Elucidating genetic diversity and variability in Chickpea (Cicer arietinum L.) using yield attribution traits

Fifty-six desi chickpea (Cicer arietinum L.) advance breeding lines were evaluated in order to explore the possibility of genetic divergence for yield and its contributing traits using Mahalanobis’s D2 Statistics and Principal Component Analysis. High estimates of heritability, genetic advance, GCV and PCV were recorded for seed yield per plant (92.2%, 12.4%, 37.1% and 38.7%), biological yield per plant (88.1%, 21.9%, 29.1% and 31.0%) and harvest index (87.3%, 25.0%, 22.7% and 24.3%). All the test genotypes were sort into five discrete clusters. Biological yield/plant (23.5%), days to maturity (17.3%), harvest index (14.6%), seed yield/plant (11.3%), total number of pods/plant (7.4%) and 100 seed weight (6.49%) were found to have highest percentage contributions to genetic diversity in the present research. The first six principal components (PC1 19.7%, PC 16.2%, PC3 11.2%, PC4 9.69%, PC5 7.2% and PC6 6.69%) could explain 70.68% of the total of the interaction variation and have Eigen value more than one.  Genotypes JG 2016-1411, JG 2016-9605, JG 2017-46, ICCV 16105, ICCV 16109, ICCV 16112 and ICCV 16116 were present in more than one PCs hence contributed maximum towards yield and can be used in various breeding programmes for yield improvement.

NUrse-led COntinuum of care for people with Diabetes and prediabetes (NUCOD) in Nepal: study protocol for a cluster randomized controlled trial

Background The purpose of this study will be to improve diabetes prevention, access to care and advocacy through a novel cost-effective nurse-led continuum of care approach that incorporates diabetes prevention, awareness, screening and management for low-income settings, and furthermore utilizes the endeavor to advocate for establishing a standard diabetes program in Nepal. Methods We will conduct a two-arm, parallel group, stratified cluster randomized controlled trial of the NUrse-led COntinuum of care for people with Diabetes (N1 = 200) and prediabetes (N2 = 1036) (NUCOD) program, with primary care centers (9 outreach centers and 17 government health posts) as a unit of randomization. The NUCOD program will be delivered through the trained diabetes nurses in the community to the intervention group and the outcomes will be compared with the usual treatment group at 6 and 12 months of the intervention. The primary outcome will be the change in glycated hemoglobin (HbA1c) level among diabetes individuals and progression to type 2 diabetes among prediabetes individuals, and implementation outcomes measured using the RE-AIM (reach, effectiveness, adoption, implementation and maintenance) framework. Outcomes will be analyzed on an intention-to-treat basis. Discussion The results of this trial will provide information about the effectiveness of the NUCOD program in improving clinical outcomes for diabetes and prediabetes individuals, and implementation outcomes for the organization. The continuum of care model can be used for the prevention and management of diabetes and other noncommunicable diseases within and beyond Nepal with similar context. Trial registration ClinicalTrials.gov, NCT04131257. Registered on 18 October 2019.This study will be conducted under the umbrella of a large implementation project and will be supported by a World Diabetes Foundation (WDF17-1483) grant, a China Medical Board (CMB16–260) grant and Dhulikhel Hospital Kathmandu University. However, the funding organizations will have no role in the design of the study, data collection, data analysis, data interpretation or writing of the report

Azithromycin and cefixime combination versus azithromycin alone for the out-patient treatment of clinically suspected or confirmed uncomplicated typhoid fever in South Asia: a randomised controlled trial protocol.

Background: Typhoid and paratyphoid fever (enteric fever) is a common cause of non-specific febrile infection in adults and children presenting to health care facilities in low resource settings such as the South Asia.  A 7-day course of a single oral antimicrobial such as ciprofloxacin, cefixime, or azithromycin is commonly used for its treatment. Increasing antimicrobial resistance threatens the effectiveness of these treatment choices. We hypothesize that combined treatment with azithromycin (active mainly intracellularly) and cefixime (active mainly extracellularly) will be a better option for the treatment of clinically suspected and culture-confirmed typhoid fever in South Asia. Methods: This is a phase IV, international multi-center, multi-country, comparative participant-and observer-blind, 1:1 randomised clinical trial. Patients with suspected uncomplicated typhoid fever will be randomized to one of the two interventions: Arm A: azithromycin 20mg/kg/day oral dose once daily (maximum 1gm/day) and cefixime 20mg/kg/day oral dose in two divided doses (maximum 400mg bd) for 7 days, Arm B: azithromycin 20mg/kg/day oral dose once daily (max 1gm/day) for 7 days AND cefixime-matched placebo for 7 days. We will recruit 1500 patients across sites in Bangladesh, India, Nepal, and Pakistan. We will assess whether treatment outcomes are better with the combination after one week of treatment and at one- and three-months follow-up. Discussion: Combined treatment may limit the emergence of resistance if one of the components is active against resistant sub-populations not covered by the other antimicrobial activity. If the combined treatment is better than the single antimicrobial treatment, this will be an important result for patients across South Asia and other typhoid endemic areas. Clinicaltrials.gov registration: NCT04349826 (16/04/2020)

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

Factors Associated with Medication Adherence among Patients with Type 2 Diabetes Mellitus: A Hospital-Based Cross-Sectional Study in Nepal

As diabetes increases globally, high mortality increases due to complications of uncontrolled sugar. Medication adherence is important to control blood sugar and prevent its complications. Objective of the study was to identify factors associated with medication adherence among type 2 diabetes patients. A cross-sectional study was conducted among 343 patients visiting Dhulikhel Hospital, Nepal, for their fasting blood sugar test from September to December 2016. Inclusion criteria: patients with type 2 diabetes, under diabetes medication for past three months (minimum), age ≥ 18 years. The outcome of the study was medication adherence measured using the eight-item Morisky medication adherence scale (MMAS-8) (© 2006 Donald E. Morisky). Multivariate logistic regression was used for the analysis. Results showed that 61% of respondents had high medication adherence; adherence was positively associated with formal education [AOR: 2.43 (95% CI: 1.34, 4.39)] and attendance at diabetes counseling [AOR: 1.76 (95% CI: 1.02, 3.04)] after adjusting for age, occupation, medicine intake duration and diabetes medicine types. The study concluded that formal education and attendance at diabetes counseling positively affected patients’ adherence to medicine. We encourage healthcare institutions to provide counseling services to all the patients with type 2 diabetes and focus more on those who are less educated

Designing and Developing a Mobile App for Management and Treatment of Gestational Diabetes in Nepal: User-Centered Design Study

BackgroundMobile apps can aid with the management of gestational diabetes mellitus (GDM) by providing patient education, reinforcing regular blood glucose monitoring and diet/lifestyle modification, and facilitating clinical and social support. ObjectiveThis study aimed to describe our process of designing and developing a culturally tailored app, Garbhakalin Diabetes athawa Madhumeha—Dhulikhel Hospital (GDM-DH), to support GDM management among Nepalese patients by applying a user-centered design approach. MethodsA multidisciplinary team of experts, as well as health care providers and patients in Dhulikhel Hospital (Dhulikhel, Nepal), contributed to the development of the GDM-DH app. After finalizing the app’s content and features, we created the app’s wireframe, which illustrated the app’s proposed interface, navigation sequences, and features and function. Feedback was solicited on the wireframe via key informant interviews with health care providers (n=5) and a focus group and in-depth interviews with patients with GDM (n=12). Incorporating their input, we built a minimum viable product, which was then user-tested with 18 patients with GDM and further refined to obtain the final version of the GDM-DH app. ResultsParticipants in the focus group and interviews unanimously concurred on the utility and relevance of the proposed mobile app for patients with GDM, offering additional insight into essential modifications and additions to the app’s features and content (eg, inclusion of example meal plans and exercise videos).The mean age of patients in the usability testing (n=18) was 28.8 (SD 3.3) years, with a mean gestational age of 27.2 (SD 3.0) weeks. The mean usability score across the 10 tasks was 3.50 (SD 0.55; maximum score=5 for “very easy”); task completion rates ranged from 55.6% (n=10) to 94.4% (n=17). Findings from the usability testing were reviewed to further optimize the GDM-DH app (eg, improving data visualization). Consistent with social cognitive theory, the final version of the GDM-DH app supports GDM self-management by providing health education and allowing patients to record and self-monitor blood glucose, blood pressure, carbohydrate intake, physical activity, and gestational weight gain. The app uses innovative features to minimize the self-monitoring burden, as well as automatic feedback and data visualization. The app also includes a social network “follow” feature to add friends and family and give them permission to view logged data and a progress summary. Health care providers can use the web-based admin portal of the GDM-DH app to enter/review glucose levels and other clinical measures, track patient progress, and guide treatment and counseling accordingly. ConclusionsTo the best of our knowledge, this is the first mobile health platform for GDM developed for a low-income country and the first one containing a social support feature. A pilot clinical trial is currently underway to explore the clinical utility of the GDM-DH app

Diabetes Prevention Education Program in a population with pre-diabetes in Nepal: a study protocol of a cluster randomised controlled trial (DiPEP)

Introduction Evidence suggests that diabetes burden can be reduced by implementing early lifestyle intervention programmes in population with pre-diabetes in high-income countries. However, little is known in developing nations like Nepal. This study aims to assess effectiveness of community-based Diabetes Prevention Education Program (DiPEP) on haemoglobin A1c (HbA1c) level, proportion of pre-diabetes reverting to normoglycaemia, diet, physical activity, weight reduction, diabetes knowledge and health literacy after 6 months of follow-up. Furthermore, we will also conduct qualitative studies to explore experiences of participants of intervention sessions and perception of healthcare workers/volunteers about DiPEP. Methods and analyses This is a community-based two-arm, open-label, cluster randomised controlled trial. We will randomise 14 clusters into intervention arm and control arm. Estimated total sample size is 448. We will screen individuals without diabetes, aged 18–64 years, and permanent residents of study sites. HbA1c test will be only performed if both Indian Diabetes Risk Score and random blood sugar value are ≥60 and 140–250 mg/dL, respectively. At baseline, participants in intervention arm will receive DiPEP package (including intensive intervention classes, diabetes prevention brochure, exercise calendar and food record booklet), and participants in control arm will be provided only with diabetes prevention brochure. The change in outcome measures will be compared between intervention to control arm after 6 months of follow-up by linear mixed models. Also, we will conduct individual interviews among participants and healthcare workers as part of a qualitative study. We will use thematic analysis to analyse qualitative data. Ethics and dissemination Regional Committee for Medical and Health Research Ethics, Norway; Nepal Health Research Council, Nepal and Institutional Review Committee, Kathmandu University School of Medical Sciences have approved the study. The DiPEP package can be implemented in other communities of Nepal if it is effective in preventing diabetes. Trial registration number NCT04074148, 2019/783