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

this happen or why is it mistaken?

A second gravida with normal antenatal period delivered a baby within an hour of admission and also expelled placenta which appeared at vagina. This placenta was adhererent to the fundus of uterus which was inverted but was persistently pulled out as uterine inversion was unrecognized. This case report will be of help to many of us who may mistake such condition. A habit to palpate the fundus of uterus and make sure it is contracted before controlled cord traction will help making the diagnosis in time

Challenges in Effective Referral of Cardiovascular Diseases in Nepal: A Qualitative Study from Health Workers’ and Patients’ Perspective

Background. Nepal, currently facing a high burden of noncommunicable diseases (NCDs), including cardiovascular diseases (CVDs), which poses the highest mortality rate in the country, does not seem to have a proper referral strategy. This study explored the wide range of factors and challenges that affect the referral system of CVD cases in Nepal. Methods. In this qualitative study, we conducted face-to-face and telephone interviews with purposely selected 57 key participants which included 35 healthcare professionals from tertiary, secondary, and primary levels from Bagmati Province and 22 CVD patients (myocardial infarction and stroke) from Bagmati and Madhesh Provinces. We interviewed them using an interview guide with open-ended questions for in-depth information in a local language and in a private space. The interviews were audio-recorded, transcribed verbatim, coded, and analyzed using the thematic approach. Results. The findings indicated that the referral system for CVD cases from primary- to secondary- to tertiary-level care is inadequate and malfunctioning. The major factors affecting referral of CVD cases are centralization of CVD-specific services in few urban areas, inadequate systematic communication between the centers, self-referential, lack of human resources for CVD care, and obstacles to patient transfer due to geographical and financial reasons. Conclusion. A referral system for CVD patients is absent in the context of Nepal. Understanding and addressing key factors that affect the referral system of CVD patients may help to improve cardiac outcomes and ultimately save lives

Stakeholder Engagement in Planning the Design of a National Needs Assessment for Cardiovascular Disease Prevention and Management in Nepal

International audienceBackgroundThere is growing support for stakeholder engagement in health research, but the actual impact of such engagement has not been well established.ObjectivesThis paper describes the stakeholder engagement process and evaluation during the planning of the national needs assessment for cardiovascular disease in Nepal.MethodsWe used personal and professional networks to identify relevant stakeholders within the 7Ps framework (Patients and the Public, Providers, Purchasers, Payers, Public Policy Makers and Policy Advocates, Product Makers and the Principal Investigators) to develop a plan for assessing cardiovascular health needs in Nepal. We consulted 40 stakeholders through 2 meetings in small groups and a workshop in a large group to develop the study methods, conceptual framework, and stakeholder engagement process. We interviewed 33 stakeholders to receive feedback on the stakeholder engagement process.ResultsWe engaged 80% of the targeted stakeholders through small group discussions and a workshop. Three of 5 recommendations from the small group discussion were aimed at improving the stakeholder engagement process and 2 were aimed to improve the research methods. Eleven of 27 recommendations from the workshop aimed to improve the research methods, 4 aimed to improve stakeholder engagement, and 2 helped to expand the scope of dissemination. Ten were irrelevant or could not be incorporated due to resource limitation. Most stakeholders noted that the workshop provided an open platform for a multisectoral group to colearn from one another and share ideas. Others highlighted that the discussion generated insights to enhance research by incorporating expertise and ideas from different perspectives. The major challenges discussed were about committing the time for engagement.ConclusionsThe stakeholder engagement process positively affected the design of our research. This study provides important insights for future researchers that aim to engage stakeholders in national-level assessment programs in the health care system in the context of Nepal

Health system gaps in cardiovascular disease prevention and management in Nepal

BACKGROUND: Cardiovascular diseases (CVDs) are the leading cause of deaths and disability in Nepal. Health systems can improve CVD health outcomes even in resource-limited settings by directing efforts to meet critical system gaps. This study aimed to identify Nepal's health systems gaps to prevent and manage CVDs. METHODS: We formed a task force composed of the government and non-government representatives and assessed health system performance across six building blocks: governance, service delivery, human resources, medical products, information system, and financing in terms of equity, access, coverage, efficiency, quality, safety and sustainability. We reviewed 125 national health policies, plans, strategies, guidelines, reports and websites and conducted 52 key informant interviews. We grouped notes from desk review and transcripts' codes into equity, access, coverage, efficiency, quality, safety and sustainability of the health system. RESULTS: National health insurance covers less than 10% of the population; and more than 50% of the health spending is out of pocket. The efficiency of CVDs prevention and management programs in Nepal is affected by the shortage of human resources, weak monitoring and supervision, and inadequate engagement of stakeholders. There are policies and strategies in place to ensure quality of care, however their implementation and supervision is weak. The total budget on health has been increasing over the past five years. However, the funding on CVDs is negligible. CONCLUSION: Governments at the federal, provincial and local levels should prioritize CVDs care and partner with non-government organizations to improve preventive and curative CVDs services.</p

The Kathmandu Declaration on Global CVD/Hypertension Research and Implementation Science: A Framework to Advance Implementation Research for Cardiovascular and Other Noncommunicable Diseases in Low- and Middle-Income Countries

Highlights NCD represent a serious challenge globally, particularly in LMIC.Implementation research capacity building are critical to inform the prevention and control of NCD in LMIC.Sustainable evidence-based strategies can reduce mortality and prevent avoidable illness from NCD.Strategic change agents (i.e., key stakeholders, institutions, communities, health systems, patients, and families) should work collaboratively to make the necessary advancements to reducing the burden of NCD in LMIC.Fil: Aifah, Angela. No especifíca;Fil: Iwelunmor, Juliet. No especifíca;Fil: Akwanalo, Constantine. No especifíca;Fil: Allison, Jeroan. Massachusetts Institute of Technology; Estados UnidosFil: Amberbir, Alemayehu. No especifíca;Fil: Asante, Kwaku P.. No especifíca;Fil: Baumann, Ana. Washington University in St. Louis; Estados UnidosFil: Brown, Angela. Washington University in St. Louis; Estados UnidosFil: Butler, Mark. No especifíca;Fil: Dalton, Milena. No especifíca;Fil: Davila Roman, Victor. Washington University in St. Louis; Estados UnidosFil: Fitzpatrick, Annette L.. No especifíca;Fil: Fort, Meredith. State University of Colorado at Boulder; Estados UnidosFil: Goldberg, Robert. No especifíca;Fil: Gondwe, Austrida. No especifíca;Fil: Ha, Duc. No especifíca;Fil: He, Jiang. University of Tulane; Estados UnidosFil: Hosseinipour, Mina. No especifíca;Fil: Irazola, Vilma. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones en Epidemiología y Salud Pública. Instituto de Efectividad Clínica y Sanitaria. Centro de Investigaciones en Epidemiología y Salud Pública; ArgentinaFil: Kamano, Jemima. No especifíca;Fil: Karengera, Stephen. Washington University in St. Louis; Estados UnidosFil: Karmacharya, Biraj M.. No especifíca;Fil: Koju, Rajendra. No especifíca;Fil: Maharjan, Rashmi. No especifíca;Fil: Mohan, Sailesh. No especifíca;Fil: Mutabazi, Vincent. No especifíca;Fil: Mutimura, Eugene. No especifíca;Fil: Muula, Adamson. No especifíca;Fil: Narayan, K.M.V.. University of Emory; Estados UnidosFil: Nguyen, Hoa. No especifíca;Fil: Njuguna, Benson. No especifíca;Fil: Nyirenda, Moffat. No especifíca;Fil: Ogedegbe, Gbenga. No especifíca;Fil: van Oosterhout, Joep. No especifíca;Fil: Onakomaiya, Deborah. No especifíca;Fil: Patel, Shivani. University of Emory; Estados UnidosFil: Paniagua-Ávila, Alejandra. No especifíca;Fil: Ramirez zea, Manuel. No especifíca;Fil: Plange Rhule, Jacob. No especifíca;Fil: Roche, Dina. No especifíca;Fil: Shrestha, Archana. No especifíca;Fil: Sharma, Hanspria. No especifíca;Fil: Tandon, Nikhil. No especifíca;Fil: Thu Cuc, Nguyen. No especifíca;Fil: Vaidya, Abhinav. No especifíca;Fil: Vedanthan, Rajesh. No especifíca;Fil: Weber, Mary Beth. University of Emory; Estados Unido