Onchee Yu

The burden of community-acquired pneumonia in seniors: results of a population-based study.

Abstract Background. Pneumonia is recognized as a leading cause of morbidity in seniors. However, the overall burden of this disease—and, in particular, the contribution of ambulatory cases to that burden—is not well defined. To estimate rates of community-acquired pneumonia and to identify risk factors for this disease, we conducted a large, population-based cohort study of persons aged ⩾65 years that included both hospitalizations and outpatient visits for pneumonia. Methods. The study population consisted of 46,237 seniors enrolled at Group Health Cooperative who were observed over a 3-year period. Pneumonia episodes presumptively identified by International Classification of Diseases, Ninth Revision, Clinical Modification codes assigned to medical encounters were validated by medical record review. Characteristics of participants were defined by administrative data sources. Results. The overall rate of community-acquired pneumonia ranged from 18.2 cases per 1000 person-years among persons aged 65–69 years to 52.3 cases per 1000 person-years among those aged ⩾85 years. In this population, 59.3% of all pneumonia episodes were treated on an outpatient basis. In multivariate analysis, risk factors for community-acquired pneumonia included age, male sex, chronic obstructive pulmonary disease, asthma, diabetes mellitus, congestive heart failure, and smoking. Conclusions. On the basis of these data, we estimate that roughly 915,900 cases of community-acquired pneumonia occur annually among seniors in the United States and that ∼1 of every 20 persons aged ⩾85 years will have a new episode of community-acquired pneumonia each year.

Cumulative Use of Strong Anticholinergics and Incident Dementia: A Prospective Cohort Study

IMPORTANCE Many medications have anticholinergic effects. In general, anticholinergic-induced cognitive impairment is considered reversible on discontinuation of anticholinergic therapy. However, a few studies suggest that anticholinergics may be associated with an increased risk for dementia. OBJECTIVE To examine whether cumulative anticholinergic use is associated with a higher risk for incident dementia. DESIGN, SETTING, AND PARTICIPANTS Prospective population-based cohort study using data from the Adult Changes in Thought study in Group Health, an integrated health care delivery system in Seattle, Washington. We included 3434 participants 65 years or older with no dementia at study entry. Initial recruitment occurred from 1994 through 1996 and from 2000 through 2003. Beginning in 2004, continuous replacement for deaths occurred. All participants were followed up every 2 years. Data through September 30, 2012, were included in these analyses. EXPOSURES Computerized pharmacy dispensing data were used to ascertain cumulative anticholinergic exposure, which was defined as the total standardized daily doses (TSDDs) dispensed in the past 10 years. The most recent 12 months of use was excluded to avoid use related to prodromal symptoms. Cumulative exposure was updated as participants were followed up over time. MAIN OUTCOMES AND MEASURES Incident dementia and Alzheimer disease using standard diagnostic criteria. Statistical analysis used Cox proportional hazards regression models adjusted for demographic characteristics, health behaviors, and health status, including comorbidities. RESULTS The most common anticholinergic classes used were tricyclic antidepressants, first-generation antihistamines, and bladder antimuscarinics. During a mean follow-up of 7.3 years, 797 participants (23.2%) developed dementia (637 of these [79.9%] developed Alzheimer disease). A 10-year cumulative dose-response relationship was observed for dementia and Alzheimer disease (test for trend, P < .001). For dementia, adjusted hazard ratios for cumulative anticholinergic use compared with nonuse were 0.92 (95% CI, 0.74-1.16) for TSDDs of 1 to 90; 1.19 (95% CI, 0.94-1.51) for TSDDs of 91 to 365; 1.23 (95% CI, 0.94-1.62) for TSDDs of 366 to 1095; and 1.54 (95% CI, 1.21-1.96) for TSDDs greater than 1095. A similar pattern of results was noted for Alzheimer disease. Results were robust in secondary, sensitivity, and post hoc analyses. CONCLUSIONS AND RELEVANCE Higher cumulative anticholinergic use is associated with an increased risk for dementia. Efforts to increase awareness among health care professionals and older adults about this potential medication-related risk are important to minimize anticholinergic use over time.

Incidence of Herpes Zoster, Before and After Varicella-Vaccination-Associated Decreases in the Incidence of Varicella, 1992–2002

BACKGROUND Varicella zoster virus (VZV) causes varicella and, later in the life of the host, may reactivate to cause herpes zoster (HZ). Because it is hypothesized that exposure to varicella may boost immunity to latent VZV, the vaccination-associated decrease in varicella disease has led some to suggest that the incidence of HZ might increase. We assessed the impact that varicella vaccination has on the incidence of varicella and of HZ. METHODS Codes for cases of varicella and of HZ in an HMO were determined in automated databases of inpatients and outpatients, on the basis of the Ninth Revision of the International Classification of Diseases. We calculated the incidence, during 1992-2002, of varicella and of HZ. RESULTS The incidence of HZ remained stable as the incidence of varicella decreased. Age-adjusted and -specific annual incidence rates of varicella decreased steadily, starting with 1999. The age-adjusted rates decreased from 2.63 cases/1000 person-years during 1995 to 0.92 cases/1000 person-years during 2002; among children 1-4 years old, there was a 75% decrease between 1992-1996 and 2002. Age-adjusted and -specific annual incidence rates of HZ fluctuated slightly over time; the age-adjusted rate was highest, at 4.05 cases/1000 person-years, in 1992, and was 3.71 cases/1000 person-years in 2002. CONCLUSIONS Our findings revealed that the vaccination-associated decrease in varicella disease did not result in an increase in the incidence of HZ. These early findings will have to be confirmed as the incidence of varicella disease continues to decrease.

Efficacy of Prophylactic Mastectomy in Women With Unilateral Breast Cancer: A Cancer Research Network Project

PURPOSE We investigated the efficacy of contralateral prophylactic mastectomy (CPM) in reducing contralateral breast cancer incidence and breast cancer mortality among women who have already been diagnosed with breast cancer. METHODS This retrospective cohort study comprised approximately 50,000 women who were diagnosed with unilateral breast cancer during 1979 to 1999. Using computerized data confirmed by chart review, we identified 1,072 women (1.9%) who had CPM. We obtained covariate information for these women and for a sample of 317 women who did not undergo CPM. RESULTS The median time from initial breast cancer diagnosis to the end of follow-up was 5.7 years. Contralateral breast cancer developed in 0.5% of women with CPM, metastatic disease developed in 10.5%, and subsequent breast cancer developed in 12.4%; 8.1% died from breast cancer. Contralateral breast cancer developed in 2.7% of women without CPM, and 11.7% died of breast cancer. After adjustment for initial breast cancer characteristics, treatment, and breast cancer risk factors, the hazard ratio (HR) for the occurrence of contralateral breast cancer after CPM was 0.03 (95% CI, 0.006 to 0.13). After adjustment for breast cancer characteristics and treatment, the HRs for the relationship of CPM with death from breast cancer, with death from other causes, and with all-cause mortality were 0.57 (95% CI, 0.45 to 0.72), 0.78 (95% CI, 0.57 to 1.06), and 0.60 (95% CI, 0.50 to 0.72), respectively. CONCLUSION CPM seems to protect against the development of contralateral breast cancer, and although women who underwent CPM had relatively low all-cause mortality, CPM also was associated with decreased breast cancer mortality.

Statin use and cancer risk: a comprehensive review

Importance of the field: HMG-CoA inhibitors (statins), a class of drugs that reduce cholesterol, are used to manage and prevent coronary heart disease. They are among the most commonly prescribed drugs worldwide. Contrary to early concerns over the carcinogenicity of statins, a growing body of evidence suggests statins may in fact have a chemopreventive potential against cancer. Areas covered in this review: In this paper, we review evidence on the association between statin use and cancer risk. Specifically, we report on clinical trials and observational studies that measured all cancer or site-specific cancers of the breast, colorectal, lung, prostate and reproductive organs associated with statin use. What the reader will gain: An understanding of the evidence, including strengths and limitations, to support an association between statins and cancer. Information on the current state of the field and future directions are also discussed. Take home message: Few strong or consistent associations between statins and cancer incidence overall or for any of the sites reviewed were detected. Data for any effects of statins on cancer prognosis and secondary prevention are lacking; with the exception of consistent evidence that statins are associated with reduced risk of advanced/aggressive prostate cancer. Statins appear safe in relation to cancer risk but any chemopreventive effect in humans remains to be established and should not be recommended outside the context of clinical trials. It is encouraging that numerous trials are ongoing. The prospect of reducing the incidence and burden of some of the most prevalent cancers with safe, affordable and tolerable medication that already reduces the risk of the leading cause of death and cardiovascular disease warrants further exploration in clinical trials and observational studies of prognosis and survival.

Impact of the introduction of pneumococcal conjugate vaccine on rates of community acquired pneumonia in children and adults.

Pneumococcal conjugate vaccine use among young children has led to significant declines in invasive pneumococcal disease in the United States, but the impact on community-acquired pneumonia is unknown. We conducted population-based pneumonia surveillance among 794,282 Group Health members before and after infant vaccine introduction in 2000. We presumptively identified pneumonia episodes using diagnosis codes assigned to medical encounters and confirmed 17,513 outpatient and 6318 hospitalized events by reviewing chest radiograph reports or hospitalization records. There was evidence for a decline in rates of both outpatient and hospitalized pneumonia in children less than 1 year of age following vaccine introduction but there were no consistent reductions in pneumonia rates among older children and adults.

Safety and immunogenicity of varying dosages of trivalent inactivated influenza vaccine administered by needle-free jet injectors

To evaluate the perceived pain, other adverse events, and immunogenicity of influenza virus vaccine administered by needle-free jet injector (JI) compared with that of vaccine administered by needle and syringe (N&S), we randomly assigned 304 healthy young adults to receive one of three dosages (0.5, 0.3, or 0.2 ml) of the 1998-1999 season vaccine administered by either of two JI devices or by N&S. In multivariate analysis, female gender and JI administration were associated with higher levels of pain reported at the time of vaccination as well as with the occurrence of local injection site reactions following vaccination. Immune response did not vary significantly by dosage but administration by one JI device was associated with higher post-vaccination H1N1 antibody titers.

Statin use and breast cancer risk in a large population-based setting.

Background: Mechanistic studies suggest that 3-hydroxy-3-methylglutaryl CoA inhibitors (statins) reduce the risk of breast cancer. Observational studies offer mixed results. Methods: To evaluate the relation between statin use and breast cancer risk, we conducted a cohort study among women ages 45 to 89 years within an integrated health care delivery system. Information on statin use and covariates were obtained from automated databases. We identified breast cancer cases through the Surveillance, Epidemiology, and End Results registry. We used Cox proportional hazards models to estimate the hazard ratios (HR) and 95% confidence intervals (95% CI) for invasive breast cancer among statin users compared with nonusers. Results: Among 92,788 women studied from 1990 to 2004, median follow-up time was 6.4 years, and 2,707 breast cancer cases were identified. During the study period, 7.4% of women used statins for at least 1 year, and the median duration of use was 3.1 years. We found no difference in breast cancer risk among statin users (HR, 1.07; 95% CI, 0.88-1.29) compared with nonusers. Risk of breast cancer did not differ by duration of use (1-2.9, 3-4.9, or ≥5 years) or hydrophobic statin use. We found a suggestive increased risk of breast cancer among statin users of ≥5 years (HR, 1.27; 95% CI, 0.89-1.81 for any statins and HR, 1.47; 95% CI, 0.89-2.44 for hydrophobic statins) and of estrogen receptor–negative tumors with increasing duration of statin use (1-2.9 years: HR, 1.33; 95% CI, 0.64-2.77; 3-4.9 years: HR, 1.68; 95% CI, 0.72-3.92; ≥5 years: HR, 1.81; 95% CI, 0.75-4.36). Conclusion: This study does not support an association between statin use and breast cancer risk. (Cancer Epidemiol Biomarkers Prev 2007;16(3):416–21)

Benzodiazepine use and risk of incident dementia or cognitive decline: prospective population based study

Objective To determine whether higher cumulative use of benzodiazepines is associated with a higher risk of dementia or more rapid cognitive decline. Design Prospective population based cohort. Setting Integrated healthcare delivery system, Seattle, Washington. Participants 3434 participants aged ≥65 without dementia at study entry. There were two rounds of recruitment (1994-96 and 2000-03) followed by continuous enrollment beginning in 2004. Main outcomes measures The cognitive abilities screening instrument (CASI) was administered every two years to screen for dementia and was used to examine cognitive trajectory. Incident dementia and Alzheimer’s disease were determined with standard diagnostic criteria. Benzodiazepine exposure was defined from computerized pharmacy data and consisted of the total standardized daily doses (TSDDs) dispensed over a 10 year period (a rolling window that moved forward in time during follow-up). The most recent year was excluded because of possible use for prodromal symptoms. Multivariable Cox proportional hazard models were used to examine time varying use of benzodiazepine and dementia risk. Analyses of cognitive trajectory used linear regression models with generalized estimating equations. Results Over a mean follow-up of 7.3 years, 797 participants (23.2%) developed dementia, of whom 637 developed Alzheimer’s disease. For dementia, the adjusted hazard ratios associated with cumulative benzodiazepine use compared with non-use were 1.25 (95% confidence interval 1.03 to 1.51) for 1-30 TSDDs; 1.31 (1.00 to 1.71) for 31-120 TSDDs; and 1.07 (0.82 to 1.39) for ≥121 TSDDs. Results were similar for Alzheimer’s disease. Higher benzodiazepine use was not associated with more rapid cognitive decline. Conclusion The risk of dementia is slightly higher in people with minimal exposure to benzodiazepines but not with the highest level of exposure. These results do not support a causal association between benzodiazepine use and dementia.

Population-Based Ectopic Pregnancy Trends, 1993–2007

BACKGROUND The accuracy of ectopic pregnancy rates based on nationally representative data has been compromised for many years, impairing surveillance and evaluation of the continued public health importance of this condition. PURPOSE To estimate long-term population-based ectopic pregnancy rates and trends within a defined population over a largely unevaluated time period, including the evaluation of trends in outpatient versus inpatient management and medical versus surgical treatment modalities. METHODS Using computerized Group Health Cooperative inpatient and outpatient data, age-adjusted and age-specific ectopic pregnancy rates were calculated from 1993 to 2007 among enrollees aged 15-44 years. Overall trends and trends for care setting (inpatient versus outpatient) and treatment modality (medical versus surgical) were also evaluated. Analyses were conducted in 2009. RESULTS Between 1993 and 2007, a total of 2114 ectopic pregnancy cases (726 inpatient; 1388 outpatient) were identified among 1,180,070 woman-years, an annual age-adjusted ectopic pregnancy rate of 17.9 per 10,000 woman-years. Rates were stable from 1993 to 2004 and increased in the most recent 3 years (2005-2007, rate=21.1 per 10,000 woman-years). Rates per 1000 pregnancies increased over the 15-year period from 19.2 to 26.2 per 1000 pregnancies (p-value=0.001). Inpatient-diagnosed cases decreased from 45.4% in 1993-1995 to 26.9% in 2005-2007 (p-value<0.0001) and the percentage with surgical treatment decreased from 48.1% to 30.7% (p-value<0.0001). CONCLUSIONS The results suggest a trend toward increasing ectopic pregnancy rates over a recent 15-year period. Rates are similar to the last available national estimate, suggesting that the significance of ectopic pregnancy as a public health problem has not diminished in these intervening years.