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Recombinant zoster vaccine (RZV) (Shingrix; GlaxoSmithKline, Brentford, United Kingdom) is an adjuvanted glycoprotein vaccine that was licensed in 2017 to prevent herpes zoster (shingles) and its complications in older adults. In this prospective, postlicensure Vaccine Safety Datalink study using electronic health records, we sequentially monitored a real-world population of adults aged ≥50 years who received care in multiple US Vaccine Safety Datalink health systems to identify potentially increased risks of 10 prespecified health outcomes, including stroke, anaphylaxis, and Guillain-Barré syndrome (GBS). Among 647,833 RZV doses administered from January 2018 through December 2019, we did not detect a sustained increased risk of any monitored outcome for RZV recipients relative to either historical (2013–2017) recipients of zoster vaccine live, a live attenuated virus vaccine (Zostavax; Merck & Co., Inc., Kenilworth, New Jersey), or contemporary non-RZV vaccine recipients who had an annual well-person visit during the 2018–2019 study period. We confirmed prelicensure trial findings of increased risks of systemic and local reactions following RZV. Our study provides additional reassurance about the overall safety of RZV. Despite a large sample, uncertainty remains regarding potential associations with GBS due to the limited number of confirmed GBS cases that were observed.

AIM: International studies have shown that most colon cancers are diagnosed among people with symptoms, but research is limited in the United States. We conducted a retrospective study with adults aged 50–85 years diagnosed with stage I-IIIA colon cancer in 1995–2014 in two US healthcare systems. METHOD: Mode of detection (screening or symptomatic) was ascertained from medical records. We estimated unadjusted odds ratios (OR) and 95% confidence intervals (CI) comparing detection mode by patient factors at diagnosis (year, age, sex, race, smoking status, body mass index [BMI], Charlson score), pre-diagnostic primary care utilization, and tumor characteristics (stage, location). RESULTS: Of 1,675 people with colon cancer, 38.4% were screen-detected, while 61.6% were diagnosed following symptomatic presentation. Screen-detected cancer was more common among those diagnosed in 2010–2014 vs. 1995–1999 (OR=1.65, 95%CI=1.19–2.28), and those with a BMI of 25-0 (OR=0.71, 95%CI=0.56–0.91 for score=1, OR=0.34, 95%CI=0.26–0.45 for score=2+), and those with 2+ pre-diagnostic primary care visits (OR=0.53, 95%CI=0.37–0.76) vs. 0 visits. The odds of screen detection were lower among patients diagnosed with stage IIA (OR=0.33, 95%CI=0.27–0.41) or IIB (OR=0.12, 95%CI=0.06–0.24) cancers vs. stage I. CONCLUSION: Most colon cancers among screen-eligible adults were diagnosed following symptomatic presentation. Even with increasing screening rates over time, research is needed to better understand why specific groups are more likely to be diagnosed when symptomatic and identify opportunities for interventions.

To estimate the positive predictive value (PPV) of International Classification of Diseases, Tenth Revision, Clinical Modification (ICD-10-CM) diagnosis codes for identifying HF subtypes.We validated ICD-10-CM HF diagnosis codes among Kaiser Permanente Washington enrollees who were ≥18 years of age and had an ICD-10-CM HF diagnosis code during 2017-2018 and a procedure code for an echocardiogram in the 12 months before through 6 months after the HF code. Left ventricular ejection fraction (LVEF) ascertained from medical chart review was used as the gold standard for classifying patients as having reduced ejection fraction (rEF), mid-range ejection fraction (mEF), or preserved ejection fraction (pEF).Among 6194 eligible patients, we randomly sampled 1000 for medical chart review. A total of 974 patients had LVEF information in their chart. The ICD-10-CM HF code group with the highest PPV for rEF was I50.20-I50.23, "Systolic (congestive) heart failure," PPV = 41.4% (95% CI, 34.5-48.7%); and the highest PPV for mEF or rEF was also I50.20-I50.23, PPV = 70.2% (95% CI, 63.1-76.4%). The highest PPV for pEF was the I50.30-I50.33 group, "Diastolic (congestive) heart failure," PPV = 92.0% (95% CI, 88.1-94.7%); and the highest PPV for mEF or pEF was also I50.30-I50.33, PPV = 97.7% (95% CI, 95.1-99.0%).If the accuracy measure of greatest interest is PPV, our results suggest that ICD-10-CM HF codes alone may not be adequate for identifying patients with rEF but may be adequate for identifying patients with pEF. HF coding practices may vary across settings, which may impact generalizability of our findings.

Background Clinician perceptions before and after inviting patients to read office notes (open notes) are unknown. Objective To describe changes in clinicians’ attitudes about sharing notes with patients. Design, Participants, and Main Measure Survey of outpatient primary and specialty care clinicians who were from a large group practice and had one or more patients who accessed notes. The main outcome was percent change (before vs. after implementation) in clinician perception that online visit notes are beneficial overall. Key Results Of the 563 invited clinicians, 400 (71%) took the baseline survey; 295 were eligible for a follow-up survey with 192 (65%) responding (119 primary care, 47 medical specialties, 26 surgical specialties). Before implementation, 29% agreed or somewhat agreed that visit notes online are beneficial overall, increasing to 71% following implementation (p

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.

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.

BackgroundThis study was aimed to determine whether incident dementia and HbA1c levels are associated with increased rates of potentially preventable hospitalizations (PPHs) in persons with diabetes.MethodA total of 565 adults aged 65+ ever treated for diabetes were enrolled from Adult Changes in Thought study. PPHs were from principal discharge diagnoses and included diabetes PPH (dPPH), respiratory PPH (rPPH), urinovolemic PPH (uPPH), cardiovascular PPH, and other PPH. Poisson generalized estimating equations estimated rate ratios (RRs) and 95% confidence intervals (CIs) for the associations between dementia or HbA1c measures and rate of PPHs.ResultsA total of 562 individuals contributed 3 602 dementia-free years, and 132 individuals contributed 511 dementia follow-up years. One hundred twenty-eight (23%) dementia-free individuals had 210 PPH admissions and a crude rate of 58 per 1 000 person-years, while 55 (42%) individuals with dementia had 93 PPH admissions and a crude rate of 182 per 1 000 person-years. The adjusted RR (95% CI) comparing rates between dementia and dementia-free groups were 2.27 (1.60, 3.21) for overall PPH; 5.90 (2.70, 12.88) for dPPH; 5.17 (2.49, 10.73) for uPPH; and 2.01 (1.06, 3.83) for rPPH. Compared with HbA1c of 7%–8% and adjusted for dementia, the RR (95% CI) for overall PPH was 1.43 (1.00, 2.06) for >8% HbA1c and 1.18 (0.85, 1.65) for 8% and ConclusionIncident dementia is associated with higher rates of PPHs among people with diabetes, especially PPHs due to diabetes, urinary tract infection (UTI), and dehydration. Potential evidence suggested that HbA1c levels of >8% versus lower levels are associated with higher rates of overall PPHs and UTI- and dehydration-related PPHs.

OBJECTIVE:To compare perinatal outcomes before and after a clinical guideline change from a two-step to a one-step approach to screening for gestational diabetes mellitus (GDM).METHODS:We conducted a before–after cohort study of women with singleton live birth deliveries within Kaiser Permanente Was

Objectives To determine whether higher cumulative proton pump inhibitor (PPI) exposure is associated with greater dementia risk. Design Prospective population-based cohort study. Setting Kaiser Permanente Washington, an integrated healthcare delivery system in Seattle, Washington. Participants Individuals aged 65 and older without dementia at study entry (N = 3,484). Measurements Participants were screened for dementia every 2 years, and those who screened positive underwent extensive evaluation. Dementia outcomes were determined using standard diagnostic criteria. Time-varying PPI exposure was determined from computerized pharmacy data and consisted of total standardized daily doses (TSDDs) dispensed to an individual in the prior 10 years. We also assessed duration of use. Multivariable Cox regression was used to estimate the association between PPI exposure and time to dementia or Alzheimer's disease (AD). Results Over a mean follow-up of 7.5 years, 827 participants (23.7%) developed dementia (670 with possible or probable AD). PPI exposure was not associated with risk of dementia (P = .66) or AD (P = .77). For dementia, the risk for specific levels of cumulative exposure compared to no use was: 365 TSDDs (HR 0.87, 95% CI 0.65–1.18), 1,095 TSDDs (HR 0.99, CI 0.75–1.30) and 1,825 TSDDs (HR 1.13, CI 0.82–1.56). These TSDD levels represent approximately 1, 3 and 5 years of daily use respectively. Duration of PPI use was not associated with dementia outcomes either. Conclusion Proton pump inhibitor use was not associated with dementia risk, even for people with high cumulative exposure. Although there are other safety concerns with long-term PPI use, results from our study do not support that these medications should be avoided out of concern about dementia risk.

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.

BACKGROUND Women with breast cancer have worse health outcomes with co-occurring type 2 diabetes, possibly due to suboptimal breast cancer treatment. METHODS We created a cohort of women ages 66 to 85 y with stage I to III breast cancer from 1993 to 2012 from an integrated health care delivery system (n=1612) and fee-for-service Medicare beneficiaries (n=98,915), linked to Surveillance, Epidemiology, and End Results (SEER) data (total n=100,527). We evaluated associations between type 2 diabetes and other factors with undergoing guideline-concordant cancer treatment. We estimated χ tests for univariate analysis and relative risks (RRs) using multivariable log-binomial models for outcomes of (1) overall guideline-concordant treatment, (2) definitive surgical therapy (mastectomy or lumpectomy with radiation), (3) chemotherapy if indicated, and (4) endocrine therapy. RESULTS Our cohort included 60% of subjects with stage 1 tumors, one quarter below 70 years old, 23% had diabetes, 35% underwent overall guideline-concordant treatment, 24% chemotherapy, and 83% endocrine therapy. Women with diabetes were less likely to undergo overall guideline-concordant treatment (RR: 0.96; 95% confidence interval: 0.94-0.98), and only slightly less likely to undergo guideline-concordant definitive surgical therapy (RR: 0.99; 95% confidence interval: 0.99-1.00). No differences were found for chemotherapy or endocrine therapy. Other factors significantly associated with a lower risk of guideline-concordant care were cancer stages II to III (vs. I; RR=0.47-0.69, P

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.

Introduction: Uterine fibroids are the most common benign tumors of the uterus and are associated with considerable morbidity. Diagnosis codes have been used to identify fibroid cases, but their accuracy, especially for incident cases, is uncertain.Methods: We performed medical record review on a random sample of 617 women who received a fibroid diagnosis during 2012–2014 to assess diagnostic accuracy for incident fibroids. We developed 2 algorithms aimed at improving incident case-finding using classification and regression tree analysis that incorporated additional electronic health care data on demographics, symptoms, treatment, imaging, health care utilization, comorbidities and medication. Algorithm performance was assessed using medical record as gold standard.Results: Medical record review confirmed 482 fibroid cases as incident, resulting a 78 percent positive predictive value (PPV) for incident cases based on diagnosis codes alone. Incorporating additional electronic data, the first algorithm classified 395 women with a pelvic ultrasound on diagnosis date but none before as incident cases. Of these, 344 were correctly classified, yielding an 87 percent PPV, 71 percent sensitivity, and 62 percent specificity. A second algorithm built on the first algorithm and further classified women based on a fibroid diagnosis code of 218.9 in 2 years after incident diagnosis and lower body mass index; yielded 93 percent PPV, 53 percent sensitivity, and 85 percent specificity.Conclusions: Compared to diagnosis codes alone, our algorithms using fibroid diagnosis codes and additional electronic data improved identification of incident cases with higher PPV, and high sensitivity or specificity to meet different aims of future studies seeking to identify incident fibroids from electronic data.

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.

Objectives To determine whether prescription opioid use is associated with higher dementia risk or greater cognitive decline. Design Prospective cohort study. Setting Group Health, an integrated healthcare delivery system. Participants Community-dwelling individuals aged 65 and older without dementia with at least 10 years of Group Health enrollment at baseline (N = 3,434; median age 74). Measurements The Cognitive Abilities Screening Instrument (CASI) was administered every 2 years. Low scores triggered detailed evaluation, and a multidisciplinary committee assigned dementia diagnoses. From computerized pharmacy data, cumulative opioid exposure was defined as total standardized doses (TSDs) dispensed over 10 years (excluding the most recent year because of possible prodromal symptoms). For comparison, use of nonsteroidal anti-inflammatory drugs (NSAIDs), characterized similarly, was examined. Dementia risk was analyzed using Cox proportional hazards models and CASI trajectory using linear regression models and generalized estimating equations. Results Seven hundred ninety-seven participants (23%) developed dementia over a mean follow-up of 7.3 years; 637 (19%) had possible or probable Alzheimer's disease. For cumulative opioid use, the hazard ratios (HRs) for dementia were 1.06 (95% confidence interval (CI) = 0.88–1.26) for 11 to 30 TSDs, 0.88 (95% CI = 0.70–1.09) for 31 to 90 TSDs, and 1.29 (95% CI = 1.02–1.62) for 91 or more TSDs, versus 0 to 10 TSDs. A similar pattern was seen for NSAID use. Heavier opioid use was not associated with more-rapid cognitive decline. Conclusion People with the heaviest opioid or NSAID use had slightly higher dementia risk than people with little or no use. These results may reflect an effect of chronic pain on cognition or residual confounding. Although opioids have other risks, little evidence of long-term cognitive harm specific to opioids was found.

BACKGROUND Anticholinergic medication exposure has been associated with increased risk for dementia. No study has examined the association between anticholinergic medication use and neuropathologic lesions in a community-based sample. OBJECTIVE To examine the relationship between anticholinergic exposure and dementia-related neuropathologic changes. METHODS Within a community-based autopsy cohort (N = 420), we ascertained use of anticholinergic medications over a 10-year period from automated pharmacy data and calculated total standardized daily doses (TSDD). We used modified Poisson regression to calculate adjusted relative risks (RRs) and 95% confidence intervals (CIs) for the association between anticholinergic exposure and dementia-associated neuropathology. Inverse probability weighting was used to account for selection into the autopsy cohort. RESULTS Heavy anticholinergic exposure (≥1,096 TSDD) was not associated with greater neuropathologic changes of Alzheimer's disease; the adjusted RRs for heavy use of anticholinergics (≥1,096 TSDD) compared to no use were 1.22 (95% CI 0.81-1.88) for neuritic plaque scores and 0.89 (0.47-1.66) for extent of neurofibrillary degeneration. Moderate (91-1,095 TSDD) and heavy use of anticholinergics was associated with a significantly lower cerebral microinfarct burden compared with no use with adjusted RRs of 0.44 (0.21-0.89) and 0.24 (0.09-0.62), respectively. Anticholinergic exposure was not associated with macroscopic infarcts or atherosclerosis. CONCLUSIONS Use of anticholinergic medications is not associated with Alzheimer's disease-related neuropathologic changes but is associated with lower cerebral microinfarct burden. Further research into biological mechanisms underlying the anticholinergic-dementia link is warranteds.

Background Opioids may influence the development of Alzheimer's disease (AD). Some studies have observed AD pathology in the brains of opioid abusers. No study has examined the association between prescription opioid use and dementia-related neuropathologic changes. Objective To examine the relationship between prescription opioid or NSAID use and dementia-related neuropathologic changes. Methods Within a community-based autopsy cohort (N = 420), we ascertained opioid and nonsteroidal anti-inflammatory drug (NSAID) use over a 10-year period from automated pharmacy data and calculated total standardized daily doses (TSDDs). A neuropathologist assessed outcomes including neuritic plaques, neurofibrillary tangles, and macroscopic infarcts. Outcome measures were dichotomized using established cutpoints. We used modified Poisson regression to calculate adjusted relative risks (RR) and 95% confidence intervals (CI), accounting for participant characteristics and using weighting to account for possible selection bias related to selection into the autopsy sample. Results Heavier opioid exposure was not associated with greater neuropathologic changes. For neuritic plaques, the adjusted RR [95% CI] was 0.99 [0.64-1.47] for 91+ TSDDs of opioids versus little to no use, and for neurofibrillary tangles, 0.97 [0.49-1.78]. People with heavy NSAID use had higher risk of neuritic plaques (RR 1.39 [1.01-1.89]) than those with little to no use, as we have previously reported. Neither opioid nor NSAID use was associated with higher risk of macroscopic infarcts or with Lewy body disease. Conclusion Prescription opioid use is not associated with dementia-related neuropathologic changes, but heavy NSAID use may be. More research is needed examining chronic pain, its pharmacologic treatments, and neuropathologic changes.

Objectives To evaluate the associations between anesthesia and dementia or Alzheimer's disease (AD) risk using prospectively collected data. Design Cohort study. Participants Community-dwelling members of the Adult Changes in Thought cohort aged 65 and older and free of dementia at baseline (N = 3,988). Measurements Participants self-reported all prior surgical procedures with general or neuraxial (spinal or epidural) anesthesia at baseline and reported new procedures every 2 years. People undergoing high-risk surgery with general anesthesia, other surgery with general anesthesia, and other surgery with neuraxial anesthesia exposures were compared with those with no surgery and no anesthesia. Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for dementia and AD associated with time-varying lifetime and recent (past 5 years) anesthesia exposures. Results At baseline, 254 (6%) people reported never having anesthesia; 248 (6%) had had one or more high-risk surgeries with general anesthesia, 3,363 (84%) had had one or more other surgeries with general anesthesia, and 123 (3%) had had one or more surgeries with neuraxial anesthesia. High-risk surgery with general anesthesia was not associated with greater risk of dementia (HR = 0.86, 95% CI = 0.58–1.28) or AD (HR = 0.95, 95% CI = 0.61–1.49) than no history of anesthesia. People with any history of other surgery with general anesthesia had a lower risk of dementia (HR = 0.63, 95% CI = 0.46–0.85) and AD (HR = 0.65, 95% CI = 0.46–0.93) than people with no history of anesthesia. There was no association between recent anesthesia exposure and dementia or AD. Conclusion Anesthesia exposure was not associated with of dementia or AD in older adults.

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.

Preinfluenza periods have been used to test for uncontrolled confounding in studies of influenza vaccine effectiveness, but some authors have claimed that confounding differs in preinfluenza and influenza periods. We tested this claim by comparing estimates of the vaccine-mortality association during the 2009/2010 influenza year, when there was essentially no circulation of seasonal influenza in the United States, and 2007/2008, a typical influenza year. We pooled data on seniors (adults aged ≥65 years) from 7 US managed care organizations that participated in the Vaccine Safety Datalink Project. We defined influenza vaccination, all-cause mortality, and potential confounders from administrative databases. We quantified the vaccine-mortality association using Cox regression. During 2007/2008, the adjusted hazard ratio was 0.44 prior to influenza season, 0.62 during influenza season, and 0.71 after influenza season. A similar pattern was observed during 2009/2010, when any effect of seasonal influenza vaccine observed during all time periods must have resulted from confounding: 0.65 during the autumn, 0.80 during the winter, and 0.84 during the summer. In a year with minimal seasonal influenza, we found no evidence that confounding in autumn preinfluenza periods is qualitatively different from confounding in winter. This supports the use of preinfluenza periods as control time periods in studies of influenza vaccine effectiveness.

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.

To address gaps in traditional postlicensure vaccine safety surveillance and to promote rapid signal identification, new prospective monitoring systems using large health-care database cohorts have been developed. We newly adapted clinical trial group sequential methods to this observational setting in an original safety study of a combination diphtheria and tetanus toxoids and acellular pertussis adsorbed (DTaP), inactivated poliovirus (IPV), and Haemophilus influenzae type b (Hib) conjugate vaccine (DTaP-IPV-Hib) among children within the Vaccine Safety Datalink population. For each prespecified outcome, we conducted 11 sequential Poisson-based likelihood ratio tests during September 2008-January 2011 to compare DTaP-IPV-Hib vaccinees with historical recipients of other DTaP-containing vaccines. No increased risk was detected among 149,337 DTaP-IPV-Hib vaccinees versus historical comparators for any outcome, including medically attended fever, seizure, meningitis/encephalitis/myelitis, nonanaphylactic serious allergic reaction, anaphylaxis, Guillain-Barré syndrome, or invasive Hib disease. In end-of-study prespecified subgroup analyses, risk of medically attended fever was elevated among 1- to 2-year-olds who received DTaP-IPV-Hib vaccine versus historical comparators (relative risk = 1.83, 95% confidence interval: 1.34, 2.50) but not among infants under 1 year old (relative risk = 0.83, 95% confidence interval: 0.73, 0.94). Findings were similar in analyses with concurrent comparators who received other DTaP-containing vaccines during the study period. Although lack of a controlled experiment presents numerous challenges, implementation of group sequential monitoring methods in observational safety surveillance studies is promising and warrants further investigation.

Introduction: The large-scale assembly of electronic health care data combined with the use of sequential monitoring has made proactive postmarket drug- and vaccine-safety surveillance possible. Although sequential designs have been used extensively in randomized trials, less attention has been given to methods for applying them in observational electronic health care database settings.Existing Methods: We review current sequential-surveillance planning methods from randomized trials, and the Vaccine Safety Datalink (VSD) and Mini-Sentinel Pilot projects—two national observational electronic health care database safety monitoring programs.Future Surveillance Planning: Based on this examination, we suggest three steps for future surveillance planning in health care databases: (1) prespecify the sequential design and analysis plan, using available feasibility data to reduce assumptions and minimize later changes to initial plans; (2) assess existing drug or vaccine uptake, to determine if there is adequate information to proceed with surveillance, before conducting more resource-intensive planning; and (3) statistically evaluate and clearly communicate the sequential design with all those designing and interpreting the safety-surveillance results prior to implementation. Plans should also be flexible enough to accommodate dynamic and often unpredictable changes to the database information made by the health plans for administrative purposes.Conclusions: This paper is intended to encourage dialogue about establishing a more systematic, scalable, and transparent sequential design-planning process for medical-product safety-surveillance systems utilizing observational electronic health care databases. Creating such a framework could yield improvements over existing practices, such as designs with increased power to assess serious adverse events.

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.

To evaluate tamoxifen and aromatase inhibitor (AI) initiation over time and by patient characteristics among women diagnosed with breast cancer in a community setting.We conducted a retrospective cohort study of 1,501 women age ≥ 18 years diagnosed with stages I to II invasive, hormone receptor-positive breast cancer from 2001 to 2008 in an integrated delivery system. Using automated pharmacy dispensings, we determined endocrine therapy receipt within 12 months of diagnosis. We used generalized linear models to estimate adjusted relative risks (RRs) with 95% CIs for any endocrine therapy use (v none), tamoxifen use (v none), AI use (v none), and AIs first (v tamoxifen). Each model adjusted for age, stage, body mass index, tumor size, lymph node status, comorbidities, other treatment, and diagnosis year.Tamoxifen use was at its highest (56.9%) in 2001 and then decreased; AI use was lowest in 2001 (5.5%) and then peaked in 2005 (36.8%). In multivariate models, women age ≥ 65 years were less likely to use any endocrine therapy compared with women age 55 to 64 years (age 65 to 74 years: RR, 0.86; 95% CI, 0.78 to 0.96; age ≥ 75 years: RR, 0.71; 95% CI, 0.61 to 0.81). Women age ≥ 75 years were significantly less likely to begin AIs versus no treatment (RR, 0.46; 95% CI, 0.32 to 0.64) and versus tamoxifen (RR, 0.67; 95% CI, 0.46 to 0.97). Women with tumor sizes 1.0 to 1.9 cm and ≥ 2.0 cm were significantly more likely to use any endocrine therapy compared with women with tumor sizes1.0 cm (RR, 1.41; 95% CI, 1.23 to 1.61 and RR, 1.52; 95% CI, 1.27 to 2.81, respectively).Differential initiation over time, as well as by age and tumor size, suggests patient preferences and provider recommendations for endocrine therapy vary, despite guideline recommendations.

Purpose Many challenges arise when conducting a sequentially monitored medical product safety surveillance evaluation using observational electronic data captured during routine care. We review existing sequential approaches for potential use in this setting, including a continuous sequential testing method that has been utilized within the Vaccine Safety Datalink (VSD) and group sequential methods, which are used widely in randomized clinical trials. Methods Using both simulated data and preliminary data from an ongoing VSD evaluation, we discuss key sequential design considerations, including sample size and duration of surveillance, shape of the signaling threshold, and frequency of interim testing. Results and Conclusions All designs control the overall Type 1 error rate across all tests performed, but each yields different tradeoffs between the probability and timing of true and false positive signals. Designs tailored to monitor efficacy outcomes in clinical trials have been well studied, but less consideration has been given to optimizing design choices for observational safety settings, where the hypotheses, population, prevalence and severity of the outcomes, implications of signaling, and costs of false positive and negative findings are very different. Analytic challenges include confounding, missing and partially accrued data, high misclassification rates for outcomes presumptively defined using diagnostic codes, and unpredictable changes in dynamically accessed data over time (e.g., differential product uptake). Many of these factors influence the variability of the adverse events under evaluation and, in turn, the probability of committing a Type 1 error. Thus, to ensure proper Type 1 error control, planned sequential thresholds should be adjusted over time to account for these issues. Copyright © 2012 John Wiley & Sons, Ltd. key words—observational study; pharmacovigilance; postmarketing; sequential testing; study design; vaccine and drug safety

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.

Research and surveillance work addressing ectopic pregnancy often rely on diagnosis and procedure codes available from automated data sources. However, the use of these codes may result in misclassification of cases. Our aims were to evaluate the accuracy of standard ectopic pregnancy codes; and, through the use of additional automated data, to develop and validate a classification algorithm that could potentially improve the accuracy of ectopic pregnancy case identification.Using automated databases from two US managed-care plans, Group Health Cooperative (GH) and Kaiser Permanente Colorado (KPCO), we sampled women aged 15-44 with an ectopic pregnancy diagnosis or procedure code from 2001 to 2007 and verified their true case status through medical record review. We calculated positive predictive values (PPV) for code-selected cases compared with true cases at both sites. Using additional variables from the automated databases and classification and regression tree (CART) analysis, we developed a case-finding algorithm at GH (n = 280), which was validated at KPCO (n = 500).Compared with true cases, the PPV of code-selected cases was 68 and 81% at GH and KPCO, respectively. The case-finding algorithm identified three predictors: ≥ 2 visits with an ectopic pregnancy code within 180 days; International Classification of Diseases, 9th Revision, Clinical Modification codes for tubal pregnancy; and methotrexate treatment. Relative to true cases, performance measures for the development and validation sets, respectively, were: 93 and 95% sensitivity; 81 and 81% specificity; 91 and 96% PPV; 84 and 79% negative predictive value. Misclassification proportions were 32% in the development set and 19% in the validation set when using standard codes; they were 11 and 8%, respectively, when using the algorithm.The ectopic pregnancy algorithm improved case-finding accuracy over use of standard codes alone and generalized well to a second site. When using administrative data to select potential ectopic pregnancy cases, additional widely available automated health plan data offer the potential to improve case identification.

OBJECTIVE: To assess whether the risk of medically attended local reactions to the fifth dose of the diphtheria and tetanus toxoids and acellular pertussis (DTaP) vaccine varies according to injection site (arm versus thigh). METHODS: We conducted a retrospective cohort study of children aged 4 through 6 years in the Vaccine Safety Datalink population who received a DTaP vaccination during the period from 2002 through 2006. Medically attended local reactions to the DTaP vaccine were presumptively identified from administrative data and were confirmed by medical record review. RESULTS: Among the 233 616 children in the study population, 1017 (0.4%) had a confirmed medically attended local reaction to the fifth dose of the DTaP vaccine. The rate of those reactions was significantly higher with vaccinations given in the arm (47.4 per 10 000 vaccinations) compared with vaccinations given in the thigh (32.1 per 10 000 vaccinations) (P < .001). In a multivariable analysis adjusted for age, gender, and study site, children vaccinated in the arm had a 78% higher risk of a local reaction (relative risk: 1.78 [95% confidence interval: 1.43–2.21]). CONCLUSIONS: Local reactions to the fifth dose of the DTaP vaccine that require medical evaluation are uncommon, but the risk of those reactions is significantly higher when the vaccine is injected in the arm. These findings suggest that the thigh should be considered as an acceptable site of injection for this vaccination.

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%).

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.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.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.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.

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.