Vaccination Timeliness Among US Children Aged 0-19 Months, National Immunization Survey-Child 2011-2021.

Importance: Delays in receiving vaccinations lead to greater vaccine-preventable disease risk. Timeliness of receipt of recommended vaccinations is not routinely tracked in the US, either overall or for populations that have known barriers to accessing routine health care, including lower-income families and children. Objective: To measure vaccination timeliness among US children aged 0 to 19 months, overall and by socioeconomic indicators. Design, Setting, and Participants: This serial, cross-sectional study analyzed nationally representative data from the 2011 to 2021 National Immunization Survey-Child (NIS-Child), an annual survey of parents, with immunization histories collected from clinicians administering vaccines. The 2020 and 2021 surveys largely reflected vaccinations in the US before the COVID-19 pandemic. Study participants included US children surveyed at ages 19 to 35 months. Data were analyzed from January to August 2023. Exposure: Survey year. Main Outcomes and Measures: The primary outcomes were average days undervaccinated (ADU) and percentage of children who received all vaccine doses on time (ie, 0 days undervaccinated) for the combined 7-vaccine series up to age 19 months. The mean adjusted annual change in on-time vaccination by socioeconomic indicators was calculated by use of multivariable log-linked binomial regression models. Results: The surveys included 179 154 children (92 248 boys [51.2%]); 74 479 (31.4%, weighted) lived above the federal poverty level with more than $75 000 in annual family income, 58 961 (32.4%) lived at or above the poverty level with $75 000 or less in annual family income, and 39 564 (30.2%) lived below the poverty level. Overall, the median (IQR) ADU for the combined 7-vaccine series in the US decreased from 22.3 (0.4-71.5) days in the 2011 survey to 11.9 (0.0-55.5) days in the 2021 survey. The prevalence of on-time receipt of the combined 7-vaccine series increased from 22.5% (95% CI, 21.4%-23.6%) to 35.6% (95% CI, 34.2%-37.0%). Although children with more than $75 000 in annual family income had a 4.6% (95% CI, 4.0%-5.2%) mean annual increase in on-time vaccination, the mean annual increase was 2.8% (95% CI, 2.0%-3.6%) for children living at or above the poverty level with $75 000 or less in annual family income and 2.0% (95% CI, 1.0%-3.0%) for children living below the poverty level. Conclusions and Relevance: In this cross-sectional study of NIS-Child data, improvements in vaccination timeliness were observed from the 2011 to the 2021 survey. However, widening disparities by socioeconomic indicators signal that increased efforts to facilitate timely vaccination among children in lower-income families are needed.

A Randomized Control Trial of a Digital Health Tool for Safer Firearm and Medication Storage for Patients with Suicide Risk.

Most patients with suicide risk do not receive recommendations to reduce access to lethal means due to a variety of barriers (e.g., lack of provider time, training). Determine if highly efficient population-based EHR messaging to visit the Lock to Live (L2L) decision aid impacts patient-reported storage behaviors. Randomized trial. Integrated health care system serving Denver, CO. Served by primary care or mental health specialty clinic in the 75-99.5th risk percentile on a suicide attempt or death prediction model. Lock to Live (L2L) is a web-based decision aid that incorporates patients' values into recommendations for safe storage of lethal means, including firearms and medications. Anonymous survey that determined readiness to change: pre-contemplative (do not believe in safe storage), contemplative (believe in safe storage but not doing it), preparation (planning storage changes) or action (safely storing). There were 21,131 patients randomized over a 6-month period with a 27% survey response rate. Many (44%) had access to a firearm, but most of these (81%) did not use any safe firearm storage behaviors. Intervention patients were more likely to be categorized as preparation or action compared to controls for firearm storage (OR = 1.30 (1.07-1.58)). When examining action alone, there were no group differences. There were no statistically significant differences for any medication storage behaviors. Selection bias in those who responded to survey. Efficiently sending an EHR invitation message to visit L2L encouraged patients with suicide risk to consider safer firearm storage practices, but a stronger intervention is needed to change storage behaviors. Future studies should evaluate whether combining EHR messaging with provider nudges (e.g., brief clinician counseling) changes storage behavior.ClinicalTrials.gov: NCT05288517.

The association between buprenorphine treatment duration and mortality: a multi-site cohort study of people who discontinued treatment.

BACKGROUND AND AIMS: Buprenorphine is an effective medication for opioid use disorder that reduces mortality; however, many patients are not retained in buprenorphine treatment, and an optimal length of treatment after which patients can safely discontinue treatment has not been identified. This study measured the association between buprenorphine treatment duration and all-cause mortality among patients who discontinued treatment. Secondary objectives were to measure the association between treatment duration and drug overdose and opioid-related overdoses. DESIGN: Multi-site cohort study. SETTING: Eight US health systems. PARTICIPANTS: Patients who initiated and discontinued buprenorphine treatment between 1 January 2012 and 31 December 2018 (n = 6550). Outcomes occurring after patients discontinued buprenorphine treatment were compared between patients who initiated and discontinued treatment after 8-30, 31-90, 91-180, 181-365 and > 365 days. MEASUREMENTS: Covariate data were obtained from electronic health records (EHRs). Mortality outcomes were derived from EHRs and state vital statistics. Non-fatal opioid and drug overdoses were obtained from diagnostic codes. Four sites provided cause-of-death data to identify fatal drug and opioid-related overdoses. Adjusted frailty regression was conducted on a propensity-weighted cohort to assess associations between duration of the final treatment episode and outcomes. FINDINGS: The mortality rate after buprenorphine treatment was 1.82 per 100 person-years (n = 191 deaths). In regression analyses with > 365 days as the reference group, treatment duration was not associated with all-cause mortality and drug overdose (P > 0.05 for both). However, compared with > 365 days of treatment, 91-180 days of treatment was associated with increased opioid overdose risk (hazard ratio = 2.94, 95% confidence interval = 1.11-7.79). CONCLUSIONS: Among patients who discontinue buprenorphine treatment, there appears to be no treatment duration period associated with a reduced risk for all-cause mortality. Patients who discontinue buprenorphine treatment after 91-180 days appear to be at heightened risk for opioid overdose compared with patients who discontinue after > 365 days of treatment.

Development and implementation of a prescription opioid registry across diverse health systems.

Objective: Develop and implement a prescription opioid registry in 10 diverse health systems across the US and describe trends in prescribed opioids between 2012 and 2018. Materials and Methods: Using electronic health record and claims data, we identified patients who had an outpatient fill for any prescription opioid, and/or an opioid use disorder diagnosis, between January 1, 2012 and December 31, 2018. The registry contains distributed files of prescription opioids, benzodiazepines and other select medications, opioid antagonists, clinical diagnoses, procedures, health services utilization, and health plan membership. Rates of outpatient opioid fills over the study period, standardized to health system demographic distributions, are described by age, gender, and race/ethnicity among members without cancer. Results: The registry includes 6 249 710 patients and over 40 million outpatient opioid fills. For the combined registry population, opioid fills declined from a high of 0.718 per member-year in 2013 to 0.478 in 2018, and morphine milligram equivalents (MMEs) per fill declined from 985 MMEs per fill in 2012 to 758 MMEs in 2018. MMEs per member declined from 692 MMEs per member in 2012 to 362 MMEs per member in 2018. Conclusion: This study established a population-based opioid registry across 10 diverse health systems that can be used to address questions related to opioid use. Initial analyses showed large reductions in overall opioid use per member among the combined health systems. The registry will be used in future studies to answer a broad range of other critical public health issues relating to prescription opioid use.

Developing an algorithm across integrated healthcare systems to identify a history of cancer using electronic medical records.

OBJECTIVE: Tumor registries in integrated healthcare systems (IHCS) have high precision for identifying incident cancer but often miss recently diagnosed cancers or those diagnosed outside of the IHCS. We developed an algorithm using the electronic medical record (EMR) to identify people with a history of cancer not captured in the tumor registry to identify adults, aged 40-65 years, with no history of cancer. MATERIALS AND METHODS: The algorithm was developed at Kaiser Permanente Colorado, and then applied to 7 other IHCS. We included tumor registry data, diagnosis and procedure codes, chemotherapy files, oncology encounters, and revenue data to develop the algorithm. Each IHCS adapted the algorithm to their EMR data and calculated sensitivity and specificity to evaluate the algorithm's performance after iterative chart review. RESULTS: We included data from over 1.26 million eligible people across 8 IHCS; 55 601 (4.4%) were in a tumor registry, and 44848 (3.5%) had a reported cancer not captured in a registry. The common attributes of the final algorithm at each site were diagnosis and procedure codes. The sensitivity of the algorithm at each IHCS was 90.65%-100%, and the specificity was 87.91%-100%. DISCUSSION: Relying only on tumor registry data would miss nearly half of the identified cancers. Our algorithm was robust and required only minor modifications to adapt to other EMR systems. CONCLUSION: This algorithm can identify cancer cases regardless of when the diagnosis occurred and may be useful for a variety of research applications or quality improvement projects around cancer care.

The Kaiser Permanente Research Bank Cancer Cohort: a collaborative resource to improve cancer care and survivorship.

BACKGROUND: The Kaiser Permanente Research Bank (KPRB) is collecting biospecimens and surveys linked to electronic health records (EHR) from approximately 400,000 adult KP members. Within the KPRB, we developed a Cancer Cohort to address issues related to cancer survival, and to understand how genetic, lifestyle and environmental factors impact cancer treatment, treatment sequelae, and prognosis. We describe the Cancer Cohort design and implementation, describe cohort characteristics after 5 years of enrollment, and discuss future directions. METHODS: Cancer cases are identified using rapid case ascertainment algorithms, linkage to regional or central tumor registries, and direct outreach to KP members with a history of cancer. Enrollment is primarily through email invitation. Participants complete a consent form, survey, and donate a blood or saliva sample. All cancer types are included. RESULTS: As of December 31, 2020, the cohort included 65,225 cases (56% female, 44% male) verified in tumor registries. The largest group was diagnosed between 60 and 69 years of age (31%) and are non-Hispanic White (83%); however, 10,076 (16%) were diagnosed at ages 18-49 years, 4208 (7%) are Hispanic, 3393 (5%) are Asian, and 2389 (4%) are Black. The median survival time is 14 years. Biospecimens are available on 98% of the cohort. CONCLUSIONS: The KPRB Cancer Cohort is designed to improve our understanding of treatment efficacy and factors that contribute to long-term cancer survival. The cohort's diversity - with respect to age, race/ethnicity and geographic location - will facilitate research on factors that contribute to cancer survival disparities.

The Childhood Vaccination Schedule and the Lack of Association With Type 1 Diabetes.

OBJECTIVES: Safety studies assessing the association between the entire recommended childhood immunization schedule and autoimmune diseases, such as type 1 diabetes mellitus (T1DM), are lacking. To examine the association between the recommended immunization schedule and T1DM, we conducted a retrospective cohort study of children born between 2004 and 2014 in 8 US health care organizations that participate in the Vaccine Safety Datalink. METHODS: Three measures of the immunization schedule were assessed: average days undervaccinated (ADU), cumulative antigen exposure, and cumulative aluminum exposure. T1DM incidence was identified by International Classification of Disease codes. Cox proportional hazards models were used to analyze associations between the 3 exposure measures and T1DM incidence. Adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs) were calculated. Models were adjusted for sex, race and ethnicity, birth year, mother's age, birth weight, gestational age, number of well-child visits, and study site. RESULTS: In a cohort of 584 171 children, the mean ADU was 38 days, the mean cumulative antigen exposure was 263 antigens (SD = 54), and the mean cumulative aluminum exposure was 4.11 mg (SD = 0.73). There were 1132 incident cases of T1DM. ADU (aHR = 1.01; 95% CI, 0.99-1.02) and cumulative antigen exposure (aHR = 0.98; 95% CI, 0.97-1.00) were not associated with T1DM. Cumulative aluminum exposure >3.00 mg was inversely associated with T1DM (aHR = 0.77; 95% CI, 0.60-0.99). CONCLUSIONS: The recommended schedule is not positively associated with the incidence of T1DM in children. These results support the safety of the recommended childhood immunization schedule.

Sensitivity analyses of unmeasured and partially-measured confounders using multiple imputation in a vaccine safety study.

PURPOSE: Sensitivity analyses have played an important role in pharmacoepidemiology studies using electronic health records data. Despite the existence of quantitative bias analysis in pharmacoepidemiologic studies, simultaneously adjusting for unmeasured and partially measured confounders is challenging in vaccine safety studies. Our objective was to develop a flexible approach for conducting sensitivity analyses of unmeasured and partially-measured confounders concurrently for a vaccine safety study. METHODS: We derived conditional probabilities for an unmeasured confounder based on bias parameters, used these conditional probabilities and Monte Carlo simulations to impute the unmeasured confounder, and re-constructed the analytic datasets as if the unmeasured confounder had been observed. We simultaneously imputed a partially measured confounder using a prediction model. We considered unmeasured breastfeeding and partially measured family history of Type 1 diabetes (T1DM) in a study examining the association between exposure to rotavirus vaccination and T1DM. RESULTS: Before sensitivity analyses, the hazard ratios (HR) were 1.50 (95% CI, 0.81-2.77) for those partially exposed and 1.03 (95% CI, 0.62-1.72) for those fully exposed with unexposed children as the referent group. When breastfeeding and family history of T1DM were adjusted, the HR was 1.55 (95% CI, 0.84-2.87) for the partially exposed group; the HR was 0.98 (95% CI, 0.58-1.63) for the fully exposed group. CONCLUSIONS: We conclude that adjusting for unmeasured breastfeeding and partially measured family history of T1DM did not alter the conclusion that there was no evidence of association between rotavirus vaccination and developing T1DM. This novel approach allows for simultaneous adjustment for multiple unmeasured and partially-measured confounders.

Association Between Rotavirus Vaccination and Type 1 Diabetes in Children.

Importance: Because rotavirus infection is a hypothesized risk factor for type 1 diabetes, live attenuated rotavirus vaccination could increase or decrease the risk of type 1 diabetes in children. Objective: To examine whether there is an association between rotavirus vaccination and incidence of type 1 diabetes in children aged 8 months to 11 years. Design, Setting, and Participants: A retrospective cohort study of 386 937 children born between January 1, 2006, and December 31, 2014, was conducted in 7 US health care organizations of the Vaccine Safety Datalink. Eligible children were followed up until a diagnosis of type 1 diabetes, disenrollment, or December 31, 2017. Exposures: Rotavirus vaccination for children aged 2 to 8 months. Three exposure groups were created. The first group included children who received all recommended doses of rotavirus vaccine by 8 months of age (fully exposed to rotavirus vaccination). The second group had received some, but not all, recommended rotavirus vaccines (partially exposed to rotavirus vaccination). The third group did not receive any doses of rotavirus vaccines (unexposed to rotavirus vaccination). Main Outcomes and Measures: Incidence of type 1 diabetes among children aged 8 months to 11 years. Type 1 diabetes was identified by International Classification of Diseases codes: 250.x1, 250.x3, or E10.xx in the outpatient setting. Cox proportional hazards regression models were used to analyze time to type 1 diabetes incidence from 8 months to 11 years. Hazard ratios and 95% CIs were calculated. Models were adjusted for sex, race/ethnicity, birth year, mother's age, birth weight, gestational age, number of well-child visits, and Vaccine Safety Datalink site. Results: In a cohort of 386 937 children (51.1% boys and 41.9% non-Hispanic white), 360 169 (93.1%) were fully exposed to rotavirus vaccination, 15 765 (4.1%) were partially exposed to rotavirus vaccination, and 11 003 (2.8%) were unexposed to rotavirus vaccination. Children were followed up a median of 5.4 years (interquartile range, 3.8-7.8 years). The total person-time follow-up in the cohort was 2 253 879 years. There were 464 cases of type 1 diabetes in the cohort, with an incidence rate of 20.6 cases per 100 000 person-years. Compared with children unexposed to rotavirus vaccination, the adjusted hazard ratio was 1.03 (95% CI, 0.62-1.72) for children fully exposed to rotavirus vaccination and 1.50 (95% CI, 0.81-2.77) for children partially exposed to rotavirus vaccination. Conclusions and Relevance: The findings of this study suggest that rotavirus vaccination does not appear to be associated with type 1 diabetes in children.

Predictors of Long-Term Survival among High-Grade Serous Ovarian Cancer Patients.

BACKGROUND: Relatively little is known about factors associated with long-term survival (LTS) following a diagnosis of ovarian cancer. METHODS: We conducted a retrospective study of high-grade serous ovarian cancer (HGSOC) to explore predictors of LTS (defined as ≥7 years of survival) using electronic medical record data from a network of integrated health care systems. Multivariable logistic regression with forward selection was used to compare characteristics of women who survived ≥7 years after diagnosis (n = 148) to those who died within 7 years of diagnosis (n = 494). RESULTS: Our final model included study site, age, stage at diagnosis, CA-125, comorbidity score, receipt of chemotherapy, BMI, and four separate comorbid conditions: weight loss, depression, hypothyroidism, and liver disease. Of these, only younger age, lower stage, and depression were statistically significantly associated with LTS. CONCLUSIONS: We did not identify any new characteristics associated with HGSOC survival. IMPACT: Prognosis of ovarian cancer generally remains poor. Large, pooled studies of ovarian cancer are needed to identify characteristics that may improve survival.

Analyzing self-controlled case series data when case confirmation rates are estimated from an internal validation sample.

Vaccine safety studies are often electronic health record (EHR)-based observational studies. These studies often face significant methodological challenges, including confounding and misclassification of adverse event. Vaccine safety researchers use self-controlled case series (SCCS) study design to handle confounding effect and employ medical chart review to ascertain cases that are identified using EHR data. However, for common adverse events, limited resources often make it impossible to adjudicate all adverse events observed in electronic data. In this paper, we considered four approaches for analyzing SCCS data with confirmation rates estimated from an internal validation sample: (1) observed cases, (2) confirmed cases only, (3) known confirmation rate, and (4) multiple imputation (MI). We conducted a simulation study to evaluate these four approaches using type I error rates, percent bias, and empirical power. Our simulation results suggest that when misclassification of adverse events is present, approaches such as observed cases, confirmed case only, and known confirmation rate may inflate the type I error, yield biased point estimates, and affect statistical power. The multiple imputation approach considers the uncertainty of estimated confirmation rates from an internal validation sample, yields a proper type I error rate, largely unbiased point estimate, proper variance estimate, and statistical power.

The safety of live attenuated influenza vaccine in children and adolescents 2 through 17 years of age: A Vaccine Safety Datalink study.

PURPOSE: To evaluate the safety of live attenuated influenza vaccine (LAIV) in children 2 through 17 years of age. METHODS: The study was conducted in 6 large integrated health care organizations participating in the Vaccine Safety Datalink (VSD). Trivalent LAIV safety was assessed in children who received LAIV between September 1, 2003 and March 31, 2013. Eighteen pre-specified adverse event groups were studied, including allergic, autoimmune, neurologic, respiratory, and infectious conditions. Incident rate ratios (IRRs) were calculated for each adverse event, using self-controlled case series analyses. For adverse events with a statistically significant increase in risk, or an IRR > 2.0 regardless of statistical significance, manual medical record review was performed to confirm case status. RESULTS: During the study period, 396 173 children received 590 018 doses of LAIV. For 13 adverse event groups, there was no significant increased risk of adverse events following LAIV. Five adverse event groups (anaphylaxis, syncope, Stevens-Johnson syndrome, adverse effect of drug, and respiratory failure) met criteria for manual medical record review. After review to confirm cases, 2 adverse event groups remained significantly associated with LAIV: anaphylaxis and syncope. One confirmed case of anaphylaxis was observed following LAIV, a rate of 1.7 per million LAIV doses. Five confirmed cases of syncope were observed, a rate of 8.5 per million doses. CONCLUSIONS: In a study of trivalent LAIV safety in a large cohort of children, few serious adverse events were detected. Anaphylaxis and syncope occurred following LAIV, although rarely. These data provide reassurance regarding continued LAIV use.

Developing an Algorithm to Identify History of Cancer Using Electronic Medical Records.

INTRODUCTION/OBJECTIVE: The objective of this study was to develop an algorithm to identify Kaiser Permanente Colorado (KPCO) members with a history of cancer. BACKGROUND: Tumor registries are used with high precision to identify incident cancer, but are not designed to capture prevalent cancer within a population. We sought to identify a cohort of adults with no history of cancer, and thus, we could not rely solely on the tumor registry. METHODS: We included all KPCO members between the ages of 40-75 years who were continuously enrolled during 2013 (N=201,787). Data from the tumor registry, chemotherapy files, inpatient and outpatient claims were used to create an algorithm to identify members with a high likelihood of cancer. We validated the algorithm using chart review and calculated sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) for occurrence of cancer. FINDINGS: The final version of the algorithm achieved a sensitivity of 100 percent and specificity of 84.6 percent for identifying cancer. If we relied on the tumor registry alone, 47 percent of those with a history of cancer would have been missed. DISCUSSION: Using the tumor registry alone to identify a cohort of patients with prior cancer is not sufficient. In the final version of the algorithm, the sensitivity and PPV were improved when a diagnosis code for cancer was required to accompany oncology visits or chemotherapy administration. CONCLUSION: Electronic medical record (EMR) data can be used effectively in combination with data from the tumor registry to identify health plan members with a history of cancer.

Natural history of left ventricular ejection fraction in patients with heart failure.

BACKGROUND: Patients with heart failure (HF) are typically designated as having reduced or preserved ejection fraction (HFREF, HFPEF) because of the importance of left ventricular ejection fraction (LVEF) on therapeutic decisions and prognosis. Such designations are not necessarily static, yet few data exist to describe the natural history of LVEF over time. METHODS AND RESULTS: We identified 2413 patients from Kaiser Permanente Colorado with a primary discharge diagnosis of HF between January 1, 2001, and December 31, 2008, who had ≥2 LVEF measurements separated by ≥30 days. We used multi-state Markov modeling to examine transitions among HFREF, HFPEF, and death. We observed a total of 8183 transitions. Women were more likely than men to transition from HFREF to HFPEF (hazard ratio, 1.85; 95% confidence interval, 1.38-2.47). Patients who were adherent to ß-blockers were more likely to transition from HFREF to HFPEF (hazard ratio, 1.53; 95% confidence interval, 1.10-2.13) compared with patients who were nonadherent to ß-blockers, whereas angiotensin-converting enzyme or angiotensin II receptor blocker adherence was not associated with LVEF transitions. Patients who had a previous myocardial infarction were more likely to transition from HFPEF to HFREF (hazard ratio, 1.75; 95% confidence interval, 1.26-2.42). CONCLUSIONS: In this cohort of patients with HF, LVEF is a dynamic factor related to sex, coexisting conditions, and drug therapy. These findings have implications for left ventricular systolic function ascertainment in patients with HF and support evidence-based therapy use, especially ß-blockers.

Patterns of beta-blocker intensification in ambulatory heart failure patients and short-term association with hospitalization.

BACKGROUND: In response to the short-term negative inotropic and chronotropic effects of ß-blockers, heart failure (HF) guidelines recommend initiating ß-blockers at low dose with gradual uptitration as tolerated to doses used in clinical trials. However, patterns and safety of ß-blocker intensification in routine practice are poorly described. METHODS: We described ß-blocker intensification among Kaiser Colorado enrollees with a primary discharge diagnosis of HF between 2001-2009. We then assessed ß-blocker intensification in the 30 days prior to first hospital readmission for cases compared to the same time period following index hospitalization for non-rehospitalized matched controls. In separate analysis of the subgroup initiated on ß-blocker after index hospital discharge, we compared adjusted rates of 30-day hospitalization following initiation of high versus low dose ß-blocker. RESULTS: Among 3,227 patients, median age was 76 years and 37% had ejection fraction ≤ 40% (LVSD). During a median follow up of 669 days, 14% were never on ß-blocker, 21% were initiated on ß-blocker, 43% were discharged on ß-blocker but never uptitrated, and 22% had discharge ß-blocker uptitrated; 63% were readmitted and 49% died. ß-blocker intensification occurred in the 30 days preceding readmission for 39 of 1,674 (2.3%) readmitted cases compared to 27 (1.6%) of matched controls (adjusted OR 1.36, 95% CI 0.81-2.27). Among patients initiated on therapy, readmission over the subsequent 30 days occurred in 6 of 155 (3.9%) prescribed high dose and 9 of 513 (1.8%) prescribed low dose ß-blocker (adjusted OR 3.10, 95% CI 1.02-9.40). For the subgroup with LVSD, findings were not significantly different. CONCLUSION: While ß-blockers were intensified in nearly half of patients following hospital discharge and high starting dose was associated with increased readmission risk, the prevailing finding was that readmission events were rarely preceded by ß-blocker intensification. These data suggest that ß-blocker intensification is not a major precipitant of hospitalization, provided recommended dosing is followed.

Health literacy and outcomes among patients with heart failure.

CONTEXT: Little is known about the effects of low health literacy among patients with heart failure, a condition that requires self-management and frequent interactions with the health care system. OBJECTIVE: To evaluate the association between low health literacy and all-cause mortality and hospitalization among outpatients with heart failure. DESIGN, SETTING, AND PATIENTS: Retrospective cohort study conducted at Kaiser Permanente Colorado, an integrated managed care organization. Outpatients with heart failure were identified between January 2001 and May 2008, were surveyed by mail, and underwent follow-up for a median of 1.2 years. Health literacy was assessed using 3 established screening questions and categorized as adequate or low. Responders were excluded if they did not complete at least 1 health literacy question or if they did not have at least 1 year of enrollment prior to the survey date. MAIN OUTCOME MEASURES: All-cause mortality and all-cause hospitalization. RESULTS: Of the 2156 patients surveyed, 1547 responded (72% response rate). Of 1494 included responders, 262 (17.5%) had low health literacy. Patients with low health literacy were older, of lower socioeconomic status, less likely to have at least a high school education, and had higher rates of coexisting illnesses. In multivariable Cox regression, low health literacy was independently associated with higher mortality (unadjusted rate, 17.6% vs 6.3%; adjusted hazard ratio, 1.97 [95% confidence interval, 1.3-2.97]; P = .001) but not hospitalization (unadjusted rate, 30.5% vs 23.2%; adjusted hazard ratio, 1.05 [95% confidence interval, 0.8-1.37]; P = .73). CONCLUSION: Among patients with heart failure in an integrated managed care organization, low health literacy was significantly associated with higher all-cause mortality.

Adverse events after stopping clopidogrel in post-acute coronary syndrome patients: Insights from a large integrated healthcare delivery system.

BACKGROUND: A prior study from the Veterans Health Administration found a clustering of cardiovascular events after clopidogrel cessation. We sought to confirm and expand these findings. METHODS AND RESULTS: This was a retrospective cohort study of 2017 patients with acute coronary syndrome discharged on clopidogrel from an integrated health care delivery system. Rates of all-cause mortality or acute myocardial infarction (MI) within 1 year after stopping clopidogrel were assessed among patients who did not have an event before stopping clopidogrel. Death/MI occurred in 4.3% (n=71) of patients. The rates of death/MI were 3.07, 1.62, 0.70, and 0.95 per 10 000 patient-days for the time intervals of 0 to 90, 91 to 180, 181 to 270, and 271 to 360 days after stopping clopidogrel. In multivariable analysis, the 0- to 90-day interval after stopping clopidogrel was associated with higher risk of death/MI (incidence rate ratio, 2.74; 95% confidence interval, 1.69 to 4.44) compared with 91- to 360-day interval. There was a similar trend of increased events after stopping clopidogrel for various subgroups (women versus men, medical therapy versus percutaneous coronary intervention, stent type, and > or =6 months or <6 months of clopidogrel treatment). Among patients taking clopidogrel but stopping ACE inhibitor medications, the event rates were similar in the 0- to 90-day versus the 91- to 360-day interval (2.67 versus 2.91 per 10 000 patient-days; P=0.91). CONCLUSIONS: We observed a clustering of adverse events in the 0 to 90 days after stopping clopidogrel. This clustering of events was not present among patients stopping ACE inhibitors. These findings are consistent with a possible rebound platelet hyper-reactivity after stopping clopidogrel and additional platelet studies are needed to confirm this effect.

Association of longitudinal measures of hemoglobin and outcomes after hospitalization for heart failure.

BACKGROUND: Cross-sectional assessments of hemoglobin (Hb) are associated with mortality in patients with heart failure (HF). Our objectives were to characterize patterns of change in Hb over time in patients with HF and to evaluate the relationship between longitudinal measures of Hb and adverse outcomes. METHODS: The study included 2,478 patients with a primary discharge diagnosis of HF from January 2001 to December 2006. Outcomes included time to death and time to death or HF hospitalization. The association between baseline Hb and outcomes was evaluated using multivariable Cox regression. The longitudinal association was evaluated using a time-dependent Hb predictor variable and using anemia trajectory groups. RESULTS: For a median of 475 days, baseline Hb was associated with a trend toward increased mortality (hazard ratio [HR] 1.02, 95% CI 0.99-1.06 per g/dL decline). With a time-dependent approach, the magnitude of the association was greater (HR 1.35, 95% CI 1.30-1.39 per g/dL decline). In trajectory analysis, 35% of the cohort had variable patterns of anemia. Persistently low Hb (HR 1.65, 95% CI 1.27-2.14) and a progressive decline in Hb (HR 1.54, 95% CI 1.16-2.05) were associated with increased mortality risk. Patients with recovery of anemia had similar outcomes as those patients who are persistently nonanemic. Results were similar for the composite of death or HF hospitalization. CONCLUSIONS: Variability in Hb over time is common in patients with HF, and declining Hb is associated with a poor prognosis. Longitudinal characterization of Hb levels has greater prognostic significance than a single measurement. Systematic surveillance of Hb levels may help identify high-risk patients with heart failure.