RESUMEN
BACKGROUND: Improving health-related quality of life (HRQOL) has emerged as a priority in the management of nontuberculous mycobacterial pulmonary disease (NTM-PD). We aimed to evaluate HRQOL and its changes after 6 months' treatment in patients with NTM-PD. METHODS: The NTM-KOREA is a nationwide prospective cohort enrolling patients initiating treatment for NTM-PD in 8 institutions across South Korea. We conducted the Quality of Life-Bronchiectasis (QOL-B) at 6-month intervals and evaluated baseline scores (higher scores indicate better quality of life) and changes after 6 months' treatment. Multivariate logistic regression was performed to identify factors associated with improvement in the QOL-B physical functioning and respiratory symptoms domains. RESULTS: Between February 2022 and August 2023, 411 patients were included in the analysis. Baseline scores (95% confidence interval [CI]) for physical functioning and respiratory symptoms were 66.7 (46.7-86.7) and 81.5 (70.4-92.6), respectively. Among 228 patients who completed the QOL-B after 6 months' treatment, improvements in physical functioning and respiratory symptoms were observed in 61 (26.8%) and 71 (31.1%) patients, respectively. A lower score (adjusted odds ratio; 95% CI) for physical functioning (0.93; 0.91-0.96) and respiratory symptoms (0.92; 0.89-0.95) at treatment initiation was associated with a greater likelihood of physical functioning and respiratory symptom improvement, respectively; achieving culture conversion was not associated with improvement in physical functioning (0.62; 0.28-1.39) or respiratory symptoms (1.30; 0.62-2.74). CONCLUSIONS: After 6 months of antibiotic treatment for NTM-PD, HRQOL improved in almost one-third, especially in patients with severe initial symptoms, regardless of culture conversion. CLINICAL TRIALS REGISTRATION: ClinicalTrials.gov identifier: NCT03934034.
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Antibacterianos , Infecciones por Mycobacterium no Tuberculosas , Calidad de Vida , Humanos , Masculino , Femenino , Infecciones por Mycobacterium no Tuberculosas/tratamiento farmacológico , Infecciones por Mycobacterium no Tuberculosas/microbiología , República de Corea , Antibacterianos/uso terapéutico , Persona de Mediana Edad , Anciano , Estudios Prospectivos , Micobacterias no Tuberculosas/efectos de los fármacos , Resultado del TratamientoRESUMEN
Nontuberculous mycobacterial pulmonary disease (NTM-PD) prevalence is a rising public health concern. We assessed the long-term healthcare systems perspective of costs incurred by 147 NTM-PD patients at a tertiary hospital in South Korea. Median cumulative total medical cost in managing NTM-PD patients was US $5,044 (interquartile range US $3,586-$9,680) over 49.7 months (interquartile range 33.0-68.2 months) of follow-up. The major cost drivers were diagnostic testing and medication, accounting for 59.6% of total costs. Higher costs were associated with hospitalization for Mycobacterium abscessus infection and pulmonary comorbidities. Of the total medical care costs, 50.2% were patient co-payments resulting from limited national health insurance coverage. As South Korea faces significant problems of poverty during old age and increasing NTM-PD prevalence, the financial and socio-economic burden of NTM-PD may become a major public health concern that should be considered with regard to adequate strategies for NTM-PD patients.
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Costos de la Atención en Salud , Infecciones por Mycobacterium no Tuberculosas , Humanos , República de Corea/epidemiología , Infecciones por Mycobacterium no Tuberculosas/epidemiología , Infecciones por Mycobacterium no Tuberculosas/economía , Infecciones por Mycobacterium no Tuberculosas/microbiología , Masculino , Femenino , Anciano , Persona de Mediana Edad , Micobacterias no Tuberculosas , Enfermedades Pulmonares/epidemiología , Enfermedades Pulmonares/economía , Enfermedades Pulmonares/microbiología , Historia del Siglo XXI , PrevalenciaRESUMEN
BACKGROUND: Effective strategies are needed to facilitate the prompt diagnosis and treatment of tuberculosis in countries with a high burden of the disease. METHODS: We conducted a cluster-randomized trial in which Ugandan community health centers were assigned to a multicomponent diagnostic strategy (on-site molecular testing for tuberculosis, guided restructuring of clinic workflows, and monthly feedback of quality metrics) or routine care (on-site sputum-smear microscopy and referral-based molecular testing). The primary outcome was the number of adults treated for confirmed tuberculosis within 14 days after presenting to the health center for evaluation during the 16-month intervention period. Secondary outcomes included completion of tuberculosis testing, same-day diagnosis, and same-day treatment. Outcomes were also assessed on the basis of proportions. RESULTS: A total of 20 health centers underwent randomization, with 10 assigned to each group. Of 10,644 eligible adults (median age, 40 years) whose data were evaluated, 60.1% were women and 43.8% had human immunodeficiency virus infection. The intervention strategy led to a greater number of patients being treated for confirmed tuberculosis within 14 days after presentation (342 patients across 10 intervention health centers vs. 220 across 10 control health centers; adjusted rate ratio, 1.56; 95% confidence interval [CI], 1.21 to 2.01). More patients at intervention centers than at control centers completed tuberculosis testing (adjusted rate ratio, 1.85; 95% CI, 1.21 to 2.82), received a same-day diagnosis (adjusted rate ratio, 1.89; 95% CI, 1.39 to 2.56), and received same-day treatment for confirmed tuberculosis (adjusted rate ratio, 2.38; 95% CI, 1.57 to 3.61). Among 706 patients with confirmed tuberculosis, a higher proportion in the intervention group than in the control group were treated on the same day (adjusted rate ratio, 2.29; 95% CI, 1.23 to 4.25) or within 14 days after presentation (adjusted rate ratio, 1.22; 95% CI, 1.06 to 1.40). CONCLUSIONS: A multicomponent diagnostic strategy that included on-site molecular testing plus implementation supports to address barriers to delivery of high-quality tuberculosis evaluation services led to greater numbers of patients being tested, receiving a diagnosis, and being treated for confirmed tuberculosis. (Funded by the National Heart, Lung, and Blood Institute; XPEL-TB ClinicalTrials.gov number, NCT03044158.).
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Centros Comunitarios de Salud/organización & administración , Técnicas de Diagnóstico Molecular , Pruebas en el Punto de Atención , Tuberculosis/diagnóstico , Adulto , Femenino , Infecciones por VIH/complicaciones , Infecciones por VIH/diagnóstico , Humanos , Masculino , Persona de Mediana Edad , Modelos Estadísticos , Técnicas de Amplificación de Ácido Nucleico , Tiempo de Tratamiento , Tuberculosis/complicaciones , Tuberculosis/tratamiento farmacológico , UgandaRESUMEN
OBJECTIVES: Digital adherence technologies like 99DOTS are increasingly considered as an alternative to directly observed therapy for tuberculosis (TB) treatment supervision. We evaluated the cost and cost-effectiveness of 99DOTS in a high-TB-burden setting. METHODS: We assessed the costs of implementing 99DOTS in Uganda through a pragmatic, stepped-wedge randomized trial. We measured costs from the health system perspective at 5 of 18 study facilities. Self-reported service activity time data were used to assess activity-based service costs; other costs were captured from budgets and key informant discussions using standardized forms. We estimated costs and effectiveness considering the 8-month study period ("trial specific") and using a 5-year time horizon ("extended activities"), the latter including a "marginal clinic" expansion scenario that ignored above-site implementation costs. Cost-effectiveness was assessed as cost per patient successfully completing treatment, using Monte Carlo simulation, cost-effectiveness acceptability curves, and sensitivity analyses to evaluate uncertainty and robustness of results. RESULTS: The total cost of implementing 99DOTS in the "trial-specific" scenario was $99 554 across 18 clinics (range $3771-$6238 per clinic). The cost per treatment success in the "trial-specific" scenario was $355 (range $229-$394), falling to $59 (range $50-$70) assuming "extended activities," and $49 (range $42-$57) in the "marginal clinic" scenario. The incremental cost-effectiveness of 99DOTS in the "extended-activity" scenario was $355 per incremental treatment success. CONCLUSIONS: Costs and cost-effectiveness of 99DOTS were influenced by the degree to which infrastructure is scaled over time. If sustained and scaled up, 99DOTS can be a cost-effective option for TB treatment adherence support in high-TB-burden settings like Uganda.
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Tuberculosis , Presupuestos , Análisis Costo-Beneficio , Humanos , Tecnología , Tuberculosis/tratamiento farmacológico , UgandaRESUMEN
BACKGROUND: Countries with high TB burden have expanded access to molecular diagnostic tests. However, their impact on reducing delays in TB diagnosis and treatment has not been assessed. Our primary aim was to summarize the quantitative evidence on the impact of nucleic acid amplification tests (NAAT) on diagnostic and treatment delays compared to that of the standard of care for drug-sensitive and drug-resistant tuberculosis (DS-TB and DR-TB). METHODS: We searched MEDLINE, EMBASE, Web of Science, and the Global Health databases (from their inception to October 12, 2020) and extracted time delay data for each test. We then analysed the diagnostic and treatment initiation delay separately for DS-TB and DR-TB by comparing smear vs Xpert for DS-TB and culture drug sensitivity testing (DST) vs line probe assay (LPA) for DR-TB. We conducted random effects meta-analyses of differences of the medians to quantify the difference in diagnostic and treatment initiation delay, and we investigated heterogeneity in effect estimates based on the period the test was used in, empiric treatment rate, HIV prevalence, healthcare level, and study design. We also evaluated methodological differences in assessing time delays. RESULTS: A total of 45 studies were included in this review (DS = 26; DR = 20). We found considerable heterogeneity in the definition and reporting of time delays across the studies. For DS-TB, the use of Xpert reduced diagnostic delay by 1.79 days (95% CI - 0.27 to 3.85) and treatment initiation delay by 2.55 days (95% CI 0.54-4.56) in comparison to sputum microscopy. For DR-TB, use of LPAs reduced diagnostic delay by 40.09 days (95% CI 26.82-53.37) and treatment initiation delay by 45.32 days (95% CI 30.27-60.37) in comparison to any culture DST methods. CONCLUSIONS: Our findings indicate that the use of World Health Organization recommended diagnostics for TB reduced delays in diagnosing and initiating TB treatment. Future studies evaluating performance and impact of diagnostics should consider reporting time delay estimates based on the standardized reporting framework.
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Mycobacterium tuberculosis , Tuberculosis Resistente a Múltiples Medicamentos , Tuberculosis Pulmonar , Tuberculosis , Humanos , Rifampin/uso terapéutico , Tuberculosis Pulmonar/diagnóstico , Mycobacterium tuberculosis/genética , Diagnóstico Tardío , Tiempo de Tratamiento , Patología Molecular , Sensibilidad y Especificidad , Tuberculosis/diagnóstico , Tuberculosis/tratamiento farmacológico , Tuberculosis Resistente a Múltiples Medicamentos/tratamiento farmacológicoRESUMEN
BACKGROUND: Public-private mix (PPM) programs on tuberculosis (TB) have a critical role in engaging and integrating the private sector into the national TB control efforts in order to meet the End TB Strategy targets. South Korea's PPM program can provide important insights on the long-term impact and policy gaps in the development and expansion of PPM as a nationwide program. METHODS AND FINDINGS: Healthcare is privatized in South Korea, and a majority (80.3% in 2009) of TB patients sought care in the private sector. Since 2009, South Korea has rapidly expanded its PPM program coverage under the National Health Insurance (NHI) scheme as a formal national program with dedicated PPM nurses managing TB patients in both the private and public sectors. Using the difference in differences (DID) analytic framework, we compared relative changes in TB treatment outcomes-treatment success (TS) and loss to follow-up (LTFU)-in the private and public sector between the 2009 and 2014 TB patient cohorts. Propensity score matching (PSM) using the kernel method was done to adjust for imbalances in the covariates between the 2 population cohorts. The 2009 cohort included 6,195 (63.0% male, 37.0% female; mean age: 42.1) and 27,396 (56.1% male, 43.9% female; mean age: 45.7) TB patients in the public and private sectors, respectively. The 2014 cohort included 2,803 (63.2% male, 36.8% female; mean age: 50.1) and 29,988 (56.5% male, 43.5% female; mean age: 54.7) patients. In both the private and public sectors, the proportion of patients with transfer history decreased (public: 23.8% to 21.7% and private: 20.8% to 17.6%), and bacteriological confirmed disease increased (public: 48.9% to 62.3% and private: 48.8% to 58.1%) in 2014 compared to 2009. After expanding nationwide PPM, absolute TS rates improved by 9.10% (87.5% to 93.4%) and by 13.6% (from 70.3% to 83.9%) in the public and private sectors. Relative to the public, the private saw 4.1% (95% confidence interval [CI] 2.9% to 5.3%, p-value < 0.001) and -8.7% (95% CI -9.7% to -7.7%, p-value <0.001) higher rates of improvement in TS and reduction in LTFU. Treatment outcomes did not improve in patients who experienced at least 1 transfer during their TB treatment. Study limitations include non-longitudinal nature of our original dataset, inability to assess the regional disparities, and verify PPM program's impact on TB mortality. CONCLUSIONS: We found that the nationwide scale-up of the PPM program was associated with improvements in TB treatment outcomes in the private sector in South Korea. Centralized financial governance and regulatory mechanisms were integral in facilitating the integration of highly diverse South Korean private sector into the national TB control program and scaling up of the PPM intervention nationwide. However, TB care gaps continued to exist for patients who transferred at least once during their treatment. These programmatic gaps may be improved through reducing administrative hurdles and making programmatic amendments that can help facilitate management TB patients between institutions and healthcare sectors, as well as across administrative regions.
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Programas Nacionales de Salud , Sector Privado , Sector Público , Tuberculosis/terapia , Conjuntos de Datos como Asunto , Erradicación de la Enfermedad , Femenino , Programas de Gobierno , Política de Salud , Humanos , Masculino , Persona de Mediana Edad , República de Corea , Resultado del Tratamiento , Tuberculosis/prevención & controlRESUMEN
We consider the problem of meta-analyzing two-group studies that report the median of the outcome. Often, these studies are excluded from meta-analysis because there are no well-established statistical methods to pool the difference of medians. To include these studies in meta-analysis, several authors have recently proposed methods to estimate the sample mean and standard deviation from the median, sample size, and several commonly reported measures of spread. Researchers frequently apply these methods to estimate the difference of means and its variance for each primary study and pool the difference of means using inverse variance weighting. In this work, we develop several methods to directly meta-analyze the difference of medians. We conduct a simulation study evaluating the performance of the proposed median-based methods and the competing transformation-based methods. The simulation results show that the median-based methods outperform the transformation-based methods when meta-analyzing studies that report the median of the outcome, especially when the outcome is skewed. Moreover, we illustrate the various methods on a real-life data set.
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Biometría/métodos , Metaanálisis como Asunto , Análisis de Varianza , Modelos EstadísticosRESUMEN
BACKGROUND: India and many other high-burden countries have committed to providing universal access to high-quality diagnosis and drug susceptibility testing (DST) for tuberculosis (TB), but the most cost-effective approach to achieve this goal remains uncertain. Centralized testing at district-level hub facilities with a supporting sample transport network can generate economies of scale, but decentralization to the peripheral level may provide faster diagnosis and reduce losses to follow-up (LTFU). METHODS: We generated functions to evaluate the costs of centralized and decentralized molecular testing for tuberculosis with Xpert MTB/RIF (Xpert), a WHO-endorsed test which can be performed at centralized and decentralized levels. We merged the cost estimates with an agent-based simulation of TB transmission in a hypothetical representative region in India to assess the impact and cost-effectiveness of each strategy. RESULTS: Compared against centralized Xpert testing, decentralization was most favorable when testing volume at decentralized facilities and pre-treatment LTFU were high, and specimen transport network was exclusively established for TB. Assuming equal quality of centralized and decentralized testing, decentralization was cost-saving, saving a median $338,000 (interquartile simulation range [IQR] - $222,000; $889,000) per 20 million people over 10 years, in the most cost-favorable scenario. In the most cost-unfavorable scenario, decentralized testing would cost a median $3161 [IQR $2412; $4731] per disability-adjusted life year averted relative to centralized testing. CONCLUSIONS: Decentralization of Xpert testing is likely to be cost-saving or cost-effective in most settings to which these simulation results might generalize. More decentralized testing is more cost-effective in settings with moderate-to-high peripheral testing volumes, high existing clinical LTFU, inability to share specimen transport costs with other disease entities, and ability to ensure high-quality peripheral Xpert testing. Decision-makers should assess these factors when deciding whether to decentralize molecular testing for tuberculosis.
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Accesibilidad a los Servicios de Salud/economía , Técnicas de Amplificación de Ácido Nucleico/economía , Técnicas de Amplificación de Ácido Nucleico/métodos , Pruebas en el Punto de Atención/economía , Tuberculosis/diagnóstico , Análisis Costo-Beneficio , Humanos , India , Modelos Económicos , Mycobacterium tuberculosisRESUMEN
BACKGROUND: The mass scale-up of antiretroviral therapy (ART) in Zambia has taken place in the context of limited infrastructure and human resources resulting in many operational side-effects. In this study, we aimed to empirically measure current workload of ART clinic staff and patient wait times and service utilization. METHODS: We conducted time and motion (TAM) studies from both the healthcare worker (HCW) and patient perspectives at 10 ART clinics throughout Zambia. Trained personnel recorded times for consecutive discrete activities based on direct observation of clinical and non-clinical activities performed by counselors, clinical officers, nurses, and pharmacy technicians. For patient TAM, we recruited consenting patients and recorded times of arrival and departure and major ART services utilized. Data from 10 clinics were pooled to evaluate median time per patient spent for each activity and patient duration of stay in the clinic. RESULTS: The percentage of observed clinical time for direct patient interaction (median time per patient encounter) was 43.1% for ART counselors (4 min, interquartile range [IQR] 2-7), 46.1% for nurses (3 min, IQR 2-4), 57.2% for pharmacy technicians (2 min, IQR 1-2), and 78.5% for clinical officers (3 min, IQR 2-5). Patient workloads for HCWs were heaviest between 8 AM and 12 PM with few clinical activities observed after 2 PM. The length of patient visits was inversely associated with arrival time - patients arriving prior to 8 AM spent 61% longer at the clinic than those arriving after 8 AM (277 vs. 171 min). Overall, patients spent 219 min on average for non-clinical visits, and 244 min for clinical visits, but this difference was not significant in rural clinics. In comparison, total time patients spent directly with clinic staff were 9 and 12 min on average for non-clinical and clinical visits. CONCLUSION: Current Zambian ART clinic operations include substantial inefficiencies for both patients and HCWs, with workloads heavily concentrated in the first few hours of clinic opening, limiting HCW and patient interaction time. Use of a differentiated care model may help to redistribute workloads during operational hours and prevent backlogs of patients waiting for hours before clinic opening, which may substantially improve ART delivery in the Zambian context.
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Instituciones de Atención Ambulatoria/organización & administración , Antirretrovirales/uso terapéutico , Infecciones por VIH/tratamiento farmacológico , Personal de Salud , Estudios de Tiempo y Movimiento , Humanos , Servicios de Salud Rural/organización & administración , Carga de Trabajo , ZambiaRESUMEN
Background: A short-course regimen of 3 months of weekly rifapentine and isoniazid (3HP) has recently been recommended by the World Health Organization as an alternative to at least 6 months of daily isoniazid (isoniazid preventive therapy [IPT]) for prevention of tuberculosis (TB). The contexts in which 3HP may be cost-effective compared to IPT among people living with human immunodeficiency virus are unknown. Methods: We used a Markov state transition model to estimate the incremental cost-effectiveness of 3HP relative to IPT in high-burden settings, using a cohort of 1000 patients in a Ugandan HIV clinic as an emblematic scenario. Cost-effectiveness was expressed as 2017 US dollars per disability-adjusted life year (DALY) averted from a healthcare perspective over a 20-year time horizon. We explored the conditions under which 3HP would be considered cost-effective relative to IPT. Results: Per 1000 individuals on antiretroviral therapy in the reference scenario, treatment with 3HP rather than IPT was estimated to avert 9 cases of TB and 1 death, costing $9402 per DALY averted relative to IPT. Cost-effectiveness depended strongly on the price of rifapentine, completion of 3HP, and prevalence of latent TB. At a willingness to pay of $1000 per DALY averted, 3HP is likely to be cost-effective relative to IPT only if the price of rifapentine can be greatly reduced (to approximately $20 per course) and high treatment completion (85%) can be achieved. Conclusions: 3HP may be a cost-effective alternative to IPT in high-burden settings, but cost-effectiveness depends on the price of rifapentine, achievable completion rates, and local willingness to pay.
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Análisis Costo-Beneficio , Isoniazida/uso terapéutico , Rifampin/análogos & derivados , Tuberculosis/prevención & control , Fármacos Anti-VIH/uso terapéutico , Antituberculosos/administración & dosificación , Antituberculosos/economía , Antituberculosos/uso terapéutico , Quimioterapia Combinada , Infecciones por VIH/complicaciones , Infecciones por VIH/tratamiento farmacológico , Humanos , Isoniazida/administración & dosificación , Isoniazida/economía , Cadenas de Markov , Rifampin/administración & dosificación , Rifampin/economía , Rifampin/uso terapéutico , Tuberculosis/complicacionesRESUMEN
BACKGROUND: The successful cure of tuberculosis (TB) is dependent on adherence to treatment. Various factors influence adherence, however, few are easily modifiable. There are limited data regarding correlates of psychological distress and their association with non-adherence to anti-TB treatment. METHODS: In a trial of a new TB test, we measured psychological distress (K-10 score), TB-related health literacy, and morbidity (TBscore), prior to diagnosis in 1502 patients with symptoms of pulmonary TB recruited from clinics in Cape Town (n = 419), Harare (n = 400), Lusaka (n = 400), Durban (n = 200), and Mbeya (n = 83). Socioeconomic, demographic, and alcohol usage-related data were captured. Patients initiated on treatment had their DOTS cards reviewed at two-and six-months. RESULTS: 22 %(95 % CI: 20 %, 25 %) of patients had severe psychological distress (K-10 ≥ 30). In a multivariable linear regression model, increased K-10 score was independently associated with previous TB [estimate (95 % CI) 0.98(0.09-1.87); p = 0.0304], increased TBscore [1(0.80, 1.20); p <0.0001], and heavy alcohol use [3.08(1.26, 4.91); p = 0.0010], whereas male gender was protective [-1.47(-2.28, -0.62); p = 0.0007]. 26 % (95 % CI: 21 %, 32 %) of 261 patients with culture-confirmed TB were non-adherent. In a multivariable logistic regression model for non-adherence, reduced TBscore [OR (95 % CI) 0.639 (0.497, 0.797); p = 0.0001], health literacy score [0.798(0.696, 0.906); p = 0.0008], and increased K-10 [1.082(1.033, 1.137); p = 0.0012], and heavy alcohol usage [14.83(2.083, 122.9); p = 0.0002], were independently associated. Culture-positive patients with a K-10 score ≥ 30 were more-likely to be non-adherent (OR = 2.290(1.033-5.126); p = 0.0416]. CONCLUSION: Severe psychological distress is frequent amongst TB patients in Southern Africa. Targeted interventions to alleviate psychological distress, alcohol use, and improve health literacy in newly-diagnosed TB patients could reduce non-adherence to treatment.
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Consumo de Bebidas Alcohólicas/epidemiología , Antituberculosos/uso terapéutico , Cumplimiento de la Medicación/estadística & datos numéricos , Estrés Psicológico/epidemiología , Tuberculosis Pulmonar/tratamiento farmacológico , Adulto , Consumo de Bebidas Alcohólicas/psicología , Ansiedad/epidemiología , Ansiedad/psicología , Depresión/epidemiología , Depresión/psicología , Femenino , Humanos , Modelos Logísticos , Masculino , Cumplimiento de la Medicación/psicología , Persona de Mediana Edad , Análisis Multivariante , Factores Sexuales , Sudáfrica/epidemiología , Estrés Psicológico/psicología , Tanzanía/epidemiología , Tuberculosis Pulmonar/epidemiología , Tuberculosis Pulmonar/psicología , Zambia/epidemiología , Zimbabwe/epidemiologíaRESUMEN
BACKGROUND: Xpert MTB/RIF, the first automated molecular test for tuberculosis, is transforming the diagnostic landscape in low-income countries. However, little information is available on its performance in low-incidence, high-resource countries. METHODS: We evaluated the accuracy of Xpert in a university hospital tuberculosis clinic in Montreal, Canada, for the detection of pulmonary tuberculosis on induced sputum samples, using mycobacterial cultures as the reference standard. We also assessed the potential reduction in time to diagnosis and treatment initiation. RESULTS: We enrolled 502 consecutive patients who presented for evaluation of possible active tuberculosis (most with abnormal chest radiographs, only 18% symptomatic). Twenty-five subjects were identified to have active tuberculosis by culture. Xpert had a sensitivity of 46% (95% confidence interval [CI], 26%-67%) and specificity of 100% (95% CI, 99%-100%) for detection of Mycobacterium tuberculosis. Sensitivity was 86% (95% CI, 42%-100%) in the 7 subjects with smear-positive results, and 28% (95% CI, 10%-56%) in the remaining subjects with smear-negative, culture-positive results; in this latter group, positive Xpert results were obtained a median 12 days before culture results. Subjects with positive cultures but negative Xpert results had minimal disease: 11 of 13 had no symptoms on presentation, and mean time to positive liquid culture results was 28 days (95% CI, 25-47 days) compared with 14 days (95% CI, 8-21 days) in Xpert/culture-positive cases. CONCLUSIONS: Our findings suggest limited potential impact of Xpert testing in high-resource, low-incidence ambulatory settings due to lower sensitivity in the context of less extensive disease, and limited potential to expedite diagnosis beyond what is achieved with the existing, well-performing diagnostic algorithm.
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Tuberculosis/diagnóstico , Adulto , Canadá , ADN Bacteriano/química , Países Desarrollados , Farmacorresistencia Bacteriana , Femenino , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Mycobacterium tuberculosis/efectos de los fármacos , Mycobacterium tuberculosis/genética , Mycobacterium tuberculosis/aislamiento & purificación , Técnicas de Amplificación de Ácido Nucleico , Sistemas de Atención de Punto , Sensibilidad y EspecificidadRESUMEN
BACKGROUND: Despite the global increase in nontuberculous mycobacterial pulmonary disease (NTM-PD), clinical characteristics show geographical variations. We investigated the clinical characteristics of patients with NTM-PD in South Korea. METHODS: We systematically reviewed articles concerning patients with NTM-PD in South Korea until February 2022. Individual participant data, regardless of treatment, were collected using a standard case report form. RESULTS: Data of 6,489 patients from 11 hospitals between 2002 and 2019 were analyzed. The mean age was 61.5±11.7 years, of whom 57.7% were women. Mycobacterium avium (41.4%) and Mycobacterium intracellulare (38.4%) comprised most of the causative species, followed by Mycobacterium abscessus subspecies abscessus (8.6%) and M. abscessus subspecies massiliense (7.8%). Bronchiectasis (59.4%) was the most common pulmonary comorbidity. Although reported cases of NTM-PD increased over the years, the proportions of causative species and radiologic forms remained similar. Distinct clinical characteristics were observed according to age and sex. Men were older at the time of diagnosis (median 63.8 years vs. 59.9 years, p<0.001), and had more cavitary lesions than women (38.8% vs. 21.0%, p<0.001). The older group (≥65 years) had higher proportions of patients with body mass index <18.5 kg/m2 (27.4% vs. 18.6%, p<0.001) and cavitary lesions (29.9% vs. 27.6%, p=0.009) than the younger group. CONCLUSION: We conducted a meta-analysis of the clinical characteristics of patients with NTM-PD in South Korea, and found age- and sex-related differences in disease- specific severity. Further investigation would enhance our comprehension of the nature of the disease, and inherited and acquired host factors.
RESUMEN
BACKGROUND: In settings with large case detection gaps, active case-finding (ACF) may play a critical role in the uberculosis (TB) response. However, ACF is resource intensive, and its effectiveness depends on whether people detected with TB through ACF might otherwise spontaneously resolve or be diagnosed through routine care. We analysed the potential effectiveness of ACF for TB relative to the counterfactual scenario of routine care alone. METHODS: We constructed a Markov simulation model of TB natural history, diagnosis, symptoms, ACF and treatment, using a hypothetical reference setting using data from South East Asian countries. We calibrated the model to empirical data using Bayesian methods, and simulated potential 5-year outcomes with an 'aspirational' ACF intervention (reflecting maximum possible effectiveness) compared with the standard-of-care outcomes. RESULTS: Under the standard of care, 51% (95% credible interval, CrI: 31%, 75%) of people with prevalent TB at baseline were estimated to be diagnosed and linked to care over 5 years. With aspirational ACF, this increased to 88% (95% CrI: 84%, 94%). Most of this difference represented people who were diagnosed and treated through ACF but experienced spontaneous resolution under standard-of-care. Aspirational ACF was projected to reduce the average duration of TB disease by 12 months (95% CrI: 6%, 18%) and TB-associated disability-adjusted life-years by 71% (95% CrI: 67%, 76%). CONCLUSION: These data illustrate the importance of considering outcomes in a counterfactual standard of care scenario, as well as trade-offs between overdiagnosis and averted morbidity through earlier diagnosis-not just for TB, but for any disease in which population-based screening is recommended.
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Nivel de Atención , Tuberculosis , Humanos , Asia Sudoriental , Teorema de Bayes , Tamizaje Masivo/métodos , Tuberculosis/diagnóstico , Tuberculosis/tratamiento farmacológico , Tuberculosis/epidemiologíaRESUMEN
BACKGROUND: In Vietnam and other global settings, men who have sex with men (MSM) have become the population at greatest risk of HIV infection. Although HIV pre-exposure prophylaxis (PrEP) has been implemented as a prevention strategy, PrEP outcomes may be affected by low persistence and adherence among MSM with unhealthy alcohol use. MSM have a high prevalence of unhealthy alcohol use in Vietnam, which may affect PrEP outcomes. METHODS: Design: We will conduct a two-arm hybrid type 1 effectiveness-implementation randomized controlled trial of a brief alcohol intervention (BAI) compared to the standard of care (SOC) at the Sexual Health Promotion (SHP) clinic Hanoi, Vietnam. PARTICIPANTS: Sexually active MSM (n=564) who are newly initiating PrEP or re-initiating PrEP and have unhealthy alcohol use will be recruited and randomized 1:1 to the SOC or BAI arm. A subgroup of participants (n=20) in each arm will be selected for longitudinal qualitative interviews; an additional subset (n=48) in the BAI arm will complete brief quantitative and qualitative interviews after completion of the BAI to assess the acceptability of the intervention. Additional implementation outcomes will be assessed through interviews with clinic staff and stakeholders (n=35). INTERVENTION: Study participants in both arms will receive standard care for PrEP clients. In the BAI arm, each participant will receive two face-to-face intervention sessions and two brief booster phone sessions, based on cognitive behavioral therapy and delivered in motivational interviewing informed style, to address their unhealthy alcohol use. OUTCOMES: Effectiveness (PrEP and alcohol use) and cost-effectiveness outcomes will be compared between the two arms. Intervention implementation outcomes (acceptability, feasibility, adoption) will be assessed among MSM participants, clinic staff, and stakeholders. DISCUSSION: This proposed trial will assess an alcohol intervention for MSM with unhealthy alcohol use who initiate or re-initiate PrEP, while simultaneously preparing for subsequent implementation. The study will measure the effectiveness of the BAI for increasing PrEP persistence through reducing unhealthy alcohol use in a setting where excessive alcohol consumption is a normative behavior. If effective, implementation-focused results will inform future scale-up of the BAI in similar settings. TRIAL REGISTRATION: NCT06094634 on clinicaltrials.gov. Registered 16 October 2023.
Asunto(s)
Consumo de Bebidas Alcohólicas , Infecciones por VIH , Homosexualidad Masculina , Profilaxis Pre-Exposición , Ensayos Clínicos Controlados Aleatorios como Asunto , Humanos , Masculino , Vietnam , Homosexualidad Masculina/psicología , Infecciones por VIH/prevención & control , Consumo de Bebidas Alcohólicas/prevención & control , Consumo de Bebidas Alcohólicas/efectos adversos , Profilaxis Pre-Exposición/métodos , Resultado del Tratamiento , Adulto , Adulto JovenRESUMEN
BACKGROUND: Evidence-based interventions (EBIs) often address normative behaviors. If a behavior is also common among clinicians, they may be skeptical about the necessity or effectiveness of an EBI. Alternatively, clinicians' attitudes and behaviors may be misaligned, or they may lack the knowledge and self-efficacy to deliver the EBI. Several EBIs address unhealthy alcohol use, a common and often culturally acceptable behavior. But unhealthy alcohol use may be particularly harmful to people with HIV (PWH). Here, we present an implementation trial using an experiential implementation strategy to address clinicians' knowledge, attitudes, and behaviors. Clinicians receive the experiential intervention before they begin delivering an evidence-based brief alcohol intervention (BAI) to PWH with unhealthy alcohol use. METHODS: Design: In this hybrid type 3 implementation-effectiveness cluster randomized controlled trial, ART clinics (n = 30) will be randomized 1:1 to facilitation, a flexible strategy to address implementation barriers, or facilitation plus the experiential brief alcohol intervention (EBAI). In the EBAI arm, clinicians, irrespective of their alcohol use, will be offered the BAI as experiential learning. EBAI will address clinicians' alcohol-related attitudes and behaviors and increase their knowledge and confidence to deliver the BAI. PARTICIPANTS: ART clinic staff will be enrolled and assessed at pre-BAI training, post-BAI training, 3, 12, and 24 months. All PWH at the ART clinics who screen positive for unhealthy alcohol use will be offered the BAI. A subset of PWH (n = 810) will be enrolled and assessed at baseline, 3, and 12 months. OUTCOMES: We will compare implementation outcomes (acceptability, fidelity, penetration, costs, and sustainability) and effectiveness outcomes (viral suppression and alcohol use) between the two arms. We will assess the impact of site-level characteristics on scaling-up the BAI. We will also evaluate how experiencing the BAI affected clinical staff's alcohol use and clinic-level alcohol expectations in the EBAI arm. DISCUSSION: This trial contributes to implementation science by testing a novel strategy to implement a behavior change intervention in a setting in which clinicians themselves may engage in the behavior. Experiential learning may be useful to address normative and difficult to change lifestyle behaviors that contribute to chronic diseases. TRIAL REGISTRATION: NCT06358885 (04/10/2024), https://clinicaltrials.gov/study/NCT06358885 .
Asunto(s)
Infecciones por VIH , Humanos , Infecciones por VIH/prevención & control , Vietnam , Ciencia de la Implementación , Conocimientos, Actitudes y Práctica en Salud , Consumo de Bebidas Alcohólicas/prevención & control , Alcoholismo/prevención & control , Masculino , Femenino , Actitud del Personal de SaludRESUMEN
Background: The burden of childhood tuberculosis remains high globally, largely due to under-diagnosis. Decentralising childhood tuberculosis diagnosis services to lower health system levels could improve case detection, but there is little empirically based evidence on cost-effectiveness or budget impact. Methods: In this mathematical modelling study, we assessed the cost-effectiveness and budget impact of decentralising a comprehensive diagnosis package for childhood tuberculosis to district hospitals (DH-focused) or primary health centres (PHC-focused) compared to standard of care (SOC). The project was conducted in Cambodia, Cameroon, Côte d'Ivoire, Mozambique, Sierra Leone, and Uganda between August 1st, 2018 and September 30th, 2021. A mathematical model was developed to assess the health and economic outcomes of the intervention from a health system perspective. Estimated outcomes were tuberculosis cases, deaths, disability-adjusted life years (DALYs) and incremental cost-effectiveness ratios (ICERs). We also calculated the budget impact of nationwide implementation. The TB-Speed Decentralization study is registered with ClinicalTrials.gov, NCT04038632. Findings: For the DH-focused strategy versus SOC, ICERs ranged between $263 (Cambodia) and $342 (Côte d'Ivoire) per DALY averted. For the PHC-focused strategy versus SOC, ICERs ranged between $477 (Cambodia) and $599 (Côte d'Ivoire) per DALY averted. Results were sensitive to TB prevalence and the discount rate used. The additional costs of implementing the DH-focused strategy ranged between $12.8 M (range 10.8-16.4) (Cambodia) and $50.4 M (36.5-74.4) (Mozambique), and between $13.9 M (12.6-15.6) (Sierra Leone) and $134.6 M (127.1-143.0) (Uganda) for the PHC-focused strategy. Interpretation: The DH-focused strategy may be cost-effective in some countries, depending on the cost-effectiveness threshold used for policy making. Either intervention would require substantial early investment. Funding: Unitaid.
RESUMEN
BACKGROUND: Accurate and rapid detection of tuberculosis (TB) and drug resistance are critical for improving patient care and decreasing the spread of TB. Xpert® MTB/RIF assay (Xpert) is a rapid, automated test that can detect both TB and rifampicin resistance, within two hours after starting the test, with minimal hands-on technical time, but is more expensive than conventional sputum microscopy. OBJECTIVES: To assess the diagnostic accuracy of Xpert for pulmonary TB (TB detection), both where Xpert was used as an initial test replacing microscopy, and where Xpert was used as an add-on test following a negative smear microscopy result.To assess the diagnostic accuracy of Xpert for rifampicin resistance detection where Xpert was used as the initial test, replacing conventional culture-based drug susceptibility testing.The population of interest was adults suspected of having pulmonary TB or multidrug-resistant TB (MDR-TB), with or without HIV infection. SEARCH METHODS: We performed a comprehensive search of the following databases: Cochrane Infectious Diseases Group Specialized Register; MEDLINE; EMBASE; ISI Web of Knowledge; MEDION; LILACS; BIOSIS; and SCOPUS. We also searched the metaRegister of Controlled Trials (mRCT) and the search portal of the WHO International Clinical Trials Registry Platform to identify ongoing trials. We performed searches on 25 September 2011 and we repeated them on 15 December 2011, without language restriction. SELECTION CRITERIA: We included randomized controlled trials, cross-sectional, and cohort studies that used respiratory specimens to compare Xpert with culture for detecting TB and Xpert with conventional phenotypic drug susceptibility testing for detecting rifampicin resistance. DATA COLLECTION AND ANALYSIS: For each study, two review authors independently extracted a set of data using a standardized data extraction form. When possible, we extracted data for subgroups by smear and HIV status. We assessed the quality of studies using the QUADAS-2 tool. We carried out meta-analyses to estimate the pooled sensitivity and specificity of Xpert separately for TB detection and rifampicin resistance detection using a bivariate random-effects model. We estimated the median pooled sensitivity and specificity and their 95% credible intervals (CrI). MAIN RESULTS: We identified 18 unique studies as eligible for this review, including two multicentre international studies, one with five and the other with six distinct study centres. The majority of studies (55.6%) were performed in low-income and middle-income countries. In 17 of the 18 studies, Xpert was performed by trained technicians in reference laboratories.When used as an initial test replacing smear microscopy (15 studies, 7517 participants), Xpert achieved a pooled sensitivity of 88% (95% CrI 83% to 92%) and pooled specificity of 98% (95% CrI 97% to 99%). As an add-on test following a negative smear microscopy result (14 studies, 5719 participants), Xpert yielded a pooled sensitivity of 67% (95% CrI 58% to 74%) and pooled specificity of 98% (95% CrI 97% to 99%). In clinical subgroups, we found the following accuracy estimates: the pooled sensitivity was 98% (95% CrI 97% to 99%) for smear-positive, culture-positive TB and 68% (95% CrI 59% to 75%) for smear-negative, culture-positive TB (15 studies); the pooled sensitivity was 80% (95% CrI 67% to 88%) in people living with HIV and 89% (95% CrI 81% to 94%) in people without HIV infection (four studies). For rifampicin resistance detection (11 studies, 2340 participants), Xpert achieved a pooled sensitivity of 94% (95% CrI 87% to 97%) and pooled specificity of 98% (95% CrI 97% to 99%). In a separate analysis, Xpert could distinguish between TB and nontuberculous mycobacteria (NTM) in clinical samples with high accuracy: among 139 specimens with NTM, Xpert was positive in only one specimen that grew NTM.In a hypothetical cohort of 1000 individuals suspected of having rifampicin resistance (a proxy for MDR-TB), where the prevalence of rifampicin resistance is 30%, we estimated that on average Xpert would wrongly identify 14 patients as being rifampicin resistant. In comparison, where the prevalence of rifampicin resistance is only 2%, we estimated that the number of individuals wrongly identified as rifampicin resistant would increase to 20, an increase of 43%. AUTHORS' CONCLUSIONS: This review shows that Xpert used as an initial diagnostic test for TB detection and rifampicin resistance detection in patients suspected of having TB, MDR-TB, or HIV-associated TB is sensitive and specific. Xpert may also be valuable as an add-on test following microscopy for patients who have previously been found to be smear-negative. An Xpert result that is positive for rifampicin resistance should be carefully interpreted and take into consideration the risk of MDR-TB in a given patient and the expected prevalence of MDR-TB in a given setting.Studies in this review mainly assessed sensitivity and specificity of the test when used in reference laboratories in research investigations. Most studies were performed in high TB burden countries. Ongoing use of Xpert in high TB burden countries will contribute to the evidence base on the diagnostic accuracy and clinical impact of Xpert in routine programmatic and peripheral health care settings, including settings where the test is performed at the point of care.
Asunto(s)
Antibióticos Antituberculosos/uso terapéutico , Farmacorresistencia Bacteriana , Mycobacterium tuberculosis/efectos de los fármacos , Mycobacterium tuberculosis/aislamiento & purificación , Rifampin/uso terapéutico , Tuberculosis Pulmonar/tratamiento farmacológico , Adulto , Humanos , Mycobacterium tuberculosis/genética , Reacción en Cadena de la Polimerasa/métodos , Sensibilidad y Especificidad , Análisis de Secuencia de ADN/métodosRESUMEN
BACKGROUND AND OBJECTIVE: The global prevalence and incidence of nontuberculous mycobacterial (NTM) infections are increasing; however, population-level data on healthcare use and medical costs for people with NTM infections are limited. Thus, we investigated the rates of healthcare use and medical costs of people with NTM infections in South Korea using the National Health Insurance Service-National Sample Cohort from 2002 to 2015. METHODS: In this cohort study, people with and without NTM infection aged 20-89 years were matched 1 to 4 by sex, age, Charlson comorbidity index, and year of diagnosis. The overall and annual average healthcare use and medical costs were calculated. In addition, trends in healthcare use and medical costs for each of the 3 years before and after NTM diagnosis were investigated for people diagnosed with NTM infection. RESULTS: A total of 798 individuals (336 men and 462 women) diagnosed with NTM infection and 3192 controls were included in the study. NTM-infected patients had significantly higher rates of healthcare use and medical costs than those in the control group (p < 0.05). NTM-infected patients showed 1.5 times the medical cost and 4.5 times the respiratory disease cost of the control group. People diagnosed with NTM infection incurred the highest medical costs in the 6 months before diagnosis. CONCLUSION: NTM infection increases the economic burden on Korean adults. Appropriate diagnostic tests and treatment plans for NTM infections are needed to reduce the burden of the disease caused by such infection.