NeuroMotion smartphone application for remote General Movements Assessment: a feasibility study in Nepal.

OBJECTIVES: To evaluate the feasibility of using the NeuroMotion smartphone application for remote General Movements Assessment for screening infants for cerebral palsy in Kathmandu, Nepal. METHOD: Thirty-one term-born infants at risk of cerebral palsy due to birth asphyxia or neonatal seizures were recruited for the follow-up at Paropakar Maternity and Women's Hospital, 1 October 2021 to 7 January 2022. Parents filmed their children at home using the application at 3 months' age and the videos were assessed for technical quality using a standardised form and for fidgety movements by Prechtl's General Movements Assessment. The usability of the application was evaluated through a parental survey. RESULTS: Twenty families sent in altogether 46 videos out of which 35 had approved technical quality. Sixteen children had at least one video with approved technical quality. Three infants lacked fidgety movements. The level of agreement between assessors was acceptable (Krippendorf alpha 0.781). Parental answers to the usability survey were in general positive. INTERPRETATION: Engaging parents in screening of cerebral palsy with the help of a smartphone-aided remote General Movements Assessment is possible in the urban area of a South Asian lower middle-income country.

Effect of COVID-19 Pandemic on Emergency Department Admissions and Outcome.

BACKGROUND: Emergency Department admissions have changed significantly during the COVID-19 pandemic. Understanding this variation may play a crucial role in rearranging hospital resources for better outcome. In this study, we aimed to assess the impact of COVID-19 pandemic on emergency department admission and outcome. METHODS: This is a cross-sectional retrospective study conducted at Bharatpur Hospital, Nepal comparing pre- pandemic data of the 4 months (March 24 to July 21, 2019) with the initial 4 months of the pandemic (March 24 to July 21, 2020). RESULTS: Admission in emergency ward decreased during covid period among female admission (47%vs43%), age-group(0-14)(18%vs12%), Dalit(17%vs11%) p<0.0001.Diagnosis increased during covid for acute abdomen(11%vs13%), animal and insect bite(10%vs13%), psychiatric illness(2%vs6%),poisoning and drug over dose(0.9%vs2.6%)(p<0.0001).The odds for referral(cOR 3.62,95% CI:2.70-4.84), Left against medical advice(cOR 6.03,95% CI:.06-8.94) and death(cOR 3.28,95% CI:1.64-6.68) increased during the covid respectively. CONCLUSIONS: There was decrease in rates of emergency department utilization during the Covid-19 pandemic. Admissions due to trauma, gastrointestinal, respiratory, neurological, musculoskeletal and coronary artery disease showed a decline whereas psychiatric disorders, diabetes and hypertension, animal and insect bites cases increased. Overall, mortality rate was increased.

Triubiquitin Probes for Identification of Reader and Eraser Proteins of Branched Polyubiquitin Chains.

The important roles played by branched polyubiquitin chains were recently uncovered in proteasomal protein degradation, mitotic regulation, and NF-κB signaling. With the new realization of a wide presence of branched ubiquitin chains in mammalian cells, there is an urgent need of identifying the reader and eraser proteins of the various branched ubiquitin chains. In this work, we report the generation of noncleavable branched triubiquitin probes with combinations of K11-, K48-, and K63-linkages. Through a pulldown approach using the branched triUb probes, we identified human proteins that recognize branched triubiquitin structures including ubiquitin-binding proteins and deubiquitinases (DUBs). Proteomics analysis of the identified proteins enriched by the branched triubiquitin probes points to possible roles of branched ubiquitin chains in cellular processes including DNA damage response, autophagy, and receptor endocytosis. In vitro characterization of several identified UIM-containing proteins demonstrated their binding to branch triubiquitin chains with moderate to high affinities. Availability of this new class of branched triubiquitin probes will enable future investigation into the roles of branched polyubiquitin chains through identification of specific reader and eraser proteins, and the modes of branched ubiquitin chain recognition and processing using biochemical and biophysical methods.

Molecular Dynamics Analysis of Fast-Spreading Severe Acute Respiratory Syndrome Coronavirus 2 Variants and Their Effects on the Interaction with Human Angiotensin-Converting Enzyme 2.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is evolving with mutations in the spike protein, especially in the receptor-binding domain (RBD). The failure of public health measures in some countries to contain the spread of the disease has given rise to novel viral variants with increased transmissibility. However, key questions about how quickly the variants can spread remain unclear. Herein, we performed a structural investigation using molecular dynamics simulations and determined dissociation constant (K D) values using surface plasmon resonance assays of three fast-spreading SARS-CoV-2 variants, alpha, beta, and gamma, as well as genetic factors in host cells that may be related to the viral infection. Our results suggest that the SARS-CoV-2 variants facilitate their entry into the host cell by moderately increased binding affinities to the human ACE2 receptor, different torsions in hACE2 mediated by RBD variants, and an increased spike exposure time to proteolytic enzymes. We also found that other host cell aspects, such as gene and isoform expression of key genes for the infection (ACE2, FURIN, and TMPRSS2), may have few contributions to the SARS-CoV-2 variant infectivity. In summary, we concluded that a combination of viral and host cell factors allows SARS-CoV-2 variants to increase their abilities to spread faster than the wild type.

Clinical Profile and Outcome of Corona Virus Disease-19 Infection in Pregnant Women.

BACKGROUND: The corona virus disease 19 pandemic has affected the whole world with pregnant ladies being more vulnerable population. This study aimed to evaluate characteristics of corona virus disease 19 infection in pregnancy and neonates and whether close proximity to the mother increases the incidence of corona virus disease infection in neonates.. METHODS: This is a hospital based prospective cross sectional observational study done among pregnant women presenting to Paropakar maternity and womens hospital from 1st September 2020 to 31st march 2021 with confirmed corona virus disease 19 infection. RESULTS: The total 160 cases were included in study. Most of the women (33.8%) were of 20- 25 years of age, 55 % were multigravida and 77.6 % were full term. Around 74 % of cases were symptomatic with predominant symptoms being cough, fever and sore throat present in 33.1 %, 18% and 14% respectively. Out of 125 deliveries 71 % of cases underwent cesarean section of which fetal distress was most common indication. Six newborns were positive for corona virus disease 19 infection within 48 hours of life. Mortality was seen in four mothers and three neonates. CONCLUSIONS: The clinical presentation of corona virus disease infection in pregnant ladies is similar to general population. There is no increased risk of vertical transmission to the baby.

Predictors for timely initiation of breastfeeding after birth in the hospitals of Nepal- a prospective observational study.

BACKGROUND: Timely initiation of breastfeeding can reduce neonatal morbidities and mortality. We aimed to study predictors for timely initiation of breastfeeding (within 1 h of birth) among neonates born in hospitals of Nepal. METHOD: A prospective observational study was conducted in four public hospitals between July and October 2018. All women admitted in the hospital for childbirth and who consented were included in the study. An independent researchers observed whether the neonates were placed in skin-to-skin contact, delay cord clamping and timely initiation of breastfeeding. Sociodemographic variables, obstetric and neonate information were extracted from the maternity register. We analysed predictors for timely initiation of breastfeeding with Pearson chi-square test and multivariate logistic regression. RESULTS: Among the 6488 woman-infant pair observed, breastfeeding was timely initiated in 49.5% neonates. The timely initiation of breastfeeding was found to be higher among neonates who were placed skin-to-skin contact (34.9% vs 19.9%, p - value < 0.001). The timely initiation of breastfeeding was higher if the cord clamping was delayed than early cord clamped neonates (44.5% vs 35.3%, p - value < 0.001). In multivariate analysis, a mother with no obstetric complication during admission had 57% higher odds of timely initiation of breastfeeding (aOR 1.57; 95% CI 1.33, 1.86). Multiparity was associated with less timely initiation of breastfeeding (aOR 1.56; 95% CI 1.35, 1.82). Similarly, there was more common practice of timely initiation of breastfeeding among low birthweight neonates (aOR 1.46; 95% CI 1.21, 1.76). Neonates who were placed skin-to-skin contact with mother had more than two-fold higher odds of timely breastfeeding (aOR 2.52; 95% CI 2.19, 2.89). Likewise, neonates who had their cord intact for 3 min had 37% higher odds of timely breastfeeding (aOR 1.37; 95% CI 1.21, 1.55). CONCLUSIONS: The rate of timely initiation of breastfeeding practice is low in the health facilities of Nepal. Multiparity, no obstetric complication at admission, neonates placed in skin-to-skin contact and delay cord clamping were strong predictors for timely initiation of breastfeeding. Quality improvement intervention can improve skin-to-skin contact, delayed cord clamping and timely initiation of breastfeeding.

A multicenter study of incidence, risk factors and outcomes of babies with birth asphyxia in Nepal.

BACKGROUND: Perinatal events which result in compromised oxygen delivery to the fetus can lead to Birth Asphyxia (BA). While the incidence, risk factors and outcomes of BA have been characterized, less is known in low resource settings. AIM: To determine the incidence of Birth Asphyxia (BA) in Nepal and to evaluate associated risk factors and outcomes of this condition. METHODS: A nested observational study was conducted in 12 hospitals of Nepal for a period of 14 months. Babies diagnosed as BA at ≥37 weeks of gestation were identified and demographics were reviewed. Data were analyzed using binary logistic regression followed by multiple logistic regression analysis. RESULTS: The incidence of BA in this study was 6 per 1000 term livebirths and was higher among women 35 years and above. Predictors for BA were instrumented vaginal delivery (aOR:4.4, 95% CI, 3.1-6.1), fetal distress in labour (aOR:1.9, 95% CI, 1.0-3.6), malposition (aOR:1.8, 95% CI, 1.0-3.0), birth weight less than 2500 g (aOR:2.0, 95% CI, 1.3-2.9), gestational age ≥ 42 weeks (aOR:2.0, 95% CI, 1.3-3.3) and male gender (aOR:1.6, 95% CI, 1.2-2.0). The risk of pre-discharge mortality was 43 times higher in babies with BA (aOR:42.6, 95% CI, 32.2-56.3). CONCLUSION: The incidence of Birth asphyxia in Nepal higher than in more resourced setting. A range of obstetric and neonatal risk factors are associated with BA with an associated high risk of pre-discharge mortality. Interventions to improve management and decrease rates of BA could have marked impact on outcomes in low resource settings.

Burden and consequence of birth defects in Nepal-evidence from prospective cohort study.

BACKGROUND: Every year an estimated 7.9 million babies are born with birth defect. Of these babies, more than 3 million die and 3.2 million have disability. Improving nationwide information on prevalence of birth defect, risk factor and consequence is required for better resource allocation for prevention, management and rehabilitation. In this study, we assess the prevalence of birth defect, associated risk factors and consequences in Nepal. METHOD: This is a prospective cohort study conducted in 12 hospitals of Nepal for 18 months. All the women who delivered in the hospitals during the study period was enrolled. Independent researchers collected data on the social and demographic information using semi-structured questionnaire at the time of discharge and clinical events and birth outcome information from the clinical case note. Data were analyzed on the prevalence and type of birth defect. Logistic regression was done to assess the risk factor and consequences for birth defect. RESULTS: Among the total 87,242 livebirths, the prevalence of birth defects was found to be 5.8 per 1000 live births. The commonly occurring birth defects were anencephaly (3.95%), cleft lip (2.77%), cleft lip and palate (6.13%), clubfeet (3.95%), eye abnormalities (3.95%) and meningomyelocele (3.36%). The odds of birth defect was higher among mothers with age < 20 years (adjusted Odds ratio (aOR) 1.64; 95% CI, 1.18-2.28) and disadvantaged ethnicity (aOR 1.78; 95% CI, 1.46-2.18). The odds of birth asphyxia was twice fold higher among babies with birth defect (aOR 1.88; 95% CI, 1.41-2.51) in reference with babies without birth defect. The odds of neonatal infection was twice fold higher among babies with birth defect (aOR 1.82; 95% CI, 1.12-2.96) in reference with babies without birth defect. Babies with birth defect had three-fold risk of pre-discharge mortality (aOR 3.00; 95% CI, 1.93-4.69). CONCLUSION: Maternal age younger than 20 years and advantaged ethnicity were risk factors of birth defects. Babies with birth defect have high risk for birth asphyxia, neonatal infection and pre-discharge mortality at birth. Further evaluation on the care provided to babies who have birth defect is warranted. FUNDING: Swedish Research Council (VR).

REFINE (Rapid Feedback for quality Improvement in Neonatal rEsuscitation): an observational study of neonatal resuscitation training and practice in a tertiary hospital in Nepal.

BACKGROUND: Simulation-based training in neonatal resuscitation is more effective when reinforced by both practice and continuous improvement processes. We aim to evaluate the effectiveness of a quality improvement program combined with an innovative provider feedback device on neonatal resuscitation practice and outcomes in a public referral hospital of Nepal. METHODS: A pre- and post-intervention study will be implemented in Pokhara Academy of Health Sciences, a hospital with 8610 deliveries per year. The intervention package will include simulation-based training (Helping Babies Breathe) enhanced with a real-time feedback system (the NeoBeat newborn heart rate meter with the NeoNatalie Live manikin and upright newborn bag-mask with PEEP) accompanied by a quality improvement process. An independent research team will collect perinatal data and conduct stakeholder interviews. DISCUSSION: This study will provide further information on the efficiency of neonatal resuscitation training and implementation in the context of new technologies and quality improvement processes. TRIAL REGISTRATION: https://doi.org/10.1186/ISRCTN18148368 , date of registration-31 July 2018.

Adherence to World Health Organisation guidelines for treatment of early onset neonatal sepsis in low-income settings; a cohort study in Nepal.

BACKGROUND: Neonatal sepsis is one of the major causes of death during the first month of life and early empirical treatment with injectable antibiotics is a life-saving intervention. Adherence to World Health Organisation guidelines on first line antibiotics is crucial to mitigate the risks of increased antimicrobial resistance. The aim of this paper was to evaluate if treatment of early onset neonatal sepsis in a low-income facility setting observe current guidelines and if compliance is influenced by contextual factors. METHODS: This cohort study used data on antimicrobial treatment of neonatal sepsis onset within 72 h of life from 12 regional hospitals participating in a scale-up trial of a neonatal resuscitation quality improvement package intervention in Nepal. Infants treated according to guidelines were compared with those receiving other antimicrobials. A multiple logistic regression analysis adjusted for the intervention and time trend was applied. RESULTS: 1564 infants with a preliminary diagnosis of early onset sepsis were included. A majority (74.9%) were treated according to guidelines and adherence was increasing over time. Infants born at larger facilities (adjusted Odds Ratio 5.6), those that were inborn (adjusted Odds Ratio 1.97) or belonging to a family of dis-advantaged caste (adjusted Odds Ratio 2.15) had higher odds for treatment according to guidelines. A clinical presentation of lethargy or tachypnoea was associated with adherence to guidelines. CONCLUSION: Adherence to guidelines for antibiotic treatment of early neonatal sepsis was moderately high in this low-income setting. Odds for observing guidelines increased with facility size, for inborn infants and if the family belonged to a dis-advantaged caste. Cefotaxime was a common alternative choice when guidelines were not followed, highly relevant for the risk of increased antimicrobial resistance. TRIAL REGISTRATION: ISRCTN, ISRCTN30829654 , registered 17th of May, 2017.

Effect of the COVID-19 pandemic response on intrapartum care, stillbirth, and neonatal mortality outcomes in Nepal: a prospective observational study.

BACKGROUND: The COVID-19 pandemic response is affecting maternal and neonatal health services all over the world. We aimed to assess the number of institutional births, their outcomes (institutional stillbirth and neonatal mortality rate), and quality of intrapartum care before and during the national COVID-19 lockdown in Nepal. METHODS: In this prospective observational study, we collected participant-level data for pregnant women enrolled in the SUSTAIN and REFINE studies between Jan 1 and May 30, 2020, from nine hospitals in Nepal. This period included 12·5 weeks before the national lockdown and 9·5 weeks during the lockdown. Women were eligible for inclusion if they had a gestational age of 22 weeks or more, a fetal heart sound at time of admission, and consented to inclusion. Women who had multiple births and their babies were excluded. We collected information on demographic and obstetric characteristics via extraction from case notes and health worker performance via direct observation by independent clinical researchers. We used regression analyses to assess changes in the number of institutional births, quality of care, and mortality before lockdown versus during lockdown. FINDINGS: Of 22 907 eligible women, 21 763 women were enrolled and 20 354 gave birth, and health worker performance was recorded for 10 543 births. From the beginning to the end of the study period, the mean weekly number of births decreased from 1261·1 births (SE 66·1) before lockdown to 651·4 births (49·9) during lockdown-a reduction of 52·4%. The institutional stillbirth rate increased from 14 per 1000 total births before lockdown to 21 per 1000 total births during lockdown (p=0·0002), and institutional neonatal mortality increased from 13 per 1000 livebirths to 40 per 1000 livebirths (p=0·0022). In terms of quality of care, intrapartum fetal heart rate monitoring decreased by 13·4% (-15·4 to -11·3; p<0·0001), and breastfeeding within 1 h of birth decreased by 3·5% (-4·6 to -2·6; p=0·0032). The immediate newborn care practice of placing the baby skin-to-skin with their mother increased by 13·2% (12·1 to 14·5; p<0·0001), and health workers' hand hygiene practices during childbirth increased by 12·9% (11·8 to 13·9) during lockdown (p<0·0001). INTERPRETATION: Institutional childbirth reduced by more than half during lockdown, with increases in institutional stillbirth rate and neonatal mortality, and decreases in quality of care. Some behaviours improved, notably hand hygiene and keeping the baby skin-to-skin with their mother. An urgent need exists to protect access to high quality intrapartum care and prevent excess deaths for the most vulnerable health system users during this pandemic period. FUNDING: Grand Challenges Canada.

Incidence, risk factors and consequences of preterm birth - findings from a multi-centric observational study for 14 months in Nepal.

BACKGROUND: Preterm birth is a worldwide epidemic and a leading cause of neonatal mortality. In this study, we aimed to evaluate the incidence, risk factors and consequences of preterm birth in Nepal. METHODS: This was an observational study conducted in 12 public hospitals of Nepal. All the babies born during the study period were included in the study. Babies born < 37 weeks of gestation were classified as preterm births. For the association and outcomes for preterm birth, univariate followed by multiple regression analysis was conducted. RESULTS: The incidence of preterm was found to be 93 per 1000 live births. Mothers aged less than 20 years (aOR 1.26;1.15-1.39) had a high risk for preterm birth. Similarly, education of the mother was a significant predictor for preterm birth: illiterate mothers (aOR 1.41; 1.22-1.64), literate mothers (aOR 1.21; 1.08-1.35) and mothers having basic level of education (aOR 1.17; 1.07-1.27). Socio-demographic factors such as smoking (aOR 1.13; 1.01-1.26), use of polluted fuel (aOR 1.26; 1.17-1.35) and sex of baby (aOR 1.18; 1.11-1.26); obstetric factors such as nulliparity (aOR 1.33; 1.20-1.48), multiple delivery (aOR 6.63; 5.16-8.52), severe anemia during pregnancy (aOR 3.27; 2.21-4.84), antenatal visit during second trimester (aOR 1.13; 1.05-1.22) and third trimester (aOR 1.24; 1.12-1.38), < 4 antenatal visits during pregnancy (aOR 1.49; 1.38-1.61) were found to be significant risk factors of preterm birth. Preterm has a risk for pre-discharge mortality (10.60; 9.28-12.10). CONCLUSION: In this study, we found high incidence of preterm birth. Various socio-demographic, obstetric and neonatal risk factors were associated with preterm birth. Risk factor modifications and timely interventions will help in the reduction of preterm births and associated mortalities. TRIAL REGISTRATION: ISRCTN30829654.

Epidemiology of neonatal infections in hospitals of Nepal: evidence from a large- scale study.

BACKGROUND: Every year, neonatal infections account for approximately 750,000 neonatal deaths globally. It is the third major cause of neonatal death, globally and in Nepal. There is a paucity of data on clinical aetiology and outcomes of neonatal infection in Nepal. This paper aims to assess the incidence and risk factors of neonatal infection in babies born in public hospitals of Nepal. METHODS: This is a prospective cohort study conducted for a period of 14 months, nested within a large-scale cluster randomized control trial which evaluated the Helping Babies Breathe Quality Improvement package in 12 public hospitals in Nepal. All the mothers who consented to participate within the study and delivered in these hospitals were included in the analysis. All neonates admitted into the sick newborn care unit weighing > 1500 g or/and 32 weeks or more gestation with clinical signs of infection or positive septic screening were taken as cases and those that did not have an infection were the comparison group. Bivariate and multi-variate analysis of socio-demographic, maternal, obstetric and neonatal characteristics of case and comparison group were conducted to assess risk factors associated with neonatal infection. RESULTS: The overall incidence of neonatal infection was 7.3 per 1000 live births. Babies who were born to first time mothers were at 64% higher risk of having infection (aOR-1.64, 95% CI, 1.30-2.06, p-value< 0.001). Babies born to mothers who had no antenatal check-up had more than three-fold risk of infection (aOR-3.45, 95% CI, 1.82-6.56, p-value< 0.001). Babies born through caesarean section had more than two-fold risk (aOR-2.06, 95% CI, 1.48-2.87, p-value< 0.001) and babies with birth asphyxia had more than three-fold risk for infection (aOR-3.51, 95% CI, 1.71-7.20, p-value = 0.001). CONCLUSION: Antepartum factors, such as antenatal care attendance, and intrapartum factors such as mode of delivery and birth asphyxia, were risk factors for neonatal infections. These findings highlight the importance of ANC visits and the need for proper care during resuscitation in babies with birth asphyxia.

Prevalence, risk factors and consequences of newborns born small for gestational age: a multisite study in Nepal.

OBJECTIVE: To identify the prevalence, risk factors and health impacts associated with small for gestational age (SGA) births in Nepal. METHODS: A cross-sectional study was conducted in 12 public hospitals in Nepal from 1 July 2017 to 29 August 2018. A total of 60 695 babies delivered in these hospitals during the study period were eligible for inclusion. Clinical information of mothers and newborns was collected by data collectors using a data retrieval form. A semistructured interview was conducted at the time of discharge to gather sociodemographic information from women who provided the consent (n=50 392). Babies weighing less than the 10th percentile for their gestational age were classified as SGA. Demographic, obstetric and neonatal characteristics of study participants were analysed for associations with SGA. The association between SGA and likelihood of babies requiring resuscitation or resulting in stillbirth and neonatal death was also explored. RESULTS: The prevalence of SGA births across the 12 hospitals observed in Nepal was 11.9%. After multiple variable adjustment, several factors were found to be associated with SGA births, including whether mothers were illiterate compared with those completing secondary and higher education (adjusted OR (AOR)=1.73; 95% CI 1.09 to 2.76), use of polluted fuel compared with use of clean fuel for cooking (AOR=1.51; 95% CI 1.16 to 1.97), first antenatal care (ANC) visit occurring during the third trimester compared with first trimester (AOR=1.82; 95% CI 1.27 to 2.61) and multiple deliveries compared with single delivery (AOR=3.07; 95% CI 1.46 to 6.46). SGA was significantly associated with stillbirth (AOR=7.30; 95% CI 6.26 to 8.52) and neonatal mortality (AOR=5.34; 95% CI 4.65 to 6.12). CONCLUSIONS: Low literacy status of mothers, use of polluted fuel for cooking, time of first ANC visit and multiple deliveries are associated with SGA births. Interventions encouraging pregnant women to attend ANC visits early can reduce the burden of SGA births.

Meconium aspiration syndrome: incidence, associated risk factors and outcome-evidence from a multicentric study in low-resource settings in Nepal.

AIM: The aim of this study was to identify the incidence, risk factors and outcome associated with meconium aspiration syndrome (MAS). METHODS: An observational study was conducted in 12 public hospitals in Nepal from 1 July 2017 to 29 August 2018. All babies born within the study period were included in the study. Babies who were diagnosed as MAS were designated as outcome. Data were analysed with bivariate analysis followed by multiple regression analysis. RESULTS: The overall incidence of MAS was 2.0 per 1000 livebirths. Babies born at post-term gestation (adjusted odds ratio (AOR) = 2.41; 95% confidence interval (CI): 1.05-5.55), nulliparity (AOR = 2.26; 95% CI: 1.20-4.28), instrumental delivery (AOR = 4.79; 95% CI: 2.52-9.10) and caesarean delivery (AOR = 3.67; 95% CI: 2.29-5.89) were significantly associated with MAS. Babies with MAS had a 10-fold risk for pre-discharge mortality (odds ratio = 9.87; 95% CI: 5.81-16.76). CONCLUSIONS: The findings in this study are consistent with that reported in other studies. MAS has a high risk of neonatal mortality. Thus, monitoring during pregnancy and labour is necessary for early identification of high-risk conditions associated with MAS. Strengthening of newborn care services is essential to curtail mortality.

Equity and Coverage in the Continuum of Reproductive, Maternal, Newborn and Child Health Services in Nepal-Projecting the Estimates on Death Averted Using the LiST Tool.

INTRODUCTION: The third Sustainable Development Goal, focused on health, includes two targets related to the reduction in maternal, newborn and under-five childhood mortality. We found it imperative to examine the equity and coverage of reproductive, maternal, newborn and child health (RMNCH) interventions from 2001 to 2016 in Nepal; and the death aversion that will take place during the SDG period. METHODS: We used the datasets from the Nepal Demographic Health Surveys (NDHS) 2001, 2006, 2011 and 2016. We calculated the coverage and equity for RMNCH interventions and the composite coverage index (CCI). Based on the Annualized Rate of Change (ARC) in the coverage for selected RMNCH indicators, we projected the trend for the RMNCH interventions by 2030. We used the Lives Saved Tools (LiST) tool to estimate the maternal, newborn, under-five childhood deaths and stillbirths averted. We categorised the interventions into four different patterns based on coverage and inequity gap. RESULTS: Between 2001 and 2016, a significant improvement is seen in the overall RMNCH intervention coverage-CCI increasing from 46 to 75%. The ARC was highest for skilled attendance at birth (11.7%) followed by care seeking for pneumonia (8.2%) between the same period. In 2016, the highest inequity existed for utilization of the skilled birth attendance services (51%), followed by antenatal care (18%). The inequity gap for basic immunization services reduced significantly from 27.4% in 2001 to 5% in 2016. If the current ARC continues, then an additional 3783 maternal deaths, 36,443 neonatal deaths, 66,883 under-five childhood deaths and 24,024 stillbirths is expected to be averted by the year 2030. CONCLUSION: Nepal has experienced an improvement in the coverage and equity in RMNCH interventions. Reducing inequities will improve coverage for skilled birth attendants and antenatal care. The current annual rate of change in RMNCH coverage will further reduce the maternal, neonatal, under-five childhood deaths and stillbirths.

Effect of a scaled-up neonatal resuscitation quality improvement package on intrapartum-related mortality in Nepal: A stepped-wedge cluster randomized controlled trial.

BACKGROUND: Improving quality of intrapartum care will reduce intrapartum stillbirth and neonatal mortality, especially in resource-poor settings. Basic neonatal resuscitation can reduce intrapartum stillbirth and early neonatal mortality, if delivered in a high-quality health system, but there is a dearth of evidence on how to scale up such evidence-based interventions. We evaluated the scaling up of a quality improvement (QI) package for neonatal resuscitation on intrapartum-related mortality (intrapartum stillbirth and first day mortality) at hospitals in Nepal. METHODS AND FINDINGS: We conducted a stepped-wedge cluster randomized controlled trial in 12 hospitals over a period of 18 months from April 14, 2017, to October 17, 2018. The hospitals were assigned to one of four wedges through random allocation. The QI package was implemented in a stepped-wedge manner with a delay of three months for each step. The QI package included improving hospital leadership on intrapartum care, building health workers' competency on neonatal resuscitation, and continuous facilitated QI processes in clinical units. An independent data collection system was set up at each hospital to gather data on mortality through patient case note review and demographic characteristics of women using semi-structured exit interviews. The generalized linear mixed model (GLMM) and multivariate logistic regression were used for analyses. During this study period, a total of 89,014 women-infant pairs were enrolled. The mean age of the mother in the study period was 24.0 ± 4.3 years, with 54.9% from disadvantaged ethnic groups and 4.0% of them illiterate. Of the total birth cohort, 54.4% were boys, 16.7% had gestational age less than 37 weeks, and 17.1% had birth weight less than 2,500 grams. The incidence of intrapartum-related mortality was 11.0 per 1,000 births during the control period and 8.0 per 1,000 births during the intervention period (adjusted odds ratio [aOR], 0.79; 95% CI, 0.69-0.92; p = 0.002; intra-cluster correlation coefficient [ICC], 0.0286). The incidence of early neonatal mortality was 12.7 per 1,000 live births during the control period and 10.1 per 1,000 live births during the intervention period (aOR, 0.89; 95% CI, 0.78-1.02; p = 0.09; ICC, 0.1538). The use of bag-and-mask ventilation for babies with low Apgar score (<7 at 1 minute) increased from 3.2% in the control period to 4.0% in the intervention period (aOR, 1.52; 95% CI, 1.32-1.77, p = 0.003). There were two major limitations to the study; although a large sample of women-infant pairs were enrolled in the study, the clustering reduced the power of the study. Secondly, the study was not sufficiently powered to detect reduction in early neonatal mortality with the number of clusters provided. CONCLUSION: These results suggest scaled-up implementation of a QI package for neonatal resuscitation can reduce intrapartum-related mortality and improve clinical care. The QI intervention package is likely to be effective in similar settings. More implementation research is required to assess the sustainability of QI interventions and quality of care. TRIAL REGISTRATION: ISRCTN30829654.

Scaling Up Safer Birth Bundle Through Quality Improvement in Nepal (SUSTAIN)-a stepped wedge cluster randomized controlled trial in public hospitals.

BACKGROUND: Each year, 2.2 million intrapartum-related deaths (intrapartum stillbirths and first day neonatal deaths) occur worldwide with 99% of them taking place in low- and middle-income countries. Despite the accelerated increase in the proportion of deliveries taking place in health facilities in these settings, the stillborn and neonatal mortality rates have not reduced proportionately. Poor quality of care in health facilities is attributed to two-thirds of these deaths. Improving quality of care during the intrapartum period needs investments in evidence-based interventions. We aim to evaluate the quality improvement package-Scaling Up Safer Bundle Through Quality Improvement in Nepal (SUSTAIN)-on intrapartum care and intrapartum-related mortality in public hospitals of Nepal. METHODS: We will conduct a stepped wedge cluster randomized controlled trial in eight public hospitals with each having least 3000 deliveries a year. Each hospital will represent a cluster with an intervention transition period of 2 months in each. With a level of significance of 95%, the statistical power of 90% and an intra-cluster correlation of 0.00015, a study period of 19 months should detect at least a 15% change in intrapartum-related mortality. Quality improvement training, mentoring, systematic feedback, and a continuous improvement cycle will be instituted based on bottleneck analyses in each hospital. All concerned health workers will be trained on standard basic neonatal resuscitation and essential newborn care. Portable fetal heart monitors (Moyo®) and neonatal heart rate monitors (Neobeat®) will be introduced in the hospitals to identify fetal distress during labor and to improve neonatal resuscitation. Independent research teams will collect data in each hospital on intervention inputs, processes, and outcomes by reviewing records and carrying out observations and interviews. The dose-response effect will be evaluated through process evaluations. DISCUSSION: With the global momentum to improve quality of intrapartum care, better understanding of QI package within a health facility context is important. The proposed package is based on experiences from a similar previous scale-up trial carried out in Nepal. The proposed evaluation will provide evidence on QI package and technology for implementation and scale up in similar settings. TRIAL REGISTRATION NUMBER: ISRCTN16741720 . Registered on 2 March 2019.

Crystal structure and activity-based labeling reveal the mechanisms for linkage-specific substrate recognition by deubiquitinase USP9X.

USP9X is a conserved deubiquitinase (DUB) that regulates multiple cellular processes. Dysregulation of USP9X has been linked to cancers and X-linked intellectual disability. Here, we report the crystal structure of the USP9X catalytic domain at 2.5-Å resolution. The structure reveals a canonical USP-fold comprised of fingers, palm, and thumb subdomains, as well as an unusual ß-hairpin insertion. The catalytic triad of USP9X is aligned in an active configuration. USP9X is exclusively active against ubiquitin (Ub) but not Ub-like modifiers. Cleavage assays with di-, tri-, and tetraUb chains show that the USP9X catalytic domain has a clear preference for K11-, followed by K63-, K48-, and K6-linked polyUb chains. Using a set of activity-based diUb and triUb probes (ABPs), we demonstrate that the USP9X catalytic domain has an exo-cleavage preference for K48- and endo-cleavage preference for K11-linked polyUb chains. The structure model and biochemical data suggest that the USP9X catalytic domain harbors three Ub binding sites, and a zinc finger in the fingers subdomain and the ß-hairpin insertion both play important roles in polyUb chain processing and linkage specificity. Furthermore, unexpected labeling of a secondary, noncatalytic cysteine located on a blocking loop adjacent to the catalytic site by K11-diUb ABP implicates a previously unreported mechanism of polyUb chain recognition. The structural features of USP9X revealed in our study are critical for understanding its DUB activity. The new Ub-based ABPs form a set of valuable tools to understand polyUb chain processing by the cysteine protease class of DUBs.

The burden of misclassification of antepartum stillbirth in Nepal.

BACKGROUND: Globally, every year 1.1 million antepartum stillbirths occur with 98% of these deaths taking place in countries where the health system is poor. In this paper we examine the burden of misclassification of antepartum stillbirth in hospitals of Nepal and factors associated with misclassification. METHOD: A prospective observational study was conducted in 12 hospitals of Nepal for a period of 6 months. If fetal heart sounds (FHS) were detected at admission and during the intrapartum period, the antepartum stillbirth (fetal death ≥22 weeks prior labour) recorded in patient's case note was recategorised as misclassified antepartum stillbirth. We further compared sociodemographic, obstetric and neonatal characteristics of misclassified and correctly classified antepartum stillbirths using bivariate and multivariate analysis. RESULT: A total of 41 061 women were enrolled in the study and 39 562 of the participants' FHS were taken at admission. Of the total participants whose FHS were taken at admission, 94.8% had normal FHS, 4.7% had abnormal FHS and 0.6% had no FHS at admission. Of the total 119 recorded antepartum stillbirths, 29 (24.4%) had FHS at admission and during labour and therefore categorised as misclassified antepartum stillbirths. Multivariate analysis performed to adjust the risk of association revealed that complications during pregnancy resulted in a threefold risk of misclassification (adjusted OR-3.35, 95% CI 1.95 to 5.76). CONCLUSION: Almost 25% of the recorded antepartum stillbirths were misclassified. Improving quality of data is crucial to improving accountability and quality of care. As the interventions to reduce antepartum stillbirth differ, accurate measurement of antepartum stillbirth is critical. TRIAL REGISTRATION NUMBER: ISRCTN30829654.