SummaryBackgroundThe Xpert MTB/RIF assay is an automated molecular test that has improved the detection of tuberculosis and rifampicin resistance, but its sensitivity is inadequate in patients with paucibacillary disease or HIV. Xpert MTB/RIF Ultra (Xpert Ultra) was developed to overcome this limitation. We compared the diagnostic performance of Xpert Ultra with that of Xpert for detection of tuberculosis and rifampicin resistance.MethodsIn this prospective, multicentre, diagnostic accuracy study, we recruited adults with pulmonary tuberculosis symptoms presenting at primary health-care centres and hospitals in eight countries (South Africa, Uganda, Kenya, India, China, Georgia, Belarus, and Brazil). Participants were allocated to the case detection group if no drugs had been taken for tuberculosis in the past 6 months or to the multidrug-resistance risk group if drugs for tuberculosis had been taken in the past 6 months, but drug resistance was suspected. Demographic information, medical history, chest imaging results, and HIV test results were recorded at enrolment, and each participant gave at least three sputum specimen on 2 separate days. Xpert and Xpert Ultra diagnostic performance in the same sputum specimen was compared with culture tests and drug susceptibility testing as reference standards. The primary objectives were to estimate and compare the sensitivity of Xpert Ultra test with that of Xpert for detection of smear-negative tuberculosis and rifampicin resistance and to estimate and compare Xpert Ultra and Xpert specificities for detection of rifampicin resistance. Study participants in the case detection group were included in all analyses, whereas participants in the multidrug-resistance risk group were only included in analyses of rifampicin-resistance detection.FindingsBetween Feb 18, and Dec 24, 2016, we enrolled 2368 participants for sputum sampling. 248 participants were excluded from the analysis, and 1753 participants were distributed to the case detection group (n=1439) and the multidrug-resistance risk group (n=314). Sensitivities of Xpert Ultra and Xpert were 63% and 46%, respectively, for the 137 participants with smear-negative and culture-positive sputum (difference of 17%, 95% CI 10 to 24); 90% and 77%, respectively, for the 115 HIV-positive participants with culture-positive sputum (13%, 6·4 to 21); and 88% and 83%, respectively, across all 462 participants with culture-positive sputum (5·4%, 3·3 to 8·0). Specificities of Xpert Ultra and Xpert for case detection were 96% and 98% (−2·7%, −3·9 to −1·7) overall, and 93% and 98% for patients with a history of tuberculosis. Xpert Ultra and Xpert performed similarly in detecting rifampicin resistance.InterpretationFor tuberculosis case detection, sensitivity of Xpert Ultra was superior to that of Xpert in patients with paucibacillary disease and in patients with HIV. However, this increase in sensitivity came at the expense of a decrease in specificity.FundingGovernment of Netherlands, Government of Australia, Bill & Melinda Gates Foundati...

The aim of the present research was to determine the association between historical physical activity and baseline bone measurements in a group of 223 postmenopausal women participating in a clinical trial in Pittsburgh, Pennsylvania, from 1981 to 1986 by evaluating the effect of moderate physical activity on bone loss. Historical physical activity was assessed by a survey which divided the life span into four time periods (14-21, 22-34, 35-50, and 50+ years) and inquired about participation in leisure time physical activities for each period. From the responses, kilocalories of energy expenditure were calculated. Cortical bone density and area were measured in the radius with a computerized tomography scanner. The historical physical activity survey was administered a second time two to three months after the initial test to a 10% random sample of the women in order to determine the test-retest reliability of the instrument. Since the measurements of historical physical activity proved to be reliable, estimates of kilocalories determined for the entire population of women were correlated with bone area and density. A significant relation was found to exist between historical physical activity and dimensions of adult bone, particularly bone area. This association remained significant after adjustment for potential confounding variables and seemed to be strongest in the earlier age periods. To the authors' knowledge, this is the first report of a significant association between historical physical activity and bone.

ABSTRACT. Background. The neurodevelopmental outcomes of human immunodeficiency virus type 1 (HIV-1)-infected Ugandan infants of nondrug-using mothers were studied using controlled, prospective methodology.Method. The sample of 436 full-term infants included 79 HIV-infected infants of HIV-1-infected mothers, 241 uninfected infants of HIV-1-infected mothers (seroreverters), and 116 uninfected infants born to HIV-negative mothers. Neurologic status, information processing ability, and motor and mental development were assessed from 6 to 24 months of age. Observations of caretaker-child interaction and home environments were made at 6 and 12 months. All evaluators were blinded to the HIV status of the child and family.Results. Compared with seroreverters and uninfected infants, HIV-infected infants demonstrated greater deficits in motor development and neurologic status, and more frequent and earlier onset of motor and neurologic abnormalities. Compared with controls, HIV-infected infants had more abnormalities in mental development at 6 and 18 months and an earlier onset of abnormalities. By 12 months, 30% of HIV-infected infants demonstrated motor abnormalities and 26% cognitive abnormalities as compared with 11% and 6% among seroreverters and 5% and 6% among seronegative infants. HIV-infected infants (62%) demonstrated a higher probability of developing an abnormal neurologic examination by 12 months, compared with seroreverters (17%) or seronegative infants (15%). Information-processing abilities did not differ as a function of HIV infection. Home environments and infants' interactions with caretakers were similar across groups.Conclusion. We conclude that HIV infection results in more frequent and earlier abnormalities in infants' neurologic status and motor development that are not attributable to other biological and environmental risk factors. More frequent mental developmental abnormalities were evident at several ages. However, informationprocessing abilities, such as recognition memory, may be spared from HIV-related deficits. Pediatrics 1997;100(1). URL: http://www.pediatrics.org/cgi/content/full/100/1/e5; HIV infection, neurodevelopment, mental development, motor development, neurological status, information processing ability.ABBREVIATION. HIV, human immunodeficiency virus.T he prevalence of human immunodeficiency virus type 1 (HIV-1) in infants and young children in the United States and in the world has dramatically increased. [1][2][3][4] Prevalence rates of HIV infection, which are now more than one million children worldwide, indicate that HIV-1-related central nervous system disease will become a significant cause of mental deficiency and developmental disabilities in the United States and worldwide. 5 Generalized cognitive deficiencies, 6 -14 language 15 and motor 9 deficits, and variation in the type and severity of developmental and neurologic deficits have been consistently reported. 8 -16 For this reason, there is a continuing need for controlled studies of neurodevelopmental outcomes amon...

Six months of INH provided short-term protection against tuberculosis in PPD-positive HIV-infected adults. Three month regimens including INH plus rifampicin or INH, rifampicin and pyrazinamide provided sustained protection for up to 3 years.