Parkinson's disease and occupation: differences in associations by case identification method suggest referral bias.

METHODS: We used a population-based sample of 403 Parkinson's disease cases and 405 controls to examine risks by occupation. Results were compared to a previous clinic-based analysis. RESULTS: With censoring of jobs held within 10 years of diagnosis, the following had significantly or strongly increased risks: social science, law and library jobs (OR = 1.8); farming and horticulture jobs (OR = 2.0); gas station jobs (OR = 2.6); and welders (OR = 3.0). The following had significantly decreased risks: management and administration jobs (OR = 0.70); and other health care jobs (OR = 0.44). CONCLUSIONS: These results were consistent with other findings for social science and farming occupations. Risks for teaching, medicine and health occupations were not elevated, unlike our previous clinic-based study. This underscores the value of population-based over clinic-based samples. Occupational studies may be particularly susceptible to referral bias because social networks may spread preferentially via jobs.

Head injuries and Parkinson's disease in a case-control study.

BACKGROUND: Head injury is a hypothesised risk factor for Parkinson's disease, but there is a knowledge gap concerning the potential effect of injury circumstances (eg, work-related injuries) on risk. The objective of this study is to address this gap while addressing issues of recall bias and potential for reverse causation by prediagnosis symptoms. METHODS: We conducted a population based case-control study of Parkinson's disease in British Columbia, Canada (403 cases, 405 controls). Interviews queried injury history; whether injuries occurred at work, in a motor vehicle accident or during sports. Participants were also asked to report their suspicions about the causes of Parkinson's disease to provide an indicator of potential recall bias. Associations were estimated with logistic regression, adjusted for age, sex and smoking history. RESULTS: Associations were strongest for injuries involving concussion (OR: 2.08, 95% CI 1.30 to 3.33) and unconsciousness (OR: 2.64, 95% CI 1.39 to 5.03). Effects remained for injuries that occurred long before diagnosis and after adjustment for suspicion of head injury as a cause of Parkinson's disease. Injuries that occurred at work were consistently associated with stronger ORs, although small numbers meant that estimates were not statistically significant. CONCLUSIONS: This study adds to the body of literature suggesting a link between head injury and Parkinson's disease and indicates further scrutiny of workplace incurred head injuries is warranted.

Association of Parkinson's disease with infections and occupational exposure to possible vectors.

The ultimate causes of idiopathic Parkinson's disease (PD) are not fully known, but environmental and occupational causes are suspected. Postencephalitic parkinsonism has been linked to influenza, and other viral infections have also been suspected to relate to PD. We estimated the relationship between PD and both infections and possible vectors of infection (i.e., animal and human) in a population-based, case-control study in British Columbia, Canada. We recruited 403 cases detected by their use of antiparkinsonian medications and 405 controls from the registrants of the provincial universal health insurance plan. Severe influenza was associated with PD (odds ratio [OR]: 2.01; 95% confidence interval [CI]: 1.16-3.48), although this effect was attenuated when reports were restricted to those occurring 10 or more years before diagnosis. Childhood illnesses were inversely associated with PD, particularly red measles (OR: 0.65; 95% CI: 0.48-0.90). Several animal exposures were associated with PD, with statistically significant effects for cats (OR: 2.06; 95% CI: 1.09-3.92) and cattle (OR: 2.23; 95% CI: 1.22-4.09). Influenza infection may be associated with PD. The inverse relationships with childhood infections may suggest an increased risk with subclinical or asymptomatic childhood infections. Occupational exposure to animals may increase risk through transmission of infections or may indicate exposure to another agent of interest (e.g., bacterial endotoxin).

Occupational exposure to whole-body vibration and Parkinson's disease: results from a population-based case-control study.

Mechanical stress producing head injury is associated with Parkinson's disease, suggesting that relations with other physical hazards such as whole-body vibration (WBV) should be tested. In this study, the authors evaluated the relation between occupational exposure to WBV and Parkinson's disease. A population-based case-control study with 403 cases and 405 controls was conducted in British Columbia, Canada, between 2001 and 2008. From detailed occupational histories and published measurements, metrics of occupational WBV exposure were constructed and tested for associations with Parkinson's disease using logistic regression and adjusting for age and sex first, and then also for smoking and history of head injury. While ever being occupationally exposed to WBV was inversely associated with Parkinson's disease (odds ratio = 0.67, 95% confidence interval: 0.48, 0.94), higher intensities had consistently elevated odds ratios, with a statistically significant effect being noted for intermediate intensities when exposures were restricted to the 10 years or more prior to diagnosis. Possible mechanisms of an inverse relation between low levels of WBV exposure and Parkinson's disease could include direct protective effects or correlation with other protective effects such as exercise. Higher intensities of WBV could result in micro-injury, leading to vascular or inflammatory pathology in susceptible neurons.

Pesticide exposure and risk of Parkinson's disease--a population-based case-control study evaluating the potential for recall bias.

OBJECTIVE: The aim of this study was to investigate whether pesticide exposure was associated with Parkinson's disease in a population-based case-control study in British Columbia, Canada. METHODS: Patients reimbursed for anti-parkinsonian agents were identified and screened for eligibility as cases. Controls were selected from the universal health insurance database, frequency-matched to the case sample on birth year, gender, and geographic region. A total of 403 cases and 405 controls were interviewed about their job, medical and personal habits histories, and beliefs about disease risk factors. Among those reporting pesticide exposure, an occupational hygiene review selected participants exposed "beyond background" (ie, above the level expected in the general population). Unconditional logistic regression was used to estimate associations for different pesticide categories. RESULTS: Of the cases, 74 (18%) self-reported pesticide exposure and 37 (9%) were judged to be exposed beyond background. Self-reported exposure was associated with increased risk [odds ratio (OR) 1.76, 95% confidence interval (95% CI) 1.15-2.70], however the risk estimate was reduced following the hygiene review when restricted to those considered exposed (OR, 1.51, 95% CI, 0.85-2.69). When agricultural work was added to the model, the risk for hygiene-reviewed pesticide exposure was not elevated (OR 0.83, 95% CI 0.43-1.61), but agricultural work was (OR 2.47, 95% CI 1.18-5.15). More than twice as many cases as controls thought chemicals cause Parkinson's disease. Discussion This study provides little support for pesticide exposure as a cause of Parkinson's disease. The observed pattern of step-wise decreases in risk estimates might indicate differential recall by case status. The relationship to agricultural jobs suggests that farming exposures--other than pesticides--should be considered as risk factors for Parkinson's disease.

Public opinions about participating in health research.

OBJECTIVES: Privacy legislation has limited options for recruiting subjects to health studies. Policy changes are motivated by assumptions about public attitudes towards participation, yet surveys of attitudes have rarely been done. We investigated public willingness to participate in health research and how willingness was affected by various factors. METHODS: A survey of adults randomly selected from the telephone directory was conducted in British Columbia, Canada. Mailed self-administered questionnaires asked about willingness to participate in health research and the influence on willingness of the method of subject selection, the organization making the contact, and other factors. RESULTS: There were 1,477 respondents (58% of eligible); 85% were willing to participate in health research at least sometimes. The organization making the contact influenced comfort about participation: 10% of respondents felt uncomfortable if contacted by a university, 12% if by a hospital, 26% if by government, and 55% if by private research firms. Factors most positively influencing choice to participate were future health benefits to society (87%) and oneself (87%), and receiving a copy of the study results (81%). CONCLUSIONS: Participation in health research appears to be viewed favourably by members of the public, and participation may be highest when university or hospital-based researchers are able to contact subjects directly using information from government databases.

In-hospital death of critically ill patients who have congestive heart failure: does size of hospital matter?

Data from the British Columbia Linked Health Database were analyzed to determine if size of hospital is associated with in-hospital death of critically ill adults whose admitting diagnosis is congestive heart failure (CHF). Patients who were <19 years of age, transferred from or to other hospitals, or who developed CHF as a complication were excluded. In unadjusted logistic regression analysis of 2616 patients, the odds ratio (OR) for in-hospital death associated with a doubling of the number of hospital beds was 1.12 (95% confidence interval [CI] = 1.03-1.23; P = .01). After adjustment for age, sex, CHF-specific comorbidity index, number of cardiac and noncardiac procedures, number of hospital admissions for CHF in the preceding year, and socioeconomic variables, the OR was 1.08 (95% CI = 0.96-1.20; P = .21). The conclusion is that the adjusted rate of in-hospital deaths for this patient group does not differ significantly based solely on the number of acute hospital beds.

The effect of patterns of infectiousness on epidemic size.

In the course of an infectious disease in a population, each infected individual presents a different pattern of progress through the disease, producing a corresponding pattern of infectiousness. We postulate a stochastic infectiousness process for each individual with an almost surely finite integral, or total infectiousness. Individuals also have different contact rates. We show that the distribution of the final epidemic size depends only on the contact rates and the integrated infectiousness. As a particular case, zero infectiousness on an initial time interval corresponds to a period of latency, which does not affect the final epidemic size in general stochastic and deterministic epidemic models, as is well known from the literature.

Bimodal epidemic size distributions for near-critical SIR with vaccination.

We introduce a recursive algorithm which enables the computation of the distribution of epidemic size in a stochastic SIR model for very large population sizes. In the important parameter region where the model is just slightly supercritical, the distribution of epidemic size is decidedly bimodal. We find close agreement between the distribution for large populations and the limiting case where the distribution is that of the time a Brownian motion hits a quadratic curve. The model includes the possibility of vaccination during the epidemic. The effects of the parameters, including vaccination level, on the form of the epidemic size distribution are explored.

Participant-collected, mail-delivered oral fluid specimens can replace traditional serosurveys: a demonstration-of-feasibility survey of hepatitis A virus-specific antibodies in adults.

BACKGROUND: Although population-based serosurveys offer an optimal measure of cumulative infection rates, they are seldom performed due to high cost and complex logistics. Use of participant self-collected oral fluid as a diagnostic specimen and mail for specimen delivery has the potential of generating reliable, population-representative data at limited cost. METHODS: A survey of oral fluid HAV-specific immunoglobulin G (an indicator of past HAV infection) was undertaken in a provincially representative sample of 20-39 year olds as a pilot study. A provincial administrative database served as the sampling frame. Potential participants were invited by mail to collect oral fluid and complete a questionnaire at home and return both by mail. Additional telephone prompting was directed at slow responders. Oral fluid was tested using a validated ELISA. RESULTS: From among 2,448 potential participants, contact by mail or telephone was made with 1,009 eligible subjects; 59% (585) participated. Materials withstood mailing and the quality of self-collected specimens was excellent. A positive test result was found in 22.1% overall and in 15.7% of self-reported non-vaccinated subjects. Among Canadian-born, non-vaccinated individuals, the positive test rate increased progressively from 1.2% (95% CI: 0-6.3) in 20-24 year olds to 16.4% (95% CI: 9.5-23.3) in 35-39 year olds. Antibody prevalence was higher among Canadian-born non-immunized 20-29 year olds who reported travel to developing countries (33.3%, 95% CI: 11.6-55.1) than in non-travellers (2.5%, 95% CI: 0.7-6.2). CONCLUSIONS: Mail-based population surveys of infection markers in oral fluid are feasible provided an appropriate sampling frame is used. This survey revealed a high anti-HAV antibody prevalence in young Canadian adults, increasing with age and travel to developing countries.

Mixed models and empirical bayes estimation for retrospective exposure assessment of dust exposures in Canadian sawmills.

OBJECTIVES: Data on job histories is commonly available from study subjects and worksites, therefore jobs are often used for assigning exposures in historical epidemiological studies. Exposure estimates are often derived by offering jobs as fixed effects in statistical models. An alternative approach would be to offer job as a random effect to obtain empirical Bayes estimates of exposure. This approach is more efficient since it weights exposure estimates according to the within-job and between-job variability and the number of measurements for each job. We assess three models for predicting historical dust exposures of sawmill workers. METHODS: Models were developed using 407 inhalable dust measurements collected from 58 jobs in four sawmills. The first model incorporated all variables as fixed effects; the second added a random term to account for correlation within workers; and the third offered random terms for worker, job and mill (hierarchical model). Empirical Bayes estimates were used to calculate job-specific exposures from the hierarchical model. RESULTS: The fixed effects and random worker mixed models performed nearly identically because there was low within-worker correlation (r = 0.26). The Bayesian exposure predictions from the hierarchical model were slightly more correlated with the observed mill-job arithmetic means than those from the models where jobs were fixed effects (0.74 versus 0.70). CONCLUSIONS: While we observed no large differences in exposure estimates by treating job as a fixed or random effect, treating job as a random effect allowed for job-specific coefficients to be estimated for every job while borrowing strength in the presence of sparse data by assuming that the job means are normally distributed around the group mean. In addition, empirical Bayes job estimates can be used for a posteriori job grouping. The use of this method for retrospective exposure assessment should continue to be examined.

Enzyme immunoassay of Cryptosporidium-specific immunoglobulin G antibodies to assess longitudinal infection trends in six communities in British Columbia, Canada.

A newly developed enzyme-linked immunosorbent assay (ELISA) that detects immunoglobulin G antibodies to the 27-kDa Cryptosporidium parvum sporozoite surface antigen was used to test 4,097 sera collected from pregnant women in 6 communities in British Columbia, Canada, between January 1996, and December 1997. Waterborne outbreaks of cryptosporidiosis occurred in two of the study communities during the period of follow-up, and ELISA seropositivity was high in all six communities during the study period (77% positive to 92% positive). In the community with the largest outbreak, levels of antibody to the 27-kDa antigen increased rapidly and then decayed to background levels within 3-4 months of the peak of the epidemic curve. Trends in serologic reactivity were complex in all communities, and increased antibody levels not related temporally to known waterborne outbreaks were also observed. Serological assays may provide more accurate information regarding community levels of Cryptosporidium infection.

Back to work: correlates of employment among persons receiving highly active antiretroviral therapy.

The aim of this study was to quantify the level of employment at one-year and to determine potential predictors of future employment among HIV-positive persons on highly active antiretroviral therapy (HAART) in the province of British Columbia. Of the 392 individuals that were initially unemployed at baseline 63 (16.1%) found a job over the subsequent year. Factors associated with becoming employed included a baseline income over 10,000 dollars, having long-term disability or unemployment insurance as an income source, having higher CD4 cell counts, and better physical, social, and role functioning. Factors negatively associated with finding employment included having provincial assistance as an income source and having ever been an injection drug user (IDU). In multivariate analyses, not using provincial assistance as a source of income (Odds Ratio [OR] = 7.39; 95% CI: 3.26-16.7; p < 0.001) and higher MOS-SF role functioning (OR = 1.12 per 10 point increment; 95% CI: 1.03-1.21; p = 0.005) were independent predictors of becoming employed. In conclusion, our study demonstrates that while significant advances have been made in the reduction of HIV-related mortality, the majority of HIV-infected individuals on adequate treatment are still unable to be gainfully employed.

Are questions from the Italian National Health Survey adequate to measure prevalence of smoking among teens.

OBJECTIVES: Studies on the prevalence of smoking among Italian adolescents have generated inconsistent estimates. Notably, the Italian National Health Survey (INHS) generates relatively lower estimates than estimates reported in other studies. The INHS asks adults and adolescents if they are smokers or nonsmokers. Research has shown that adolescent smoking is unstable compared to that of adults, and that adolescents may acquire their identity as smokers only after smoking becomes more established. We hypothesized that the INHS prevalence estimates of adolescent smoking could be improved by adding questions on smoking behavior. METHODS: During the school year 1993-1994, 471 participants responded to a brief survey on smoking experiences. We compared the prevalence of smoking behavior with the prevalence of smoking identity of participants (mean age = 16.18) who attended five high schools in two Northern Italian cities, Padova and Bergamo. RESULTS: Measures of smoking behavior generated higher prevalence estimates than did measures of identity, particularly among occasional smokers. CONCLUSIONS: The INHS should add behavioral measures of smoking to maximize the accuracy of prevalence estimates.

Estimating mortality rates: the role of proportional life expectancy.

The computation of long-term survival is usually based on adjustments to the conventional life table. Assessing the validity of different types of adjustments can be difficult, partly because of the need to allow for two age-related trends-the decline in the average (normal) life expectancy, as well as in the new (abnormal) estimate. In this paper, we illustrate the value of routinely expressing each new estimate as a percentage of normal at each age. An additional finding has been that in some common disorders this proportional life expectancy (PLE) remains remarkably constant over many years.

Reducing attenuation in exposure-response relationships by exposure modeling and grouping: the relationship between wood dust exposure and lung function.

BACKGROUND: In a study of wood dust exposure and lung function, we tested the effect on the exposure-response relationship of six different exposure metrics using the mean measured exposure of each subject versus the mean exposure based on various methods of grouping subjects, including job-based groups and groups based on an empirical model of the determinants of exposure. METHODS: Multiple linear regression was used to examine the association between wood dust concentration and forced expiratory volume in 1s (FEV(1)), adjusting for age, sex, height, race, pediatric asthma, and smoking. RESULTS: Stronger point estimates of the exposure-response relationships were observed when exposures were based on increasing levels of aggregation, allowing the relationships to be found statistically significant in four of the six metrics. The strongest point estimates were found when exposures were based on the determinants of exposure model. CONCLUSIONS: Determinants of exposure modeling offers the potential for improvement in risk estimation equivalent to or beyond that from job-based exposure grouping.

Highly active antiretroviral therapy: physician experience and enhanced adherence to prescription refill.

OBJECTIVE: To identify patient and physician characteristics that may act as determinants of adherence to prescription refill of triple combination antiretroviral therapy. METHODS: A population-based analysis of antiretroviral therapy-naive HIV-positive men and women in British Columbia, Canada, who initiated triple combination therapy between August 1 1996 and October 31 1998. Study participants were considered adherent if they were actually dispensed antiretrovirals > or = 95% over the first year of therapy. Log-binomial regression was used to identify patient and physician characteristics associated with adherence to prescription refill. RESULTS: Of the 886 individuals eligible for analysis, 495 (56%) were > or = 95% adherent to prescription refill. In multivariate analysis, adherence was positively associated with increased age [adjusted relative rate (ARR) 1.19; 95% CI: 1.07-1.32], having a diagnosis of AIDS (ARR 1.66; 95% CI: 1.29-2.15), being male (ARR 1.79; 95% CI: 1.27-2.53), and with greater experience of the treating physician (ARR 1.27; 95% CI: 1.13-1.42). History of injection drug use was negatively associated with adherence to prescription refill (ARR 0.65; 95% CI: 0.51-0.83), as was increased pill burden (per pill daily) (ARR 0.95; 95% CI: 0.92-0.99). A sub-analysis of 316 patients who provided additional data regarding psychosocial characteristics indicated that adherence was positively associated with physician experience (ARR: 1.28; 95% CI: 1.09-1.51) and being employed (ARR: 1.55; 95% CI: 1.14-2.21), and negatively associated with a history of injection drug use (ARR: 0.61; 95% CI: 0.43-0.85). CONCLUSION: While patient disease stage and personal characteristics may play an important role in patient adherence to prescription refill of complex therapeutic regimens, our findings indicate that HIV-experienced physicians may have greater success in maintaining patients on prescribed therapy.

How does direct-to-consumer advertising (DTCA) affect prescribing? A survey in primary care environments with and without legal DTCA.

BACKGROUND: Direct-to-consumer advertising (DTCA) of prescription drugs has increased rapidly in the United States during the last decade, yet little is known about its effects on prescribing decisions in primary care. We compared prescribing decisions in a US setting with legal DTCA and a Canadian setting where DTCA of prescription drugs is illegal, but some cross-border exposure occurs. METHODS: We recruited primary care physicians working in Sacramento, California, and Vancouver, British Columbia, and their group practice partners to participate in the study. On pre- selected days, patients aged 18 years or more completed a questionnaire before seeing their physician. We asked these patients' physicians to complete a brief questionnaire immediately following the selected patient visit. By pairing individual patient and physician responses, we determined how many patients had been exposed to some form of DTCA, the frequency of patients' requests for prescriptions for advertised medicines and the frequency of prescriptions that were stimulated by the patients' requests. We measured physicians' confidence in treatment choice for each new prescription by asking them whether they would prescribe this drug to a patient with the same condition. RESULTS: Seventy-eight physicians (Sacramento n = 38, Vancouver n = 40) and 1431 adult patients (Sacramento n = 683, Vancouver n = 748), or 61% of patients who consulted participating physicians on pre-set days, participated in the survey. Exposure to DTCA was higher in Sacramento, although 87.4% of Vancouver patients had seen prescription drug advertisements. Of the Sacramento patients, 7.2% requested advertised drugs as opposed to 3.3% in Vancouver (odds ratio [OR] 2.2, 95% confidence interval [CI] 1.2-4.1). Patients with higher self- reported exposure to advertising, conditions that were potentially treatable by advertised drugs, and/or greater reliance on advertising requested more advertised medicines. Physicians fulfilled most requests for DTCA drugs (for 72% of patients in Vancouver and 78% in Sacramento); this difference was not statistically significant. Patients who requested DTCA drugs were much more likely to receive 1 or more new prescriptions (for requested drugs or alternatives) than those who did not request DTCA drugs (OR 16.9, 95% CI 7.5-38.2). Physicians judged 50.0% of new prescriptions for requested DTCA drugs to be only "possible" or "unlikely" choices for other similar patients, as compared with 12.4% of new prescriptions not requested by patients (p < 0.001). INTERPRETATION: Our results suggest that more advertising leads to more requests for advertised medicines, and more prescriptions. If DTCA opens a conversation between patients and physicians, that conversation is highly likely to end with a prescription, often despite physician ambivalence about treatment choice.

Oculo-respiratory syndrome: a new influenza vaccine-associated adverse event?

During the 2000-2001 influenza immunization campaign in Canada, a new adverse event, oculo-respiratory syndrome (ORS), was noted in association with administration of vaccine supplied by one manufacturer. The original case definition for ORS specified bilateral conjunctivitis, facial edema, or respiratory symptoms beginning 2-24 h after influenza vaccination and resolving within 48 h after onset. To characterize the spectrum, severity, and impact of ORS, we contacted persons who had reported any influenza vaccine-associated adverse event in British Columbia, Canada, during the 2000-2001 vaccination campaign. With use of a standardized telephone interview, we collected information from 609 (79%) of 769 eligible persons. Thirteen percent of ORS-affected persons reported onset 48 h, and 42% considered the symptoms to be severe. The surveillance case definition for ORS for 2001-2002 was revised to include onset

Clinical decision analysis in the treatment of acute otitis media in a child over 2 years of age.

Acute otitis media (AOM) is the most common infection diagnosed in children. In Canada and the United States, the standard of care for treatment of children over 2 years of age diagnosed with AOM is a course of antibiotics for 5 to 10 days. However, in other countries, treatment is primarily symptomatic, and antibiotics are prescribed only if symptoms fail to resolve. Clinical decision analysis is a process whereby different treatment options are assessed systematically. All clinical pathways are incorporated into a model, probabilities for each event are determined from the literature, and clinical outcomes are quantified as to the preference of patients. The decision analysis then determines the most appropriate treatment option for the disease process. For AOM in a child over 2 years of age, four treatment options were considered including observation followed by 10 days of antibiotic therapy if required for failure of symptoms to resolve, observation followed by 5 days of antibiotic therapy if required, 10 days of antibiotic therapy when the child was initially diagnosed with AOM, and 5 days of antibiotic therapy when the child was initially diagnosed with AOM. Using a clinical decision analysis model for the treatment of AOM in a child over 2 years of age, the most appropriate treatment was found to be initial observation followed by 5 days of an antibiotic if the child failed to improve spontaneously. The decision analysis model developed was designed to be free of construction bias and was found to be robust in multiple sensitivity analysis.