Conducting a phase III clinical trial in children during the COVID- 19 pandemic: Experience and lessons learnt from a clinical research facility of Nepal.

Clinical trials in humans are vital to test safety and efficacy of new interventions and are accompanied with the complexity of related regulatory guidelines, stringent time frame and financial burden particularly when participants are children. Conducting clinical trials in low and middle income countries, where 90% of global diseases occur, increases the complexity as resources, infrastructures, and experience related to clinical trials may be limited in some countries. During the COVID-19 pandemic, due to multiple infection control measures such as social distancing, lock-down of the societies, and increased work load of hospital workers, conducting clinical trials seemed very challenging. Related guidelines and recommendations on clinical trials required updates to adapt the situation for ongoing clinical trials to be continued and new clinical trials to be initiated. In this review report, we described the lessons learnt through our experiences, challenges we faced, and the mitigation measures implemented as a response while conducting a phase III clinical trial on a non-COVID-19 vaccine at a government children's hospital during the COVID-19 pandemic. We hope this report will contribute in lowering the obstacles to allow the successful completion of future studies, in countries where people live with the burden of vaccine-preventable diseases.

Pathways to effective surgical coverage in a lower-middle-income country: A multiple methods study of the family physician-led generalist surgical team in rural Nepal.

The Lancet Commission on Global Surgery (LCoGS) recommends using specialist surgical workforce density as one of 6 core indicators for monitoring universal access to safe, affordable surgical and anaesthesia care. Using Nepal as a case study, we explored the capacity of a generalist workforce (led by a family physician or MD general practitioner and non-physician anaesthetist) to enable effective surgical delivery through task-shifting. Using a multiple-methods approach, we retrospectively mapped essential surgical care and the enabling environment for surgery in 39 hospitals in 25 remote districts in Nepal and compared it with LCoGS indicators. All 25 districts performed surgery, 21 performed Caesarean section (CS), and 5 met at least 50% of district CS needs. Generalist surgical teams performed CS, the essential major operation at the district level, and very few laparotomies, but no operative orthopaedics. The density of specialist Surgeon/Anaesthesiologist/Obstetrician (SAO) was 0·4/100,000; that of Generalist teams (gSAO) led by a family physician (MD General Practitioners-MDGP) supported by non-physician anaesthetists was eight times higher at 3·1/100,000. gSAO presence was positively associated with a two-fold increase in CS availability. All surgical rates were well below LCoGS targets. 46% of hospitals had adequate enabling environments for surgery, 28% had functioning anaesthesia machines, and 75% had blood transfusion services. Despite very low SAO density, and often inadequate enabling environment, surgery can be done in remote districts. gSAO teams led by family physicians are providing essential surgery, with CS the commonest major operation. gSAO density is eight times higher than specialists and they can undertake more complex operations than just CS alone. These family physician-led functional teams are providing a pathway to effective surgical coverage in remote Nepal.

Clinical Competency Retention after Mid-Level Practicum Training and It's Associated Factors among Health Workers of Nepal.

BACKGROUND: Mid-level health workers are deployed in a large proportion with the expectation of similar patient outcomes as with physicians. Mid-level practitioners are Health Assistants and Auxiliary Health Workers who provide clinical care at remote locations. National Health Training Center has been providing 60 days in-service Mid-level Practicum training since 2009 AD for the mid-level practitioners with the aim to enhance quality of patient care in Nepal. METHODS: An observational study conducted using retrospective data from onsite follow-up assessment of 180 Mid-level Practitioner from 18 districts of Nepal between July 2015 to June 2019. The retention of competency onsite follow-up was calculated as percentage of assessment score at the end of Mid-level Practicum training. Percentage retention of competency and association of retention with factors were analyzed using independent t-test. RESULTS: Majority of participants were male (85.6%), and working in a Health Post (84.4%). Average clinical competency retention in each domain at their work place was 68.79% in knowledge, 73.80% in patient encounter skill, 82.84% in clinical decision-making skill and 87.58% in clinical procedure skill. Higher age groups, longer years of experience and participants from Terai region found to be associated with lower retention of knowledge. A better enabling environment and higher case load retained higher patient encounter skill. CONCLUSIONS: The competency retention among Mid-level Practicum trained mid-level health workers was found to be higher. Factors found associated with competency retention were age, geographic region, years of experience, case load and enabling environment.

Effect of deploying biomedical equipment technician on the functionality of medical equipment in the government hospitals of rural Nepal.

BACKGROUND: Medical equipment plays a crucial role in the provision of quality healthcare services, despite this more than 50% of equipment in developing countries are non-functioning due to a lack of appropriate human resources to maintain. To address this problem some government hospitals of Nepal have deployed a mid-level technical cadre called 'Biomedical Equipment Technician' (BMET). This study aims to evaluate the effectiveness of deploying a BMET on the functionality of medical equipment in government hospitals of rural Nepal. METHODS: We used a mixed-methods approach with a comparative research design. A comprehensive range of 2189 pieces of medical equipment at 22 hospitals with and without BMET were observed to assess their functional status. Medical equipment were stratified into 6 categories based on department and T tests were conducted. We collected qualitative data from 9 BMETs, 22 medical superintendents, and 22 health staff using semi-structured interviews and focus-group discussions. Thematic content analysis was conducted to explore how the BMET's work was perceived. FINDINGS: The quantity of non-functional devices in hospitals without BMETs was double that of hospitals with BMETs (14% and 7% respectively, p < 0.005). Results were similar across all departments including General (16% versus 3%, p = 0.056), Lab (15% versus 7%, p < 0.005) and Operation Theater (14% versus 5%, p < 0.005). Hospitals with BMETs had fewer overall non-functional devices requiring simple or advanced repair compared to hospitals without BMETs [3% versus 7% (p < 0.005) simple; 4% versus 6% (p < 0.005) advanced]. In our qualitative analysis, we found that BMETs were highly appreciated by hospital staff. Hospital workers perceived that having a BMET on staff, rather than twice-yearly visits from central-level maintenance technicians, is an effective way to keep medical equipment functional. However, without a favorable working environment, the BMET alone cannot perform optimally. CONCLUSIONS: Having a BMET at a rural government hospital has a substantial positive effect on the functional status of medical devices at the hospital. BMETs should be deployed at all rural hospitals to increase the functionality of medical devices, thereby improving the working environment and quality of health services provided.

Factors affecting willingness to participate in vaccine clinical trials in an underdeveloped country: perspective from Nepal.

Due to the inherent complex nature of clinical trials, individual's willingness to participate and hence, enrollment in a clinical trial maybe challenging. When it comes to vaccine clinical trial in children, informed consent needs to be secured from the parents or legally acceptable representatives (LARs). Some of the factors which contribute to hesitancy in taking part in clinical trials are based on the level of education, living standards, part of the world they live, associated burden of disease, fear of different procedures in clinical trial, side effects, limited understanding, limited time, and mistrust with Investigational product. This study included 201 parents/LARs, who approached Kanti Children Hospital site in Kathmandu with the interest to get their children enrolled in a vaccine clinical trial with objectives of describing the reasons for agreeing or disagreeing to participate in the vaccine clinical trial, factors affecting decision making, and finding the major concerns of parents/LARs. The acceptance for the study vaccine was 136 (67.7%) whereas denial was 65 (32.3%). This study showed that age, education level, family structure, advice from family and friends, and medical guidance play important roles in willingness of parents to get their child enrolled in the trial. If a proper counseling is done, fear of blood sampling is not a big factor which is contrary to the belief among clinical researchers. Safety of vaccine, frequency of injections, and cost of vaccine were the main concerns of the parents, which need to be addressed extensively while planning for any clinical trial in children.

Maternity Waiting Home Interventions as a Strategy for Improving Birth Outcomes: A Scoping Review and Meta-Analysis.

BACKGROUND AND OBJECTIVE: Over 300 000 women worldwide die due to pregnancy-related complications annually, with most occurring in developing countries where access to skilled obstetric care is limited. Maternity waiting homes (MWHs) are one intervention designed to increase access to skilled prenatal care in resource-limited settings. MWHs are defined as accommodations at or near a health facility where pregnant women can stay in the final weeks of their pregnancy so they can be easily transferred to the health facility to give birth. While MWHs have existed for decades, evidence regarding their effectiveness in reducing adverse birth outcomes has been mixed. The objective of this study is to comprehensively assess all available MWH research reporting quantitative maternal and childbirth data to determine whether MWHs are an effective maternal health strategy in resource-limited settings. METHODOLOGY: We conducted a scoping review and meta-analysis of existing literature on MWHs according to PRISMA guidelines. Descriptive statistics and odds ratios were calculated for the following birth outcomes: maternal mortality, perinatal mortality, and caesarian section. Quantitative analysis was conducted in RStudio and Stata Version 16. RESULTS: One hundred seventy-one records were retrieved from our initial database search, of which 66 were identified as relevant. Only 15 of these records reported quantitative data on the health outcomes of interest and therefore met inclusion criteria for our meta-analysis. All studies reporting maternal mortality demonstrated a protective effect of MWHs (aggregate OR: 0.19 [0.10, 0.40]), as did all studies reporting perinatal mortality (aggregate OR: 0.29 [0.16, 0.53]). Studies reporting caesarian section were more varied and indicated less of a protective effect (aggregate OR: 1.80 [1.18, 2.75]). CONCLUSIONS: There is some indication that MWHs are an effective strategy for reducing maternal and perinatal mortality in resource-limited settings. However, our analysis was constrained by the observational design of most prior MWH studies. More rigorous MWH evaluations, ideally in the form of randomized-control trials, are needed to better determine MWH effectiveness.

Content of antenatal care and perception about services provided by primary hospitals in Nepal: a convergent mixed methods study.

BACKGROUND: Nepal has made significant strides in maternal and neonatal mortality over the last three decades. However, poor quality of care can threaten the gains, as maternal and newborn services are particularly sensitive to quality of care. Our study aimed to understand current gaps in the process and the outcome dimensions of the quality of antenatal care (ANC), particularly at the sub-national level. We assessed these dimensions of the quality of ANC in 17 primary, public hospitals across Nepal. We also assessed the variation in the ANC process across the patients' socio-economic gradient. METHODS: We used a convergent mixed methods approach, whereby we triangulated qualitative and quantitative data. In the quantitative component, we observed interactions between providers (17 hospitals from all 7 provinces) and 198 women seeking ANC and recorded the tasks the providers performed, using the Service Provision Assessments protocol available from the Demographic and Health Survey program. The main outcome variable was the number of tasks performed by the provider during an ANC consultation. The tasks ranged from identifying potential signs of danger to providing counseling. We analyzed the resulting data descriptively and assessed the relationship between the number of tasks performed and users' characteristics. In the qualitative component, we synthesized users' and providers' narratives on perceptions of the overall quality of care obtained through focus group discussions and in-depth interviews. RESULTS: Out of the 59 tasks recommended by the World Health Organization, providers performed only 22 tasks (37.3%) on average. The number of tasks performed varied significantly across provinces, with users in province 3 receiving significantly higher quality care than those in other provinces. Educated women were treated better than those with no education. Users and providers agreed that the overall quality of care was inadequate, although providers mentioned that the current quality was the best they could provide given the constraints they faced. CONCLUSION: The quality of ANC in Nepal's primary hospitals is poor and inequitable across education and geographic gradients. While current efforts, such as the provision of 24/7 birthing centers, can mitigate gaps in service availability, additional equipment, infrastructure and human resources will be needed to improve quality. Providers also need additional training focused on treating patients from different backgrounds equally. Our study also points to the need for additional research, both to document the quality of care more objectively and to establish key determinants of quality to inform policy.

Colorectal Cancer Screening at the Nexus of HIV, Minority Statuses, and Cultural Safety.

BACKGROUND: The incidence of non-AIDS-defining cancers has increased significantly among persons living with HIV (PLHIV). Screening education is recommended. PURPOSE: Social learning, minority stress, and cultural safety theories informed this pilot to assess the feasibility of a colorectal cancer screening intervention targeted to PLHIV, with additional tailoring for relevance to Native Hawaiians, a group with low participation in cancer screening. METHOD: The targeted education included behavioral modeling and barriers counseling in a culturally safe environment. Using a 2-group, pre/posttest design, AIDS service organizations were randomized to culturally responsive or standard education. AIDS service organizations consumers recruited through venue-based promotions were the unit of analysis. Knowledge-attitudes-practices, fecal occult blood test screening completion, and intervention feasibility were measured. RESULTS: Treatment arm participants, regardless of ethnicity, adhered to fecal occult blood test instructions and achieved increases in screening knowledge, attitudes, and practices. Relevance and acceptability of the educational intervention were endorsed. DISCUSSION: The culturally responsive intervention was successful in this group of PLHIV. Additional tailoring may be needed to reach PLHIV who do not participate in organizational activities. CONCLUSION/TRANSLATION TO HEALTH EDUCATION PRACTICE: This culturally responsive intervention shows promise for efficacy testing in a broader PLHIV population. Constituent-involving strategies were central to its development and delivery.

An assessment of the Pacific Regional Cancer Coalition: outcomes and implications of a regional coalition internal and external assessment.

SIGNIFICANCE: The Pacific Regional Cancer Coalition (PRCC) provides regional leadership in the U.S. Affiliated Pacific Islands (USAPI) to implement the Regional Comprehensive Control Plan: 2007-2012, and to evaluate its coalition and partnerships. The Pacific Center of Excellence in the Elimination of Disparities (CEED), aims to reduce cancer disparities and conducts evaluation activities relevant to cancer prevention and control in the USAPI. PURPOSE: The PRCC Self (internal) and Partner (external) Assessments were conducted to assess coalition functioning, regional and national partnerships, sustainability, and the role of regionalism for integrating all chronic disease prevention and control in the Pacific. METHODS: Self-administered questionnaires and key informant telephone interviews with PRCC members (N=20), and representatives from regional and national partner organizations were administered (N=26). Validated multi item measures using 5-point scales on coalition and partnership characteristics were used. Chronbach's alphas and averages for the measures were computed. RESULTS: Internal coalition measures: satisfaction (4.2, SD=0.48) communication (4.0, SD=0.56), respect (4.0, SD=0.60) were rated more highly than external partnership measures: resource sharing (3.5, SD=0.74), regionalism (3.9, SD=0.47), use of findings (3.9, SD=0.50). The PRCC specifically identified its level of "collaboration" with external partners including Pacific CEED. External partners identified its partnership with the PRCC in the "coalition" stage. PRINCIPAL CONCLUSIONS: PRCC members and external partners are satisfied with their partnerships. All groups should continue to focus on building collaboration with partners to reflect a truly regional approach to sustain the commitment, the coalitions and the programming to reduce cancer in the USAPI. PRCC and partners should also work together to integrate all chronic disease prevention and control efforts in the Pacific.

Economic assessment of a women's group intervention to improve birth outcomes in rural Nepal.

We did a cost-effectiveness analysis alongside a cluster-randomised controlled trial of a participatory intervention with women's groups to improve birth outcomes in rural Nepal. The average provider cost of the women's group intervention was US0.75 dollars per person per year (0.90 dollars with health-service strengthening) in a population of 86,704. The incremental cost per life-year saved (LYS) was 211 dollars (251 dollars), and expansion could rationalise on start-up costs and technical assistance, reducing the cost per LYS to 138 dollars (179 dollars). Sensitivity analysis showed a variation from 83 dollars to 263 dollars per LYS for most variables. This intervention could provide a cost-effective way of reducing neonatal deaths.

Women's health groups to improve perinatal care in rural Nepal.

BACKGROUND: Neonatal mortality rates are high in rural Nepal where more than 90% of deliveries are in the home. Evidence suggests that death rates can be reduced by interventions at community level. We describe an intervention which aimed to harness the power of community planning and decision making to improve maternal and newborn care in rural Nepal. METHODS: The development of 111 women's groups in a population of 86 704 in Makwanpur district, Nepal is described. The groups, facilitated by local women, were the intervention component of a randomized controlled trial to reduce perinatal and neonatal mortality rates. Through participant observation and analysis of reports, we describe the implementation of this intervention: the community entry process, the facilitation of monthly meetings through a participatory action cycle of problem identification, community planning, and implementation and evaluation of strategies to tackle the identified problems. RESULTS: In response to the needs of the group, participatory health education was added to the intervention and the women's groups developed varied strategies to tackle problems of maternal and newborn care: establishing mother and child health funds, producing clean home delivery kits and operating stretcher schemes. Close linkages with community leaders and community health workers improved strategy implementation. There were also indications of positive effects on group members and health services, and most groups remained active after 30 months. CONCLUSION: A large scale and potentially sustainable participatory intervention with women's groups, which focused on pregnancy, childbirth and the newborn period, resulted in innovative strategies identified by local communities to tackle perinatal care problems.

Effect of a participatory intervention with women's groups on birth outcomes in Nepal: cluster-randomised controlled trial.

BACKGROUND: Neonatal deaths in developing countries make the largest contribution to global mortality in children younger than 5 years. 90% of deliveries in the poorest quintile of households happen at home. We postulated that a community-based participatory intervention could significantly reduce neonatal mortality rates. METHODS: We pair-matched 42 geopolitical clusters in Makwanpur district, Nepal, selected 12 pairs randomly, and randomly assigned one of each pair to intervention or control. In each intervention cluster (average population 7000), a female facilitator convened nine women's group meetings every month. The facilitator supported groups through an action-learning cycle in which they identified local perinatal problems and formulated strategies to address them. We monitored birth outcomes in a cohort of 28?931 women, of whom 8% joined the groups. The primary outcome was neonatal mortality rate. Other outcomes included stillbirths and maternal deaths, uptake of antenatal and delivery services, home care practices, infant morbidity, and health-care seeking. Analysis was by intention to treat. The study is registered as an International Standard Randomised Controlled Trial, number ISRCTN31137309. FINDINGS: From 2001 to 2003, the neonatal mortality rate was 26.2 per 1000 (76 deaths per 2899 livebirths) in intervention clusters compared with 36.9 per 1000 (119 deaths per 3226 livebirths) in controls (adjusted odds ratio 0.70 [95% CI 0.53-0.94]). Stillbirth rates were similar in both groups. The maternal mortality ratio was 69 per 100000 (two deaths per 2899 livebirths) in intervention clusters compared with 341 per 100000 (11 deaths per 3226 livebirths) in control clusters (0.22 [0.05-0.90]). Women in intervention clusters were more likely to have antenatal care, institutional delivery, trained birth attendance, and hygienic care than were controls. INTERPRETATION: Birth outcomes in a poor rural population improved greatly through a low cost, potentially sustainable and scalable, participatory intervention with women's groups.

Care for perinatal illness in rural Nepal: a descriptive study with cross-sectional and qualitative components.

BACKGROUND: Maternal, perinatal and neonatal mortality rates remain high in rural areas of developing countries. Most deliveries take place at home and care-seeking behaviour is often delayed. We report on a combined quantitative and qualitative study of care seeking obstacles and practices relating to perinatal illness in rural Makwanpur district, Nepal, with particular emphasis on consultation strategies. METHODS: The analysis included a survey of 8798 women who reported a birth in the previous two years [of whom 3557 reported illness in their pregnancy], on 30 case studies of perinatal morbidity and mortality, and on 43 focus group discussions with mothers, other family members and health workers. RESULTS: Early pregnancy was often concealed, preparation for birth was minimal and trained attendance at birth was uncommon. Family members were favoured attendants, particularly mothers-in-law. The most common recalled maternal complications were prolonged labour, postpartum haemorrhage and retained placenta. Neonatal death, though less definable, was often associated with cessation of suckling and shortness of breath. Many home-based care practices for maternal and neonatal illness were described. Self-medication was common.There were delays in recognising and acting on danger signs, and in seeking care beyond the household, in which the cultural requirement for maternal seclusion, and the perceived expense of care, played a part. Of the 760 women who sought care at a government facility, 70% took more than 12 hours from the decision to seek help to actual consultation. Consultation was primarily with traditional healers, who were key actors in the ascription of causation. Use of the government primary health care system was limited: the most common source of allopathic care was the district hospital. CONCLUSIONS: Major obstacles to seeking care were: a limited capacity to recognise danger signs; the need to watch and wait; and an overwhelming preference to treat illness within the community. Safer motherhood and newborn care programmes in rural communities, must address both community and health facility care to have an impact on morbidity and mortality. The roles of community actors such as mothers-in-law, husbands, local healers and pharmacies, and increased access to properly trained birth attendants need to be addressed if delays in reaching health facilities are to be shortened.

Implementing a community-based participatory intervention to improve essential newborn care in rural Nepal.

The persistence of high perinatal and neonatal mortality rates in many developing countries make efforts to improve perinatal care in the home and at local health facilities important public health concerns. We describe a study which aims to evaluate a community-level participatory intervention in rural Nepal. The effectiveness of community-based action research interventions with mothers and other key members of the community in improving perinatal health outcomes is being examined using a cluster randomized, controlled trial covering a population of 28,000 married women of reproductive age. The unit of randomization was the village development committee (VDC): 12 VDCs receive the intervention while 12 serve as controls. The key elements of the intervention are the activities of female facilitators, each of whom works in one VDC facilitating the activities of women's groups in addressing problems in pregnancy, childbirth and the newborn period. Each group moves through a participatory planning cycle of assessment, sharing experiences, planning, action and reassessment, with the aim of improving essential maternal and newborn care. Outcomes assessed are neonatal and perinatal mortality rates, changes in patterns of home care, health care seeking and referral. The study also aims to generate programmatic information on the process of implementation in communities.