Risk factors for developing tuberculosis: a 12-year follow-up of contacts of tuberculosis cases.

BACKGROUND: Many risk factors for the development of tuberculosis (TB) have been reported but have not been simultaneously assessed. OBJECTIVE: To determine the risk of developing TB associated with each risk factor, after adjusting for all others. METHODS: We performed a population-based, retrospective cohort study of the contacts of TB cases recorded in British Columbia, Canada. Known risk factors for the development of TB were assessed over a 12-year period; Cox regression was used to estimate the hazard ratios (HRs) of TB, adjusting for the other factors. RESULTS: Among 33 146 TB contacts, 228 developed TB during the study period (TB rate 668 per 100,000 population, 95%CI 604-783). The main risk factors for TB development were malnutrition (HR 37.5), no treatment of latent TB infection (HR 25) or <6 months of treatment (HR 5.38), age 0-10 years (HR 7.87), being a household contact (HR 8.47) and having a tuberculin skin test induration of >or=5 mm (HR >or=4.99). Bacille Calmette-Guérin vaccination significantly reduced the risk of TB development (HR 0.32, 95%CI 0.20-0.50). CONCLUSIONS: Among contacts of TB cases, we have identified the few factors that carry a very high risk for developing TB. These factors identify populations at highest risk and permit more effective TB control.

Tuberculin skin test size and risk of tuberculosis development: a large population-based study in contacts.

SETTING: Contacts of tuberculosis (TB) cases identified from eight Provincial databases in British Columbia, Canada, between 1990 and 2000. OBJECTIVE: To assess the risk of developing TB based on tuberculin skin test (TST) sizes in contacts of TB cases who did not receive treatment for latent TB infection. DESIGN: Retrospective, population-based cohort study with a 12-year follow-up. RESULTS: Among 26,542 contacts, 180 individuals developed TB (TB rate 678/100,000). Household contacts with a TST size 0-4 mm had a TB rate of 1014/100,000, those with 5-9 mm a TB rate of 2162/100,000 and those with 10-14 mm a rate of 4478/100,000. Children aged 0-10 years with 0-4 mm had a TB rate of 806/100,000, those with 5-9 mm a TB rate of 5556/100,000 and those with 10-14 mm a rate of 42,424/100,000. Immunosuppressed contacts with TST sizes 0-4 mm had a TB rate of 630/100,000, those with 5-9 mm a TB rate of 1923/100,000, and those with 10-14 mm a rate of 1770/100,000. CONCLUSIONS: TB rates were high for all TST sizes in household contacts, 0-10 year old contacts and immunosuppressed contacts. These contacts may benefit from treatment for latent TB infection, regardless of the size of their TST.

Not all "quality-adjusted life years" are equal.

BACKGROUND: There is evidence that utility elicitation methods used in the calculation of quality-adjusted life years (QALYs) yield different results. It is not clear how these differences impact economic evaluations. METHODS: Using a mathematical model incorporating data on efficacy, costs, and utility values, we simulated the experiences of 100,000 hypothetical rheumatoid arthritis patients over 10 years (50,000 exposed to infliximab plus methotrexate [MTX] and 50,000 exposed to MTX alone). QALYs, were derived from the Health Utilities Index 2 and 3 (HUI2 and HUI3), the Short Form 6-D (SF-6D), and the Euroqol 5-D (EQ-5D). Incremental cost-utility ratios were determined using each instrument to calculate QALYs and the results were compared using cost-effectiveness acceptability curves. RESULTS: Using the different utility measurement methods, the mean difference in QALYs between the infliximab plus MTX and MTX groups ranged from a high of 1.95 QALYs (95% CI=1.93-1.97) using the HUI3 to 0.89 QALYs (95% CI=0.88-0.91) using the SF-6D. Adopting the commonly cited value of society's willingness to pay for a QALY of $50,000, 91% of the simulations favored the cost utility of infliximab plus MTX when using the HUI3 to calculate QALYs. However, when using the EQ-5D, HUI2, or the SF-6D utility values to calculate QALYS, the proportion of simulations that favored the cost utility of infliximab were 63%, 45%, and 12%, respectively. CONCLUSION: Depending on the method for determining utility values used in the calculation of QALYs, very different incremental cost-utility ratios are generated.

Evidence for imprinting on chromosome 16: the effect of uniparental disomy on the outcome of mosaic trisomy 16 pregnancies.

Although a number of infants with maternal uniparental disomy of chromosome 16 (upd(16)mat) have been reported, the evidence for imprinting on chromosome 16 is not yet conclusive. To test the hypothesis that upd(16)mat has a distinct phenotype, which would support the existence of imprinted gene(s) on chromosome 16, statistical analysis was performed on a large series (n = 83) of mosaic trisomy 16 cases with molecular determination of uniparental disomy status. The incidence of upd(16)mat was 40%, which is consistent with the expected one third from random chromosome loss during trisomy rescue (P = 0.262). In pairwise comparisons, upd(16)mat was found to be associated with fetal growth restriction (P = 0.029) and with increased risk of major malformation (RR = 1.43; P = 0.053). Regression modeling showed that the effect of upd(16)mat on fetal/neonatal weight and malformation is independent of the degree of trisomy detected in the fetus. Regression modeling to control for the degree of trisomy detected in the placenta was not possible due to limited sample size. We conclude that upd(16)mat is associated with more severe growth restriction, and possibly, with higher risk of malformation. Our hypothesis is that imprinted gene(s) exist on chromosome 16 and that abnormal expression of these gene(s) in upd(16)mat cells during development results in decreased cell proliferation. Although we do not advocate prenatal testing for upd(16), studies on the long-term outcome of upd(16)mat neonates is necessary for counseling purposes.

Occupational and environmental risk factors for Parkinson's disease.

The etiology of Parkinson's disease (PD) remains obscure. Current research suggests that a variety of occupational and environmental risk factors may be linked to PD. This paper provides an overview of major occupational and environmental factors that have been associated with the development of PD and tries to assess current thinking about these factors and their possible mechanisms of operation. While clear links to rural living, dietary factors, exposure to metals, head injury, and exposure to infectious diseases during childhood have not been established, there is general agreement that smoking and exposure to pesticides affect the probability of developing PD.

Influenza revaccination of elderly travelers: antibody response to single influenza vaccination and revaccination at 12 weeks.

The antibody response to a single influenza vaccination and the effect of influenza revaccination was assessed in healthy elderly persons. Travelers > or =65 years old who had received influenza vaccine before travel were enrolled in the study and were offered a second vaccination after 12 weeks. Geographic and age-matched control subjects received a single vaccination. A second influenza vaccination was not associated with increased adverse effects. There was no significant difference between log(10) hemagglutinin-inhibiting (HI) antibody titers or an HI antibody titer > or =1:40 (considered to be protective) in 28 control subjects and 28 revaccinated travelers for any antigen. Probable protection for influenza A antigens remained high 24 weeks after a single immunization and revaccination (A/Sydney/05/97 [H3N2], 92% and 96%, and A/Beijing/262/95 [H1N1], 80% and 96%, respectively). Response to B/Harbin was less throughout the study. A/Sydney antibody titer was lower with more times vaccinated in the previous 5 years. Therefore, a second vaccine did not enhance the immune response.

Measuring psychosocial job strain with the job content questionnaire using experienced job evaluators.

BACKGROUND: A union/management system of job evaluation has been in place in the British Columbia (BC) sawmill industry since the late 1960s. This system uses an instrument, very similar to the job content questionnaire (JCQ) to evaluate psychosocial work conditions for sawmill jobs. METHODS: Four experienced evaluators, one from the union and three from industry, independently estimated psychosocial work conditions for 54 current job titles in a "typical" coastal sawmill using a shortened, 18-question version of the JCQ questionnaire. RESULTS: Inter-rater reliability was acceptable for control but not for co-worker social support, physical demand, or psychological demand. Reliability was least for psychological demand. CONCLUSIONS: Experienced job evaluators in the sawmill industry were able to reliably estimate only the control dimension of the JCQ. The observed lowest reliability for psychological job demand may be due to the imprecise construct definition in the domain of the JCQ instrument.

Comparison of expert-rater methods for assessing psychosocial job strain.

OBJECTIVES: This study tested the reliability and validity of industry- and mill-level expert methods for measuring psychosocial work conditions in British Columbia sawmills using the demand-control model. METHODS: In the industry-level method 4 sawmill job evaluators estimated psychosocial work conditions at a generic sawmill. In the mill-level method panels of experienced sawmill workers estimated psychosocial work conditions at 3 sawmills. Scores for psychosocial work conditions were developed using both expert methods and applied to job titles in a sawmill worker database containing self-reported health status and heart disease. The interrater reliability and the concurrent and predictive validity of the expert rater methods were assessed. RESULTS: The interrater reliability and concurrent reliability were higher for the mill-level method than for the industry-level method. For all the psychosocial variables the reliability for the mill-level method was greater than 0.90. The predictive validity results were inconclusive. CONCLUSIONS: The greater reliability and concurrent validity of the mill-level method indicates that panels of experienced workers should be considered as potential experts in future studies measuring psychosocial work conditions.

Previous creatinine levels safely predict amantadine dose for influenza A outbreak control.

BACKGROUND: Amantadine, an antiviral agent, is the only drug currently approved in Canada for prophylaxis of influenza A virus infection. To minimize side effects, the amantadine dose is adjusted for age and estimated creatinine clearance (CrCl) based on plasma creatinine (Cr) levels. As amantadine is used more frequently for influenza A outbreak control in care facilities for elderly people, physicians are increasingly called on to prescribe it for residents and to consider the necessity of requesting plasma Cr levels. OBJECTIVE: To determine whether previous Cr levels are predictive in estimating current CrCl and safe amantadine dose determination. DESIGN AND SETTING: Residents' charts were reviewed in two facilities in Vancouver, British Columbia. CrCl estimated using previous or current Cr results, current weight and age, as well as recommended amantadine doses based on Canadian National Advisory Committee on Immunization guidelines, were studied. RESULTS: 165 charts with Cr results in March 1998 were included; 122 had results before March 1998, and 103 had Cr results after March 1998. Pearson's correlation coefficient for CrCl estimated from current and previous Cr values was 0.929 for results less than six months previously, 0.974 for six to 12 months previously and 0.952 for 12 to 18 months previously. The same or a more conservative dose of amantadine was predicted in 92% of cases when using a Cr result taken within the previous year and in 76% of cases when using a Cr result taken 12 to 18 months previously. CONCLUSION: In long term care facilities, Cr levels measured up to 12 months previously can usually safely be used to estimate CrCl. Using previous Cr results permits advance preparation of doctor's orders for amantadine prophylaxis and avoids repeating Cr testing on every resident when an outbreak occurs, reducing related staff time and cost.

Childhood cancer in the offspring of male sawmill workers occupationally exposed to chlorophenate fungicides.

The objective of this study was to determine whether paternal occupational exposure to chlorophenol fungicides and their dioxin contaminants is associated with childhood cancer in the offspring of sawmill workers. We used data from 23,829 British Columbian sawmill workers employed for at least 1 continuous year between 1950 and 1985 in 11 sawmills that used chlorophenates. Probabilistic linkage of the sawmill worker cohort to the provincial marriage and birth files produced an offspring cohort of 19,674 children born at least 1 year after the initiation of employment in the period 1952-1988. We then linked the offspring cohort to the British Columbia Cancer Registry. We included all malignancies in cases younger than 20 years of age that appeared on the cancer registry between 1969 and 1993. We calculated standardized incidence ratios (SIRs) using the British Columbia population as a reference. A nested case-control analysis assessed the effects of paternal cumulative exposure and windows of exposure on the risk of developing cancer in the offspring. We identified 40 cases of cancer during 259,919 person-years of follow-up. The all-cancer SIR was 1.0 [95% confidence interval (CI), 0.7-1.4]; the SIR for leukemia was 1.0 (CI, 0.5-1.8); and the SIR for brain cancer was 1.3 (CI, 0.6-2.5). The nested case-control analysis showed slightly increased risks in the highest categories of chlorophenol exposure, although none was statistically significant. Our analyses provide little evidence to support a relationship between the risk of childhood cancer and paternal occupational exposure to chlorophenate fungicides in British Columbian sawmills.

Computer-generated dot maps as an epidemiologic tool: investigating an outbreak of toxoplasmosis.

We used computer-generated dot maps to examine the spatial distribution of 94 Toxoplasma gondii infections associated with an outbreak in British Columbia, Canada. The incidence among patients served by one water distribution system was 3.52 times that of patients served by other sources. Acute T. gondii infection among 3, 812 pregnant women was associated with the incriminated distribution system.

Occupational risk factors in Parkinson's disease.

BACKGROUND: An apparent excess of teachers and healthcare workers among the Parkinson's disease patients of a large tertiary care movement disorders clinic suggested the hypothesis that high exposure to viral (or other) respiratory infections in these occupations might be a risk factor for Parkinson's disease. METHODS: A case-control study of the association between occupation and Parkinson's disease was conducted. Cases (414) were all Parkinson's disease patients seen at the University of British Columbia Hospital Movement Disorders Clinic between 1986 and 1993, residing in Greater Vancouver, and under 65 in 1991. Controls (6,659) were randomly selected from the 1991 Canadian Census. FINDINGS: Parkinson's disease was associated with teaching (OR 2.50, 95% CI 1.67-3.74) and occupation in healthcare services (OR 2.07, 95% CI 1.34-3.20), but there were several other substantial associations, both positive and negative. INTERPRETATION: While referral bias cannot be ruled out, the authors find the consistency of the overall pattern of associations with the respiratory infection hypothesis striking.

Determinants of exposure to inhalable particulate, wood dust, resin acids, and monoterpenes in a lumber mill environment.

In a lumber mill in the northern inland region of British Columbia, Canada, we measured inhalable particulate, resin acid, and monoterpene exposures, and estimated wood dust exposures. Potential determinants of exposure were documented concurrently, including weather conditions, tree species, wood conditions, jobs, tasks, equipment used, and certain control measures. Over 220 personal samples were taken for each contaminant. Geometric mean concentrations were 0.98 mg/m3 for inhalable particulate, 0.49 mg/m3 for estimated wood dust, 8.04 micrograms/m3 for total resin acids, and 1.11 mg/m3 for total monoterpenes. Multiple regression models for all contaminants indicated that spruce and pine produced higher exposures than alpine fir or mixed tree species, cleaning up sawdust increased exposures, and personnel enclosure was an effective means of reducing exposures. Sawing wood in the primary breakdown areas of the mill was the main contributor to monoterpene exposures, so exposures were highest for the barker operator, the head rig operator, the canter operator, the board edgers, and a roving utility worker in the sawmill, and lowest in the planer mills (after kiln drying of the lumber) and yard. Cleaning up sawdust, planing kiln-dried lumber, and driving mobile equipment in the yard substantially increased exposures to both inhalable particulate and estimated wood dust. Jobs at the front end of the sawmill where primary breakdown of the logs takes place had lower exposures. Resin acid exposures followed a similar pattern, except that yard driving jobs did not increase exposures.

Examination for sexual assault: is the documentation of physical injury associated with the laying of charges? A retrospective cohort study.

BACKGROUND: Few studies have examined whether there is an association between individual medical findings and legal outcome in cases of sexual assault. This study was undertaken to determine the relation between the extent of documented physical injury and a positive legal outcome in cases of sexual assault and to determine other factors associated with the laying of charges in such cases. METHODS: In this retrospective cohort study, the authors reviewed the charts and medicolegal reports for all cases of sexual assault that were handled by the BC Women's Sexual Assault Service in 1992 for which a police report had been filed. Information on patients' characteristics, the nature of the assault and the extent of injury was extracted from these records. A system for scoring clinical injury was developed by 4 of the physicians at the Sexual Assault Service, and a clinical injury score was assigned for each case by one physician. The relation between the outcome (in terms of whether charges were laid) and the circumstances of the case was examined by logistic regression. RESULTS: A total of 95 cases with complete medical records and information about legal outcome were identified during the 1992 calendar year. After adjustment for income level and the patient's knowledge of the assailant (either as an acquaintance or as his or her partner), the odds ratio (OR) for charge-laying in a sexual assault case with documented moderate to severe injury was 3.33 (95% confidence interval [CI] 1.06-10.42). Socioeconomic status above the group median (defined as annual income greater than $21,893) (OR 3.26, 95% CI 1.09-9.71) and knowledge of the assailant (OR 4.58, 95% CI 1.52-13.79) were also associated with charge-laying. Presence of genital injury per se, age of the patient and detection of sperm by microscopy at the time of examination were not associated with the laying of charges. INTERPRETATION: The results of this study show that the extent of documented injury is associated with the laying of charges in cases of sexual assault. However, many questions remain about the effectiveness of the medical component of gathering such evidence.

Exposures to wood dust in U.S. industries and occupations, 1979 to 1997.

BACKGROUND: We analyzed 1,632 measurements of airborne wood dust reported to OSHA's Integrated Management Information System in the period 1979 to 1997. METHODS: The relationships between wood dust concentrations and various factors documented in the OSHA database were examined in a multiple regression model. RESULTS: Exposures ranged from less than 0.03 to 604 mg/m3, with an arithmetic mean of 7.93 and a geometric mean of 1.86. Reported exposure levels decreased substantially over time (e.g., unadjusted geometric mean in 1979 = 4.59 mg/m3; in 1997 = 0.14 mg/m3). High exposure jobs included sanders in the transportation equipment industry (unadjusted geometric mean = 17.5 mg/m3), press operators in the wood products industry (12.3 mg/m3), lathe operators in the furniture industry (7.46 mg/m3), and sanders in the wood cabinet industry (5.83 mg/m3). CONCLUSIONS: In the multiple regression model, year, state, job, and industry were found to be predictors of exposure. Year and state were likely surrogates for other factors which directly influence exposure, but which were not included in the IMIS database, such as the use of engineering control measures.

Mortality rates after cataract extraction.

Senile cataract may be a marker of generalized tissue aging. We examined this hypothesis using population-based linked health data. We hypothesized that any such association would diminish with increased use of cataract surgery. Mortality rates of those 50-95 years of age undergoing cataract surgery in British Columbia during either 1985 or 1989 were compared with the provincial population of comparable age who did not undergo cataract surgery during the study period. The 1985 cohort included 8,262 patients undergoing surgery and a comparison population of 804,303, and the 1989 cohort included 11,952 patients and a comparison population of 839,393. Using Cox regression, for the 1985 cohort, the hazard ratios for dying during follow-up were 3.2 for males 50-54.9 years of age [95% confidence limits (CL) = 2.0, 5.0] and 3.3 for females (95% CL = 1.9, 5.7). Hazard ratios for older age groups decreased with age. We also fit an additive risk model that produced excess mortalities that were less age dependent. In the 1985 analysis, these ranged from +7.1 per 1,000 (95% CL = +0.44, +13.76) to +20.3 (95% CL = +13.24, +27.36) for males and -17.5 (95% CL = -28.28, -6.72) to +2.0 (95% CL = -2.12, +6.12) for females. Findings for the 1989 analyses were similar, indicating that the association between cataracts and generalized aging remained constant despite a large increase in the use of cataract surgery.

Effectiveness of community-directed diabetes prevention and control in a rural Aboriginal population in British Columbia, Canada.

This report presents the process and summative evaluation results from a community-based diabetes prevention and control project implemented in response to the increasing prevalence and impact of non-insulin-dependent diabetes mellitus (NIDDM) in the Canadian Aboriginal population. The 24-month project targeted the registered Indian population in British Columbia's rural Okanagan region. A participatory approach was used to plan strategies by which diabetes could be addressed in ways acceptable and meaningful to the intervention community. The strategies emphasised a combination of changing behaviours and changing environments. The project was quasi-experimental. A single intervention community was matched to two comparison communities. Workers in the intervention community conducted interviews of individuals with or at risk for diabetes during a seven-month pre-intervention phase (n = 59). Qualitative analyses were conducted to yield strategies for intervention. Implementation began in the eighth month of the project. Trend measurements of diabetes risk factors were obtained for 'high-risk' cohorts (persons with or at familial risk for NIDDM) (n = 105). Cohorts were tracked over a 16-month intervention phase, with measurements at baseline, the midpoint and completion of the study. Cross-sectional population surveys of diabetes risk factors were conducted at baseline and the end of the intervention phase (n = 295). Surveys of community systems were conducted three times. The project yielded few changes in quantifiable outcomes. Activation of the intervention community was insufficient to enable individual and collective change through dissemination of quality interventions for diabetes prevention and control. Theory and previous research were not sufficiently integrated with information from pre-intervention interviews. Interacting with these limitations were the short planning and intervention phases, just 8 and 16 months, respectively. The level of penetration of the interventions mounted was too limited to be effective. Attention to process is warranted and to the feasibility of achieving effects within 24 months.

Variation by body mass index and age in waist-to-hip ratio associations with glycemic status in an aboriginal population at risk for type 2 diabetes in British Columbia, Canada.

BACKGROUND: It is unclear whether obesity and age modify or confound relations between abdominal adiposity and metabolic risk factors for type 2 diabetes. OBJECTIVE: Our objective was assess the consistency of relations between abdominal adiposity and glycemic variables across discrete categories of obesity and age. DESIGN: We performed a stratified analysis of prevalence data from a rural screening initiative in British Columbia, Canada. Subjects were Salishan Indians, all healthy relatives of individuals with type 2 diabetes [n = 151; age: 18-80 y; body mass index (BMI, in kg/m2): 17.0-48.2]. We measured waist-to-hip ratio (WHR) (2 categories); insulin, glycated hemoglobin (Hb A1c), and 2-h glucose concentrations (2 categories); and BMI (4 categories). BMI and age-specific odds ratios (ORs) and 95% CIs were calculated. RESULTS: WHR-glycemic variable relations were not consistent across BMI and age strata. Risks associated with high WHR were: for persons with BMIs from 25 to 29, elevated insulin (OR: 6.71; 95% CI: 1.41, 34.11) and Hb A1c (OR: 16.23; 95% CI: 2.04, 101.73) concentrations; for persons aged 18-34 y, elevated insulin concentrations [OR: indeterminate (+infinity); 95% CI: 1.89, +infinity]; and, for persons aged 35-49 y, elevated Hb A1c (OR: +infinity; 95% CI: 3.17, +infinity) and 2-h glucose (OR: 9.15; 95% CI: 1.74, 59.91) concentrations. CONCLUSIONS: WHR discriminates risk of type 2 diabetes in overweight but not obese individuals. Abdominal adiposity is associated with elevated insulin concentrations in younger age groups and with impaired glucose control in middle-aged groups, suggesting metabolic staging by age on a continuum from insulin resistance to impaired glucose tolerance.