Implementation of a clinical breast exam and referral program in a rural district of Pakistan.

BACKGROUND: The role of clinical breast examination (CBE) for early detection of breast cancer is extremely important in lower-middle-income countries (LMICs) where access to breast imaging is limited. Our study aimed to describe the outcomes of a community outreach breast education, home CBE and referral program for early recognition of breast abnormalities and improvement of breast cancer awareness in a rural district of Pakistan. METHODS: Eight health care workers (HCW) and a gynecologist were educated on basic breast cancer knowledge and trained to create breast cancer awareness and conduct CBE in the community. They were then deployed in the Dadu district of Pakistan where they carried out home visits to perform CBE in the community. Breast cancer awareness was assessed in the community using a standardized questionnaire and standard educational intervention was performed. Clinically detectable breast lesions were identified during home CBE and women were referred to the study gynecologist to confirm the presence of clinical abnormalities. Those confirmed to have clinical abnormalities were referred for imaging. Follow-up home visits were carried out to assess reasons for non-compliance in patients who did not follow-through with the gynecologist appointment or prescribed imaging and re-enforce the need for follow-up. RESULTS: Basic breast cancer knowledge of HCWs and study gynecologist improved post-intervention. HCWs conducted home CBE in 8757 women. Of these, 149 were warranted a CBE by a physician (to avoid missing an abnormality), while 20 were found to have a definitive lump by HCWs, all were referred to the study gynecologist (CBE checkpoint). Only 50% (10/20) of those with a suspected lump complied with the referral to the gynecologist, where 90% concordance was found between their CBEs. Follow-up home visits were conducted in 119/169 non-compliant patients. Major reasons for non-compliance were a lack of understanding of the risks and financial constraints. A significant improvement was observed in the community's breast cancer knowledge at the follow-up visits using the standardized post-test. CONCLUSIONS: Basic and focused education of HCWs can increase their knowledge and dispel myths. Hand-on structured training can enable HCWs to perform CBE. Community awareness is essential for patient compliance and for early-detection, diagnosis, and treatment.

Implementation research to increase treatment coverage of possible serious bacterial infections in young infants when a referral is not feasible: lessons learnt.

BACKGROUND: The objective was to achieve high coverage of possible serious bacterial infections (PSBI) treatment using the World Health Organization (WHO) guideline for managing it on an outpatient basis when referral to a hospital is not feasible. METHODS: We implemented this guideline in the programme settings at 10 Basic Health Units (BHU) in two rural districts of Sindh in Pakistan using implementation research. A Technical Support Unit supported the programme to operationalize guidelines, built capacity of health workers through training, monitored their clinical skills, mentored them and assured quality. The community-based health workers visited households to identify sick infants and referred them to the nearest BHU for further management. The research team collected data. RESULTS: Of 17 600 identified livebirths, 1860 young infants with any sign of PSBI sought care at BHUs and 1113 (59.8%) were brought by families. We achieved treatment coverage of 95%, assuming an estimated 10% incidence of PSBI in the first 2 months of life and that 10% of young infants came from outside the study catchment area. All 923 infants (49%; 923/1860) 7-59 days old with only fast breathing (pneumonia) treated with outpatient oral amoxicillin were cured. Hospital referral was refused by 83.4% (781/937) families who accepted outpatient treatment; 92.2% (720/781) were cured and 0.8% (6/781) died. Twelve (7.6%; 12/156) died among those treated in a hospital. CONCLUSION: It is feasible to achieve high coverage by implementing WHO PSBI management guidelines in a programmatic setting when a referral is not feasible.

National cervical cancer burden estimation through systematic review and analysis of publicly available data in Pakistan.

BACKGROUND: Cervical cancer is a major cause of cancer-related deaths among women worldwide. Paucity of data on cervical cancer burden in countries like Pakistan hamper requisite resource allocation. OBJECTIVE: To estimate the burden of cervical cancer in Pakistan using available data sources. METHODS: We performed a systematic review to identify relevant data on Pakistan between 1995 to 2022. Study data identified through the systematic review that provided enough information to allow age specific incidence rates and age standardized incidence rates (ASIR) calculations for cervical cancer were merged. Population at risk estimates were derived and adjusted for important variables in the care-seeking pathway. The calculated ASIRs were applied to 2020 population estimates to estimate the number of cervical cancer cases in Pakistan. RESULTS: A total of 13 studies reported ASIRs for cervical cancer for Pakistan. Among the studies selected, the Karachi Cancer Registry reported the highest disease burden estimates for all reported time periods: 1995-1997 ASIR = 6.81, 1998-2002 ASIR = 7.47, and 2017-2019 ASIR = 6.02 per 100,000 women. Using data from Karachi, Punjab and Pakistan Atomic Energy Cancer Registries from 2015-2019, we derived an unadjusted ASIR for cervical cancer of 4.16 per 100,000 women (95% UI 3.28, 5.28). Varying model assumptions produced adjusted ASIRs ranging from 5.2 to 8.4 per 100,000 women. We derived an adjusted ASIR of 7.60, (95% UI 5.98, 10.01) and estimated 6166 (95% UI 4833, 8305) new cases of cervical cancer per year. CONCLUSION: The estimated cervical cancer burden in Pakistan is higher than the WHO target. Estimates are sensitive to health seeking behavior, and appropriate physician diagnostic intervention, factors that are relevant to the case of cervical cancer, a stigmatized disease in a low-lower middle income country setting. These estimates make the case for approaching cervical cancer elimination through a multi-pronged strategy.

An integrated newborn care kit (iNCK) to save newborn lives and improve health outcomes in Gilgit Baltistan (GB), Pakistan: study protocol for a cluster randomized controlled trial.

BACKGROUND: Ongoing high neonatal mortality rates (NMRs) represent a global challenge. In 2021, of the 5 million deaths reported worldwide for children under five years of age, 47% were newborns. Pakistan has one of the five highest national NMRs in the world, with an estimated 39 neonatal deaths per 1,000 live births. Reducing newborn deaths requires sustainable, evidence-based, and cost-effective interventions that can be integrated within existing community healthcare infrastructure across regions with high NMR. METHODS: This pragmatic, community-based, parallel-arm, open-label, cluster randomized controlled trial aims to estimate the effect of Lady Health Workers (LHWs) providing an integrated newborn care kit (iNCK) with educational instructions to pregnant women in their third trimester, compared to the local standard of care in Gilgit-Baltistan, Pakistan, on neonatal mortality and other newborn and maternal health outcomes. The iNCK contains a clean birth kit, 4% chlorhexidine topical gel, sunflower oil emollient, a ThermoSpot™ temperature monitoring sticker, a fleece blanket, a click-to-heat reusable warmer, three 200 µg misoprostol tablets, and a pictorial instruction guide and diary. LHWs are also provided with a handheld scale to weigh the newborn. The primary study outcome is neonatal mortality, defined as a newborn death in the first 28 days of life. DISCUSSION: This study will generate policy-relevant knowledge on the effectiveness of integrating evidence-based maternal and newborn interventions and delivering them directly to pregnant women via existing community health infrastructure, for reducing neonatal mortality and morbidity, in a remote, mountainous area with a high NMR. TRIAL REGISTRATION: NCT04798833, March 15, 2021.

Perpetuation of gender discrimination in Pakistani society: results from a scoping review and qualitative study conducted in three provinces of Pakistan.

BACKGROUND: Gender discrimination is any unequal treatment of a person based on their sex. Women and girls are most likely to experience the negative impact of gender discrimination. The aim of this study is to assess the factors that influence gender discrimination in Pakistan, and its impact on women's life. METHODS: A mixed method approach was used in the study in which a systematic review was done in phase one to explore the themes on gender discrimination, and qualitative interviews were conducted in phase two to explore the perception of people regarding gender discrimination. The qualitative interviews (in-depth interviews and focus group discussions) were conducted from married men and women, adolescent boys and girls, Healthcare Professionals (HCPs), Lady Health Visitors (LHVs) and Community Midwives (CMWs). The qualitative interviews were analyzed both manually and electronically through QSR NVivo 10. The triangulation of data from the systematic review and qualitative interviews were done to explore the gender discrimination related issues in Pakistan. RESULTS: The six major themes have emerged from the systematic review and qualitative interviews. It includes (1) Status of a woman in the society (2) Gender inequality in health (3) Gender inequality in education (4) Gender inequality in employment (5) Gender biased social norms and cultural practices and (6) Micro and macro level recommendations. In addition, a woman is often viewed as a sexual object and dependent being who lacks self identity unless being married. Furthermore, women are restricted to household and child rearing responsibilities and are often neglected and forced to suppress self-expression. Likewise, men are viewed as dominant figures in lives of women who usually makes all family decisions. They are considered as financial providers and source of protection. Moreover, women face gender discrimination in many aspects of life including education and access to health care. CONCLUSION: Gender discrimination is deeply rooted in the Pakistani society. To prevent gender discrimination, the entire society, especially women should be educated and gendered sensitized to improve the status of women in Pakistan.

Evaluation the Effectiveness of Abridged IMNCI (7-Day) Course v Standard (11-Day) Course in Pakistan.

BACKGROUND: The conventional IMCI training for healthcare providers is delivered in 11 days, which can be expensive and disruptive to the normal clinical routines of the providers. An equally effective, shorter training course may address these challenges. METHODS: We conducted a quasi-experimental study in two provinces (Sindh and Punjab) of Pakistan. 104 healthcare providers were conveniently selected to receive either the abridged (7-day) or the standard (11-day) training. Knowledge and clinical skills of the participants were assessed before, immediately on conclusion of, and six months after the training. RESULTS: The improvement in mean knowledge scores of the 7-day and 11-day training groups was 31.6 (95% CI 24.3, 38.8) and 29.4 (95% CI 23.9, 34.9) respectively, p = 0.630 while the improvement in mean clinical skills scores of the 7-day and 11-day training groups was 23.8 (95% CI: 19.3, 28.2) and 23.0 (95% CI 18.9, 27.0) respectively, p = 0.784. The decline in mean knowledge scores six months after the training was - 12.4 (95% CI - 18.5, - 6.4) and - 6.4 (95% CI - 10.5, - 2.3) in the 7-day and 11-day groups respectively, p = 0.094. The decline in mean clinical skills scores six months after the training was - 6.3 (95% CI - 11.3, - 1.3) in the 7-day training group and - 9.1 (95% CI - 11.5, - 6.6) in the 11-day group, p = 0.308. CONCLUSION: An abridged IMNCI training is equally effective as the standard training. However, training for certain illnesses may be better delivered by the standard course.

Impact of interpregnancy intervals on perinatal and neonatal outcomes in a multiethnic Pakistani population.

BACKGROUND: Short birth intervals (SBIs) and long birth intervals (LBIs) have been shown to have serious implications for health of both mothers and their children. This study was aimed to investigate the determinants and reproductive outcome of SBI and LBI in a multiethnic Pakistani population. METHODS: In a cross-sectional prospective study design, 2798 women admitted in a tertiary-care hospital in Islamabad for delivery were recruited and data on second or higher birth order deliveries were collected. Birth intervals were defined as short (<24 months) and long (>36 months). The reproductive outcome was defined in terms of perinatal and neonatal mortalities, and neonatal complications. Univariate and multivariate logistic regression analyses were performed. RESULTS: Pregnancies with SBI and LBI were observed in 20% and 24% of 2798 women, respectively. Women with SBI had increased odds of perinatal death [adjusted odd ratio (AOR): 1.50] and neonatal death (AOR: 1.47) as compared to women with optimal birth intervals, while women with LBI had slightly lower odds of perinatal deaths (AOR: 0.96), but increased odds of neonatal deaths (AOR: 1.12). Further, the pregnancies with both SBI and LBI were associated with increased odds of short body length, low birth weight, small head circumference and low APGAR score. CONCLUSION: Nearly half of all pregnancies do not have optimal birth spacing albeit there is wide heterogeneity in the distribution of BI in various Pakistani ethnicities. Pregnancies with SBI and LBI had high risk of adverse reproductive outcome. Intervention programs for maternal and child health need to emphasize optimal birth spacing.

Birth interval (BI) or interpregnancy interval is the length of time between a birth and conception of the next pregnancy. Short birth intervals (SBIs) as well as long birth intervals (LBIs) have been shown to have serious implications for health of both mothers and their children. WHO recommendation for optimal spacing between 3 and 5 years. In this study, we aimed to investigate the effect of SBI and LBI on pregnancy outcome in the Pakistani population. A total of 2798 pregnant women admitted in a tertiary-care hospital in Islamabad for delivery were recruited and data on BI and pregnancy outcomes, i.e. perinatal and neonatal mortalities, and neonatal complications, were obtained. Results revealed that pregnancies with SBI and LBI were 20% and 24% of the total pregnancies, respectively. Women with SBI had higher likelihood of perinatal and neonatal death as compared to women with optimal birth intervals. Similarly, the women with LBI had higher likelihood of neonatal deaths. Furthermore, the pregnancies with both SBI and LBI were associated neonatal complications like short body length, low birth weight, small head circumference and low APGAR score. In conclusion, nearly half of all pregnancies do not have optimal birth spacing. Intervention programs for maternal and child health need to emphasize optimal birth spacing.

Dietary diversity and social determinants of nutrition among late adolescent girls in rural Pakistan.

The conditions in which adolescent girls mature shape their health, development and nutrition. Nutrient requirements increase to support growth during adolescence, but gaps between consumption and requirements exist in low- and middle-income countries. We aimed to identify and quantify the relationship between dietary intake and diverse social determinants of nutrition (SDN) among a subset of adolescent girls 15-18.9 years (n = 390) enrolled within the Matiari emPowerment and Preconception Supplementation (MaPPS) Trial. The primary outcome, dietary diversity score (DDS), was derived by applying the Minimum Dietary Diversity for Women 10-item scale to 24-h dietary recall data collected three times per participant. To examine the associations between the SDN-related explanatory variables and DDS, we generated a hierarchical, causal model using mixed effects linear regression to account for the cluster-randomized trial design. Using all data, diets lacked diversity (DDS mean ± SD: 3.35 ± 1.03 [range: 1-7; n = 1170]), and the minimum cut-off for dietary diversity was infrequently achieved (13.5%; 95% CI: 11.6-15.6%). Consumption of starches was reported in all recalls, but micronutrient-rich food consumption was less common. Of the SDN considered, wealth quintile had the strongest association with DDS (P < 0.0001). The diets of the sampled Pakistani adolescent girls were insufficient to meet micronutrient requirements. Poverty was the most important predictor of a diet lacking in diversity, indicating limited purchasing power or access to nutritious foods. Dietary diversification and nutrition education strategies alone are unlikely to lead to improved diets without steps to tackle this barrier, for example, through fortification of staple foods and provision of supplements.

Conducting household surveys on reproductive health in urban settings: lessons from Karachi, Pakistan.

BACKGROUND: Data collection is the most critical stage in any population health study and correctly implementing fieldwork enhances the quality of collected information. However, even the most carefully planned large-scale household surveys can encounter many context-specific issues. This paper reflected on our research team's recent experience conducting surveys for a quasi-experimental evaluation of a reproductive health program in urban areas of Karachi, Pakistan. We aim to describe the issues encountered and lessons learned from this process, and present some potential solutions for conducting future household surveys in similar urban environments. METHODS: The study followed a three-stage random sampling design. Initially, a Geographical Information System (GIS) was used to construct the sampling frame with union council (UC) area mapping and cluster demarcation followed by random selection of clusters in the selected UCs within the intervention and control sites. The second stage involved a complete household listing in selected clusters and the final stage was a random sampling of households with eligible women. RESULT: This paper describes the issues that were encountered including technical problems related to GIS demarcation of cluster boundaries and hand-held devices for computer assisted personal interviews (CAPI), household listing, interviewing respondents on sensitive topics and their expectations, and ensuring privacy during the survey. CONCLUSION: This study identifies a number of unique barriers to conducting household surveys in Karachi and highlights some key lessons for survey research in urban settlements. GIS mapping technology is a cost-effective method for developing sampling frames in resource-constrained settings. Secondly, the strategy of interviewing women immediately after the cluster is listed may be applied to make it easier to re-locate selected respondents and to reduce loss-to-follow up. Understanding local norms and developing culturally appropriate strategies to build trust with communities may significantly improve survey participation. Researchers should hire experienced female enumerators and provide continuous training on best practices for interviewing women on sensitive reproductive health topics in urban communities.

Effectiveness of management of severe acute malnutrition (SAM) through community health workers as compared to a traditional facility-based model: a cluster randomized controlled trial.

PURPOSE: We compared the impact of management of severe acute malnutrition (SAM) by lady health workers (LHWs) at a community level with the standard CMAM program provided at the health facility. METHODS: A two-arm cluster randomised controlled trial was conducted in a rural district in sindh Pakistan. The primary outcome was recovery from SAM and secondary outcomes were relapse, defaulter and mortality rate. RESULTS: A total of 829 children were recruited in the trial (430 in intervention and 399 in control groups). No significant difference was noted in recovery rate between the intervention and control groups (79.2% vs 85.6%, p = 0.276). Similarly, no significant differences were noted in relapse (p = 0.757), weight gain (p = 0.609), deaths (p = 0.775) and defaulter rate (p = 0.324) across the groups. Compliance of RUTF was significantly higher in the control group (93%) than in the intervention group (87%), p < 0.000. CONCLUSION: Our results showed no impact of SAM treatment on performance indicators of CMAM (recovery, relapse, death and default) between the standard CMAM programme performed at the health facility by the government and NGO staff and the programme performed at health house level by the LHWs in Pakistan. We recommend further robust trials in other settings to confirm our results.

Effectiveness of wheat soya blend supplementation during pregnancy and lactation on pregnancy outcomes and nutritional status of their infants at 6 months of age in Thatta and Sujawal districts of Sindh, Pakistan: a cluster randomized-controlled trial.

PURPOSE: We aimed to assess the effectiveness of wheat soya blend plus (WSBP) provided during pregnancy and lactation on weight gain during pregnancy, reduction of low birthweight (LBW), and improvement in nutritional status in infants at 6 months of age in Thatta and Sujawal districts of Sindh, Pakistan. METHODS: A cluster randomized-controlled trial was conducted in Thatta and Sujawal districts in Pakistan from August 2014 to December 2016. A total of 2030 pregnant women were enrolled in the study. These women and their infants were followed during pregnancy and first 6 months of life. Pregnant women received a monthly ration of 5 kg (i.e., 165 g/day) of WSB + during pregnancy and the first 6 months of their lactation period. RESULTS: There was no difference in weight gain during pregnancy between the intervention and control groups (n = 496, 326.7 g/week 95% CI 315.2-338.1 vs. (n = 507, 306.9 g/week, 95% CI 279.9-333.9 P = 0.192), after adjustment with different factors. The reduction in the prevalence of LBW was not different between intervention and control groups (n = 325, 34.0%, 95% CI 31.7-36.4, vs. (n = 127, 34.3%, 95% CI 27.2-41.5, P = 0.932). Significant reductions in risk of stunting (n = 1319 RR 0.85, 95% CI 0.73-0.99, P = 0.041), wasting (n = 1330 RR 0.77, 95% CI 0.65-0.91, P = 0.003), and underweight (n = 1295 RR 0.77, 95% CI 0.69-0.87, P < 0.001) were observed in infants at 6 months of age in the intervention as compared to the control group. However, no difference was noted on reduction in the risk of stunting among infants at 6 months of age in the intervention and control group (n = 1318 RR 0.91, 95% CI 0.78-1.07, P = 0.253) after adjustment. A significant reduction in anemia was noted (n = 1328 RR 0.94, 95% CI 0.91-0.98, P = 0.002) in infants at 6 months of age in the intervention as compared to the control group in adjusted analysis. CONCLUSIONS: Provision of WSB + during pregnancy and the first 6 months of lactation is effective in reducing the risk of under nutrition and anemia in infants at 6 months of age. This study can potentially guide the government and donor agencies in investing in nutritional programmes, especially for pregnant and lactating women living in vulnerable settings.

The relationship between pubertal timing and under-nutrition in rural Pakistan.

INTRODUCTION: Sexual development in females and males are routinely measured according to the Tanner Stages. Sparse data exist on the timing of pubertal milestones in Pakistan. To fill this gap, the age of attainment of pubertal milestones and their relationship with nutritional status was explored among children and adolescents living in the rural district of Matiari, Pakistan. METHODS: Anthropometry, nutrition biomarkers and Tanner Stage were assessed among girls aged 9.0-14.9 years (n = 723) and boys aged 10.0-15.9 years (n = 662) who were free from known disease in the rural District of Matiari, Pakistan. Median age was calculated for all Tanner Stages and menarche. Multivariable linear regressions were undertaken to determine covariates associated with the timing (age) of pubertal milestones. RESULTS: Among participants living in this rural community, the median age of puberty onset for girls was 11.9 years (95%CI:10.9; 12.5) and boys was 12.3 years (95%CI:11.5; 12.9). Age at first menarche was 12.9 years (95%CI:12.1; 13.3). Undernutrition was widespread among adolescents in this community. Thirty-seven percent of females and 27.0% of males were stunted while 20.5% of females and 31.3% of males were thin. Only 8% (n = 58) of females and 12% (n = 78) of males were free from any nutrient deficiency with most adolescents having two or three nutrient deficiencies. CONCLUSIONS: Undernutrition (stunting or thinness) was associated with relatively older ages for early puberty stages but not puberty completion. This may decrease the duration of the pubertal growth spurt and curtail potential catch-up growth that may occur during puberty. Efforts to decrease nutrient deficiencies, stunting and thinness beyond childhood should be made in rural Pakistan.

Food supplements to reduce stunting in Pakistan: a process evaluation of community dynamics shaping uptake.

BACKGROUND: There is an increasing interest in use of food supplements to prevent childhood stunting, however the evidence on the process indicators is scarce. We in this study explore the barriers to the effective implementation of food supplementation programs and the possible mitigation strategies which can guide the design of future programs. METHODS: We undertook a process evaluation of a stunting prevention food supplementation pilot program in rural Pakistan that distributed Wheat Soy Blend (WSB) to pregnant & lactating women, and Lipid-based Nutrient Supplement (LNS) and micronutrient powder (MNP) to < 5 years children. We used a mixed methods approach through a quantitative survey of 800 households and conducted 18 focused group discussion (FGDs) (with male and female caregivers), 4 FGDs (with Community Health Workers (CHWs)) and 22 key informant interviews (with district stakeholders) to evaluate the community side factors affecting uptake through five parameters: value, acceptability, receipt of supplement, usage and correct dosage. RESULTS: The findings show that proportionately few beneficiaries consumed the full dose of supplements, despite reasonable knowledge amongst caregivers. Sharing of supplements with other household member was common, and the full monthly stock was usually not received. Qualitative findings suggest that caregivers did not associate food supplements with stunting prevention. WSB was well accepted as an extra ration, LNS was popular due its chocolaty taste and texture, whereas MNP sprinkles were perceived to be of little value. The cultural food practices led to common sharing, whereas interaction with CHWs was minimal for nutrition counselling. Qualitative findings also indicate CHWs related programmatic constraints of low motivation, multi-tasking, inadequate counselling skills and weak supervision. CONCLUSION: We conclude that the community acceptability of food supplements does not translate into optimal consumption. Hence a greater emphasis is needed on context specific demand creation and focusing on the supply side constraints with improved logistical planning, enhanced motivation and supervision of community workers with involvement of multiple stakeholders. While, similar studies are needed in varying contexts to help frame universal guidelines. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02422953 . Registered on April 22, 2015.

Simulator-based ultrasound training for identification of endotracheal tube placement in a neonatal intensive care unit using point of care ultrasound.

BACKGROUND: Simulators are an extensively utilized teaching tool in clinical settings. Simulation enables learners to practice and improve their skills in a safe and controlled environment before using these skills on patients. We evaluated the effect of a training session utilizing a novel intubation ultrasound simulator on the accuracy of provider detection of tracheal versus esophageal neonatal endotracheal tube (ETT) placement using point-of-care ultrasound (POCUS). We also investigated whether the time to POCUS image interpretation decreased with repeated simulator attempts. METHODS: Sixty neonatal health care providers participated in a three-hour simulator-based training session in the neonatal intensive care unit (NICU) of Aga Khan University Hospital (AKUH), Karachi, Pakistan. Participants included neonatologists, neonatal fellows, pediatric residents and senior nursing staff. The training utilized a novel low-cost simulator made with gelatin, water and psyllium fiber. Training consisted of a didactic session, practice with the simulator, and practice with intubated NICU patients. At the end of training, participants underwent an objective structured assessment of technical skills (OSATS) and ten rounds of simulator-based testing of their ability to use POCUS to differentiate between simulated tracheal and esophageal intubations. RESULTS: The majority of the participants in the training had an average of 7.0 years (SD 4.9) of clinical experience. After controlling for gender, profession, years of practice and POCUS knowledge, linear mixed model and mixed effects logistic regression demonstrated marginal improvement in POCUS interpretation over repeated simulator testing. The mean time-to-interpretation decreased from 24.7 (SD 20.3) seconds for test 1 to 10.1 (SD 4.5) seconds for Test 10, p < 0.001. There was an average reduction of 1.3 s (ß = - 1.3; 95% CI: - 1.66 to - 1.0) in time-to-interpretation with repeated simulator testing after adjusting for the covariates listed above. CONCLUSION: We found a three-hour simulator-based training session had a significant impact on technical skills and performance of neonatal health care providers in identification of ETT position using POCUS. Further research is needed to examine whether these skills are transferable to intubated newborns in various health settings. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03533218 . Registered May 2018.

Causes and incidence of community-acquired serious infections among young children in south Asia (ANISA): an observational cohort study.

BACKGROUND: More than 500 000 neonatal deaths per year result from possible serious bacterial infections (pSBIs), but the causes are largely unknown. We investigated the incidence of community-acquired infections caused by specific organisms among neonates in south Asia. METHODS: From 2011 to 2014, we identified babies through population-based pregnancy surveillance at five sites in Bangladesh, India, and Pakistan. Babies were visited at home by community health workers up to ten times from age 0 to 59 days. Illness meeting the WHO definition of pSBI and randomly selected healthy babies were referred to study physicians. The primary objective was to estimate proportions of specific infectious causes by blood culture and Custom TaqMan Array Cards molecular assay (Thermo Fisher, Bartlesville, OK, USA) of blood and respiratory samples. FINDINGS: 6022 pSBI episodes were identified among 63 114 babies (95·4 per 1000 livebirths). Causes were attributed in 28% of episodes (16% bacterial and 12% viral). Mean incidence of bacterial infections was 13·2 (95% credible interval [CrI] 11·2-15·6) per 1000 livebirths and of viral infections was 10·1 (9·4-11·6) per 1000 livebirths. The leading pathogen was respiratory syncytial virus (5·4, 95% CrI 4·8-6·3 episodes per 1000 livebirths), followed by Ureaplasma spp (2·4, 1·6-3·2 episodes per 1000 livebirths). Among babies who died, causes were attributed to 46% of pSBI episodes, among which 92% were bacterial. 85 (83%) of 102 blood culture isolates were susceptible to penicillin, ampicillin, gentamicin, or a combination of these drugs. INTERPRETATION: Non-attribution of a cause in a high proportion of patients suggests that a substantial proportion of pSBI episodes might not have been due to infection. The predominance of bacterial causes among babies who died, however, indicates that appropriate prevention measures and management could substantially affect neonatal mortality. Susceptibility of bacterial isolates to first-line antibiotics emphasises the need for prudent and limited use of newer-generation antibiotics. Furthermore, the predominance of atypical bacteria we found and high incidence of respiratory syncytial virus indicated that changes in management strategies for treatment and prevention are needed. Given the burden of disease, prevention of respiratory syncytial virus would have a notable effect on the overall health system and achievement of Sustainable Development Goal. FUNDING: Bill & Melinda Gates Foundation.

Oral Ondansetron Administration to Nondehydrated Children With Diarrhea and Associated Vomiting in Emergency Departments in Pakistan: A Randomized Controlled Trial.

STUDY OBJECTIVE: We determine whether single-dose oral ondansetron administration to children with vomiting as a result of acute gastroenteritis without dehydration reduces administration of intravenous fluid rehydration. METHODS: In this 2-hospital, double-blind, placebo-controlled, emergency department-based, randomized trial conducted in Karachi Pakistan, we recruited children aged 0.5 to 5.0 years, without dehydration, who had diarrhea and greater than or equal to 1 episode of vomiting within 4 hours of arrival. Patients were randomly assigned (1:1), through an Internet-based randomization service using a stratified variable-block randomization scheme, to single-dose oral ondansetron or placebo. The primary endpoint was intravenous rehydration (administration of ≥20 mL/kg of an isotonic fluid during 4 hours) within 72 hours of randomization. RESULTS: Participant median age was 15 months (interquartile range 10 to 26) and 59.4% (372/626) were male patients. Intravenous rehydration use was 12.1% (38/314) and 11.9% (37/312) in the placebo and ondansetron groups, respectively (odds ratio 0.98; 95% confidence interval [CI] 0.60 to 1.61; difference 0.2%; 95% CI of the difference -4.9% to 5.4%). Bolus fluid administration occurred within 72 hours of randomization in 10.8% (34/314) and 10.3% (27/312) of children administered placebo and ondansetron, respectively (odds ratio 0.95; 95% CI 0.56 to 1.59). A multivariable regression model fitted with treatment group and adjusted for antiemetic administration, antibiotics, zinc prerandomization, and vomiting frequency prerandomization yielded similar results (odds ratio 0.91; 95% CI 0.55 to 1.53). There was no interaction between treatment group and age, greater than or equal to 3 stools in the preceding 24 hours, or greater than or equal to 3 vomiting episodes in the preceding 24 hours. CONCLUSION: Oral administration of a single dose of ondansetron did not result in a reduction in intravenous rehydration use. In children without dehydration, ondansetron does not improve clinical outcomes.

Evaluation of the cost-effectiveness of the treatment of uncomplicated severe acute malnutrition by lady health workers as compared to an outpatient therapeutic feeding programme in Sindh Province, Pakistan.

BACKGROUND: Due to the limited evidence of the cost-effectiveness of Community Health Workers (CHW) delivering treatment for severe acute malnutrition (SAM), there is a need to better understand the costs incurred by both implementing institutions and beneficiary households. This study assessed the costs and cost-effectiveness of treatment for cases of SAM without complications delivered by government-employed Lady Health Workers (LHWs) and complemented with non-governmental organisation (NGO) delivered outpatient facility-based care compared with NGO delivered outpatient facility-based care only alongside a two-arm randomised controlled trial conducted in Sindh Province, Pakistan. METHODS: An activity-based cost model was used, employing a societal perspective to include costs incurred by beneficiaries and the wider community. Costs were estimated through accounting records, interviews and informal group discussions. Cost-effectiveness was assessed for each arm relative to no intervention, and incrementally between the two interventions, providing information on both absolute and relative costs and effects. RESULTS: The cost per child recovered in outpatient facility-based care was similar to LHW-delivered care, at 363 USD and 382 USD respectively. An additional 146 USD was spent per additional child recovered by outpatient facilities compared to LHWs. Results of sensitivity analyses indicated considerable uncertainty in which strategy was most cost-effective due to small differences in cost and recovery rates between arms. The cost to the beneficiary household of outpatient facility-based care was double that of LHW-delivered care. CONCLUSIONS: Outpatient facility-based care was found to be slightly more cost-effective compared to LHW-delivered care, despite the potential for cost-effectiveness of CHWs managing SAM being demonstrated in other settings. The similarity of cost-effectiveness outcomes between the two models resulted in uncertainty as to which strategy was the most cost-effective. Similarity of costs and effectiveness between models suggests that whether it is appropriate to engage LHWs in substituting or complementing outpatient facilities may depend on population needs, including coverage and accessibility of existing services, rather than be purely a consideration of cost. Future research should assess the cost-effectiveness of LHW-delivered care when delivered solely by the government. TRIAL REGISTRATION: NCT03043352 , ClinicalTrials.gov. Retrospectively registered.

A novel training simulator for portable ultrasound identification of incorrect newborn endotracheal tube placement - observational diagnostic accuracy study protocol.

BACKGROUND: Endotracheal tube (ETT) placement is a critical procedure for newborns that are unable to breathe. Inadvertent esophageal intubation can lead to oxygen deprivation and consequent permanent neurological impairment. Current standard-of-care methods to confirm ETT placement in neonates (auscultation, colorimetric capnography, and chest x-ray) are time consuming or unreliable, especially in the stressful resuscitation environment. Point-of-care ultrasound (POCUS) of the neck has recently emerged as a powerful tool for detecting esophageal ETTs. It is accurate and fast, and is also easy to learn and perform, especially on children. METHODS: This will be an observational diagnostic accuracy study consisting of two phases and conducted at the Aga Khan University Hospital in Karachi, Pakistan. In phase 1, neonatal health care providers that currently perform standard-of-care methods for ETT localization, regardless of experience in portable ultrasound, will undergo a two-hour training session. During this session, providers will learn to detect tracheal vs. esophageal ETTs using POCUS. The session will consist of a didactic component, hands-on training with a novel intubation ultrasound simulator, and practice with stable, ventilated newborns. At the end of the session, the providers will undergo an objective structured assessment of technical skills, as well as an evaluation of their ability to differentiate between tracheal and esophageal endotracheal tubes. In phase 2, newborns requiring intubation will be assessed for ETT location via POCUS, at the same time as standard-of-care methods. The initial 2 months of phase 2 will include a quality assurance component to ensure the POCUS accuracy of trained providers. The primary outcome of the study is to determine the accuracy of neck POCUS for ETT location when performed by neonatal providers with focused POCUS training, and the secondary outcome is to determine whether neck POCUS is faster than standard-of-care methods. DISCUSSION: This study represents the first large investigation of the benefits of POCUS for ETT confirmation in the sickest newborns undergoing intubations for respiratory support. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03533218. Registered May 2018.

Exchangeable Zinc Pool Size at Birth in Pakistani Small for Gestational Age and Appropriate for Gestational Age Infants Do Not Differ But Are Lower Than in US Infants.

OBJECTIVES: Small for gestational age (SGA) infants are more susceptible to infectious morbidity and growth faltering compared to their appropriate for gestational age (AGA) counterparts. Zinc supplementation of SGA infants may be beneficial but the underlying susceptibility to zinc deficiency of SGA infants has not been examined. METHODS: In a community-based, observational, longitudinal study in a peri-urban settlement of Karachi, Pakistan, we compared the size of the exchangeable zinc pools (EZPs) in term SGA and AGA infants at birth and at 6 months of age, hypothesizing that the EZP would be lower in the SGA group. To measure EZP size, a zinc stable isotope was intravenously administered within 48 hours of birth (n = 17 and 22) at 6 months (n = 11 and 14) in SGA and AGA infants, respectively. Isotopic enrichment in urine was used to determine EZP. RESULTS: No significant difference was detected in the mean (±standard deviation) EZP between SGA and AGA infants at birth, with values of 9.8 ±â€Š3.5 and 10.1 ±â€Š4.1 mg/kg, respectively (P = 0.86), or at 6 months. Longitudinal EZP measurements demonstrated a significant decline in EZP relative to body weight in both groups at 6 months (P < 0.001). Mean EZP (adjusted for body weight) size at birth for the combined Pakistani groups was significantly lower than AGA infants at birth in the United States (P = 0.017). CONCLUSIONS: These results did not support a difference in zinc endowment between SGA and AGA Pakistani infants. They, however, do suggest lower in utero zinc transfer to the fetus in a setting where poor maternal nutritional status may confer a high susceptibility to postnatal zinc deficiency.

Quality of care of treatment for uncomplicated severe acute malnutrition provided by lady health workers in Pakistan.

OBJECTIVE: To assess the quality of care provided by lady health workers (LHW) managing cases of uncomplicated severe acute malnutrition (SAM) in the community. DESIGN: Cross-sectional quality-of-care study. SETTING: The feasibility of the implementation of screening and treatment for uncomplicated SAM in the community by LHW was tested in Sindh Province, Pakistan. An observational, clinical prospective multicentre cohort study compared the LHW-delivered care with the existing outpatient health facility model. SUBJECTS: LHW implementing treatment for uncomplicated SAM in the community. RESULTS: Oedema was diagnosed conducted correctly for 87·5 % of children; weight and mid upper-arm circumference were measured correctly for 60·0 % and 57·4 % of children, respectively. The appetite test was conducted correctly for 42·0 % of cases. Of all cases of SAM without complications assessed during the study, 68·0 % received the correct medical and nutrition treatment. The proportion of cases that received the correct medical and nutrition treatment and key counselling messages was 4·0 %. CONCLUSIONS: This quality-of-care study supports existing evidence that LHW are able to identify uncomplicated SAM, and a majority can provide appropriate nutrition and medical treatment in the community. However, the findings also show that their ability to provide the complete package with an acceptable level of care is not assured. Additional evidence on the impact of supervision and training on the quality of SAM treatment and counselling provided by LHW to children with SAM is required. The study has also shown that, as in other sectors, it is essential that operational challenges are addressed in a timely manner and that implementers receive appropriate levels of support, if SAM is to be treated successfully in the community.