What Makes a Quality Health App-Developing a Global Research-Based Health App Quality Assessment Framework for CEN-ISO/TS 82304-2: Delphi Study.

BACKGROUND: The lack of an international standard for assessing and communicating health app quality and the lack of consensus about what makes a high-quality health app negatively affect the uptake of such apps. At the request of the European Commission, the international Standard Development Organizations (SDOs), European Committee for Standardization, International Organization for Standardization, and International Electrotechnical Commission have joined forces to develop a technical specification (TS) for assessing the quality and reliability of health and wellness apps. OBJECTIVE: This study aimed to create a useful, globally applicable, trustworthy, and usable framework to assess health app quality. METHODS: A 2-round Delphi technique with 83 experts from 6 continents (predominantly Europe) participating in one (n=42, 51%) or both (n=41, 49%) rounds was used to achieve consensus on a framework for assessing health app quality. Aims included identifying the maximum 100 requirement questions for the uptake of apps that do or do not qualify as medical devices. The draft assessment framework was built on 26 existing frameworks, the principles of stringent legislation, and input from 20 core experts. A follow-up survey with 28 respondents informed a scoring mechanism for the questions. After subsequent alignment with related standards, the quality assessment framework was tested and fine-tuned with manufacturers of 11 COVID-19 symptom apps. National mirror committees from the 52 countries that participated in the SDO technical committees were invited to comment on 4 working drafts and subsequently vote on the TS. RESULTS: The final quality assessment framework includes 81 questions, 67 (83%) of which impact the scores of 4 overarching quality aspects. After testing with people with low health literacy, these aspects were phrased as "Healthy and safe," "Easy to use," "Secure data," and "Robust build." The scoring mechanism enables communication of the quality assessment results in a health app quality score and label, alongside a detailed report. Unstructured interviews with stakeholders revealed that evidence and third-party assessment are needed for health app uptake. The manufacturers considered the time needed to complete the assessment and gather evidence (2-4 days) acceptable. Publication of CEN-ISO/TS 82304-2:2021 Health software - Part 2: Health and wellness apps - Quality and reliability was approved in May 2021 in a nearly unanimous vote by 34 national SDOs, including 6 of the 10 most populous countries worldwide. CONCLUSIONS: A useful and usable international standard for health app quality assessment was developed. Its quality, approval rate, and early use provide proof of its potential to become the trusted, commonly used global framework. The framework will help manufacturers enhance and efficiently demonstrate the quality of health apps, consumers, and health care professionals to make informed decisions on health apps. It will also help insurers to make reimbursement decisions on health apps.

A scoping review of the use of e-learning and e-consultation for healthcare workers in low- and middle-income countries and their potential complementarity.

OBJECTIVE: Although the provision of e-learning (EL) training for healthcare workers (HCWs) and provider-to-HCW e-consultation (EC) is considered useful for health outcomes, research on their joint use is limited. This scoping review aimed to create an overview of what is currently known in the literature about the use and implementation of EC and EL by HCWs in LMICs and to answer the question of whether there is evidence of complementarity. MATERIALS AND METHODS: Scientific databases were searched and peer-reviewed papers were reviewed systematically according to predefined inclusion/exclusion criteria. Data were extracted including the study focus (EC/EL), year of publication, geographical location, target population, target disease(s) under study, type(s) of study outcomes, and article type. RESULTS: A total of 3051 articles were retrieved and screened for eligibility, of which 96 were kept for analysis. Of these, only 3 addressed both EL and EC; 54 studies addressed EL; and 39 addressed EC. Most studies looked at gain in knowledge/skills usability, efficiency, competence, and satisfaction of HCW, or barriers/challenges to implementation. Descriptive studies focused on the application of EL or EC for targeting specific health conditions. Factors contributing to the success of EC or EL networks were institutional anchoring, multiple partnership, and capacity building of local experts. CONCLUSIONS: Our review found an important gap in the literature in relation to the complementary role of EL and EC for HCWs in LMICs evidenced by outcome measures. There is an important role for national and international academic institutions, learned medical societies, and networks to support regional experts in providing EL and EC for added value that will help the clinical performance of HCWs and improve health outcomes.

Lifetime burden of disease due to incident tuberculosis: a global reappraisal including post-tuberculosis sequelae.

BACKGROUND: Many individuals who survive tuberculosis disease face ongoing disability and elevated mortality risks. However, the impact of post-tuberculosis sequelae is generally omitted from policy analyses and disease burden estimates. We therefore estimated the global burden of tuberculosis, inclusive of post-tuberculosis morbidity and mortality. METHODS: We constructed a hypothetical cohort of individuals developing tuberculosis in 2019, including pulmonary and extrapulmonary disease. We simulated lifetime health outcomes for this cohort, stratified by country, age, sex, HIV status, and treatment status. We used disability-adjusted life-years (DALYs) to summarise fatal and non-fatal health losses attributable to tuberculosis, during the disease episode and afterwards. We estimated post-tuberculosis mortality and morbidity based on the decreased lung function caused by pulmonary tuberculosis disease. FINDINGS: Globally, we estimated 122 (95% uncertainty interval [UI] 98-151) million DALYs due to incident tuberculosis disease in 2019, with 58 (38-83) million DALYs attributed to post-tuberculosis sequelae, representing 47% (95% UI 37-57) of the total burden estimate. The increase in burden from post-tuberculosis varied substantially across countries and regions, driven largely by differences in estimated case fatality for the disease episode. We estimated 12·1 DALYs (95% UI 10·0-14·9) per incident tuberculosis case, of which 6·3 DALYs (5·6-7·0) were from the disease episode and 5·8 DALYs (3·8-8·3) were from post-tuberculosis. Per-case post-tuberculosis burden estimates were greater for younger individuals, and in countries with high incidence rates. The burden of post-tuberculosis was spread over the remaining lifetime of tuberculosis survivors, with almost a third of total DALYs (28%, 95% UI 23-34) accruing 15 or more years after incident tuberculosis. INTERPRETATION: Post-tuberculosis sequelae add substantially to the overall disease burden caused by tuberculosis. This hitherto unquantified burden has been omitted from most previous policy analyses. Future policy analyses and burden estimates should take better account of post-tuberculosis, to avoid the potential misallocation of funding, political attention, and research effort resulting from continued neglect of this issue. FUNDING: National Institutes of Health.

SERIES: eHealth in primary care. Part 3: eHealth education in primary care.

BACKGROUND: Education is essential to the integration of eHealth into primary care, but eHealth is not yet embedded in medical education. OBJECTIVES: In this opinion article, we aim to support organisers of Continuing Professional Development (CPD) and teachers delivering medical vocational training by providing recommendations for eHealth education. First, we describe what is required to help primary care professionals and trainees learn about eHealth. Second, we elaborate on how eHealth education might be provided. DISCUSSION: We consider four essential topics. First, an understanding of existing evidence-based eHealth applications and conditions for successful development and implementation. Second, required digital competencies of providers and patients. Third, how eHealth changes patient-provider and provider-provider relationships and finally, understanding the handling of digital data. Educational activities to address these topics include eLearning, blended learning, courses, simulation exercises, real-life practice, supervision and reflection, role modelling and community of practice learning. More specifically, a CanMEDS framework aimed at defining curriculum learning goals can support eHealth education by describing roles and required competencies. Alternatively, Kern's conceptual model can be used to design eHealth training programmes that match the educational needs of the stakeholders using eHealth. CONCLUSION: Vocational and CPD training in General Practice needs to build on eHealth capabilities now. We strongly advise the incorporation of eHealth education into vocational training and CPD activities, rather than providing it as a separate single module. How learning goals and activities take shape and how competencies are evaluated clearly requires further practice, evaluation and study.

Establishing a pulmonary rehabilitation programme in primary care in Greece: A FRESH AIR implementation study.

Pulmonary rehabilitation (PR) is an evidence-based, low-cost, non-medical treatment approach for patients with chronic respiratory diseases. This study aimed to start and assess the feasibility, acceptability and impact of a PR programme on health and quality of life of respiratory patients, for the first time in primary care in Crete, Greece and, particularly, in a low-resource rural setting. This was an implementation study with before-after outcome evaluation and qualitative interviews with patients and stakeholders. In a rural primary healthcare centre, patients with chronic obstructive pulmonary disease (COPD) and/or asthma were recruited. The implementation strategy included adaptation of a PR programme previously developed in United Kingdom and Uganda and training of clinical staff in programme delivery. The intervention comprised of 6 weeks of exercise and education sessions, supervised by physiotherapists, nurse and general practitioner. Patient outcomes (Clinical COPD Questionnaire (CCQ), COPD Assessment Test (CAT), St. George's Respiratory Questionnaire (SGRQ), Patient Health Questionnaire-9 (PHQ-9), Incremental Shuttle Walking Test (ISWT)) were analysed descriptively. Qualitative outcomes (feasibility, acceptability) were analysed using thematic content analysis. With minor adaptations to the original programme, 40 patients initiated (24 with COPD and 16 with asthma) and 31 completed PR (19 with COPD and 12 with asthma). Clinically important improvements in all outcomes were documented (mean differences (95% CIs) for CCQ: -0.53 (-0.81, -0.24), CAT: -5.93 (-8.27, -3.60), SGRQ: -23.00 (-29.42, -16.58), PHQ-9: -1.10 (-2.32, 0.12), ISWT: 87.39 (59.37, 115.40)). The direct PR benefits and the necessity of implementing similar initiatives in remote areas were highlighted. This study provided evidence about the multiple impacts of a PR programme, indicating that it could be both feasible and acceptable in low-resource, primary care settings.

Feasibility and acceptability of a midwife-led health education strategy to reduce exposure to biomass smoke among pregnant women in Uganda, A FRESH AIR project.

Biomass smoke exposure is a threat to child and maternal health in many resource-limited countries and is associated with poor pregnancy outcomes and serious lung diseases in the offspring. We aimed to assess the feasibility, acceptability and impact of a midwife-led education programme on biomass risks and prevention for women attending maternity clinics in Uganda. Education materials were co-developed through an iterative process by midwives and other stakeholders. The materials were serially tested and approved by the Ministry of Health and used by midwives and village health teams (VHTs). The district health team, 12 midwives and 40 VHTs were sensitised on biomass smoke. Two hundred and forty-four women were educated about biomass smoke by midwives; pre- and post-session questionnaires showed major improvements in knowledge of biomass smoke risks. Qualitative interviews with women three months after the sessions showed that they made behavioural changes such as avoiding smoke while cooking, using dry wood, solar power for lighting and improved ventilation. The major barrier to behavioural changes was poverty, but some improvements cost no money. The programme delivered by midwives was feasible and acceptable; implementing this programme has the potential to reduce exposure to smoke with major benefits to mother, foetus, and children throughout their lives.

Prevalence and Characteristics of Asthma-Chronic Obstructive Pulmonary Disease Overlap in Routine Primary Care Practices.

Rationale: Adults may exhibit characteristics of both asthma and chronic obstructive pulmonary disease (COPD), a situation recently described as asthma-COPD overlap (ACO). There is a paucity of information about ACO in primary care.Objectives: To estimate the prevalence and describe characteristics of individuals with ACO in primary care practices among patients currently diagnosed with asthma, COPD, or both; and to compare the prevalence and characteristics of ACO among the three source populations.Methods: The Respiratory Effectiveness Group conducted a cross-sectional study of individuals ≥40 years old and with ≥2 outpatient primary care visits over a 2-year period in the UK Optimum Patient Care Research Database. Patients were classified into one of three source populations based on diagnostic codes: 1) COPD only, 2) both asthma and COPD, or 3) asthma only. ACO was defined as the presence of all of the following 1) age ≥40 years, 2) current or former smoking, 3) post-bronchodilator airflow limitation (forced expiratory volume in 1 second/forced vital capacity <0.7), and 4) ≥12% and ≥200 ml reversibility in post-bronchodilator forced expiratory volume in 1 second.Results: Among 2,165 individuals (1,015 COPD only, 395 with both asthma and COPD, and 755 asthma only), the overall prevalence of ACO was 20% (95% confidence interval, 18-23%). Patients with ACO had a mean age of 70 years (standard deviation, 11 yr), 60% were men, 73% were former smokers (the rest were current smokers), and 66% were overweight or obese. Comorbid conditions were common in patients with ACO, including diabetes (53%), cardiovascular disease (36%), hypertension (30%), eczema (23%), and rhinitis (21%). The prevalence of ACO was higher in patients with a diagnosis of both asthma and COPD (32%) compared with a diagnosis of COPD only (20%; P < 0.001) or asthma only (14%; P < 0.001). Demographic and clinical characteristics of ACO varied across these three source populations.Conclusions: One in five individuals with a diagnosis of COPD, asthma, or both asthma and COPD in primary care settings have ACO based on the Respiratory Effectiveness Group ACO Working group criteria. The prevalence and characteristics of patients with ACO varies across the three source populations.

Chronic Respiratory Symptoms and Lung Abnormalities Among People With a History of Tuberculosis in Uganda: A National Survey.

BACKGROUND: People with pulmonary tuberculosis are at risk of developing chronic respiratory disorders due to residual lung damage. To date, the scope of the problem in high-burden tuberculosis countries is relatively unknown. METHODS: Chronic respiratory symptoms (cough and phlegm lasting >2 weeks) and radiological lung abnormalities were compared between adults with and without a history of tuberculosis among the general population of Uganda. Multivariable regression models were used to estimate odds ratios (ORs) with adjustment for age, gender, smoking, education, setting, and region. Random effects models accounted for village clustering effect. RESULTS: Of 45293 invited people from 70 villages, 41154 (90.9%) participated in the survey. A total of 798 had a history of tuberculosis and, among them, 16% had respiratory symptoms and 41% X-ray abnormalities. Adjusted ORs showed strong evidence for individuals with a history of tuberculosis having increased risk of respiratory symptoms (OR, 4.02; 95% confidence interval [CI], 3.25-4.96) and X-ray abnormalities (OR, 17.52; 95% CI, 14.76-20.79), attributing 6% and 24% of the respective population risks. CONCLUSIONS: In Uganda, a history of tuberculosis was a strong predictor of respiratory symptoms and lung abnormalities, before older age and smoking. Eliminating tuberculosis disease could reduce the prevalence of chronic respiratory symptoms as much as eliminating smoking.

International research and guidelines on post-tuberculosis chronic lung disorders: a systematic scoping review.

INTRODUCTION: Pulmonary tuberculosis (TB) is an important risk factor for chronic respiratory disease due to residual lung damage. Yet, the WHO End TB strategy does not mention post-TB chronic lung disorders (PTBLDs) and programmatic interventions to address PTBLD are lacking. This study assessed the scope of current guidelines and evidence on PTBLD to inform policy and research action. METHODS: A systematic literature search was conducted following Preferred Reporting Items for Systematic Review and Meta-Analysis guidelines. Eight databases (TRIP, International Guideline Library, MEDLINE/PubMed, EMBASE, Web of Science, Global Health, Cochrane Library) were searched for records on PTBLD published between 1 January 1990 and 1 December 2017. Non-English records, case series, conference abstracts and letters to editors were excluded. Data were extracted and charted on publication year, location, PTBLD condition(s) and main study outcome. RESULTS: A total of 212 guidelines and 3661 articles were retrieved. After screening, only three international TB guidelines mentioned TB sequelae, but none described how to identify or manage the condition. A total of 156 articles addressed PTBLD: 54 (35%) mentioned unspecified TB sequelae; 47 (30%) specific post-TB conditions including aspergillosis, bronchial stenosis or bronchiectasis; 52 (33%) post-TB obstructive disorders or lung function impairment; and 20 (13%) post-TB respiratory symptoms or chest X-ray abnormalities. The first two groups mostly assessed surgery or ventilation techniques for patient management, while the last two groups typically assessed prevalence or predictors of disease. CONCLUSION: This is the first review to provide a comprehensive overview of the current literature on PTBLD. The scope of evidence around the burden of PTBLD warrants inclusion and recognition of the problem in international TB guidelines. Research is now needed on early detection of PTBLD and patient management options that are suitable for high-burden TB countries.

The proportion of the population of England that self-identifies as lesbian, gay or bisexual: producing modelled estimates based on national social surveys.

OBJECTIVES: There is currently no widely accepted estimate of the proportion of people in England that self-identifies as lesbian, gay or bisexual (LGB), which is needed if we are to compare health inequality between different population groups. Using systematic review methods, this study identified all national social surveys with a question on sexual orientation and pooled those which represented the overall population of England. LGB proportions were synthesized into an aggregated mean estimate using weights based on sample size, response rate and missing data. The modelled estimate was stratified by socio-demographic and geographical variables. RESULTS: Twenty-two national surveys were identified of which 15 were suitable for pooling. Synthesis resulted in a weighted mean estimate of 2.50% of the adult population of England identifying as LGB or 'other'. The proportion was highest in men, people below 45 years of age and the London region. The (theoretical) upper limit was 5.89% if all non-responders were assumed to identify as LGB. The reported 2.50% presents a minimum and may be influenced by respondents' perceptions of confidentiality and social acceptance. It is however the most robust estimate currently available and can be used as baseline to understand health and wellbeing needs of different groups.

The comparative diagnostic accuracy of the Mini Mental State Examination (MMSE) and the General Practitioner assessment of Cognition (GPCOG) for identifying dementia in primary care: a systematic review protocol.

BACKGROUND: Improved dementia identification is a global health priority, and general practitioners (GPs) are often the first point of contact for people with concerns about their cognition. However, GPs often express uncertainty in using assessment tools and the evidence based on which tests are most accurate in identifying dementia is unclear. In particular, there is little certainty around how the accuracy of available brief cognitive assessments compares within a clinical family practice setting.Grounded in existing brief cognitive assessment evidence, we will compare the diagnostic test accuracy of the Mini Mental State Examination (MMSE) to the General Practitioner Assessment of Cognition (GPCOG) against the best available reference standard when used within a family practice setting. METHODS: We will employ robust systematic review methods to assess studies of diagnostic accuracy where both the MMSE and GPCOG have been evaluated as direct comparisons, i.e. within the same study population. This approach will enable us to minimise between-study heterogeneity, to eliminate the risk of bias due to confounding and increase the opportunity to make clinically useful and useable comparisons of diagnostic accuracy across both the MMSE and GPCOG. This systematic review will be conducted using a pragmatic search strategy, refining searches that build upon studies identified as part of our overview of systematic reviews of the diagnostic accuracy of brief cognitive assessments for identifying dementia in primary care. DISCUSSION: Through this systematic review, we aim to improve existing evidence on how the diagnostic accuracy of MMSE and GPCOG compares when used to identify dementia within the family practice setting. We also aim to make clinical practice recommendations based upon the variations in diagnostic accuracy identified between the MMSE and GPCOG.

Effect of Introducing Xpert MTB/RIF to Test and Treat Individuals at Risk of Multidrug-Resistant Tuberculosis in Kazakhstan: A Prospective Cohort Study.

BACKGROUND: Xpert MTB/RIF (Xpert) was piloted in Kazakhstan to detect tuberculosis (TB) and rifampicin resistance (RR-)TB among individuals at risk of multidrug-resistant (MDR-) TB. This study assessed the performance of Xpert compared to conventional diagnostic methods, RR-TB case detection among various risk groups, treatment initiation and time to diagnosis and treatment. METHODS: Eligible individuals were tested with Xpert, smear microscopy, culture and drug-susceptibility testing (DST) at the national TB reference laboratory and three provincial laboratories. Data was collected prospectively from August 2012 to May 2013 from routine laboratory and treatment registers. RESULTS: A total of 5,611 Xpert tests were performed mostly targeting contacts of MDR-TB patients, 'other' presumptive MDR-TB patients, and retreatment cases (26%, 24% and 22%, respectively). Compared to phenotypic DST, the positive predictive value of Xpert to detect RR-TB was 93.1% and 96.4% and the negative predictive value was 94.6% and 92.7% using solid and liquid culture media, respectively. RR-TB detection was highest among (former) prisoners, retreatment cases, people living with HIV/AIDS (PLWHA), and TB patients with positive smears after intensive phase of treatment (59%, 58%, 54% and 53% among TB positives, respectively). 88.9% of RR-TB patients were registered to have started second-line TB treatment. Median time to diagnosis with Xpert was 0.0 days (IQR 0.0-1.0), time from diagnosis to start of first-line treatment 3.0 days (IQR 1.0-7.0), and to start of second-line treatment 7.0 days (IQR 4.0-16). CONCLUSIONS: Compared to conventional culture and DST, Xpert had a shorter result turn-around-time and excellent concordance to detect RR-TB. Time from sputum collection to start of second-line treatment was reduced to one week. The yield of Xpert could be maximized by increasing referrals from penitentiary and HIV centers to TB centers.

Effects of Introducing Xpert MTB/RIF on Diagnosis and Treatment of Drug-Resistant Tuberculosis Patients in Indonesia: A Pre-Post Intervention Study.

BACKGROUND: In March 2012, the Xpert MTB/RIF assay (Xpert) was introduced in three provincial public hospitals in Indonesia as a novel diagnostic to detect tuberculosis and rifampicin resistance among high risk individuals. OBJECTIVE: This study assessed the effects of using Xpert in place of conventional solid and liquid culture and drug-susceptibility testing on case detection rates, treatment initiation rates, and health system delays among drug-resistant tuberculosis (TB) patients. METHODS: Cohort data on registration, test results and treatment initiation were collected from routine presumptive patient registers one year before and one year after Xpert was introduced. Proportions of case detection and treatment initiation were compared using the Pearson Chi square test and median time delays using the Mood's Median test. RESULTS: A total of 975 individuals at risk of drug-resistant TB were registered in the pre-intervention year and 1,442 in the post-intervention year. After Xpert introduction, TB positivity rate increased by 15%, while rifampicin resistance rate reduced by 23% among TB positive cases and by 9% among all tested. Second-line TB treatment initiation rate among rifampicin resistant patients increased by 19%. Time from client registration to diagnosis was reduced by 74 days to a median of a single day (IQR 0-4) and time from diagnosis to treatment start was reduced by 27 days to a median of 15 days (IQR 7-51). All findings were significant with p<0.001. CONCLUSION: Compared to solid and liquid culture and drug-susceptibility testing, Xpert detected more TB and less rifampicin resistance, increased second-line treatment initiation rates and shortened time to diagnosis and treatment. This test holds promise to improve rapid case finding and management of drug-resistant TB patients in Indonesia.

Optimal triage test characteristics to improve the cost-effectiveness of the Xpert MTB/RIF assay for TB diagnosis: a decision analysis.

BACKGROUND: High costs are a limitation to scaling up the Xpert MTB/RIF assay (Xpert) for the diagnosis of tuberculosis in resource-constrained settings. A triaging strategy in which a sensitive but not necessarily highly specific rapid test is used to select patients for Xpert may result in a more affordable diagnostic algorithm. To inform the selection and development of particular diagnostics as a triage test we explored combinations of sensitivity, specificity and cost at which a hypothetical triage test will improve affordability of the Xpert assay. METHODS: In a decision analytical model parameterized for Uganda, India and South Africa, we compared a diagnostic algorithm in which a cohort of patients with presumptive TB received Xpert to a triage algorithm whereby only those with a positive triage test were tested by Xpert. FINDINGS: A triage test with sensitivity equal to Xpert, 75% specificity, and costs of US$5 per patient tested reduced total diagnostic costs by 42% in the Uganda setting, and by 34% and 39% respectively in the India and South Africa settings. When exploring triage algorithms with lower sensitivity, the use of an example triage test with 95% sensitivity relative to Xpert, 75% specificity and test costs $5 resulted in similar cost reduction, and was cost-effective by the WHO willingness-to-pay threshold compared to Xpert for all in Uganda, but not in India and South Africa. The gain in affordability of the examined triage algorithms increased with decreasing prevalence of tuberculosis among the cohort. CONCLUSIONS: A triage test strategy could potentially improve the affordability of Xpert for TB diagnosis, particularly in low-income countries and with enhanced case-finding. Tests and markers with lower accuracy than desired of a diagnostic test may fall within the ranges of sensitivity, specificity and cost required for triage tests and be developed as such.

GeneXpert for TB diagnosis: planned and purposeful implementation.

Xpert MTB/RIF is a major advance for TB diagnostics, especially for multidrug-resistant (MDR) TB and HIV-associated TB. But implementation concerns including cost, technical support requirements, and challenging demands of providing second-line TB drugs for diagnosed MDR-TB cases call for gradual, careful introduction based on country circumstances.

Research on implementation of interventions in tuberculosis control in low- and middle-income countries: a systematic review.

BACKGROUND: Several interventions for tuberculosis (TB) control have been recommended by the World Health Organization (WHO) over the past decade. These include isoniazid preventive therapy (IPT) for HIV-infected individuals and household contacts of infectious TB patients, diagnostic algorithms for rule-in or rule-out of smear-negative pulmonary TB, and programmatic treatment for multidrug-resistant TB. There is no systematically collected data on the type of evidence that is publicly available to guide the scale-up of these interventions in low- and middle-income countries. We investigated the availability of published evidence on their effectiveness, delivery, and cost-effectiveness that policy makers need for scaling-up these interventions at country level. METHODS AND FINDINGS: PubMed, Web of Science, EMBASE, and several regional databases were searched for studies published from 1 January 1990 through 31 March 2012 that assessed health outcomes, delivery aspects, or cost-effectiveness for any of these interventions in low- or middle-income countries. Selected studies were evaluated for their objective(s), design, geographical and institutional setting, and generalizability. Studies reporting health outcomes were categorized as primarily addressing efficacy or effectiveness of the intervention. These criteria were used to draw landscapes of published research. We identified 59 studies on IPT in HIV infection, 14 on IPT in household contacts, 44 on rule-in diagnosis, 19 on rule-out diagnosis, and 72 on second-line treatment. Comparative effectiveness studies were relatively few (n = 9) and limited to South America and sub-Saharan Africa for IPT in HIV-infection, absent for IPT in household contacts, and rare for second-line treatment (n = 3). Evaluations of diagnostic and screening algorithms were more frequent (n = 19) but geographically clustered and mainly of non-comparative design. Fifty-four studies evaluated ways of delivering these interventions, and nine addressed their cost-effectiveness. CONCLUSIONS: There are substantial gaps in published evidence for scale-up for five WHO-recommended TB interventions settings at country level, which for many countries possibly precludes program-wide implementation of these interventions. There is a strong need for rigorous operational research studies to be carried out in programmatic settings to inform on best use of existing and new interventions in TB control.

Survey of the diagnostic retooling process in national TB reference laboratories, with special focus on rapid speciation tests endorsed by WHO in 2007.

BACKGROUND: Successful integration of new diagnostics in national tuberculosis (TB) control programs, also called 'retooling', is highly dependent on operational aspects related to test availability, accessibility and affordability. This survey aimed to find out whether recommendations to use new diagnostics lead to successful retooling in high TB endemic countries, using immunochromatographic tests (ICTs) for TB culture speciation as a case study. ICTs are recommended to accurately confirm the presence of bacteria of the Mycobacterium tuberculosis complex in liquid culture isolates. METHODS AND FINDINGS: Questionnaires were sent to national TB reference laboratories (NRLs) in 42 high TB endemic countries to address their access to information on ICT implementation, logistics related to availability, accessibility and affordability of ICTs, and testing algorithms. Results from 16 responding countries indicated that half of the NRLs were aware of the contents of WHO guidance documents on liquid culture and ICT implementation, as well as their eligibility for a negotiated pricing agreement for ICT procurement. No major issues with availability and accessibility of ICTs were raised. When asked about testing algorithms, ICTs were not used as stand-alone or first test for TB culture identification as recommended by WHO. CONCLUSIONS: The low response rate was a limitation of this survey and together with NRLs managers' unawareness of global guidance, suggests a lack of effective communication between partners of the global laboratory network and NRLs. TB tests could become more affordable to high TB endemic countries, if the possibility to negotiate lower prices for commercial products is communicated to them more successfully. NRLs need additional guidance to identify where available technologies can be most usefully implemented and in what order, taking into account long-term laboratory strategies.

Rapid diagnosis of tuberculosis with the Xpert MTB/RIF assay in high burden countries: a cost-effectiveness analysis.

BACKGROUND: Xpert MTB/RIF (Xpert) is a promising new rapid diagnostic technology for tuberculosis (TB) that has characteristics that suggest large-scale roll-out. However, because the test is expensive, there are concerns among TB program managers and policy makers regarding its affordability for low- and middle-income settings. METHODS AND FINDINGS: We estimate the impact of the introduction of Xpert on the costs and cost-effectiveness of TB care using decision analytic modelling, comparing the introduction of Xpert to a base case of smear microscopy and clinical diagnosis in India, South Africa, and Uganda. The introduction of Xpert increases TB case finding in all three settings; from 72%-85% to 95%-99% of the cohort of individuals with suspected TB, compared to the base case. Diagnostic costs (including the costs of testing all individuals with suspected TB) also increase: from US$28-US$49 to US$133-US$146 and US$137-US$151 per TB case detected when Xpert is used "in addition to" and "as a replacement of" smear microscopy, respectively. The incremental cost effectiveness ratios (ICERs) for using Xpert "in addition to" smear microscopy, compared to the base case, range from US$41-$110 per disability adjusted life year (DALY) averted. Likewise the ICERS for using Xpert "as a replacement of" smear microscopy range from US$52-$138 per DALY averted. These ICERs are below the World Health Organization (WHO) willingness to pay threshold. CONCLUSIONS: Our results suggest that Xpert is a cost-effective method of TB diagnosis, compared to a base case of smear microscopy and clinical diagnosis of smear-negative TB in low- and middle-income settings where, with its ability to substantially increase case finding, it has important potential for improving TB diagnosis and control. The extent of cost-effectiveness gain to TB programmes from deploying Xpert is primarily dependent on current TB diagnostic practices. Further work is required during scale-up to validate these findings.