Empirical estimation of resource constraints for use in model-based economic evaluation: an example of TB services in South Africa.

BACKGROUND: Evidence on the relative costs and effects of interventions that do not consider 'real-world' constraints on implementation may be misleading. However, in many low- and middle-income countries, time and data scarcity mean that incorporating health system constraints in priority setting can be challenging. METHODS: We developed a 'proof of concept' method to empirically estimate health system constraints for inclusion in model-based economic evaluations, using intensified case-finding strategies (ICF) for tuberculosis (TB) in South Africa as an example. As part of a strategic planning process, we quantified the resources (fiscal and human) needed to scale up different ICF strategies (cough triage and WHO symptom screening). We identified and characterised three constraints through discussions with local stakeholders: (1) financial constraint: potential maximum increase in public TB financing available for new TB interventions; (2) human resource constraint: maximum current and future capacity among public sector nurses that could be dedicated to TB services; and (3) diagnostic supplies constraint: maximum ratio of Xpert MTB/RIF tests to TB notifications. We assessed the impact of these constraints on the costs of different ICF strategies. RESULTS: It would not be possible to reach the target coverage of ICF (as defined by policy makers) without addressing financial, human resource and diagnostic supplies constraints. The costs of addressing human resource constraints is substantial, increasing total TB programme costs during the period 2016-2035 by between 7% and 37% compared to assuming the expansion of ICF is unconstrained, depending on the ICF strategy chosen. CONCLUSIONS: Failure to include the costs of relaxing constraints may provide misleading estimates of costs, and therefore cost-effectiveness. In turn, these could impact the local relevance and credibility of analyses, thereby increasing the risk of sub-optimal investments

Age-targeted tuberculosis vaccination in China and implications for vaccine development: a modelling study.

BACKGROUND: Tuberculosis is the leading single-pathogen cause of death worldwide, and China has the third largest number of cases worldwide. New tools, such as new vaccines, are needed to meet WHO tuberculosis goals. Tuberculosis vaccine development strategies mostly target infants or adolescents, but given China's ageing epidemic, vaccinating older people might be important. We modelled the potential impact of new tuberculosis vaccines in China targeting adolescents (15-19 years) or older adults (60-64 years) with varying vaccine characteristics to inform strategic vaccine development. METHODS: A Mycobacterium tuberculosis transmission model was calibrated to age-stratified demographic and epidemiological data from China. Varying scenarios of vaccine implementation (age targeting [adolescents or older adults] and coverage [30% or 70%]) and characteristics (efficacy [40%, 60%, or 80%], duration of protection [10 years or 20 years], and host infection status required for efficacy [pre-infection, post-infection in latency, post-infection in latency or recovered, or pre-infection and post-infection]) were assessed. Primary outcomes were tuberculosis incidence and mortality rate reduction in 2050 in each vaccine scenario compared with the baseline (no new vaccine) scenario and cumulative number needed to vaccinate (NNV) per case or death averted, 2025-50. FINDINGS: By 2050, results suggest that 74·5% (uncertainty interval [UI] 70·2-78·6) of incident tuberculosis cases in China would occur in people aged 65 years or older, and 75·1% (66·8-80·7) of all cases would be due to reactivation, rather than new infection. All vaccine profiles delivered to older adults had higher population-level impact (reduction of incidence and mortality rates) and lower NNV per case and per death averted than if delivered to adolescents. For an intermediate vaccine scenario of 60% efficacy, 10-year protection, and 70% coverage, the reduction of tuberculosis incidence rates with older adult vaccination was 1·9 times (UI 1·5-2·6) to 157·5 times (119·3-225·6) greater than with adolescent vaccination, and the NNV was 0·011 times (0·008-0·014) to 0·796 times (0·632-0·970) lower. Furthermore, with older adult vaccination, post-infection vaccines provided substantially greater mortality and incidence rate reductions than pre-infection vaccines. INTERPRETATION: Adolescent-targeted tuberculosis vaccines, the focus of many development plans, would have only a small impact in ageing, reactivation-driven epidemics such as those in China. Instead, an efficacious post-infection vaccine delivered to older adults will be crucial to maximise population-level impact in this setting and would provide an important contribution towards achieving WHO goals. Older adults should be included in tuberculosis vaccine clinical development and implementation planning. FUNDING: Aeras and UK MRC

Estimating the Impact of Tuberculosis Case Detection in Constrained Health Systems: An Example of Case-Finding in South Africa.

Mathematical models are increasingly being used to compare strategies for tuberculosis (TB) control and inform policy decisions. Models often do not consider financial and other constraints on implementation and may overestimate the impact that can be achieved. We developed a pragmatic approach for incorporating resource constraints into mathematical models of TB. Using a TB transmission model calibrated for South Africa, we estimated the epidemiologic impact and resource requirements (financial, human resource (HR), and diagnostic) of 9 case-finding interventions. We compared the model-estimated resources with scenarios of future resource availability and estimated the impact of interventions under these constraints. Without constraints, symptom screening in public health clinics and among persons receiving care for human immunodeficiency virus infection was predicted to lead to larger reductions in TB incidence (9.5% (2.5th-97.5th percentile range (PR), 8.6-12.2) and 14.5% (2.5th-97.5th PR, 12.2-16.3), respectively) than improved adherence to diagnostic guidelines (2.7%; 2.5th-97.5th PR, 1.6-4.1). However, symptom screening required large increases in resources, exceeding future HR capacity. Even under our most optimistic HR scenario, the reduction in TB incidence from clinic symptom screening was 0.2%-0.9%-less than that of improved adherence to diagnostic guidelines. Ignoring resource constraints may result in incorrect conclusions about an intervention's impact and may lead to suboptimal policy decisions. Models used for decision-making should consider resource constraints

Application of provincial data in mathematical modelling to inform sub-national tuberculosis program decision-making in South Africa.

South Africa has the highest tuberculosis (TB) disease incidence rate in the world, and TB is the leading infectious cause of death. Decisions on, and funding for, TB prevention and care policies are decentralised to the provincial governments and therefore, tools to inform policy need to operate at this level. We describe the use of a mathematical model planning tool at provincial level in a high HIV and TB burden country, to estimate the impact on TB burden of achieving the 90-(90)-90 targets of the Stop TB Partnership Global Plan to End TB. "TIME Impact" is a freely available, user-friendly TB modelling tool. In collaboration with provincial TB programme staff, and the South African National TB Programme, models for three (of nine) provinces were calibrated to TB notifications, incidence, and screening data. Reported levels of TB programme activities were used as baseline inputs into the models, which were used to estimate the impact of scale-up of interventions focusing on screening, linkage to care and treatment success. All baseline models predicted a trend of decreasing TB incidence and mortality, consistent with recent data from South Africa. The projected impacts of the interventions differed by province and were greatly influenced by assumed current coverage levels. The absence of provincial TB burden estimates and uncertainty in current activity coverage levels were key data gaps. A user-friendly modelling tool allows TB burden and intervention impact projection at the sub-national level. Key sub-national data gaps should be addressed to improve the quality of sub-national model predictions

Influence of Age and Nutritional Status on the Performance of the Tuberculin Skin Test and QuantiFERON®-TB Gold In-Tube in Young Children Evaluated for Tuberculosis in Southern India.

Background: Reliable identification of Mycobacterium tuberculosis infection or tuberculosis (TB) disease in young children is vital to assure adequate preventive and curative treatment. The tuberculin skin test (TST) and IFN[gamma]-release assays may supplement the diagnosis of pediatric TB as cases are typically bacteriologically unconfirmed. However, it is unclear to what extent the performance of TST and QuantiFERON-TB Gold In-Tube (QFT; Cellestis’ IFN[gamma]-release assay test) depends on the demographic, clinical and nutritional characteristics of children in whom they are tested. Methods: During a 2-year prospective observational study of 4382 neonates in Southern India, children with suspected TB were investigated and classified by a standard TB diagnostic algorithm. Results: Clinical TB was diagnosed in 13 of 705 children referred for case verification with suspected TB. TST and QFT had a susceptibility for clinical TB of 31% and 23%, respectively, in this group. Children <2 years were more likely to test QFT indeterminate. A height-for-age Z score within the lowest quartile increased the odds ratio (OR) for a positive or indeterminate QFT result [OR 2.46 (1.19–5.06), OR 3.08 (1.10–8.58)], whereas the OR for a positive TST was reduced with a weight-for-height Z score within the lowest quartile [OR 0.17 (0.06–0.47)]. Conclusion: The sensitivities of the TST and QFT for clinical TB in children <3 years of age were equally poor in this population. Stunted children were more susceptible to Mycobacterium tuberculosis infection and more prone to indeterminate QFT results. TST was less reliable in children with wasting

Circuitos Lógicos Digitales - EL245 - 202102

El curso Circuitos Lógicos Digitales es de la especialidad de la carrera de Ingeniería electrónica, de carácter teórico-práctico. El curso te ayudará a comprender inicialmente el ¿cómo funcionan los circuitos digitales básicos que componen los equipos electrónicos hoy en día? Para ello, aprenderás cómo funcionan las compuertas lógicas, codificadores, decodificadores, multiplexores, demultiplexores, máquinas de estado, contadores y registros. La sociedad actual convive con la tecnología, cada día podemos apreciar nuevos productos, nuevas formas de interrelacionarnos con las personas y todo esto es producto de la electrónica. Cada producto electrónico nuevo que se introduce al mercado necesita de un proceso de diseño que involucra conocimientos en el área de circuitos digitales. El curso contribuye directamente al desarrollo de la competencia general Manejo de Información (Nivel Básico) y a la Competencia Específica de Capacidad de comunicarse efectivamente con un rango de audiencias (Nivel Básico). Requisito: Software para ingeniería

Circuitos Lógicos Digitales-EL214-201802

El curso Circuitos Lógicos Digitales es de la especialidad de la carrera de Ingeniería electrónica de carácter teórico-práctico. El curso te ayudará a comprender inicialmente el ¿cómo funcionan los circuitos digitales básicos que componen los equipos electrónicos hoy en día? Para ello aprenderás cómo funcionan las compuertas lógicas codificadores decodificadores multiplexores demultiplexores máquinas de estado contadores y registros.La sociedad actual convive con la tecnología cada día podemos apreciar nuevos productos nuevas formas de interrelacionarnos con las personas y todo esto es producto de la electrónica. Cada producto electrónico nuevo que se introduce al mercado necesita de un proceso de diseño que involucra conocimientos en el área de circuitos digitales. El curso contribuye directamente al desarrollo de las competencias de Manejo de Información (general -UPC) y específica Manejo y uso de herramientas de ingeniería (ABET K.1) ambas a nivel de logro 1. El curso cuenta con el prerrequisito Software para ingeniería

Circuitos Lógicos Digitales - EL245 - 202101

El curso Circuitos Lógicos Digitales es de la especialidad de la carrera de Ingeniería electrónica, de carácter teórico-práctico. El curso te ayudará a comprender inicialmente el ¿cómo funcionan los circuitos digitales básicos que componen los equipos electrónicos hoy en día? Para ello, aprenderás cómo funcionan las compuertas lógicas, codificadores, decodificadores, multiplexores, demultiplexores, máquinas de estado, contadores y registros. La sociedad actual convive con la tecnología, cada día podemos apreciar nuevos productos, nuevas formas de interrelacionarnos con las personas y todo esto es producto de la electrónica. Cada producto electrónico nuevo que se introduce al mercado necesita de un proceso de diseño que involucra conocimientos en el área de circuitos digitales. El curso contribuye directamente al desarrollo de la competencia general Manejo de Información (Nivel Básico) y a la Competencia Específica de Capacidad de comunicarse efectivamente con un rango de audiencias (Nivel Básico). Requisito: Software para ingeniería

Circuitos Lógicos Digitales-EL214-201901

El curso Circuitos Lógicos Digitales es de la especialidad de la carrera de Ingeniería electrónica de carácter teórico-práctico. El curso te ayudará a comprender inicialmente el ¿cómo funcionan los circuitos digitales básicos que componen los equipos electrónicos hoy en día? Para ello aprenderás cómo funcionan las compuertas lógicas codificadores decodificadores multiplexores demultiplexores máquinas de estado contadores y registros.La sociedad actual convive con la tecnología cada día podemos apreciar nuevos productos nuevas formas de interrelacionarnos con las personas y todo esto es producto de la electrónica. Cada producto electrónico nuevo que se introduce al mercado necesita de un proceso de diseño que involucra conocimientos en el área de circuitos digitales. El curso contribuye directamente al desarrollo de las competencias de Manejo de Información (general -UPC) y específica Manejo y uso de herramientas de ingeniería (ABET K.1) ambas a nivel de logro 1. El curso cuenta con el prerrequisito Software para ingeniería