adults receiving first- or second-line ART between 2008 and 2015. Study plasma viral load (sVL) determined at baseline, every 12 months thereafter and at the time of switch served for retrospectively validating switch decisions, categorized into "necessary," "unnecessary," and "missed." Virological failure was defined as two consecutive sVL ≥1,000 HIV-RNA copies/mL. One thousand nine hundred ninety-five of the 2,420 (82.4%) study participants had continuous virological suppression during the median 30 months of follow-up. Among the 266 virological failures (11.0%), the proportion of necessary switches were similar in clinics with full (37%), phasing-in (25%), or no access (39%) to local VL testing. Documented utilization of local VL results for the switch decision was associated with higher percentage of necessary switch (87.6% vs. 67.9%). Shorter time to necessary switch was associated with higher rates of long-term virological suppression, regardless of access to local viral load. Availability of HIV VL testing capacity does not systematically result in adequate switch practices or better virological outcomes. Systems supporting sufficient test demand execution, and actual utilization of results for patient management need strengthening.

Isoniazid and Rifampin-Resistance Mutations Associated With Resistance to Second-Line Drugs and With Sputum Culture Conversion.

Mutations in the genes inhA, katG, and rpoB confer resistance to anti-tuberculosis (TB) drugs isoniazid and rifampin. We questioned whether specific mutations in these genes were associated with different clinical and microbiological characteristics. In a multicountry prospective cohort study of multidrug-resistant TB, we identified inhA, katG, and rpoB mutations in sputum isolates using the Hain MTBDRplus line probe assay. For specific mutations, we performed bivariate analysis to determine relative risk of baseline or acquired resistance to other TB drugs. We compared time to sputum culture conversion (TSCC) using Kaplan-Meier curves and stratified Cox regression. In total, 447 participants enrolled from January 2005 to December 2008 from 7 countries were included. Relative to rpoB S531L, isolates with rpoB D516V had less cross-resistance to rifabutin, increased baseline resistance to other drugs, and increased acquired fluoroquinolone resistance. Relative to mutation of katG only, mutation of inhA promoter and katG was associated with baseline extensively drug resistant (XDR) TB, increased acquired fluoroquinolone resistance, and slower TSCC (125.5 vs 89.0 days). Specific mutations in inhA and katG are associated with differences in resistance to other drugs and TSCC. Molecular testing may make it possible to tailor treatment and assess additional drug resistance risk according to specific mutation profile.

Population-based rates, timing, and causes of maternal deaths, stillbirths, and neonatal deaths in south Asia and sub-Saharan Africa: a multi-country prospective cohort study.

SummaryBackgroundModelled mortality estimates have been useful for health programmes in low-income and middle-income countries. However, these estimates are often based on sparse and low-quality data. We aimed to generate high quality data about the burden, timing, and causes of maternal deaths, stillbirths, and neonatal deaths in south Asia and sub-Saharan Africa.MethodsIn this prospective cohort study done in 11 community-based research sites in south Asia and sub-Saharan Africa, between July, 2012, and February, 2016, we conducted population-based surveillance of women of reproductive age (15–49 years) to identify pregnancies, which were followed up to birth and 42 days post partum. We used standard operating procedures, data collection instruments, training, and standardisation to harmonise study implementation across sites. Verbal autopsies were done for deaths of all women of reproductive age, neonatal deaths, and stillbirths. Physicians used standardised methods for cause of death assignment. Site-specific rates and proportions were pooled at the regional level using a meta-analysis approach.FindingsWe identified 278 186 pregnancies and 263 563 births across the study sites, with outcomes ascertained for 269 630 (96·9%) pregnancies, including 8761 (3·2%) that ended in miscarriage or abortion. Maternal mortality ratios in sub-Saharan Africa (351 per 100 000 livebirths, 95% CI 168–732) were similar to those in south Asia (336 per 100 000 livebirths, 247–458), with far greater variability within sites in sub-Saharan Africa. Stillbirth and neonatal mortality rates were approximately two times higher in sites in south Asia than in sub-Saharan Africa (stillbirths: 35·1 per 1000 births, 95% CI 28·5–43·1 vs 17·1 per 1000 births, 12·5–25·8; neonatal mortality: 43·0 per 1000 livebirths, 39·0–47·3 vs 20·1 per 1000 livebirths, 14·6–27·6). 40–45% of pregnancy-related deaths, stillbirths, and neonatal deaths occurred during labour, delivery, and the 24 h postpartum period in both regions. Obstetric haemorrhage, non-obstetric complications, hypertensive disorders of pregnancy, and pregnancy-related infections accounted for more than three-quarters of maternal deaths and stillbirths. The most common causes of neonatal deaths were perinatal asphyxia (40%, 95% CI 39–42, in south Asia; 34%, 32–36, in sub-Saharan Africa) and severe neonatal infections (35%, 34–36, in south Asia; 37%, 34–39 in sub-Saharan Africa), followed by complications of preterm birth (19%, 18–20, in south Asia; 24%, 22–26 in sub-Saharan Africa).InterpretationThese results will contribute to improved global estimates of rates, timing, and causes of maternal and newborn deaths and stillbirths. Our findings imply that programmes in sub-Saharan Africa and south Asia need to further intensify their efforts to reduce mortality rates, which continue to be high. The focus on improving the quality of maternal intrapartum care and immediate newborn care must be further enhanced. Efforts to address perinatal asphyxia and newborn infections, as well as preterm birth, are critical to achieving survival goals in the Sustainable Development Goals era.FundingBill & Melinda Gates Foundation.

Differences in the Characteristics of Dialysis Patients in Japan Compared with Those in Other Countries

Background: Japanese patients undergoing dialysis have an extremely low mortality rate compared with those in the United States and Europe. As shown in the Dialysis Outcomes & Practice Patterns Study (DOPPS), certain features of dialysis treatment, such as single treatment time and amount of blood flow, are unique to Japan, but factors contributing to the low mortality risk are unclear. Although DOPPS is a multi-country prospective cohort study, the study results may not entirely reflect the real trend in Japan because the number of Japanese institutions participating in the study is small. Summary: In this article, we review the data reported for Japan and other countries and reveal country-specific differences, particularly in patient age distribution and duration of dialysis. Key Messages: The mean age of prevalent dialysis patients is rising every year in Japan, and the proportion of patients undergoing dialysis for long periods of time is also increasing. In addition, the proportion of dialysis patients with diabetes, one of the primary diseases, has increased to a level similar to that observed in Western countries. However, no significant decline in the crude death rate among prevalent dialysis patients has been observed in Japan, presumably because of technological advances in dialysis treatment, but further studies are needed to elucidate the contributing factors.

A Risk Prediction Model for the Assessment and Triage of Women with Hypertensive Disorders of Pregnancy in Low-Resourced Settings: The miniPIERS (Pre-eclampsia Integrated Estimate of RiSk) Multi-country Prospective Cohort Study

Pre-eclampsia/eclampsia are leading causes of maternal mortality and morbidity, particularly in low- and middle- income countries (LMICs). We developed the miniPIERS risk prediction model to provide a simple, evidence-based tool to identify pregnant women in LMICs at increased risk of death or major hypertensive-related complications. From 1 July 2008 to 31 March 2012, in five LMICs, data were collected prospectively on 2,081 women with any hypertensive disorder of pregnancy admitted to a participating centre. Candidate predictors collected within 24 hours of admission were entered into a step-wise backward elimination logistic regression model to predict a composite adverse maternal outcome within 48 hours of admission. Model internal validation was accomplished by bootstrapping and external validation was completed using data from 1,300 women in the Pre-eclampsia Integrated Estimate of RiSk (fullPIERS) dataset. Predictive performance was assessed for calibration, discrimination, and stratification capacity. The final miniPIERS model included: parity (nulliparous versus multiparous); gestational age on admission; headache/visual disturbances; chest pain/dyspnoea; vaginal bleeding with abdominal pain; systolic blood pressure; and dipstick proteinuria. The miniPIERS model was well-calibrated and had an area under the receiver operating characteristic curve (AUC ROC) of 0.768 (95% CI 0.735-0.801) with an average optimism of 0.037. External validation AUC ROC was 0.713 (95% CI 0.658-0.768). A predicted probability ≥25% to define a positive test classified women with 85.5% accuracy. Limitations of this study include the composite outcome and the broad inclusion criteria of any hypertensive disorder of pregnancy. This broad approach was used to optimize model generalizability. The miniPIERS model shows reasonable ability to identify women at increased risk of adverse maternal outcomes associated with the hypertensive disorders of pregnancy. It could be used in LMICs to identify women who would benefit most from interventions such as magnesium sulphate, antihypertensives, or transportation to a higher level of care.

Family planning practices and pregnancy intentions among HIV-positive and HIV-negative postpartum women in Swaziland: a cross sectional survey

BackgroundIn settings where sexually transmitted infection (STI) and HIV prevalence is high, the postpartum period is a time of increased biological susceptibility to pregnancy related sepsis. Enabling women living with HIV to avoid unintended pregnancies during the postpartum period can reduce vertical transmission and maternal mortality associated with HIV infection. We describe family planning (FP) practices and fertility desires of HIV-positive and HIV-negative postpartum women in Swaziland.MethodsData are drawn from a baseline survey of a four-year multi country prospective cohort study under the Integra Initiative, which is measuring the benefits and costs of providing integrated HIV and sexual and reproductive health (SRH) services in Kenya and Swaziland. We compare data from 386 HIV-positive women and 483 HIV-negative women recruited in Swaziland between February and August 2010. Data was collected on hand-held personal digital assistants (PDAs) covering fertility desires, mistimed or unwanted pregnancies and contraceptive use prior to their most recent pregnancy. Data were analysed using Stata 10.0. Descriptive statistics were conducted using the chi square test for categorical variables. Measures of effect were assessed using multivariate fixed effects logistic regression model accounting for clustering at facility level and the results are presented as adjusted odds ratios.ResultsMajority (69.2%) of postpartum women reported that their most recent pregnancy was unintended with no differences between HIV-positive and HIV-negative women: OR: 0.96 (95% CI) (0.70, 1.32). Although, there were significant differences between HIV-positive and HIV-negative women who reported that their previous pregnancy was unwanted, (20.7% vs. 13.5%, p = 0.004), when adjusted this was not significant OR: 1.43 (0.92, 1.91). 47.2% of HIV-positive women said it was mistimed compared to 52.5%, OR: 0.79 (0.59, 1.06). 37.9% of all women said they do not want another child. Younger women were more likely to have unwanted pregnancies: OR: 1.12 (1.07, 1.12), while they were less likely to have mistimed births; OR: 0.82 (0.70, 0.97). Those with tertiary education were less likely to have unwanted or mistimed pregnancies OR: 0.30 (0.11, 0.86). Half of HIV-positive women and more than a third of HIV-negative women reported that they had been using a FP method when they became pregnant with no differences between the groups: OR: 1.61 (0.82,3.41). Only short-acting methods were available to these women before the most recent pregnancy; and available during the postpartum visit. One fifth of all women received an FP method during the current visit. Among the four fifths who did not receive a method 17.3% reported they were already using a method or were breastfeeding. HIV-positive women were more likely to have already started a method than HIV-negative women (20% vs. 15%, p = 0.089).ConclusionThere are few differences overall between the experiences of both HIV-positive and negative women in terms of FP experiences, unintended pregnancy and services received during the early postpartum period in Swaziland. Women attending postpartum facilities are receiving satisfactory care. Access to a wider range of effective methods is urgently needed if high levels of unintended pregnancy are to be reduced among HIV-positive and HIV-negative women living in Swaziland.

Determinants of Postoperative Outcomes of Female Genital Fistula Repair Surgery

To determine predictors of fistula repair outcomes 3 months postsurgery. We conducted a multicountry prospective cohort study between 2007 and 2010. Outcomes, measured 3 months postsurgery, included fistula closure and residual incontinence in women with a closed fistula. Potential predictors included patient and fistula characteristics and context of repair. Multivariable generalized estimating equation models were used to generate adjusted risk ratios (RRs) and 95% confidence intervals (CIs). Women who returned for follow-up 3-month postsurgery were included in predictors of closure analyses (n=1,274). Small bladder size (adjusted RR 1.57, 95% CI 1.39-1.79), prior repair (adjusted RR 1.40, 95% CI 1.11-1.76), severe vaginal scarring (adjusted RR 1.56, 95% CI 1.20-2.04), partial urethral involvement (adjusted RR 1.36, 95% CI 1.11-1.66), and complete urethral destruction or circumferential defect (adjusted RR 1.72, 95% CI 1.33-2.23) predicted failed fistula closure. Women with a closed fistula at 3-month follow-up were included in predictors of residual incontinence analyses (n=1,041). Prior repair (adjusted RR 1.37, 95% CI 1.13-1.65), severe vaginal scarring (adjusted RR 1.35, 95% CI 1.10-1.67), partial urethral involvement (adjusted RR 1.78, 95% CI 1.27-2.48), and complete urethral destruction or circumferential defect (adjusted RR 2.06, 95% CI 1.51-2.81) were significantly associated with residual incontinence. The prognosis for genital fistula closure is related to preoperative bladder size, previous repair, vaginal scarring, and urethral involvement.