A cluster randomized controlled trial of an electronic decision-support system to enhance antenatal care services in pregnancy at primary healthcare level in Telangana, India: trial protocol

BACKGROUND: India contributes 15% of the total global maternal mortality burden. An increasing proportion of these deaths are due to Pregnancy Induced Hypertension (PIH), Gestational Diabetes Mellitus (GDM), and anaemia. This study aims to evaluate the effectiveness of a tablet-based electronic decision-support system (EDSS) to enhance routine antenatal care (ANC) and improve the screening and management of PIH, GDM, and anaemia in pregnancy in primary healthcare facilities of Telangana, India. The EDSS will work at two levels of primary health facilities and is customized for three cadres of healthcare providers - Auxiliary Nurse Midwifes (ANMs), staff nurses, and physicians (Medical Officers). METHODS: This will be a cluster randomized controlled trial involving 66 clusters with a total of 1320 women in both the intervention and control arms. Each cluster will include three health facilities-one Primary Health Centre (PHC) and two linked sub-centers (SC). In the facilities under the intervention arm, ANMs, staff nurses, and Medical Officers will use the EDSS while providing ANC for all pregnant women. Facilities in the control arm will continue to provide ANC services using the existing standard of care in Telangana. The primary outcome is ANC quality, measured as provision of a composite of four selected ANC components (measurement of blood pressure, blood glucose, hemoglobin levels, and conducting a urinary dipstick test) by the healthcare providers per visit, observed over two visits. Trained field research staff will collect outcome data via an observation checklist. DISCUSSION: To our knowledge, this is the first trial in India to evaluate an EDSS, targeted to enhance the quality of ANC and improve the screening and management of PIH, GDM, and anaemia, for multiple levels of health facilities and several cadres of healthcare providers. If effective, insights from the trial on the feasibility and cost of implementing the EDSS can inform potential national scale-up. Lessons learned from this trial will also inform recommendations for designing and upscaling similar mHealth interventions in other low and middle-income countries

The odorant receptor OR2W3 on airway smooth muscle evokes bronchodilation via a cooperative chemosensory tradeoff between TMEM16A and CFTR.

The recent discovery of sensory (tastant and odorant) G protein-coupled receptors on the smooth muscle of human bronchi suggests unappreciated therapeutic targets in the management of obstructive lung diseases. Here we have characterized the effects of a wide range of volatile odorants on the contractile state of airway smooth muscle (ASM) and uncovered a complex mechanism of odorant-evoked signaling properties that regulate excitation-contraction (E-C) coupling in human ASM cells. Initial studies established multiple odorous molecules capable of increasing intracellular calcium ([Ca2+]i) in ASM cells, some of which were (paradoxically) associated with ASM relaxation. Subsequent studies showed a terpenoid molecule (nerol)-stimulated OR2W3 caused increases in [Ca2+]i and relaxation of ASM cells. Of note, OR2W3-evoked [Ca2+]i mobilization and ASM relaxation required Ca2+ flux through the store-operated calcium entry (SOCE) pathway and accompanied plasma membrane depolarization. This chemosensory odorant receptor response was not mediated by adenylyl cyclase (AC)/cyclic nucleotide-gated (CNG) channels or by protein kinase A (PKA) activity. Instead, ASM olfactory responses to the monoterpene nerol were predominated by the activity of Ca2+-activated chloride channels (TMEM16A), including the cystic fibrosis transmembrane conductance regulator (CFTR) expressed on endo(sarco)plasmic reticulum. These findings demonstrate compartmentalization of Ca2+ signals dictates the odorant receptor OR2W3-induced ASM relaxation and identify a previously unrecognized E-C coupling mechanism that could be exploited in the development of therapeutics to treat obstructive lung diseases

The Bronchoprotective Effects of Dual Pharmacology, Muscarinic Receptor Antagonist and β₂ Adrenergic Receptor Agonist Navafenterol in Human Small Airways

Bronchodilators and anti-inflammatory agents are the mainstream treatments in chronic obstructive and pulmonary disease (COPD) and asthma. The combination of β2 adrenergic receptor (β2AR) agonists and muscarinic antagonists shows superior bronchoprotective effects compared to these agents individually. Navafenterol (AZD8871) is a single-molecule, dual pharmacology agent combining muscarinic antagonist and β2AR agonist functions, currently in development as a COPD therapeutic. In precision-cut human lung slices (hPCLS), we investigated the bronchoprotective effect of navafenterol against two non-muscarinic contractile agonists, histamine and thromboxane A2 (TxA2) analog (U46619). Navafenterol pre-treatment significantly attenuated histamine-induced bronchoconstriction and β2AR antagonist propranolol reversed this inhibitory effect. TxA2 analog-induced bronchoconstriction was attenuated by navafenterol pre-treatment, albeit to a lesser magnitude than that of histamine-induced bronchoconstriction. Propranolol completely reversed the inhibitory effect of navafenterol on TxA2 analog-induced bronchoconstriction. In the presence of histamine or TxA2 analog, navafenterol exhibits bronchoprotective effect in human airways and it is primarily mediated by β2AR agonism of navafenterol

Salicylic acid amplifies Carbachol-induced bronchoconstriction in human precision-cut lung slices

Abstract Background Asthma exacerbations evoke emergency room visits, progressive loss of lung function and increased mortality. Environmental and industrial toxicants exacerbate asthma, although the underlying mechanisms are unknown. We assessed whether 3 distinct toxicants, salicylic acid (SA), toluene diisocyanate (TDI), and 1-chloro-2,4-dinitrobenzene (DNCB) induced airway hyperresponsiveness (AHR) through modulating excitation-contraction coupling in human airway smooth muscle (HASM) cells. The toxicants include a non-sensitizing irritant (SA), respiratory sensitizer (TDI) and dermal sensitizer (DNCB), respectively. We hypothesized that these toxicants induce AHR by modulating excitation-contraction (EC) coupling in airway smooth muscle (ASM) cells. Methods Carbachol-induced bronchoconstriction was measured in precision-cut human lung slices (hPCLS) following exposure to SA, TDI, DNCB or vehicle. Culture supernatants of hPCLS were screened for mediator release. In HASM cells treated with the toxicants, surrogate readouts of EC coupling were measured by phosphorylated myosin light chain (pMLC) and agonist-induced Ca2+ mobilization ([Ca2+]i). In addition, Nrf-2-dependent antioxidant response was determined by NAD(P) H quinone oxidoreductase 1 (NQO1) expression in HASM cells. Results In hPCLS, SA, but not TDI or DNCB, potentiated carbachol-induced bronchoconstriction. The toxicants had little effect on release of inflammatory mediators, including IL-6, IL-8 and eotaxin from hPCLS. In HASM cells, TDI amplified carbachol-induced MLC phosphorylation. The toxicants also had little effect on agonist-induced [Ca2+]i. Conclusion SA, a non-sensitizing irritant, amplifies agonist-induced bronchoconstriction in hPCLS via mechanisms independent of inflammation and Ca2+ homeostasis in HASM cells. The sensitizers TDI and DNCB, had little effect on bronchoconstriction or inflammatory mediator release in hPCLS. Implications Our findings suggest that non-sensitizing irritant salicylic acid may evoke AHR and exacerbate symptoms in susceptible individuals or in those with underlying lung disease

Developing the Core Pillars of Training Global Cardiovascular Health Researchers: Companionship, Light, and Fuel

The 3 pillars that are effective in improving trainee performance and retention among busy early career investigators are companionship, light, and fuel.The research training process is a long-term journey where having companionship from peers and senior colleagues is essential.Strong mentorship provides light along the way whose successes can serve as lighthouses and beacons while illuminating the paths of early career investigators.Seed grants enable trainees to actually do research, applying what they have learned into practice to make a difference in global cardiovascular health.Fil: Yan, Lijing L.. Duke Kunshan University; ChinaFil: Vedanthan, Rajesh. University of New York; Estados UnidosFil: Mensah, George A.. Kathmandu University; NepalFil: Karmacharya, Biraj. Kathmandu University; NepalFil: Shrestha, Archana. Kathmandu University; NepalFil: Fitzpatrick, Annette. University of Washington; Estados UnidosFil: Duc, Ha Anh. No especifíca;Fil: Tandon, Nikhil. No especifíca;Fil: Davila Roman, Victor G.. University of Washington; Estados UnidosFil: Huffman, Mark D.. Northwestern University; Estados Unidos. George Institute For Global Health; AustraliaFil: Miranda, J. Jaime. Universidad Peruana Cayetano Heredia; PerúFil: 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: Koju, Rajendra. Kathmandu University; NepalFil: Newsome, Brad. No especifíca;Fil: Yusuf, Salim. Hamilton Health Sciences; Canad

A cluster randomized control trial of an Electronic Decision-Support System to enhance antenatal care services in pregnancy at primary healthcare level in Telangana, India:Trial protocol

BACKGROUND: India contributes 15% of the total global maternal mortality burden. An increasing proportion of these deaths are due to Pregnancy Induced Hypertension (PIH), Gestational Diabetes Mellitus (GDM), and anaemia. This study aims to evaluate the effectiveness of a tablet-based electronic decision-support system (EDSS) to enhance routine antenatal care (ANC) and improve the screening and management of PIH, GDM, and anaemia in pregnancy in primary healthcare facilities of Telangana, India. The EDSS will work at two levels of primary health facilities and is customized for three cadres of healthcare providers – Auxiliary Nurse Midwifes (ANMs), staff nurses, and physicians (Medical Officers). METHODS: This will be a cluster randomized controlled trial involving 66 clusters with a total of 1320 women in both the intervention and control arms. Each cluster will include three health facilities—one Primary Health Centre (PHC) and two linked sub-centers (SC). In the facilities under the intervention arm, ANMs, staff nurses, and Medical Officers will use the EDSS while providing ANC for all pregnant women. Facilities in the control arm will continue to provide ANC services using the existing standard of care in Telangana. The primary outcome is ANC quality, measured as provision of a composite of four selected ANC components (measurement of blood pressure, blood glucose, hemoglobin levels, and conducting a urinary dipstick test) by the healthcare providers per visit, observed over two visits. Trained field research staff will collect outcome data via an observation checklist. DISCUSSION: To our knowledge, this is the first trial in India to evaluate an EDSS, targeted to enhance the quality of ANC and improve the screening and management of PIH, GDM, and anaemia, for multiple levels of health facilities and several cadres of healthcare providers. If effective, insights from the trial on the feasibility and cost of implementing the EDSS can inform potential national scale-up. Lessons learned from this trial will also inform recommendations for designing and upscaling similar mHealth interventions in other low and middle-income countries. Trial Registration. ClinicalTrials.gov, NCT03700034, registered 9 Oct 2018, https://www.clinicaltrials.gov/ct2/show/NCT03700034 CTRI, CTRI/2019/01/016857, registered on 3 Mar 2019, http://www.ctri.nic.in/Clinicaltrials/pdf_generate.php?trialid=28627&EncHid=&modid=&compid=%27,%2728627det%27 SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12884-022-05249-y

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