Clinical standards for the diagnosis and management of asthma in low- and middle-income countries.

BACKGROUND: The aim of these clinical standards is to aid the diagnosis and management of asthma in low-resource settings in low- and middle-income countries (LMICs).METHODS: A panel of 52 experts in the field of asthma in LMICs participated in a two-stage Delphi process to establish and reach a consensus on the clinical standards.RESULTS: Eighteen clinical standards were defined: Standard 1, Every individual with symptoms and signs compatible with asthma should undergo a clinical assessment; Standard 2, In individuals (>6 years) with a clinical assessment supportive of a diagnosis of asthma, a hand-held spirometry measurement should be used to confirm variable expiratory airflow limitation by demonstrating an acute response to a bronchodilator; Standard 3, Pre- and post-bronchodilator spirometry should be performed in individuals (>6 years) to support diagnosis before treatment is commenced if there is diagnostic uncertainty; Standard 4, Individuals with an acute exacerbation of asthma and clinical signs of hypoxaemia or increased work of breathing should be given supplementary oxygen to maintain saturation at 94-98%; Standard 5, Inhaled short-acting beta-2 agonists (SABAs) should be used as an emergency reliever in individuals with asthma via an appropriate spacer device for metered-dose inhalers; Standard 6, Short-course oral corticosteroids should be administered in appropriate doses to individuals having moderate to severe acute asthma exacerbations (minimum 3-5 days); Standard 7, Individuals having a severe asthma exacerbation should receive emergency care, including oxygen therapy, systemic corticosteroids, inhaled bronchodilators (e.g., salbutamol with or without ipratropium bromide) and a single dose of intravenous magnesium sulphate should be considered; Standard 8, All individuals with asthma should receive education about asthma and a personalised action plan; Standard 9, Inhaled medications (excluding dry-powder devices) should be administered via an appropriate spacer device in both adults and children. Children aged 0-3 years will require the spacer to be coupled to a face mask; Standard 10, Children aged <5 years with asthma should receive a SABA as-needed at step 1 and an inhaled corticosteroid (ICS) to cover periods of wheezing due to respiratory viral infections, and SABA as-needed and daily ICS from step 2 upwards; Standard 11, Children aged 6-11 years with asthma should receive an ICS taken whenever an inhaled SABA is used; Standard 12, All adolescents aged 12-18 years and adults with asthma should receive a combination inhaler (ICS and rapid onset of action long-acting beta-agonist [LABA] such as budesonide-formoterol), where available, to be used either as-needed (for mild asthma) or as both maintenance and reliever therapy, for moderate to severe asthma; Standard 13, Inhaled SABA alone for the management of patients aged >12 years is not recommended as it is associated with increased risk of morbidity and mortality. It should only be used where there is no access to ICS.The following standards (14-18) are for settings where there is no access to inhaled medicines. Standard 14, Patients without access to corticosteroids should be provided with a single short course of emergency oral prednisolone; Standard 15, Oral SABA for symptomatic relief should be used only if no inhaled SABA is available. Adjust to the individual's lowest beneficial dose to minimise adverse effects; Standard 16, Oral leukotriene receptor antagonists (LTRA) can be used as a preventive medication and is preferable to the use of long-term oral systemic corticosteroids; Standard 17, In exceptional circumstances, when there is a high risk of mortality from exacerbations, low-dose oral prednisolone daily or on alternate days may be considered on a case-by-case basis; Standard 18. Oral theophylline should be restricted for use in situations where it is the only bronchodilator treatment option available.CONCLUSION: These first consensus-based clinical standards for asthma management in LMICs are intended to help clinicians provide the most effective care for people in resource-limited settings.

Effect of the enhancing nutrition and antenatal infection treatment (ENAT) intervention on birth weight in Ethiopia: a cluster randomized controlled trial.

BACKGROUND: The Enhancing Nutrition and Antenatal Infection Treatment (ENAT) intervention was implemented in Ethiopia to improve newborn birth weight (BW) by strengthening the contents and quality of antenatal care (ANC), especially point-of-care testing for maternal infections. This study examined the effect of the ENAT intervention on birth weight. METHODS: We conducted a cluster randomized controlled trial of 22 clusters (health centers), randomized equally between 11 intervention and 11 control clusters. This study enrolled and followed pregnant women from ANC booking to the end of pregnancy or loss to follow-up. The primary outcome was mean BW, and the incidence of low birth weight (LBW) was the secondary outcome. We presented univariate comparisons of outcomes between the intervention and control arms for mean BW and LBW. Multilevel analyses using random effects models were performed to adjust for clustering and individual-level covariates. RESULTS: We enrolled and followed up 4,868 and 4,821 pregnant women in the intervention and control arms, respectively, from March 2021-July 2022. During follow-up, 3445 pregnant women in the intervention and 3192 in the control delivered in the health centers, and BW measurements of their babies were recorded within 48 h. The mean BW was 3,152 g (standard deviation (SD) = 339.8 g) in the intervention and 3,044 g (SD = 353.8 g) in the control arms (mean difference, 108 g; 95% confidence interval (CI): 91.3-124.6; P = 0.000). Adjusting for clustering and several covariates, the mean BW remained significantly higher in the intervention arm than in the control arm (adjusted ß coef., 114.3; p = 0.011). The incidence of LBW was 4.7% and 7.3% in the intervention and control arms, respectively. The adjusted risk of LBW was significantly lower by 36% in the intervention arm than in the control arm (adjusted relative risk, 0.645; p = 0.027). CONCLUSION: This study provided sufficient evidence of the effectiveness of the ENAT intervention in improving birth weight in the study population. The intervention demonstrated that an increase in birth weight can be attained by availing point-of-care testing, strengthening infection prevention, and maternal nutrition within the ANC platform of public health facilities in a low-income setting. TRIAL REGISTRATION: Registered at Pan African Clinical Trial Registry (PACTR) database dated 09/05/2023, https://pactr.samrc.ac.za/TrialDisplay.aspx?TrialID=25493 . The unique identification number for the registry is PACTR202305694761480.

Framework for developing a national surgical, obstetric and anaesthesia plan.

Background: Emergency and essential surgical, obstetric and anaesthesia (SOA) care are now recognized components of universal health coverage, necessary for a functional health system. To improve surgical care at a national level, strategic planning addressing the six domains of a surgical system is needed. This paper details a process for development of a national surgical, obstetric and anaesthesia plan (NSOAP) based on the experiences of frontline providers, Ministry of Health officials, WHO leaders, and consultants. Methods: Development of a NSOAP involves eight key steps: Ministry support and ownership; situation analysis and baseline assessments; stakeholder engagement and priority setting; drafting and validation; monitoring and evaluation; costing; governance; and implementation. Drafting a NSOAP involves defining the current gaps in care, synthesizing and prioritizing solutions, and providing an implementation and monitoring plan with a projected cost for the six domains of a surgical system: infrastructure, service delivery, workforce, information management, finance and governance. Results: To date, four countries have completed NSOAPs and 23 more have committed to development. Lessons learned from these previous NSOAP processes are described in detail. Conclusion: There is global movement to address the burden of surgical disease, improving quality and access to SOA care. The development of a strategic plan to address gaps across the SOA system systematically is a critical first step to ensuring countrywide scale-up of surgical system-strengthening activities.

Antecedentes: En la actualidad, se reconoce que la atención quirúrgica, obstétrica y anestésica urgente y esencial (surgical, obstetric, and anaesthesia, SOA) es uno de los componentes de la cobertura sanitaria universal y un elemento necesario para el funcionamiento de un sistema de salud. Para mejorar la atención quirúrgica a nivel nacional, se necesita una planificación estratégica que aborde los seis dominios de un sistema quirúrgico. En este artículo, se detalla el proceso para el desarrollo de un plan nacional de cirugía, obstetricia y anestesia (national surgical, obstetric, and anaesthesia plan, NSOAP) basado en las experiencias de los principales proveedores, los funcionarios del Ministerio de Salud, los líderes de la Organización Mundial de la Salud y consultores. Métodos: El desarrollo de un NSOAP incluye ocho pasos clave: (1) apoyo y dependencia del ministerio, (2) análisis de la situación y evaluaciones de referencia, (3) compromiso de los agentes implicados y establecimiento de prioridades, (4) redacción y validación, (5) seguimiento y evaluación, (6) análisis de costes, (7) gobernanza y (8) implementación. Redactar un NSOAP implica definir los déficits actuales en la atención, sintetizar y priorizar soluciones, y proporcionar un plan de implementación y seguimiento con unos costes proyectados para los seis dominios de un sistema quirúrgico: infraestructura, prestación de servicios, personal, gestión de la información, finanzas y gobernanza. Resultados: Hasta la fecha, cuatro países han completado un NSOAP y 23 más se han comprometido con su desarrollo. Las lecciones aprendidas de estos procesos previos de NSOAP se describen con detalle. Conclusiones: Existe un movimiento global para abordar la carga de las enfermedades que precisan cirugía, mejorar la calidad y el acceso a la atención SOA. El desarrollo de un plan estratégico para la aproximación sistemáticamente los déficits en todo el sistema SOA es un primer paso crítico para garantizar la ampliación a nivel nacional de las actividades de fortalecimiento del sistema quirúrgico.

Daily adjunctive therapy with vitamin D3 and phenylbutyrate supports clinical recovery from pulmonary tuberculosis: a randomized controlled trial in Ethiopia.

OBJECTIVE: Immunotherapy using vitamin D (vitD3 ) and phenylbutyrate (PBA) may support standard drug regimens used to treat infectious diseases. We investigated if vitD3 + PBA enhanced clinical recovery from pulmonary tuberculosis (TB). METHODS: A randomized controlled trial was conducted in Addis Ababa, Ethiopia. Patients with smear-positive or smear-negative TB received daily oral supplementation with 5000 IU vitD3 and 2 × 500 mg PBA or placebo for 16 weeks, together with 6-month chemotherapy. Primary end-point: reduction of a clinical composite TB score at week 8 compared with baseline using modified intention-to-treat (mITT, n = 348) and per-protocol (n = 296) analyses. Secondary end-points: primary and modified TB scores (week 0, 4, 8, 16, 24), sputum conversion, radiological findings and plasma 25(OH)D3 concentrations. RESULTS: Most subjects had low baseline plasma 25(OH)D3 levels that increased gradually in the vitD3 + PBA group compared with placebo (P < 0.0001) from week 0 to 16 (mean 34.7 vs. 127.4 nmol L-1 ). In the adjusted mITT analysis, the primary TB score was significantly reduced in the intervention group at week 8 (-0.52, 95% CI -0.93, -0.10; P = 0.015) while the modified TB score was reduced at week 8 (-0.58, 95% CI -1.02, -0.14; P = 0.01) and 16 (-0.34, 95% CI -0.64, -0.03; P = 0.03). VitD3 + PBA had no effect on longitudinal sputum-smear conversion (P = 0.98). Clinical adverse events were more common in the placebo group (24.3%) compared with the vitD3 + PBA group (12.6%). CONCLUSION: Daily supplementation with vitD3 + PBA may ameliorate clinical TB symptoms and disease-specific complications, while the intervention had no effect on bacterial clearance in sputum.

Raloxifene (LY139481 HCI) prevents bone loss and reduces serum cholesterol without causing uterine hypertrophy in ovariectomized rats.

There is a medical need for an agent with the positive effects of estrogen on bone and the cardiovascular system, but without the negative effects on reproductive tissue. Raloxifene (LY139481 HCI) is a benzothiophene derivative that binds to the estrogen receptor and inhibits the effects of estrogen on the uterus. In an ovariectomized (OVX) rat model we investigated the effects of raloxifene on bone loss (induced by estrogen deficiency), serum lipids, and uterine tissue. After oral administration of raloxifene for 5 wk (0.1-10 mg/kg per d) to OVX rats, bone mineral density in the distal femur and proximal tibia was significantly greater than that observed in OVX controls (ED50 of 0.03-0.3 mg/kg). Serum cholesterol was lower in the raloxifene-treated animals, which had a minimal effective dose of 0.1 mg/kg and an approximate oral ED50 of 0.2 mg/kg. The effects of raloxifene on bone and serum cholesterol were comparable to those of a 0.1-mg/kg per d oral dose of ethynyl estradiol. Raloxifene diverged dramatically from estrogen in its lack of significant estrogenic effects on uterine tissue. Ethynyl estradiol produced a marked elevation in a number of uterine histologic parameters (e.g., epithelial cell height, stromal eosinophilia). These data suggest that raloxifene has promise as an agent with beneficial bone and cardiovascular effects in the absence of significant uterine effects.