Tuberculosis active case finding: uptake and diagnostic yield among minibus drivers in urban South Africa.

BACKGROUND: Tuberculosis (TB) active case finding is a part of TB control in areas of higher TB prevalence. Congested public transportation settings may be areas of increased TB transmission. We evaluated the uptake and diagnostic yield of an active TB screening program among minibus drivers in a large public transportation facility in Johannesburg, South Africa. METHODS: Over an eight month period, we intensively recruited minibus drivers for TB screening with a goal of 80% uptake among the estimated 2000 drivers. All participants were screened for TB symptoms, offered HIV testing, and had sputum collected for smear microscopy and liquid culture. RESULTS: 686 drivers were screened for TB, representing an uptake of only 34% of all drivers (43% of the target screening). Ten drivers (1.5%) were culture positive for TB, nine of whom were sputum smear microscopy negative. Factors associated with previously undiagnosed TB included a history of incarceration (odds ratio [OR] 5.5, 95% confidence interval: 1.1, 27.3) and HIV positivity (OR 5.3, 95% confidence interval: 1.1, 26.3). CONCLUSIONS: We identified undiagnosed pulmonary TB cases among drivers but at a level that may be insufficient to justify systematic case finding in this population considering the poor uptake

Tuberculosis and Hepatic Steatosis Are Prevalent Liver Pathology Findings among HIV-Infected Patients in South Africa

Liver disease epidemiology in sub-Saharan Africa has shifted as a result of HIV and the increased use of antiretroviral therapy leading to a need for updated data on common causes of liver disease. We retrospectively reviewed records from all hospitalized patients who had liver biopsy at a single hospital in South Africa from 2001 to 2009 and compared diagnosis by HIV status. During the period of study 262 patients had liver biopsy, 108 (41%) were HIV-infected, 25 (10%) were HIV-sero-negative, and 129 (49%) had unknown or unrecorded HIV status. Overall 81% of biopsies provided additional diagnostic data. Malignancy was the most common finding reported on 56 (21%) biopsies followed by granuloma or TB, hepatic steatosis, and fibrosis or cirrhosis. HIV-infected patients were more likely to have granulomas and steatosis. Half of patients with granulomas were already on TB treatment, suggesting paradoxical reactions or drug induced liver injury may have been important causes of liver inflammation among these patients. We note that TB, paradoxical reactions during TB treatment, possible drug induced liver injury, and hepatic steatosis are important causes of liver pathology among HIV-infected hospitalized patients with unclear etiology of liver disease after initial assessment. Among HIV sero-negative patients, malignancy was the major cause of liver disease. Our findings re-enforce the importance of TB as a diagnosis among HIV-infected individuals.\ud \u

Adiposity, Cardiometabolic Risk, and Vitamin D Status: The Framingham Heart Study

OBJECTIVE: Because vitamin D deficiency is associated with a variety of chronic diseases, understanding the characteristics that promote vitamin D deficiency in otherwise healthy adults could have important clinical implications. Few studies relating vitamin D deficiency to obesity have included direct measures of adiposity. Furthermore, the degree to which vitamin D is associated with metabolic traits after adjusting for adiposity measures is unclear. RESEARCH DESIGN AND METHODS: We investigated the relations of serum 25-hydroxyvitamin D (25[OH]D) concentrations with indexes of cardiometabolic risk in 3,890 nondiabetic individuals; 1,882 had subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT) volumes measured by multidetector computed tomography (CT). RESULTS: In multivariable-adjusted regression models, 25(OH)D was inversely associated with winter season, waist circumference, and serum insulin (P < 0.005 for all). In models further adjusted for CT measures, 25(OH)D was inversely related to SAT (−1.1 ng/ml per SD increment in SAT, P = 0.016) and VAT (−2.3 ng/ml per SD, P < 0.0001). The association of 25(OH)D with insulin resistance measures became nonsignificant after adjustment for VAT. Higher adiposity volumes were correlated with lower 25(OH)D across different categories of BMI, including in lean individuals (BMI <25 kg/m2). The prevalence of vitamin D deficiency (25[OH]D <20 ng/ml) was threefold higher in those with high SAT and high VAT than in those with low SAT and low VAT (P < 0.0001). CONCLUSIONS: Vitamin D status is strongly associated with variation in subcutaneous and especially visceral adiposity. The mechanisms by which adiposity promotes vitamin D deficiency warrant further study.National Institutes of Health's National Heart, Lung, and Blood Institute (N01-HC-25195, R01-DK-80739): American Heart Associatio

Towards generic explanations for pen and paper puzzles with MUSes

This research was supported by the Royal Society URF\R\180015 .Pen and paper puzzles like Sudoku, Futoshiki and Star Battle are hugely popular. Solving such puzzles can be a trivial task for modern AI systems. However, most AI systems solve problems using a form of backtracking, while people try to avoid backtracking as much as possible. This means that existing AI systems do not output explanations about their reasoning that are meaningful to people. We present Demystify, a tool which allows puzzles to be expressed in a high-level constraint programming language and uses MUSes to allow us to produce descriptions of steps in the puzzle solving. We give several improvements to the existing techniques for solving puzzles with MUSes, which allow us to solve a range of significantly more complex puzzles and give higher quality explanations. We demonstrate the effectiveness and generality of Demystify by comparing its results to documented strategies for solving a range of pen and paper puzzles by hand, showing that our technique can find many of the same explanations.Publisher PD

Gender differences in survival among adult patients starting antiretroviral therapy in South Africa: a multicentre cohort study.

Increased mortality among men on antiretroviral therapy (ART) has been documented but remains poorly understood. We examined the magnitude of and risk factors for gender differences in mortality on ART

Using Small MUSes to Explain How to Solve Pen and Paper Puzzles

In this paper, we present Demystify, a general tool for creating human-interpretable step-by-step explanations of how to solve a wide range of pen and paper puzzles from a high-level logical description. Demystify is based on Minimal Unsatisfiable Subsets (MUSes), which allow Demystify to solve puzzles as a series of logical deductions by identifying which parts of the puzzle are required to progress. This paper makes three contributions over previous work. First, we provide a generic input language, based on the Essence constraint language, which allows us to easily use MUSes to solve a much wider range of pen and paper puzzles. Second, we demonstrate that the explanations that Demystify produces match those provided by humans by comparing our results with those provided independently by puzzle experts on a range of puzzles. We compare Demystify to published guides for solving a range of different pen and paper puzzles and show that by using MUSes, Demystify produces solving strategies which closely match human-produced guides to solving those same puzzles (on average 89% of the time). Finally, we introduce a new randomised algorithm to find MUSes for more difficult puzzles. This algorithm is focused on optimised search for individual small MUSes

Mortality associated with delays between clinic entry and ART initiation in resource-limited settings: results of a transition-state model.

OBJECTIVE: To estimate the mortality impact of delay in antiretroviral therapy (ART) initiation from the time of entry into care. DESIGN: A state-transition Markov process model. This technique allows for assessing mortality before and after ART initiation associated with delays in ART initiation among a general population of ART-eligible patients without conducting a randomized trial. METHODS: We used patient-level data from 3 South African cohorts to determine transition probabilities for pre-ART CD4 count changes and pre-ART and on-ART mortality. For each parameter, we generated probabilities and distributions for Monte Carlo simulations with 1-week cycles to estimate mortality 52 weeks from clinic entry. RESULTS: We estimated an increase in mortality from 11.0% to 14.7% (relative increase of 34%) with a 10-week delay in ART for patients entering care with our pre-ART cohort CD4 distribution. When we examined low CD4 ranges, the relative increase in mortality delays remained similar; however, the absolute increase in mortality rose. For example, among patients entering with CD4 count 50-99 cells per cubic millimeter, 12-month mortality increased from 13.3% with no delay compared with 17.0% with a 10-week delay and 22.9% with a 6-month delay. CONCLUSIONS: Delays in ART initiation, common in routine HIV programs, can lead to important increases in mortality. Prompt ART initiation for patients entering clinical care and eligible for ART, especially those with lower CD4 counts, could be a relatively low-cost approach with a potential marked impact on mortality

Sensitivity of the lateral flow urine lipoarabinomannan assay in ambulant adults with advanced HIV disease: data from the TB Fast Track study.

BACKGROUND: WHO guidelines recommend the lateral flow urine lipoarabinomannan assay (LF-LAM) for TB diagnosis in hospitalised HIV-positive individuals. The role of LF-LAM among ambulant patients remains less well defined. We investigated the sensitivity of LF-LAM among ambulant HIV-positive adults in primary health clinics in South Africa. METHODS: We enrolled adults (aged ≥18 y) with CD4 counts of ≤150 cells/mm3 who had not received TB treatment or antiretroviral therapy in the preceding 3 or 6 mo, respectively. Research nurses performed the LF-LAM test on freshly voided urine. Results were compared with a reference standard of positive mycobacterial culture (sputum or urine). RESULTS: Of 1505 (54.5% female; median age 37 y; median CD4 count 73 cells/mm3) participants, 973 (64.7%) had a mycobacterial culture result; 105/973 (10.8%) were positive for Mycobacterium tuberculosis. LF-LAM sensitivity was 41.9% (95% CI 32.3 to 51.9%) and 19.0% (95% CI 12.0 to 27.9%) using grade 1+ and grade 2+ cut-off points, respectively. Sensitivity increased with severe immunosuppression and in the presence of poor prognostic indicators (low haemoglobin, body mass index). CONCLUSIONS: When used as the only TB diagnostic test, LF-LAM sensitivity is suboptimal, particularly using the grade 2+ cut-off. More sensitive tests for TB are needed that can be used in primary care settings

Evaluation of a point-of-care tuberculosis test-and-treat algorithm on early mortality in people with HIV accessing antiretroviral therapy (TB Fast Track study): study protocol for a cluster randomised controlled trial.

BACKGROUND: Early mortality for HIV-positive people starting antiretroviral therapy (ART) remains high in resource-limited settings, with tuberculosis the most important cause. Existing rapid diagnostic tests for tuberculosis lack sensitivity among HIV-positive people, and consequently, tuberculosis treatment is either delayed or started empirically (without bacteriological confirmation). We developed a management algorithm for ambulatory HIV-positive people, based on body mass index and point-of-care tests for haemoglobin and urine lipoarabinomannan (LAM), to identify those at high risk of tuberculosis and mortality. We designed a clinical trial to test whether implementation of this algorithm reduces six-month mortality among HIV-positive people with advanced immunosuppression. METHODS/DESIGN: The TB Fast Track study is an open, pragmatic, cluster randomised superiority trial, with 24 primary health clinics randomised to implement the intervention or standard of care. Adults (aged ≥18 years) with a CD4 count of 150 cells/μL or less, who have not received any tuberculosis treatment in the last three months, or ART in the last six months, are eligible. In intervention clinics, the study algorithm is used to classify individuals as at high, medium or low probability of tuberculosis. Those classified as high probability start tuberculosis treatment immediately, followed by ART after two weeks. Medium-probability patients follow the South African guidelines for test-negative tuberculosis and are reviewed within a week, to be re-categorised as low or high probability. Low-probability patients start ART as soon as possible. The primary outcome is all-cause mortality at six months. Secondary outcomes include severe morbidity, time to ART start and cost-effectiveness. DISCUSSION: This trial will test whether a primary care-friendly management algorithm will enable nurses to identify HIV-positive patients at the highest risk of tuberculosis, to facilitate prompt treatment and reduce early mortality. There remains an urgent need for better diagnostic tests for tuberculosis, especially for people with advanced HIV disease, which may render empirical treatment unnecessary. TRIAL REGISTRATION: This trial was registered with Current Controlled Trials (identifier: ISRCTN35344604 ) on 12 September 2012