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PURPOSE Opioids may increase cancer risk and progression through multiple pathways. Our objective was to estimate the association between chronic opioid use and risk of second breast cancer events (SBCEs). METHODS Cohort study of women greater than or equal to 18 years, diagnosed with early stage breast cancer between January 1, 1990, and December 31, 2008, and enrolled in a large health plan for 1+ years before and after (unless died) diagnosis. SBCEs were defined as evidence of recurrence or second primary breast cancer in the medical chart. Chronic opioid use was defined as 75+ days of use in any moving 90-day window after breast cancer diagnosis and varied to 150+ days in a 180-day window in a sensitivity analysis. Using Cox proportional hazards models, we estimated hazard ratios (HRs) and 95% confidence intervals (CIs) for SBCE and components of SBCE by chronic opioid use. RESULTS Almost 10% met the criteria for chronic use and almost a third of users were taking opioids for greater than 3 years. Risk of SBCEs (HR = 1.20; 95% CI, 0.85-1.70), including second primary breast cancer (HR = 1.38; 95% CI, 0.71-2.70), was nonsignificantly higher among chronic users vs nonchronic/nonusers. The HR for recurrence was 1.14 (95% CI, 0.76-2.70). Results of the sensitivity analyses on longer opioid use does support an association with SBCE or recurrence. CONCLUSION This first US-based study on chronic opioid use and cancer outcomes provides some reassurance on safety. However, the question warrants further exploration in other populations and settings.

Background Cardiovascular medications may be associated with cancer development, but little is known about their association with cancer recurrence. Medications such as statins and antihypertensives may be commonly used among colon cancer survivors, who are, on average, diagnosed in their mid-60s. We described the associations between statins and antihypertensive medications and colon cancer recurrence in a large, population-based study. Methods We conducted a cohort study among adults with stage I-IIIA colon cancer diagnosed in 1995–2014 in two Kaiser Permanente regions, Colorado and Washington. Statin and antihypertensive use were obtained from electronic pharmacy dispensing data. People were classified as medication users on the date of their first dispensing after cohort entry, which started 90 days after completing cancer treatment, continuing through the earliest of death, health plan disenrollment, or chart abstraction. We collected outcome information from medical record abstraction and tumor registries on colon cancer recurrences and second primary cancers. Using Cox proportional hazards multivariable models, we estimated hazard ratios (HRs) with 95% confidence intervals (CIs) for colon cancer recurrences and any cancer event (recurrences and new primaries at any anatomic site) comparing medication users to non-users. Results Among 2039 people, 937 (46%) used statins and 1425 (70%) used antihypertensives at any point during a median of 4.9 years of follow-up; 460 people had any additional cancer event, including 152 with a colon cancer recurrence. Statin use was not associated with colon cancer recurrence (HR = 1.09, 95%CI = 0.65–1.85) or any cancer event (HR = 1.12, 95%CI = 0.85–1.47), nor was antihypertensive use associated with recurrence (HR = 0.73, 95%CI = 0.44–1.21) or any cancer event (HR = 0.93, 95%CI = 0.70–1.24). Conclusions Our results suggest no association between cardiovascular medication use and the risk of recurrence or any additional cancer, and may provide reassurance to colon cancer survivors.

Accurate estimates of incidence and prevalence of endometriosis among nonselected cohorts are lacking in the United States, and earlier reports have produced varying results.This study aimed to define endometriosis incidence and prevalence in a US population and evaluate factors influencing these estimates over time.A 10-year retrospective cohort study using Kaiser Permanente Washington electronic health records database was completed. The primary analysis included women enrollees aged 16 to 60 years, from January 2006 to December 2015, who had a uterus, were continuously enrolled for at least 2 years before cohort entry and had at least 1 healthcare utilization. Secondary analysis included all women enrollees aged 16 to 60 years during this time. Incident endometriosis was identified using the International Classification of Diseases, Ninth Revision and Tenth Revision, diagnosis codes. Annual incidence rates were age-adjusted by direct standardization to the 2015 study population. Secular trends in incidence overall and by 5-year age group, race and ethnicity, diagnosis modality, and practitioner type were assessed using Poisson regression analyses. Prevalent cases were defined as women enrolled in 2015 and had an endometriosis diagnosis before the end of 2015. The prevalence rates of chronic pelvic pain and dysmenorrhea defined by the International Classification of Diseases, Ninth Revision and Tenth Revision, diagnosis codes in 2006-2015 were estimated.Among 332,056 eligible women who contributed 1,176,329 person-years during the 10-year study period, 2863 incident endometriosis cases were identified for an average incidence of 24.3 cases per 10,000 person-years. In our primary analysis, incidence rates declined over the study interval from a high of 30.2 per 10,000 person-years in 2006 to 17.4 per 10,000 person-years in 2015 and were highest among women aged 36 to 45 years in most years. Incidence rates were similar across race and ethnicity groups. The distribution of the 2863 incident cases by the diagnosis modality was as follows: 45.5% surgical, 5.7% imaging, and 48.8% clinical. Endometriosis incidence rates per 10,000 person-years were similar in women who were surgically and clinically diagnosed and decreased significantly from 2006 to 2015 (surgically diagnosed endometriosis dropped from 13.4 to 7.4 and clinically diagnosed endometriosis dropped from 16.1 to 8.9; P value of.001 for linear trend over time for each). Incident case distribution by diagnosing provider was as follows: 73.6% obstetrician and gynecologist, 15.7% primary care provider, and 10.7% "other." Incidence of endometriosis diagnosed by an obstetrician and gynecologist and primary care provider decreased over the study interval (P.001 for linear trend over time for each). Method of diagnosis and provider type did not differ by race and ethnicity. Among 135,162 women who contributed person-time in 2015, 2521 women were diagnosed with endometriosis, a prevalence rate of 1.9%. In our secondary analysis, the frequency of chronic pelvic pain diagnosis increased over the study interval from 3.0% in 2006 to 5.6% in 2015.The incidence rates of endometriosis declined over the 10-year study interval and did so uniformly across age groups, races and ethnicities, and the main diagnosing modalities and providers. Declining rates may reflect a shift in practice patterns in the United States away from the diagnosis of endometriosis both clinically and surgically, rather than favoring more general diagnoses of chronic pelvic pain. The prevalence of endometriosis in 2015 in the United States is in keeping with data from recent studies outside the United States using health record data.

Objectives To identify women's beliefs and other factors associated with lack of osteoporosis (OP) pharmacotherapy (OP-RX) during the 6 months after a fragility fracture, including the woman's perspective on fracture risk, OP, and treatment. Design Cross-sectional. Setting Group Health Cooperative, a mixed-model delivery system. Participants Female Group Health Cooperative enrollees aged 55 and older with an OP-related fracture according to diagnostic and procedure codes from January 1, 2013, to March 30, 2014 (N = 985). Measurements OP-RX and participant characteristics were ascertained from electronic health records including medications dispensed. A mailed survey was used to obtain data on health behaviors; OP-related history; concern about, knowledge of, and perceived risk of future fracture; beliefs about OP-RX; sources of information on OP; postfracture discussions with providers; and provider recommendations. Results The response rate was 73%. Of 634 eligible respondents, 84% did not undergo OP-RX during the 6 months after fracture. Fewer than 20% of women thought that OP caused their fracture, 52% did not think they were at risk of future fracture, and 75% did not think or know whether OP-RX reduces risk of fracture. Knowledge about OP and the benefits of treatment was higher in the 16% of women who underwent OP-RX after their fracture. Women reported low levels of engagement with their healthcare providers regarding OP and fracture risk management. Conclusion These findings suggest low awareness about OP and its contribution to fracture risk, lack of understanding about the benefits of pharmacotherapy, and limited discussion about OP with primary care physicians. Information about individual's beliefs and knowledge gaps can help design targeted patient and provider education to improve treatment rates.

Adenomyosis symptoms are disabling. Population-based data on incidence and prevalence of adenomyosis are lacking that could guide future evidence-based treatments and clinical management.To evaluate the incidence, 10-year secular trends, and prevalence of adenomyosis diagnoses and to describe symptoms and treatment patterns in a large U.S. cohort.We performed a retrospective population-based cohort study of women aged 16-60 years in 2006-2015, enrolled in Kaiser Permanente Washington, a mixed-model health insurance and care delivery system. Adenomyosis diagnoses identified by ICD codes from the International Classification of Diseases 9th and 10th editions and potential covariates were extracted from computerized databases. Women with prior hysterectomy, and for incidence estimates women with prior adenomyosis diagnoses, were excluded. Linear trends in incidence rates over the 10-year study period were evaluated using Poisson regression. Rates and trend tests were examined for all women adjusting for age using direct standardization to the 2015 study population, by age groups, and by race/ethnicity. Chart reviews were performed to validate diagnostic accuracy of ICD codes in identifying adenomyosis incidence. Symptoms and treatment patterns at diagnosis and in the following 5 years were assessed.A total of 333,693 women contributed 1,185,855 woman-years (2006-2015) for incidence calculations. Associated symptom-related codes (menorrhagia or abnormal uterine bleeding, dysmenorrhea or pelvic pain, dyspareunia, and infertility) were observed in 90.8%; 18.0% had co-occurrent endometriosis codes and 47.6% had co-occurrent uterine fibroid codes. The overall adenomyosis incidence was 1.03% or 28.9 per 10,000 woman-years, with a high of 30.6 in 2007 and a low of 24.4 in 2014. Overall age-adjusted estimated incidence rates declined during the 10-year study interval (linear trend P.05). Incidence was highest for women aged 41-45 years (69.1 per 10,000 woman-years in 2008) and was higher for black (highest 44.6 per 10,000 woman-years in 2011) vs white women (highest 27.9 per 10,000 woman-years in 2010). Overall prevalence in 2015 was 0.8% and was highest among women aged 41-45 years (1.5%). Among the 624 potential adenomyosis cases identified by diagnostic codes in 2012-2015 and with sufficient information in the medical record to determine true case status, 490 were confirmed as incident cases, yielding a 78.5% (95% confidence interval, 75.1%, 81.7%) positive predictive value of adenomyosis ICD-9/ICD-10 codes for identifying an incident adenomyosis case. Health care burden was substantial: 82.0% of women had hysterectomies, nearly 70% had imaging studies suggestive of adenomyosis, and 37.6% used chronic pain medications.Adenomyosis burden to the individual and the health care system is high. Incidence rates are disproportionately high among black women. These findings are of concern, as currently available long-term medical therapies remain limited beyond hysterectomy. Our data and methodologies are novel and could serve as a foundation to guide clinicians and health care systems to develop clinical management plans and track outcomes for women with adenomyosis.

PURPOSE: To describe patterns of opioid use in cancer survivors. METHODS: In a cohort study of colon cancer patients diagnosed during 1995–2014 and enrolled at two Kaiser Permanente regions, we constructed quarterly measures of opioid use from one year before cancer diagnosis through five years after diagnosis to examine changes in use. Measures included any use, incident use, regular use (use ≥ 45 days in a 91-day quarter), and average daily dose (converted to morphine milligram equivalent, MME). We also assessed temporal trends of opioid use. RESULTS: Of 2,039 colon cancer patients, 11–15% received opioids in the four pre-diagnosis quarters, 68% in the first quarter after diagnosis, and 15–17% in each subsequent 19 quarters. Regular opioid use increased from 3–5% pre-diagnosis to 5–7% post diagnosis. Average dose increased from 15–17 MME/day pre-diagnosis to 14–22 MME/day post diagnosis (excluding the quarter in which cancer was diagnosed). Among post-diagnosis opioid users, 73–95% were on a low dose (< 20 MME/day). Over years, regular use of opioids increased in survivorship with no change in dosage. CONCLUSION: Opioid use slightly increased following a colon cancer diagnosis, but high-dose use was rare. Research is needed to differentiate under- vs. over- treatment of cancer pain.

Many women diagnosed with breast cancer have chronic conditions such as diabetes that may impact other health behaviors. Our purpose was to determine if breast cancer screening and detection differs among women with and without diabetes. We conducted a cross-sectional analysis of a retrospective cohort of women aged 52–74 years diagnosed with incident stages I–III breast cancer enrolled in an integrated health plan between 1999 and 2014 with linkage to the Surveillance, Epidemiology and End Results registry (n = 2040). Screening data were taken from electronic health records. We used multivariable modified Poisson regression models with robust standard errors to estimate relative risks (RR) and 95% confidence intervals (CI) for outcomes of (i) receipt of screening in the 2 years prior to diagnosis; (ii) symptom-detected breast cancer; and (iii) diagnosis of locally advanced stage III breast cancer. Compared to women without diabetes, women with diabetes were similar with respect to receipt of screening mammography (78% and 77%), symptom-detected breast cancer (46% and 49%), and stage III diagnosis (7% and 7%). In multivariable models adjusting for age and year of diagnosis, race, BMI, Charlson comorbidity score and depression diagnosis no differences were observed in the outcomes by presence of diabetes. Further investigation is warranted to determine how diabetes acts as a mediating factor in adverse breast cancer outcomes.

Objective Prior research examining the association between use of antidepressants after colon cancer diagnosis and risk of recurrence is scant. We evaluated this association among colon cancer patients diagnosed at two integrated health care delivery systems in the United States. Methods We conducted a cohort study of stage I to IIIA colon cancer patients diagnosed at greater than or equal to 18 years of age at Kaiser Permanente Colorado and Kaiser Permanente Washington during 1995 to 2014. We used pharmacy records to identify dispensings for antidepressants and tumor registry records and patients' medical charts to identify cancer recurrences. Using Cox proportional hazards models, we estimated the adjusted hazard ratio (HR) of colon cancer recurrence comparing patients who used antidepressants after diagnosis to those who did not. We also evaluated the risk associated with use of selective serotonin reuptake inhibitors (SSRIs) and tricyclic antidepressants (TCAs) separately. Results Among the 1923 eligible colon cancer patients, 807 (42%) used an antidepressant after diagnosis and 139 had a colon cancer recurrence during an average 5.6 years of follow-up. Use of antidepressants after colon cancer diagnosis was not associated with risk of recurrence (HR: 1.14; 95% confidence interval [CI], 0.69-1.87). The HR for use of SSRIs was 1.22 (95% CI, 0.64-2.30), and for TCAs, it was 1.18 (95% CI, 0.68-2.07). Conclusions Our findings suggest that use of antidepressants after colon cancer diagnosis was common and not associated with risk of recurrence. Future larger studies with greater power to examine risk associated with individual antidepressants would be valuable additions to the evidence base.

PURPOSE: To describe the association between diabetes and colon cancer recurrence. METHODS: We conducted a cohort study at two integrated health care delivery systems in the United States. Using tumor registry data, we identified patients aged ≥18 years when diagnosed with stage I–IIIA adenocarcinomas of the colon during 1995‒2014. Pre-existing diabetes was ascertained via diagnosis codes. Medical records were reviewed for eligibility and to abstract recurrence and covariate information. Recurrence was ascertained beginning 90 days after the end of colon cancer treatment (i.e., cohort entry). Recurrence of any cancer or a new primary cancer at any site was a secondary outcome. We used multivariable Cox proportional hazards models to estimate hazard ratios (HR) and 95% confidence intervals (CIs) for the associations between diabetes at cohort entry and study outcomes. RESULTS: Among the 1,923 eligible patients, 393 (16.7%) had diabetes at cohort entry. Diabetes was not associated with recurrence (HR = 0.87; 95% CI: 0.56–1.33) or with any subsequent cancer (HR = 1.09; 95% CI: 0.85–1.40). When the definition of recurrence included second primary colorectal cancer, risk was non-significantly higher in patients with diabetes than without diabetes. CONCLUSIONS: The risk of colon cancer recurrence appears to be similar in patients with and without diabetes at diagnosis. IMPACT: Future studies should evaluate the association between diabetes and colorectal cancer outcomes, especially second primary colon cancers, in larger populations.

Background Despite considerable public health burden, uterine fibroid population-based incidence estimates are few. Secular trends over time are even more limited. Objective We sought to evaluate the incidence, 10-year secular trends, and prevalence of uterine fibroid diagnoses and describe the proportion of symptomatic women. Study Design We performed a retrospective population-based cohort study of women, aged 18–65 years, enrolled 2005 through 2014 in Kaiser Permanente Washington. Uterine fibroid diagnoses identified by International Classification of Diseases, Ninth Revision codes and potential covariates were extracted from computerized databases. Women with prior hysterectomy and, for incidence estimates, women with prior fibroid diagnoses were excluded. Linear trends in incidence rates over the 10-year study period were evaluated using Poisson regression models. Rates and trend tests were examined for all women, by age groups, and by race/ethnicity. Results Associated International Classification of Diseases, Ninth Revision symptom-related codes were observed in 90% of incident cases. Incidence rates for fibroid diagnoses were highest for the age group 45–49 years, 240.3 per 10,000 woman-years in 2014, and for black women across all years. Overall age-adjusted estimated incidence rates declined during the 10-year study interval, from 139.4 per 10,000 woman-years in 2005 to 101.4 in 2014 (P value trend .0008). Overall prevalence in 2014 was 9.6%, and was highest among women aged 50–54 years (15.9%). Black women had higher prevalence (18.5%) than other racial/ethnic groups. Conclusion We found a decreasing trend of new uterine fibroid diagnoses among predominantly symptomatic women ages 18–65 years in a recent 10-year interval. This finding was due, perhaps in part, to secular trends of decreasing hysterectomies. Nonetheless, uterine fibroids remain a common health burden, with a prevalence of nearly 10%. Rates are disproportionately high and occur at younger ages for black women, and possibly for other non-white racial/ethnic groups. These findings are of concern, as current available long-term medical therapies remain limited.

In light of waning immunity to pertussis following receipt of tetanus toxoid, reduced diphtheria toxoid and acellular pertussis (Tdap) vaccine, maintaining protection may require repeated Tdap vaccination. We evaluated the safety of repeated doses of tetanus-containing vaccine in 68 915 nonpregnant adolescents and adults in the Vaccine Safety Datalink population who had received an initial dose of Tdap. Compared with 7521 subjects who received a subsequent dose of tetanus toxoid, reduced diphtheria (Td) vaccine, the 61 394 subjects who received a subsequent dose of Tdap did not have significantly elevated risk of medical visits for seizure, cranial nerve disorders, limb swelling, pain in limb, cellulitis, paralytic syndromes, or encephalopathy/encephalitis/meningitis. These results suggest that repeated Tdap vaccination has acceptable safety relative to Tdap vaccination followed by Td vaccination.

Breast cancer tends to occur in an older age group of women also burdened with comorbidities such as cardiovascular disease (CVD). Numerous medications used to manage CVD (e.g., statins and antihypertensives) are hypothesized to alter breast cancer risk, but there are few studies on breast cancer outcomes. The COmmonly used Medications and Breast Cancer Outcomes (COMBO) cohort was developed to study how medications and co-morbidities influence breast cancer prognosis. Cohort study among adult women, diagnosed with incident early stage breast cancer, and enrolled in an integrated health plan. Data sources included health plan administrative databases, Surveillance, Epidemiology, and End Results tumor registry, and medical records. Statins, angiotensin-converting enzyme inhibitors (ACEI), beta blockers (BB), calcium blockers, and diuretics were the exposures of interest. The outcome was second breast cancer events (SBCE) defined as recurrence or second primary breast cancer. We used multivariable Cox proportional hazards models to estimate hazard ratios (HR) and 95 % confidence intervals (CI) for SBCE, and components of SBCE. 4,216 women were followed for a median of 6.3 years, and 13.2 % experienced a SBCE (first of: n = 415 recurrences and n = 143 s primary breast cancers). Compared to non-users, we observed an increased risk of second primary breast cancer with ACEI use (HR = 1.66; 95 % CI, 1.06-2.58) and an increased risk of recurrence with BB use (HR = 1.29; 95 % CI, 1.01-1.64). There was suggestion of a reduced risk of SBCE with statin use (HR = 0.82; 95 % CI, 0.62-1.08) and second primary breast cancer with BB use (HR = 0.77; 95 % CI, 0.50-1.19). No differences in outcomes were observed by duration of medication use. A majority of CVD medications evaluated in this study appear safe with respect to SBCE, but ACEI and BB use warrant further evaluation. The study presented is one example of the questions that can be addressed using the COMBO cohort.

Objective To evaluate the accuracy of using ICD-9 codes to identify nonunions (NU) and malunions (MU) among adults with a prior fracture code and to explore case-finding algorithms. Study design Medical chart review of potential NU ( N = 300) and MU ( N = 288) cases. True NU cases had evidence of NU and no evidence of MU in the chart (and vice versa for MUs) or were confirmed by the study clinician. Positive predictive values (PPV) were calculated for ICD-9 codes. Case-finding algorithms were developed by a classification and regression tree analysis using additional automated data, and these algorithms were compared to true case status. Setting Group Health Cooperative. Results Compared to true cases as determined from chart review, the PPV of ICD-9 codes for NU and MU were 89% (95% CI, 85–92%) and 47% (95% CI, 41–53%), respectively. A higher proportion of true cases (NU: 95%; 95% CI, 90–98%; MU: 56%; 95% CI, 47–66%) were found among subjects with 1 + additional codes occurring in the 12 months following the initial code. There was no case-finding algorithm for NU developed given the high PPV of ICD-9 codes. For MU, the best case-finding algorithm classified people as an MU case if they had a fracture in the forearm, hand, or skull and had no visit with an NU diagnosis code in the 12-month post MU diagnosis. PPV for this MU case-finding algorithm increased to 84%. Conclusions Identifying NUs with its ICD-9 code is reasonable. Identifying MUs with automated data can be improved by using a case-finding algorithm that uses additional information. Further validation of the MU algorithms in different populations is needed, as well as exploration of its performance in a larger sample.

Growing evidence suggests that certain commonly used diabetes medications have the potential to differentially alter breast cancer risk. We evaluated the influence of metformin, insulin, and sulfonylureas on risk of incident invasive breast cancer. We conducted a retrospective cohort study of women ≥40 years of age enrolled in a health plan between 1996 and 2011. Ever, current (≤12 months), and duration (

Studies of breast cancer outcomes rely on the identification of second breast cancer events (recurrences and second breast primary tumors). Cancer registries often do not capture recurrences, and chart abstraction can be infeasible or expensive. An alternative is using administrative health-care data to identify second breast cancer events; however, these algorithms must be validated against a gold standard.We developed algorithms using data from 3152 women in an integrated health-care system who were diagnosed with stage I or II breast cancer in 1993-2006. Medical record review served as the gold standard for second breast cancer events. Administrative data used in algorithm development included procedures, diagnoses, prescription fills, and cancer registry records. We randomly divided the cohort into training and testing samples and used a classification and regression tree analysis to build algorithms for classifying women as having or not having a second breast cancer event. We created several algorithms for researchers to use based on the relative importance of sensitivity, specificity, and positive predictive value (PPV) in future studies.The algorithm with high specificity and PPV had 89% sensitivity (95% confidence interval [CI] = 84% to 92%), 99% specificity (95% CI = 98% to 99%), and 90% PPV (95% CI = 86% to 94%); the high-sensitivity algorithm had 96% sensitivity (95% CI = 93% to 98%), 95% specificity (95% CI = 94% to 96%), and 74% PPV (95% CI = 68% to 78%).Algorithms based on administrative data can identify second breast cancer events with high sensitivity, specificity, and PPV. The algorithms presented here promote efficient outcomes research, allowing researchers to prioritize sensitivity, specificity, or PPV in identifying second breast cancer events.

Objectives: To determine the extent of concomitant use of cholinesterase inhibitor (ChI) and anticholinergic (ACh) medications and the clinical consequences of dual use in a population-based setting. Design: Retrospective cohort study. Setting: Group Health Cooperative and Kaiser Permanente Colorado. Participants: Five thousand six hundred twenty-five adults aged 50 and older who began new use of a ChI between 2000 and 2007. Measurements: Rates and characteristics of concomitant ChI and ACh use and the association between dual use and the outcomes of death and nursing home placement (claim from a nursing home with no prior claims used as a proxy). Results: Thirty-seven percent of ChI users also received AChs. Eleven percent of ChI users were concomitantly using two or more moderate to potent AChs. Median duration of this concomitant use was approximately 4 months, but a substantial proportion (25%) continued to use both medication classes simultaneously for longer than 12 months. In 23% of ChI users, AChs were being used at the time ChI therapy was initiated. The majority of this ACh use (77%) was not stopped once ChIs were started. No association was observed between concomitant use and risk of death or nursing home placement. Conclusion: These results should raise awareness about the prevalence and potential inappropriateness of concomitant use of ChIs and AChs and promote evaluations of practices intended to improve care standards.

SUMMARYIn epidemiological studies of community-acquired pneumonia (CAP) that utilize administrative data, cases are typically defined by the presence of a pneumonia hospital discharge diagnosis code. However, not all such hospitalizations represent true CAP cases. We identified 3991 hospitalizations during 1997–2005 in a managed care organization, and validated them as CAP or not by reviewing medical records. To improve the accuracy of CAP identification, classification algorithms that incorporated additional administrative information associated with the hospitalization were developed using the classification and regression tree analysis. We found that a pneumonia code designated as the primary discharge diagnosis and duration of hospital stay improved the classification of CAP hospitalizations. Compared to the commonly used method that is based on the presence of a primary discharge diagnosis code of pneumonia alone, these algorithms had higher sensitivity (81–98%) and positive predictive values (82–84%) with only modest decreases in specificity (48–82%) and negative predictive values (75–90%).

This study describes the impact of 80% adherence to guideline concordant care for compression therapy, moist wound-healing environment, and debridement on venous ulcer outcomes. The retrospective cohort design included patients from a tertiary care Veterans Affairs Medical Center from October 2003 to September 2007. During this 5-year interval, 155 patients with 400 venous ulcers met study inclusion. A majority of ulcers (n=362) healed, with an average time to healing of 18.1 weeks (range 2-209 weeks, median 10.4 weeks). From the multivariate Poisson regression, the likelihood of ulcer healing increased when compression therapy was provided during at least 80% of visits (relative risk [RR], 1.93; 95% confidence interval [CI], 1.27-2.92) or when a moist wound-healing environment was provided during at least 80% of visits (RR, 1.63; 95% CI, 1.09-2.42). Debridement alone was not significantly associated with ulcer healing (RR, 1.0; 95% CI, 0.61-1.64). Patients who received all three treatments during at least 80% of their visits were more likely to heal than those who received < 80% treatment (RR, 2.52; 95% CI, 1.53-4.16). Guideline concordant venous ulcer care was significantly associated with venous ulcer healing, when provided at 80% or more of patient visits.

Objectives: To describe hormone therapy (HT) initiation after the 2002 publication of the Women's Health Initiative. Design: Observational cohort (1999-2003) of women ages 40 to 79 years, five health plans, used HT in July 2002 and subsequently discontinued or never used before August 2002. Results: Of discontinuers, 15.8% (3,203 of 20,205) reinitiated HT. Reinitiation was higher among estrogen users (23.8%) versus estrogen with progestin users (11.3%), and lower among those with diabetes (relative risk [RR] = 0.68, 95% CI: 0.61-0.76), cardiovascular disease (RR = 0.87, 95% CI: 0.83-0.92), and hyperlipidemia (RR = 0.83, 95% CI: 0.79-0.88). Only 2.3% (2,072 of 90,261) of never users initiated (August 2002 to December 2003). First-time initiation was associated with cardiovascular disease (RR = 1.17, 95% CI: 1.10-1.25) and hyperlipidemia (RR = 1.24, 95% CI: 1.17-1.33) and was less common among those with diabetes (RR = 0.70, 95% CI: 0.63-0.79). Conclusions: After the Women's Health Initiative, a minority of women reinitiated or became first-time initiators of HT. Women with cardiovascular disease, diabetes, and hyperlipidemia were less likely to reinitiate; women with cardiovascular disease and hyperlipidemia were more likely to be first-time initiators.

Purpose Hepatitis B vaccine has been postulated as a possible cause of autoimmune disorders, including autoimmune thyroid diseases (ATD). Cases of Graves' disease and Hashimoto's thyroiditis, following hepatitis B vaccine have been reported to the Vaccine Adverse Events Reporting System (VAERS). To test the hypothesis that hepatitis B vaccine increases the risk of ATD, we conducted a case-control study, within the Vaccine Safety Datalink project. Methods We identified potential cases of Graves' disease and Hashimoto's thyroiditis, among persons aged 18–69 years from administrative data recorded by three health maintenance organizations (HMOs) and verified cases by medical record review. Controls were frequency-matched to cases by birth year, sex, and study site. Vaccine information was collected from administrative records, chart review, and telephone interviews with study subjects. We enrolled 355 Graves' disease cases, 418 Hashimoto's thyroiditis cases, and 1102 controls. We assessed the association between ever-receipt of hepatitis B vaccine, as well as receipt of hepatitis B vaccine less than 1 year, 1–5 years and at least 5 years prior to the index date, and the risk of ATD. Results Ever-receipt of hepatitis B vaccine was not associated with risk of Graves' disease (odds ratio (OR), 0.90; 95% confidence interval (CI), 0.62–1.32) or Hashimoto's thyroiditis (OR, 1.23; 95%CI, 0.87–1.73). There was also no association between the time interval since receipt of hepatitis B vaccination and either outcome. Conclusions We did not observe an increased risk of Graves' disease or Hashimoto's thyroiditis, following receipt of hepatitis B vaccine. Copyright © 2007 John Wiley & Sons, Ltd.

Women with breast cancer frequently use antidepressants; however, questions about the effect of these medications on breast cancer recurrence remain.We identified 4,216 women ≥18 years with an incident stage I or II breast cancer diagnosed between 1990 and 2008 in a mixed-model healthcare delivery system linked to a cancer registry. Recurrences were ascertained from chart review. Medication exposures were extracted from electronic pharmacy records. We used multivariable Cox proportional hazards models to estimate hazard ratios (HR) and 95 % confidence intervals (CI) to assess the association between antidepressant use and breast cancer recurrence and mortality. We also conducted analyses restricted to tamoxifen users.Antidepressants overall, tricyclic antidepressants, and selective serotonin reuptake inhibitors were not associated with risk of breast cancer recurrence or mortality. Women taking paroxetine only (adjusted HR: 1.66; 95 % CI 1.02, 2.71) and trazodone only (adjusted HR: 1.76; 95 % CI 1.06, 2.92), but not fluoxetine only (adjusted HR: 0.92; 95 % CI 0.55, 1.53), had higher recurrence risks than antidepressant nonusers. There was some suggestion of an increased recurrence risk with concurrent paroxetine and tamoxifen use compared with users of tamoxifen only (adjusted HR: 1.49; 95 % CI 0.79, 2.83).In general, antidepressants did not appear increase risk of breast cancer recurrence, though there were some suggested increases in risk that warrant further investigation in other datasets. Our results combined systematically and quantitatively with results from other studies may be useful for patients and providers making decisions about antidepressant use after breast cancer diagnosis.

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.

Background: Antibiotic use may be associated with higher breast cancer risk and breast cancer mortality, but no study has evaluated the relation between antibiotic use and second breast cancer events (SBCE). Methods: We conducted a retrospective cohort study among women ≥18 years, diagnosed with incident stage I/II breast cancer during 1990–2008. Antibiotic use and covariates were obtained from health plan administrative databases and medical record review. Frequent antibiotic use was defined as ≥4 antibiotic dispensings in any moving 12-month period after diagnosis. Our outcome was SBCE defined as recurrence or second primary breast cancer. We used multivariable Cox proportional hazards models to estimate HR and 95% confidence intervals (CI), accounting for competing risks. Results: A total of 4,216 women were followed for a median of 6.7 years. Forty percent were frequent antibiotic users and 558 (13%) had an SBCE. Results are suggestive of a modest increased risk of SBCE (HR, 1.15; 95% CI, 0.88–1.50) among frequent antibiotic users compared with nonusers. Any potential increased risk was not supported when we evaluated recent use and past use. We observed no dose–response trends for SBCE with increasing duration of antibiotic use nor did we find evidence for altered SBCE risk in the antibiotic classes studied. Conclusions: Frequent antibiotic use may be associated with modestly elevated risk of SBCEs, but the association was not significant. Impact: Additional investigation by antibiotic class and underlying indication are important next steps given the high prevalence of frequent antibiotic use and growing number of breast cancer survivors. Cancer Epidemiol Biomarkers Prev; 22(9); 1588–99. ©2013 AACR.

Background: Approximately 20% to 50% of women diagnosed with hormone receptor–positive breast cancer discontinue endocrine therapy early; most reports come from automated pharmacy data or small self-report evaluations. We conducted a larger self-report evaluation of endocrine therapy discontinuation associated with patient characteristics and therapy-related adverse effects. Methods: We surveyed 538 women from a single health plan who were diagnosed with early-stage breast cancer from 2002 to 2008 and received endocrine therapy. Women reported adverse effects and reasons for discontinuation via mailed survey; tumor characteristics were obtained via registry linkage. We classified women as discontinuers if they self-reported stopping therapy and their self-reported duration of tamoxifen plus aromatase inhibitor (AI) use was 5 years, and nondiscontinuers if they self-reported 5 years use or current use. We estimated odds ratios (ORs) with 95% CIs for discontinuation versus continuation by using logistic regression adjusted for age and year of diagnosis. Results: Among 538 women, 98 (18.2%) discontinued endocrine therapy early. Women with positive lymph nodes (v negative) were significantly less likely to discontinue therapy (odds ratio [OR] 0.54; 95% CI, 0.31 to 0.93). Almost all women (94%) experienced adverse effects. Experiencing headaches was associated with discontinuation of AIs (OR 4.16; 95% CI, 2.16 to 8.01) and tamoxifen (OR 2.34; 95% CI, 1.24 to 4.41); few other individual adverse effects were related to discontinuation despite most discontinuers reporting they “did not like adverse effects” (AIs: 66.7%, tamoxifen: 59.1%). Conclusion: Few individual adverse effects or patient characteristics were significantly associated with endocrine therapy discontinuation, yet adverse effects were prevalent and were the most common reason women reported for discontinuing therapy.

A patient-centered medical home (PCMH) demonstration was undertaken at 1 healthcare system, with the goals of improving patient experience, lessening staff burnout, improving quality, and reducing downstream costs. Five design principles guided development of the PCMH changes to staffing, scheduling, point-of-care, outreach, and management.To report differences in patient experience, staff burnout, quality, utilization, and costs in the first year of the PCMH demonstration.Prospective before and after evaluation.Baseline (2006) and 12-month (2007) measures were compared. Patient and staff experiences were measured using surveys from a random sample of patients and all staff at the PCMH and 2 control clinics. Automated data were used to measure and compare change components, quality, utilization, and costs for PCMH enrollees versus enrollees at 19 other clinics. Analyses included multivariate regressions for the different outcomes to account for baseline case mix.After adjusting for baseline, PCMH patients reported higher ratings than controls on 6 of 7 patient experience scales. For staff burnout, 10% of PCMH staff reported high emotional exhaustion at 12 months compared with 30% of controls, despite similar rates at baseline. PCMH patients also had gains in composite quality between 1.2% and 1.6% greater than those of other patients. PCMH patients used more e-mail, phone, and specialist visits, but fewer emergency services. At 12 months, there were no significant differences in overall costs.A PCMH redesign can be associated with improvements in patient experience, clinician burnout, and quality without increasing overall cost.

Statins are an effective and commonly used cholesterol-lowering medication class, but their hypothesized effects on cancer risk remain uncertain. We evaluated the association between statin use and endometrial as well as ovarian cancer risks.We conducted a retrospective study with two cohorts of women aged 45-89 years during 1990-2004 within an integrated healthcare delivery system. Information on statin use and covariates were obtained from automated databases. We identified cancer cases through the Surveillance, Epidemiology, and End Results registry. Multivariable Cox proportional hazards models were used to estimate the hazard ratios (HR) and 95% confidence intervals (CI) for incident invasive endometrial and ovarian cancers among statin users compared to nonusers.Women were followed for a median of about six years. Among 73,336 women studied, 568 endometrial cancer cases were identified. During the study period, 6% of women used statins for at least one year and the median duration of use was 3.1 years. Although not statistically significant, we found a reduction in endometrial cancer risk among statin users (HR = 0.67; 95% CI: 0.39-1.17) compared to nonusers. We identified 326 ovarian cancer cases in a cohort of 93,619 women. There was also a nonsignificant decrease in ovarian cancer risk among statin users (HR = 0.69; 95% CI: 0.32-1.49).Our study does not support an association between statin use and endometrial as well as ovarian cancers, but a reduced risk cannot be ruled out.

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.

Statins are a commonly used cholesterol-lowering drug, which also have the potential to affect cancer risk and progression. Results from previous studies offer mixed conclusions.To evaluate the relation between statin use and prostate cancer risk, we conducted a retrospective cohort study during 1 January 1990 to 31 August 2005 among men 45-79 years receiving care within Group Health, an integrated healthcare delivery system. Information on statin use and covariates were obtained from health plan databases. We identified incident prostate cancer cases through the Surveillance, Epidemiology, and End Results cancer registry. We used Cox proportional hazards models to estimate the hazard ratios (HR) and 95% confidence intervals (CI) for prostate cancer among statin users compared to non-users.Among 83,372 men studied, median follow-up time was 5.7 years and 2,532 prostate cancer cases were identified. About 14.4% used statins over the study period and median duration of use was 3.3 years. Compared to non-users, hydrophobic statin users had a reduced risk of prostate cancer (HR = 0.79; 95% CI, 0.66-0.94), and results are suggestive of a reduced risk among ever users of statins (HR = 0.88; 95% CI, 0.76-1.02) and hydrophilic statin users (HR = 0.67; 95% CI, 0.33-1.34). There was no trend in risk by duration of statin use, and no association between statin use and cancer aggressiveness, stage, or grade.Overall, this study does not support an associated between statin use and prostate cancer but a reduced risk cannot be ruled out.

To describe footwear preferences of people with diabetes and a history of foot ulcer from two large western Washington State healthcare organizations.As part of a clinical trial of footwear, self-reported information on footwear preferences, use, and cost were obtained from persons with diabetes and a prior healed foot ulcer for the year before their study enrollment. All participants' shoes were allocated into optimal, adequate, and dangerous categories based on design, structural and safety features, and materials.The 309 males and 91 females in this study averaged 62 years of age. At baseline, men owned an average of 6 (+3) pairs of shoes, with an average purchase price of $56, while women owned an average of 8 (+5) pairs, with an average purchase price of $42. Women spent an average of 51% of their time in shoes in dangerous shoes compared to men who spent 27% of their time. Men and women spent nearly 30% of their time while out of bed in slippers, stockings, and barefoot.People with a history of diabetes and foot ulcers needed several styles of safe and attractive shoes for regular activities. Healthcare professionals can provide patients with information on good footwear choices to help them select adequate shoes while avoiding dangerous shoes. This approach is more realistic than trying to move all people with prior foot risk factors or ulcers into uniformly optimal footwear, since recent evidence does not support this practice.

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)

We use a hierarchical model for a meta-analysis that combines information from autopsy studies of adenoma prevalence and counts. The studies we included reported findings using a variety of adenoma prevalence groupings and age categories. We use a non-homogeneous Poisson model for multinomial bin probabilities. The Poisson model allows risk to depend on age and sex, and incorporates extra-Poisson variability. We evaluate model fit using the posterior predicted distribution of adenoma prevalence reported by the studies included in our analyses and validate our model using adenoma prevalence reported by more recent colonoscopy studies. For 1990, the estimated adenoma prevalence among Americans at age 60 is 40.3 per cent for men compared to 29.2 per cent for women.

Background: The effi cacy of breast cancer screening in the community may differ from that suggested by the results of randomized trials, and no data have been available on effi cacy among women who have different levels of breast cancer risk. Methods: We conducted a matched case – control study among women enrolled in six health plans in Washington, Oregon, California, Massachusetts, and Minnesota. We examined the effi cacy of screening by mammography and/or clinical breast examination among women in two age cohorts (40 – 49 years and 50 – 65 years) and in two breast cancer risk levels (average and increased risk). Women who died from breast cancer from January 1, 1983, through December 31, 1998, (N = 1351; case subjects) were matched to control subjects (N = 2501) on age and risk level. Increased risk was defi ned as a family history of breast cancer or a breast biopsy noted in the medical records before the index date (defi ned as date of fi rst suspicion of breast abnormalities in case subjects, with the same date used for matched control subjects). Data on screening, risk status, and other variables were abstracted from medical records. Conditional logistic regression was used to examine the association between breast cancer mortality and receipt of screening. All statistical tests were two-sided. Results: There were small, non- statistically signifi cant associations between breast cancer mortality and receipt of screening during the 3 years prior to the index date for both the younger women [odds ratio (OR) = 0.92; 95% confi dence interval (CI) = 0.76 to 1.13] and the older women (OR = 0.87; 95% CI = 0.68 to 1.12). The association among women at increased risk (OR = 0.74; 95% CI = 0.50 to 1.03) was stronger than that among women at average risk (OR = 0.96; 95% CI = 0.80 to 1.14), but the difference was not statistically signifi cant ( P = .17). Conclusions: In this communitybased study, screening history was not associated with breast cancer mortality. However, potential limitations of this study argue for a cautious interpretation of these fi ndings. [J Natl Cancer Inst 2005;97:1035 – 43]

Findings from several studies suggest that bilateral prophylactic mastectomy reduces breast cancer incidence by 90% or more, but the studies used highly selected patients from referral centers, and the comparison groups were not population based. We studied the efficacy of bilateral prophylactic mastectomy in women with elevated breast cancer risk cared for in community practices.We conducted a retrospective case-cohort study of women aged 18 to 80 years with 1 or more breast cancer risk factors (family history of breast cancer, history of atypical hyperplasia, oror =1 breast biopsies with benign findings). Using computerized data and medical records, we identified 276 women with bilateral prophylactic mastectomy and a stratified random sample of 196 women representing an underlying cohort of 666 800 women with elevated breast cancer risk without prophylactic mastectomy, and then we determined who developed breast cancer.Breast cancer developed in 1 woman (0.4%) after bilateral prophylactic mastectomy vs 26 800 women (4.0%) without prophylactic mastectomy. Stratifying by birth year, the hazard ratio for breast cancer occurrence after bilateral prophylactic mastectomy was 0.005 (95% confidence interval, 0.001-0.044). No woman with bilateral prophylactic mastectomy died of breast cancer vs a calculated 0.2% of women without prophylactic mastectomy.Bilateral prophylactic mastectomy reduced breast cancer incidence in women at elevated risk for breast cancer cared for in community-based practices. However, the absolute risk of breast cancer incidence and death in women who did not undergo the procedure in these settings was relatively low.

To the Editor: Colonge et al.’s manuscript on the choice of primary time scale for epidemiologic follow-up studies makes an important contribution to methods for longitudinal data analysis.1 We agree with their assessment that the choice of time scale should be based on “the goals of the study and the need for confounder adjustment.” As the authors say, in most studies of disease incidence, age will be the appropriate time scale (especially when compared to time on study), but there may be other relevant time scales for different applications. For example, in studies of disease prognosis, time since onset or diagnosis is commonly used.2, 3 In a study examining the association between the use of a particular medication and breast cancer recurrence, time since initial breast cancer diagnosis may be an important confounder and one that should be accounted for flexibly. Risk of breast cancer recurrence depends on time since diagnosis in a complex way (Figure 1, unpublished data). And, time since diagnosis might also be associated with the exposure of interest, making it a confounder. If time since diagnosis is chosen as the time scale, age should be adjusted for as a covariate in multivariable regression models as it, too, is related to the recurrence risk. The choice of age as a timescale (with adjustment for time since diagnosis) is not incorrect for this application as age is also associated with recurrence risk and, in some cases, exposure; however, we think using time since diagnosis may adjust more completely for confounding in some studies of disease prognosis. If both elements of time are potential confounders, both should be accounted for – one as the timescale and one as a covariate in the model. The interpretation of the hazard ratios is essentially the same regardless of which is selected as time scale and which is modeled; however, the choice may affect the ability to control for confounding. Whether it is better to use age or time since diagnosis as the time scale in studies of prognosis may depend on the specific application; in some cases, it may not affect the results.4 With the growing interest in follow-up studies of disease outcomes, additional research on how to select among multiple biologically relevant time scales is necessary. Figure 1 Kernel-smoothed estimate of hazard of second breast cancer event over years since diagnosis by age at diagnosis, in a cohort of early stage breast cancer patients diagnosed in 1990–2008.

Clinical studies using medical record review should include careful training and quality assurance methods to enhance the reliability and validity of data obtained from the records. Because of time and budget constraints, comprehensive assessments of data quality and reliability, including masking of medical record abstractors, are not always possible. This paper describes the abstractor training and quality control methods and results of a masked medical record review study. The medical record review study was carried out within a larger multisite study of the effectiveness of screening mammography in preventing breast cancer mortality with an observation period within 1983 and 1993, with mortality follow-up through 1998. An eight-step program was developed to train medical record abstractors and monitor the quality of their work. A key follow-up component to the training protocol was a 5% reabstraction of medical records (n = 160), masked and reviewed by a second abstractor. High agreement was found between initial (unmasked) abstractors and masked abstractors for all key exposure variables (kappa ranged from 0.76 to 0.91), with no evidence of biased directionality by unmasked reviewers. Rigorous ongoing training programs for medical record abstractors provide assurance of good quality control in large multisite studies. Additionally, a masking study with a subsample of subjects may be a feasible and cost-effective alternative to the time- and cost-intensive methodological approach of masking all medical records.

Acute respiratory infections, including influenza, have been suggested as possible precipitants of acute cardiac events. To evaluate whether influenza vaccination prevents recurrent coronary events, the authors conducted a population-based inception cohort study of 1,378 Group Health Cooperative enrollees who survived a first myocardial infarction in 1992 through 1996. Recurrent coronary events, influenza vaccinations, and other covariates were identified by chart review and from administrative data systems. A Cox proportional hazards model was used to evaluate the association of receipt of each year's influenza vaccine with subsequent risk of recurrent myocardial infarction and death from atherosclerotic cardiovascular disease. A total of 127 recurrent coronary events were identified during the median 2.3-year follow-up period. Influenza vaccination was not associated with risk of recurrent coronary events during the corresponding period of November through October (adjusted hazard ratio (HR) = 1.18, 95% confidence interval (CI): 0.79, 1.75) or during the corresponding periods of expected influenza activity (November through April) (HR = 1.06, 95% CI: 0.63, 1.78) or inactivity (May through October) (HR = 1.34, 95% CI: 0.76, 2.36). These results suggest that the benefit of influenza vaccine for older adults does not extend to protection against recurrent coronary events.

ContextMany people with diabetes experience lower-limb ulcers. Footwear has been implicated as a primary cause of foot ulcers, yet research is limited on the efficacy of shoe and insert combinations to prevent reulceration.ObjectiveTo determine whether extra-depth and -width therapeutic shoes used with 2 types of inserts reduce reulceration in diabetic individuals with a history of foot ulcer.Design, Setting, and ParticipantsRandomized clinical trial of 400 diabetes patients with history of foot ulcer in 2 Washington State health care organizations who did not require custom shoes for foot deformity and were enrolled between August 1997 and December 1998 and followed up for 2 years. Data collected at regular intervals documented physical, foot, and diabetes characteristics; footwear use; foot lesions; and ulcers.InterventionsParticipants were randomly assigned to receive 3 pairs of therapeutic shoes and 3 pairs of customized medium-density cork inserts with a neoprene closed-cell cover (n = 121); to receive 3 pairs of therapeutic shoes and 3 pairs of prefabricated, tapered polyurethane inserts with a brushed nylon cover (n = 119); or to wear their usual footwear (controls; n = 160).Main Outcome MeasureFoot reulceration, compared among the 3 groups.ResultsTwo-year cumulative reulceration incidence across the 3 groups was low: 15% in the cork-insert group, 14% in the prefabricated-insert group, and 17% in controls. In the intent-to-treat analysis, patients assigned to therapeutic shoes did not have a significantly lower risk of reulceration compared with controls (risk ratio [RR] for the cork-insert group, 0.88; 95% confidence interval [CI], 0.51-1.52 and RR the for prefabricated-insert group, 0.85; 95% CI, 0.48-1.48). All ulcer episodes in patients assigned to therapeutic shoes and 88% wearing nonstudy shoes occurred in patients with foot insensitivity.ConclusionsThis study of persons without severe foot deformity does not provide evidence to support widespread dispensing of therapeutic shoes and inserts to diabetic patients with a history of foot ulcer. Study shoes and custom cork or preformed polyurethane inserts conferred no significant ulcer reduction compared with control footwear. This study suggests that careful attention to foot care by health care professionals may be more important than therapeutic footwear but does not negate the possibility that special footwear is beneficial in persons with diabetes who do not receive such close attention to foot care by their health care providers or in individuals with severe foot deformities.