Patients who adhere to preventive therapies may be more likely to engage in a broad spectrum of behaviors consistent with a healthy lifestyle. Because many of these behaviors cannot be measured easily, observational studies of outcomes associated with the long-term use of preventive therapies are subject to the so-called "healthy user bias." To better understand this effect, the authors examined the association between adherence to statin therapy and the use of preventive health services in a Pennsylvania cohort of 20,783 new users of statins between 1996 and 2004. After adjustment for age, gender, and various comorbid conditions, patients who filled two or more prescriptions for a statin during a 1-year ascertainment period were more likely than patients who filled only one prescription to receive prostate-specific antigen tests (hazard ratio (HR)=1.57, 95% confidence interval (CI): 1.17, 2.19), fecal occult blood tests (HR=1.31, 95% CI: 1.12, 1.53), screening mammograms (HR=1.22, 95% CI: 1.09, 1.38), influenza vaccinations (HR=1.21, 95% CI: 1.12, 1.31), and pneumococcal vaccinations (HR=1.46, 95% CI: 1.17, 1.83) during follow-up. These results suggest that patients who adhere to chronic therapies are more likely to seek out preventive health services, such as screening tests and vaccinations. Further work is needed to identify study design and analysis methods that can be used to minimize the healthy user bias in studies of preventive therapies.

A ntipsychotic medications are disproportionately used in elderly populations and have been prescribed to over a quarter of US Medicare beneficiaries in nursing homes.1-3 Reasons for their use include dementia, delirium, psychosis, agitation and affective disorders, but much use is outside approved indications. 4 In addition, there have been rapid shifts away from first-generation conventional agents (e.g., chlorpromazine, haloperidol and loxapine) to more actively marketed second-generation atypical agents (e.g., clozapine, olanzapine, quetiapine and risperidone). 5In a public health advisory issued on June 15, 2005, Health Canada warned that, compared with placebo, atypical antipsychotic medications increased the risk of death by 60% in a pooled analysis of 17 short-term randomized controlled trials involving elderly patients with dementia.6 Health Canada requested that "all manufacturers of these drugs include a warning and description of this risk in the safety information sheet for each drug." The advisory did not extend to conventional antipsychotic medications, although the US Food and Drug Administration (FDA) noted that this is an important issue to study in the future. 7,8In the absence of data on the risk of death posed by conventional antipsychotic medications, there is mounting concern that clinicians may switch their elderly patients to these older agents, 9 particularly since their replacement by the newer drugs occurred so rapidly and recently.5 On the basis of extrapolations mainly from younger populations, some have suggested that the conventional formulations could, in theory, pose risks equal to or greater than those associated with the newer, atypical drugs in elderly populations.10-13 A cohort study involving US Medicare patients eligible for statefunded low-income pharmacy assistance programs showed a 37% increase in the 180-day mortality associated with the use of conventional antipsychotic medications compared with atypical ones.14 However, patients enrolled in state-funded pharmacy assistance programs are not representative of the general elderly population, since on average they have lower incomes and higher morbidity and mortality.We conducted a population-based cohort study involving all elderly people in British Columbia to compare the shortterm mortality between those prescribed a conventional antipsychotic medication and those prescribed an atypical antipsychotic medication. We also examined whether the risk of death differed by dose or duration of drug use and by dementia status and residence in a nursing home. MethodsWe conducted a cohort study involving all British Columbia residents aged 65 years or more who filled a first-recorded (index) prescription for an oral antipsychotic medication between Risk of death associated with the use of conventional versus atypical antipsychotic drugs among elderly patients Background: Public health advisories have warned that the use of atypical antipsychotic medications increases the risk of death among elderly patients. We assessed the shor...

Purpose The role of administrative databases for research on drug safety during pregnancy can be limited by their inaccurate assessment of the timing of exposure, as the gestational age at birth is typically unavailable. Therefore, we sought to develop and validate algorithms to estimate the gestational age at birth using information available in these databases. Methods Using a population-based cohort of 286,432 mother-child pairs in British Columbia (1998–2007), we validated an ICD-9/10-based preterm-status indicator, and developed algorithms to estimate the gestational age at birth based on this indicator, maternal age, singleton/multiple status, and claims for routine prenatal care tests. We assessed the accuracy of the algorithm-based estimates relative to the gold standard of the clinical gestational age at birth recorded in the delivery discharge record. Results The preterm-status indicator had specificity and sensitivity of 98% and 91%. Estimates from an algorithm that assigned 35 weeks of gestational age at birth to deliveries with the preterm-status indicator and 39 weeks to those without them were within 2 weeks of the clinical gestational age at birth in 75% of preterm and 99% of term deliveries. Conclusions Subtracting 35 weeks (245 days) from the date of birth in deliveries with codes for preterm birth and 39 weeks (273 days) in those without them provided the optimal estimate of the beginning of pregnancy among the algorithms studied.

Valid findings of causal therapeutic benefits can be produced from nonrandomized studies using an array of state-of-the-art analytic techniques. Improving the quality and uniformity of these studies will improve the value to patients, physicians, and policymakers worldwide.

Background-Bias in studies of preventive medications can occur when healthier patients are more likely to initiate and adhere to therapy than less healthy patients. We sought evidence of this bias by examining associations between statin exposure and various outcomes that should not be causally affected by statin exposure, such as workplace and motor vehicle accidents. Methods and Results-We conducted a prospective cohort study of statin patients using data from British Columbia, Canada, a multiethnic society with a population of 4.3 million people. Study subjects were 141 086 patients who initiated statins for primary prevention. We examined the association between adherence and multiple outcomes such as accidents and screening procedures using multivariable-adjusted Cox proportional hazards models. The study population was 49% female and had an average age of 61 years. The results from our multivariable-adjusted models showed that more adherent patients were less likely to have accidents than less adherent patients. This effect was greatest for motor vehicle accidents (hazard ratio, 0.75; 95% confidence interval, 0.72 to 0.79) and workplace accidents (hazard ratio, 0.77; 95% confidence interval, 0.74 to 0.81). More adherent patients had a greater likelihood of using screening services (hazard ratio, 1.17; 95% confidence interval, 1.15 to 1.20) and a lower likelihood of developing other diseases likely to be unrelated to a biological affect of a statin (hazard ratio, 0.87; 95% confidence interval, 0.86 to 0.89). Conclusions-Our study contributes compelling evidence that patients who adhere to statins are systematically more health seeking than comparable patients who do not remain adherent. Caution is warranted when interpreting analyses that attribute surprising protective effects to preventive medications.