T-Spot.TB outperforms tuberculin skin test in predicting development of active tuberculosis among household contacts.

BACKGROUND AND OBJECTIVE: In Hong Kong, neonatal Bacillus Calmette-Guerin (BCG) vaccination is practiced with 99% coverage. This study was to compare the performance of T-Spot.TB and tuberculin skin test (TST) in predicting tuberculosis (TB) among household contacts. METHODS: From 1 March 2006 to 31 July 2010, 1049 asymptomatic household contacts of smear-positive patients were simultaneously tested with T-Spot.TB and TST, and then followed for up to 5 years for development of TB. Attending clinicians and subjects were blinded to the results of T-Spot.TB. RESULTS: T-Spot.TB gave a significantly higher positive rate (32.7% vs 22.1%) and better association with exposure time than TST at the 15 mm cut-off. Agreement between T-Spot.TB and TST using cut-offs of 5, 10 and 15 mm were relatively poor (kappa 0.25-0.41) irrespective of presence or absence of BCG scar. Only T-Spot.TB positivity was negatively associated with BCG scar. Both T-Spot.TB (incidence rate ratio between test-positive and test-negative subjects, IRR: 8.2) and TST (IRR: 4.1, 6.1 and 2.8, using cut-offs of 5 mm, 10 mm and 15 mm, respectively) helped to predict TB. Using a TST cut-off of 15 mm, 56% of future TB cases and 62.5% of bacteriologically confirmed cases were missed. Lowering the TST cut-off to 10 mm or 5 mm could achieve sensitivity comparable with that of T-Spot.TB, but at the expense of lower specificities, with more positive tests (thus requiring treatment) per case of TB predicted. CONCLUSIONS: T-Spot.TB outperformed TST in predicting TB among household contacts in a high-income area with widespread BCG vaccination coverage.

The deformation and longitudinal excursion of median nerve during digits movement and wrist extension.

The use of electronic devices, such as mobile phones and computers, has increased drastically among the young generation, but the potential health effects of carpal tunnel syndrome (CTS) on university students has not been comprehensively examined. Thirty-one university students aged 18 to 25 y with no symptoms of CTS were successfully recruited in this study. By using noninvasive ultrasonography, the morphological characteristics of the median nerve of each volunteer, and the extent of its longitudinal excursion movement under experimental conditions, in which a real operating environment of electronic devices was simulated, were quantified. The results demonstrated that the median nerve at the carpal tunnel inlet was flattened during wrist extension: the flattening ratio increased from 3.40 ± 0.91 at the neutral position to 4.10 ± 1.11 at the angle of 30° and 4.09 ± 1.11 at the angle of 45°. In addition, the median nerve became swollen after the students performed rapid mobile-phone keying for 5 min, indicated by a significant increase in the cross-sectional area from 6.05 ± 0.97 mm(2) to 7.56 ± 1.39 mm(2). Passive longitudinal excursion was observed at the median nerve when the students performed mouse-clicking (2.4 ± 1.0 mm) and mobile-phone keying tasks (1.7 ± 0.6 mm), with the mouse-clicking task generating a greater extent of longitudinal excursion than the mobile-phone keying task did. In conclusion, the findings of the present study verify the potential harm caused by using electronic devices while maintaining an inappropriate wrist posture for a substantial period.

T-Spot.TB outperforms tuberculin skin test in predicting tuberculosis disease.

RATIONALE: Silicosis is a well-recognized risk factor for tuberculosis (TB). OBJECTIVES: To compare T-Spot.TB with tuberculin skin test (TST) in predicting the development of TB. METHODS: Male patients with silicosis without clinical suspicion of active TB, past history of TB, and treatment for latent TB infection (LTBI) were offered both T-Spot.TB and TST in the Pneumoconiosis Clinic of Hong Kong from 2004 to 2008, and followed prospectively until September 30, 2009, for development of TB. MEASUREMENTS AND MAIN RESULTS: Active TB and culture- or histology-confirmed TB developed in 17 (5.5%) and 14 (4.5%) of 308 recruited subjects at an annual rate of 2,247 and 1,851 per 100,000 person-years, respectively. Active TB occurred in 7.4% (15 of 204) and 1.9% (2 of 104) of T-Spot.TB-positive and -negative subjects, respectively, whereas the corresponding figures for TST (cutoff 10 mm) were 6.4% (13 of 203) and 3.9% (4 of 205), respectively. A positive T-Spot.TB test significantly predicted the subsequent development of active TB (relative risk, 4.50; 95% confidence interval, 1.03-19.68) and culture- or histology-confirmed TB (relative risk, 7.80; 95% confidence interval, 1.02-59.63). Consistent results were obtained after exclusion of subjects treated for LTBI and adjustment for potential confounders. TST did not significantly predict the development of active TB or culture- or histology-confirmed TB, irrespective of the cutoff values with or without exclusion of subjects treated for LTBI. Culture filtrate protein 10 spot count, but not early secretary antigenic target 6 spot count, was significantly associated with subsequent TB development. CONCLUSIONS: T-Spot.TB performs better than TST in the targeted screening of LTBI among patients with silicosis.

Choice of spirometric reference values for compensation assessment.

BACKGROUND AND OBJECTIVE: Two sets of local reference values are available for spirometry in Hong Kong, but it is uncertain how well they work in the assessment of occupational lung diseases. This study examined their relative performance in the compensational assessment of silicosis. METHODS: Local reference values published in 1982 and 2006 were compared in two different populations comprising normal construction/quarry workers and silicosis patients. Only men aged 20-74 years were included. RESULTS: The FVC results of 93 normal workers were significantly higher than those predicted by either the 1982 or the 2006 reference values. Compared with the 1982 reference values, the mean FEV(1)% or FVC% was age-dependent and 5.2% higher in the normal workers. Smoking decreased the forced expiratory ratio, but did not show a major effect on FEV(1) or FVC among asymptomatic subjects. Despite their derivation largely from never-smokers, the 2006 reference values better predicted FEV(1) and FVC among all smoking categories. Among the 357 silicosis patients, the 1982 reference values also gave 8.8% higher FEV(1)% and 7.4% higher FVC%. These spirometric values differed by more than 10% in patients aged 60 years or more. Despite the presence of disease, the mean FVC% was still significantly above 100%. CONCLUSIONS: Both the 1982 and 2006 local reference values underestimated the FVC of normal construction and quarry workers, reflecting possible occupational selection factors. The 2006 reference values outperformed the 1982 ones, especially among older subjects. Careful calibration with similar occupational groups in the same laboratory is highly desirable in the choice of spirometric reference values for compensation assessment. Smoking does not appear to affect this choice.

American Thoracic Society/European Respiratory Society 2005 standardization of DL measurement: impact on performance.

BACKGROUND AND OBJECTIVE: An updated standardization statement on measurement of DL(CO) was issued by the American Thoracic Society (ATS)/European Respiratory Society (ERS) Task Force in 2005. The aim of this study was to evaluate the effects of new recommendations on the success rate, test efficiency, measurement variability and reported results of DL(CO) testing. METHODS: We prospectively evaluated 55 Chinese patients without previous experience of the DL(CO) test in 2006. Performance and results of the test according to the ATS 1995 and ATS/ERS 2005 acceptability criteria were compared. RESULTS: Using the 2005 criteria, the success rate (maximum four trials) improved from 65% to 85% (change: 20%, 95% CI: 9-31%; P = 0.001). The test efficiency as measured by two-trial and three-trial success rates increased from 25% and 51% to 60% and 78%, respectively (both P < 0.0005). The measurement variability was defined as the mean of absolute differences between two acceptable trial results of DL(CO) for each patient. The means (SD) were 0.60 (0.53) and 0.53 (0.57) mL/min/mm Hg for the old and new criteria, respectively (P = 0.623). The mean DL(CO) decreased slightly by 0.5%, from 14.93 +/- 5.74 (SD) (old criteria) to 14.86 +/- 5.75 mL/min/mm Hg (new criteria) overall, with a mean difference (SD) of -0.07 (0.20) mL/min/mm Hg for the 36 subjects meeting both criteria (paired t-test, P = 0.048). CONCLUSIONS: Success rate and test efficiency for DL(CO) measurement were improved when the new recommendations were adopted. The effects on measurement variability and reported results were minimal.

Risk of active tuberculosis among schoolchildren in Hong Kong.

OBJECTIVE: To estimate the risk of active tuberculosis (TB) and its implication on preventive treatment among BCG-vaccinated schoolchildren. DESIGN: Cohort and case-control designs. SETTING: Community settings in a high-prevalence area. PARTICIPANTS: Children in primary school. The main exposure was their tuberculin response. MAIN OUTCOME MEASURES: Of 94,928 primary schoolchildren tuberculin tested during a routine school revaccination program in 1999, 656 with a tuberculin response at 20 mm or more were followed up prospectively through the territory-wide TB registry up to December 31, 2003, for the development of TB. In a separate case-control analysis, the tuberculin responses of children who subsequently had active TB (at the age of 10-15 years) were compared with those of their sex- and age-matched classmates to ascertain the relative risks of TB for different tuberculin reaction categories. The absolute and relative risks were applied to the 1999 cohort for estimating the incidence of TB among different tuberculin reactors. RESULTS: The annual incidence (95% confidence interval) of active TB was estimated to be 13.4 (5.6-40.6) per 100,000 for the entire cohort and 7.5 (2.4-24.5), 7.5 (1.7-32.0), 16.0 (4.4-57.2), 92.6 (26.6-320.2), and 340.6 (163.3-626.4) per 100,000 for children with a tuberculin reaction at 0 to 4, 5 to 9, 10 to 14, 15 to 19, and 20 mm or more, respectively. By using 10 mm as the cutoff, 482 (95% confidence interval, 163-1391) children have to be treated to prevent a single case of active TB within 5 years. Treatment will cover 17.5% of the cohort, but prevent only 54.1% of all active TB cases. CONCLUSION: It is desirable to reexamine the existing screening method for BCG-vaccinated children from high-prevalence countries.

Seasonal pattern of tuberculosis in Hong Kong.

BACKGROUND: Summer predominance of tuberculosis (TB) was reported previously in temperate regions. No consistent data were available for lower latitudes. METHOD: The monthly TB notification data in Hong Kong from 1991 to 2002 were examined for seasonal fluctuation. A seasonal model was then developed after standardization by period, sex, age, history of TB, form of disease, and bacteriological status. RESULTS: The raw monthly counts showed remarkably consistent seasonal fluctuation across different periods, sexes, and age groups. A sine model was fitted for 82 104 notifications (adjusted R(2) = 0.373, P < 0.001). A summer peak was observed with seasonal fluctuation of 18.4% (P < 0.001), which was substantially higher than that reported previously for temperate regions. The amplitudes of fluctuation were 35.0, 15.0, 19.0, and 20.2% for those aged < or =14, 15-34, 35-64, and >/=65 years, respectively (all P < 0.001). No gender difference was noted (18.2% vs 19.0%, P = 0.790). Seasonal pattern was detected among new cases (18.6%, P < 0.001), but not retreatment cases (5.2%, P = 0.333). Culture-positive cases showed greater fluctuation than culture-negative cases (29.4% vs 6.4%, P < 0.001). No significant difference was found between pulmonary and extrapulmonary cases (16.8% vs 21.6%, P = 0.356). TB cases notified in summer were more likely to be smear-positive [odds ratio (OR) 1.100, 95% confidence interval (CI) 1.045-1.158, P < 0.001] and culture-positive (OR 1.175, 95% CI 1.121-1.232, P < 0.001) than those notified in winter, even after stratification by other key variables. CONCLUSION: A consistent seasonal pattern was found, with variable amplitudes of fluctuation in different subgroups and differing disease characteristics in different seasons. These observations are suggestive of the presence of a seasonal disease-modifying factor.

Initial experience on rifampin and pyrazinamide vs isoniazid in the treatment of latent tuberculosis infection among patients with silicosis in Hong Kong.

OBJECTIVE: To compare the adverse effects and treatment adherence between 2 months of rifampin plus pyrazinamide (2RZ) and 6 months of isoniazid (6H). BACKGROUND: Patients with silicosis in Hong Kong are at high risk of acquiring tuberculosis. A previous study showed that treatment with 6H reduced the risk of silico-tuberculosis by one half. METHOD: Patients with silicosis and a Mantoux skin test reaction > or =10 mm were randomized to receive either 2RZ or 6H daily. Liver function testing was done monthly during the initial 2 months. The adverse effects and treatment adherence were compared between the two regimens. RESULTS: Forty patients (mean age, 61.6 +/- 9.1 years) and 36 patients (mean age, 57.6 +/- 9.7 years) were randomized to the 2RZ and 6H arms, respectively (p > 0.05) [+/- SD]. Baseline characteristics were comparable. Nineteen patients in the 2RZ arm had peak alanine transaminase (ALT) levels > 1.5 times the upper limit of normal (ULN) in comparison with only five study subjects of the 6H arm (47.5% vs 13.9%, p < 0.01). Fourteen patients (35%) in the 2RZ arm and 1 patient (2.8%) in the 6H arm had peak ALT levels more than five times the ULN (p < 0.001). Only seven patients had symptoms suggestive of hepatitis; none of the patients had jaundice. All recovered after withholding treatment. In the 2RZ study arm, none of the baseline characteristics predicted hepatotoxicity. Other adverse effects were generally mild and comparable between both study arms. Treatment was stopped prematurely in 45% and 36.1% of patients in the 2RZ and 6H arms, respectively (p = 0.43). The main reasons were hepatotoxicity for the 2RZ arm and voluntary withdrawal after experiencing other minor adverse effects for the 6H arm. CONCLUSION: A higher incidence of hepatotoxicity was associated with rifampin plus pyrazinamide than isoniazid in the treatment of latent tuberculosis infection among patients with silicosis in Hong Kong.