[Show abstract][Hide abstract] ABSTRACT: Delays in diagnosis of tuberculosis (TB) have been associated with previous use of antibiotics, and in particular fluoroquinolones (FQ), for suspected pulmonary infections.
We conducted a population-based cohort study with 2232 patients who had active TB between 1997 and 2006 (records obtained from the British Columbia Linked Health Databases). Patients with a record of an initial health care contact preceding the diagnosis of TB were identified for inclusion. Health care delay was defined as the time between initial health care contact and the initiation of anti-tuberculosis medication, and was compared between patients prescribed antibiotics and those not exposed to any antibiotics.
A total of 1544 patients were included. After adjusting for covariates, average health care delay for patients exposed to antibiotics was found to be significantly greater, by a factor of 2.10 (95%CI 1.80-2.44), with a median delay of 41 days in the antibiotic group compared to 14 days in the non-antibiotic group. Sex, age, foreign-born status and socio-economic status were non-significant factors. Health care delay increased with the number of antibiotic courses received, but not with the type of antibiotic.
Previous treatment with any antibiotic, and not only a FQ, is associated with a delay in TB diagnosis.
The International Journal of Tuberculosis and Lung Disease 08/2011; 15(8):1062-8. · 2.76 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To quantify patient preferences when making decisions as to whether to accept latent tuberculosis infection (LTBI) preventive treatment, using a discrete choice experiment (DCE).
A DCE survey was developed and administered to LTBI patients. Each patient was given 10 random choices along with two fixed choices to check consistency. Two hypothetical treatment options and one opt-out option were presented in each choice task. Latent class analysis was conducted to estimate preferences for six key treatment attributes.
Among the 214 respondents, 194 (90.7%) who provided valid DCE responses and complete sociodemographic information were included. Results consistently suggested that respondents were averse to higher risk of active tuberculosis and side effects and longer treatment. A three-latent-class model with five covariates was chosen. Forty-seven percent of the respondents were assigned to class 1, 32% to class 2, and 21% to class 3. Although all six attributes were shown to significantly influence the respondents' treatment decision, the risk of active tuberculosis, chance of liver damage, and frequency of clinic visits were the most important ones. Significant preference heterogeneity was observed in two attributes: frequency of clinic visits (P < 0.01) and chance of liver damage developing (P < 0.01). Class 1 individuals were most likely to have children. Class 2 had the highest employment rate. Class 3 respondents tended to choose the opt-out option on DCE tasks and were more likely to be born outside Canada, have higher education, and be unemployed.
Respondents consistently preferred preventive treatment with higher effectiveness, fewer side effects, and shorter length. Substantial preference heterogeneity existed among respondents.
Value in Health 01/2011; 14(6):937-43. · 2.19 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: British Columbia (BC), Canada.
To determine the risk factors for pulmonary colonization by non-tuberculous mycobacteria (NTM).
Retrospective study of subjects colonized by NTM from 1990 to 2006. Subjects without mycobacterial disease and with at least three negative cultures served as controls.
Mycobacterium avium complex (MAC) species were the most common NTM. Risk factors of colonization included age > or = 60 years (aOR 2.3), female sex (aOR 1.2), residency in Canada for at least 10 years (aOR 3.8), Canadian-born aboriginal (aOR 1.8), and Canadian-born non-aboriginal (aOR 1.4). Predictors of MAC colonization included White race (aOR 1.6) and residency in Canada for at least 10 years, which was the strongest predictor (aOR 6.7). Aboriginal origin was associated with non-MAC colonization (aOR 1.8), and Canadian-born people from the East/South-East Asian ethnic groups were protected from MAC colonization (aOR 0.2), all aOR P < 0.05.
Older age, female sex, having been born in Canada, long residency in BC and White race predict pulmonary NTM colonization, while Aboriginal origin predicts non-MAC colonization. Further research is needed to identify environmental NTM sources in BC and to determine their relation to colonization and disease.
The International Journal of Tuberculosis and Lung Disease 01/2010; 14(1):106-12. · 2.76 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Purpose: In North America, contacts of active TB cases who have a positive PPD skin test (>5mm induration) are offered preventive therapy with INH. However, there are concerns about the adverse effects of INH versus the risk of developing active TB. The objective of this study was to undertake a quantitative benefit-risk analysis of treatment of LTBI, with INH, for different groups of contacts using an incremental net-benefit (INB) approach.
Method: We developed a Markov model to compare treatment of LTBI in contacts compared to no treatment over a five year time horizon. Contacts were stratified on four variables: BCG status (positive vs. negative), ethnicity (Canadian-born non-aboriginal, foreign born, and Aboriginal Canadian), type of contact (household vs. casual) and age group (older vs. younger than 10y). We calculated quality-adjusted life years (QALYs) gained due to delayed or prevention of active TB vs. QALYs lost due to the adverse events to INH using societal utilities for each health state. Risk for development of TB, compliance, and prevalence of immunization with BCG were taken from the longitudinal database of TB contacts in British Columbia. Other model parameters were obtained from the literature.
Result: INH was net-beneficial in treatment of LTBI subgroups at different risk of developing active TB. It was most beneficial in household Aboriginal contacts (net QALY gain 0.177 for BCG+, 0.0983 for BCG-), household contacts<10yo (0.0872), and casual Aboriginal contacts and <10yo (0.0869). The subgroup that benefitted least from prophylactic INH therapy was Canadian-born casual contacts (0.0062 for BCG+, 0.0098 for BCG-). The number needed to treat (NNT) to avoid one case of active TB, varied from 3.38 for pediatric Aboriginal close contacts and 996 for BCG+ Canadian born, casual contacts. The chance of INH therapy having a positive INB never dropped below 60% in the probabilistic sensitivity analysis.
Conclusion: Stochastic risk-benefit analysis provides a valuable tool for assessing the merit of healthcare interventions. From this perspective, INH prophylaxis is recommended for all contacts that are tested positive in screening, even when the risk for the development of TB was low.
The 31th Annual Meeting of the Society for Medical Decision Making; 10/2009
[Show abstract][Hide abstract] ABSTRACT: TB is a serious global public health problem. Isoniazid, a key drug used to treat latent TB, can cause hepatotoxicity in some patients. This pilot study investigated the effects of genetic variation in NAT2 and CYP2E1 on isoniazid-induced hepatotoxicity in TB contacts in British Columbia, Canada.
DNA re-sequencing was used to establish the spectrum of genetic variation in the exons, promoter and conserved regions of NAT2 in all subjects. For CYP2E1, the CYP2E1*1C polymorphism was genotyped by PCR-RFLP. Association tests of NAT2 variants and haplotypes, as well acetylator types were performed.
We enrolled 170 subjects on isoniazid treatment (23 cases and 147 controls). Systematic re-sequencing of NAT2 revealed 18 known and 10 novel variants.
No single genetic variant of NAT2 and CYP2E1 showed a significant association with isoniazid-induced hepatotoxicity in this highly heterogeneous population. There was evidence of a trend for increasing hepatotoxicity risk across the rapid, intermediate and slow acetylator groups (p = 0.08).
[Show abstract][Hide abstract] ABSTRACT: British Columbia Centre for Disease Control (BCCDC), Vancouver, Canada.
To determine the incidence of non-tuberculous mycobacteria (NTM) and to assess the impact of new laboratory techniques.
Population-based study of all subjects with positive cultures for NTM from 1990 to 2006.
Mycobacterium avium complex (MAC) was the most common NTM isolate (77%). The median incidence rates per 100 000 population in the total sample were respectively 6.7, 4.5 and <0.7 for all NTMs, MAC and all non-MAC species; for NTM-treated subjects the rates were respectively 1.6, 1.4 and <0.08; and for the NTM-colonised they were respectively 4.7, 2.7 and <0.5. In the period after the introduction of new laboratory techniques, all NTM isolates, the overall MAC rate and the MAC-colonised rate increased by respectively 24%, 35.4% and 76% (P < 0.05). All NTM isolates and rates for all NTMs, NTM-treated and M. tuberculosis subjects (used as comparison group) decreased over time (P < 0.05).
The most common NTM species was MAC. Episodic increases in the number of isolates and incidence rates of subjects colonised with MAC are likely to be associated with the implementation of new laboratory techniques, which may represent an artefact. The decrease in rates of NTM-treated subjects is reassuring.
The International Journal of Tuberculosis and Lung Disease 09/2009; 13(9):1086-93. · 2.76 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Recent approval of interferon-gamma release assays that are more specific for Mycobacterium tuberculosis has given new options for the diagnosis of latent tuberculosis infection (LTBI).
To assess the cost-effectiveness of Quanti-FERON-TB Gold (QFT-G) vs. the tuberculin skin test (TST) in diagnosing LTBI in contacts of active TB cases using a decision analytic Markov model.
Three screening strategies--TST alone, QFT-G alone and sequential screening of TST then QFT-G--were evaluated. The model was further stratified according to ethnicity and bacille Calmette-Guérin (BCG) vaccination status. Data sources included published studies and empirical data. Results were reported in terms of the incremental net monetary benefit (INMB) of each strategy compared with the baseline strategy of TST-based screening in all contacts.
The most economically attractive strategy was to administer QFT-G in BCG-vaccinated contacts, and to reserve TST for all others (INMB CA$3.70/contact). The least cost-effective strategy was QFT-G for all contacts, which resulted in an INMB of CA$-11.50 per contact. Assuming a higher prevalence of recent infection, faster conversion of QFT-G, a higher rate of TB reactivation, reduction in utility or greater adherence to preventive treatment resulted in QFT-G becoming cost-effective in more subgroups.
Selected use of QFT-G appears to be cost-effective if used in a targeted fashion.
The International Journal of Tuberculosis and Lung Disease 01/2009; 12(12):1414-24. · 2.76 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Tuberculosis (TB) referral clinic in Vancouver, British Columbia, Canada.
Screening for and treatment of latent TB infection (LTBI) in at-risk populations are the cornerstone of TB control in low-incidence countries. Persons at low risk often undergo the tuberculin skin test (TST) for reasons other than contact. Little information exists on the actual risk of TB in this population.
To determine the risk of TB in screened subjects without known risk factors.
Retrospective descriptive analysis of demographics, TST reaction size and TB disease occurrence in 98333 low-risk subjects screened from 1990 to 2002.
The average annual disease rate was 0.4 per 100000 population (cumulative rate 7.4/100000) from 1990 to 2006, and TB was diagnosed only in the foreign-born. Risk of TB in the foreign-born increased with larger TST reaction size (P < 0.03). Completion of treatment for LTBI was not documented for any of the subsequent active TB cases.
In a low-risk screened population, active TB disease was found only in the foreign-born. Treatment of LTBI is not recommended in persons with a positive TST and no additional risk factors. Local screening programs should focus on populations with confirmed risk factors for disease.
The International Journal of Tuberculosis and Lung Disease 08/2008; 12(8):903-8. · 2.76 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Tuberculosis (TB) remains a major public health threat worldwide. Numerous cost-effectiveness analyses of TB screening and treatment strategies have been recently published, but none have utilized quality-adjusted life-years as recommended because of the lack of utilities for TB health states.
To characterize and compare utility scores from either active TB or latent TB infection (LTBI) participants.
Consenting patients attending a population-based screening and treatment clinic were administered the Short Form 36 (SF-36), the Health Utilities Index 2/3 (HUI2/3), and a general health visual analog scale (VAS) along with demographic questions. SF-36 scores were converted to Short Form 6D (SF-6D) utility scores using an accepted algorithm. Utility results were compared across scales, and construct validity was assessed.
A total of 162 TB patients (78 LTBI and 84 active TB) with available SF-36 and all four utility scores (Health Utilities Index 2, Health Utilities Index 3, SF-6D and VAS) were included in the analysis. Those with active TB had significantly lower SF-36 and utility scores than those with LTBI. Although all appeared to exhibit construct validity, the HUI2/3 and the VAS appeared to have significant ceiling effects, whereas the SF-6D had significant floor effects.
Health state utility values for active TB and LTBI have been determined using different instruments. The three measures did not generate identical utility scores. The HUI2/3 was limited by ceiling effects, whereas the SF-6D appeared to display floor effects.
Value in Health 06/2008; 11(7):1154-61. · 2.19 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Tuberculosis (TB) remains a public health threat with significant annual impacts on morbidity and mortality. However, few studies have examined the impact of active and latent TB infection (LTBI) on health-related quality of life (HRQL).
Patients with recently diagnosed active TB or LTBI patients were administered the Short Form-36 (SF-36) and the Beck depression inventory (DI) at baseline, 3 months, and 6 months. Mixed-effect linear regression was used to compare the trajectory of HRQL over time in the two patient groups after adjusting for potential confounders. Ordinal logistic regression was used to determine the relationship between changes in HRQL of at least the minimal important difference.
One hundred four active TB and 102 LTBI patients participated. At baseline, participants with active TB had significantly lower SF-36 mean domain and component scores (4 to 12 points lower, p < 0.03) and higher mean Beck DI scores (4 points higher, p < 0.0001) when compared to LBTI participants. In the responder analysis, those with active TB were associated with reporting improved scores at 6 months of at least the minimal important difference in vitality (odds ratio [OR], 2.7; 95% confidence interval [CI], 1.3 to 5.6), role physical (OR, 3.1; 95% CI, 1.4 to 6.5), mental component score (OR, 3.2; 95% CI, 1.5 to 6.9), social functioning (OR, 11.1; 95% CI, 3.8 to 33), and role emotional (OR, 2.7; 95% CI, 1.2 to 6.0).
Active TB patients had large improvements in most HRQL domains by 6 months. However, when compared to LTBI participants and US norms, HRQL was still low at completion of therapy.