The Impact of Primary Care Practitioner Intervention as an Adjunct to a Diabetes Case Management System.

Objective The objective of this study was to assess whether additional primary care practitioner (PCP) contacts beyond the intake visit are associated with reduced hemoglobin A1c in patients with type 2 diabetes actively engaged in the Kaiser Permanente case management system. Methods This retrospective cohort study using the Kaiser Permanente electronic health record explored the effect of enhanced PCP contact among adult patients with type 2 diabetes actively working with diabetes case managers (defined as ≥ 4 case manager contacts during the study period). Results A total of 837 patients met the inclusion and exclusion criteria. On average, patients with the highest PCP contact, < 7 contacts, had Ac levels 0.53 lower than those in the lowest PCP contact quartile, < 3 contacts (p = 0.0007). A1c decreased an average of 0.20 when the PCP contact quartile was one quartile higher (p = 0.0004). Holding the baseline A1c constant, the A1c decreased an average of 0.15 when the PCP contact quartile was one quartile higher (p = 0.0024). A1c change was significantly correlated with baseline A1c; A1c decreased by 0.64 more as the baseline A1c level increased by 1 (p < 0.0001). Additionally, the A1c level decreased by 0.02 more when patient age increased by 1 (p < 0.0001). Metformin use was associated with a decrease of A1c by 0.40 (p = 0.0057), whereas insulin use was associated with an increase of A1c by 0.29 (p = 0.0280). Conclusion In summary, a significant reduction was observed in A1c in patients with increased PCP contacts. This effect was seen in patients already receiving recommended case manager support.

Hepatitis B vaccine and risk of acute myocardial infarction among individuals with diabetes mellitus.

PURPOSE: A pre-licensure clinical trial of a two-dose cytosine phosphoguanine adjuvanted hepatitis B vaccine (HEPLISAV-B® [Dynavax, USA]; HepB-CpG vaccine) found an unanticipated numerical imbalance in acute myocardial infarction (AMI) compared to recipients of a three-dose aluminum adjuvanted hepatitis B vaccine (ENGERIX-B® [GlaxoSmithKline, Belgium]; HepB-alum vaccine). A post-licensure study was required to compare AMI rates among recipients of HepB-CpG vaccine and HepB-alum vaccine. Individuals with diabetes mellitus (DM), who are at higher risk of AMI, comprise more than half of the post-licensure study cohort. To inform the ongoing post-licensure study, we examined the association between AMI and receipt of HepB-alum vaccine in individuals with DM. METHODS: We conducted a case-control study nested in a cohort of individuals with DM ages ≥40 years at Kaiser Permanente Southern California using electronic health records. AMI cases from 2012 to 2017 were identified by principal discharge diagnosis and matched 1:1 with randomly selected controls. The adjusted odds ratio (aOR) for receipt of ≥1 HepB-alum vaccine dose was compared for AMI cases and controls using conditional logistic regression. We subsequently performed the same matched case-control analysis stratified by year. RESULTS: Of 8138 matched case-control pairs, 17.4% of cases and 15.0% of controls received HepB-alum vaccine. The aOR of HepB-alum vaccination comparing cases and controls was 0.97 (95% confidence interval 0.87-1.08). Similarly, there was no significant association between HepB-alum vaccine and AMI in any of the study years. CONCLUSIONS: HepB-alum vaccination was not associated with AMI in individuals with DM. This finding will provide contextual insight for the ongoing post-licensure study of HepB-CpG vaccine.

Anticoagulant treatment satisfaction with warfarin and direct oral anticoagulants for venous thromboembolism.

Treatment options for patients with venous thromboembolism (VTE) include warfarin and direct oral anticoagulants (DOACs). Although DOACs are easier to administer than warfarin and do not require routine laboratory monitoring, few studies have directly assessed whether patients are more satisfied with DOACs. We surveyed adults from two large integrated health systems taking DOACs or warfarin for incident VTE occurring between January 1, 2015 and June 30, 2018. Treatment satisfaction was assessed using the validated Anti-Clot Treatment Scale (ACTS), divided into the ACTS Burdens and ACTS Benefits scores; higher scores indicate greater satisfaction. Mean treatment satisfaction was compared using multivariable linear regression, adjusting for patient demographic and clinical characteristics. The effect size of the difference in means was calculated using a Cohen's d (0.20 is considered a small effect and ≥ 0.80 is considered large). We surveyed 2217 patients, 969 taking DOACs and 1248 taking warfarin at the time of survey. Thirty-one point five percent of the cohort was aged ≥ 75 years and 43.1% were women. DOAC users were on average more satisfied with anticoagulant treatment, with higher adjusted mean ACTS Burdens (50.18 v. 48.01, p < 0.0001) and ACTS Benefits scores (10.21 v. 9.84, p = 0.046) for DOACs vs. warfarin, respectively. The magnitude of the difference was small (Cohen's d of 0.29 for ACTS Burdens and 0.12 for ACTS Benefits). Patients taking DOACs for venous thromboembolism were on average more satisfied with anticoagulant treatment than were warfarin users, although the magnitude of the difference was small.

Insomnia and Susceptibility to Depressive Symptoms and Fatigue in Diverse Breast Cancer Survivors.

Background: Nearly 40% of breast cancer survivors have insomnia, yet, information how this condition affects their quality of life is lacking. We examined the association between insomnia and depressive symptoms and fatigue in breast cancer survivors. Methods: Participants were recruited from a community health plan. We conducted a cross-sectional analysis to examine the association between current insomnia (using Insomnia Severity Index [ISI]) and current depressive symptoms (using Inventory of Depressive Symptomology [IDS]) and fatigue (using Fatigue Symptom Inventory [FSI]) in 315 breast cancer survivors who did not have major depressive disorder. We calculated odds ratios (ORs) and 95% confidence intervals (CIs) using multivariable logistic regression. Results: The cohort included 30% minority women whose median time since breast cancer diagnosis was 6 years. Survivors with current insomnia symptoms (ISI ≥8) had a sixfold greater odds of current depressive symptoms (IDS >14, OR = 5.98, 95% CI: 3.04-11.76), after adjusting for lifetime insomnia history (OR = 2.01, 95% CI: 1.03-3.94) and perceived stress (OR = 6.37, 95% CI: 2.48-16.32). Insomnia symptoms were markedly associated with moderate fatigue (FSI >3, OR = 5.02, 95% CI: 2.66-9.44). Ever use of antidepressants or sleep medications post-breast cancer diagnosis was not associated with lower odds of current depressive symptoms or feeling fatigued in those with insomnia symptoms. Conclusion: Current insomnia symptoms were strongly correlated with current depressive symptoms and fatigue. Survivorship care plans should consider incorporating insomnia screening to that may potentially enhance quality of life domains.

Recurrent Atherosclerotic Cardiovascular Event Rates Differ Among Patients Meeting the Very High Risk Definition According to Age, Sex, Race/Ethnicity, and Socioeconomic Status.

Background The risk for atherosclerotic cardiovascular disease (ASCVD) events may differ by sociodemographic factors among patients meeting the definition of very high risk according to the 2018 American Heart Association/American College of Cardiology cholesterol guideline, leading to treatment disparities. We estimated the risk for recurrent ASCVD events among adults meeting the definition of very high risk by age, sex, race/ethnicity, and socioeconomic status in a US integrated healthcare system. Methods and Results The study cohort included Kaiser Permanente Southern California members aged ≥21 years with a history of clinical ASCVD on September 30, 2009. Very high risk for recurrent ASCVD was defined by a history of ≥2 major ASCVD events or a history of 1 major event along with ≥2 high-risk conditions. Patients were followed through 2015 for a first recurrent ASCVD event. Of 77 101 patients with ASCVD, 50.8% met the definition for very high risk. Among patients meeting the definition of very high risk, recurrent ASCVD rates were higher in older (>75 years) versus younger patients (21-40 years) (sex-adjusted hazard ratio [HR] [95% CI] 1.85; 1.23-2.79), non-Hispanic Black patients versus non-Hispanic White patients (age-, sex-adjusted HR, 1.32; 1.23-1.41), those who lived in neighborhoods with lower (<$35k) versus higher annual household income (≥$80k) (HR, 1.20; 1.11-1.30), or with lower (≥31.2%) versus higher education levels (<8.8% high school or lower) (HR, 1.26; 1.19-1.34). Conclusions Disparities in the risk for recurrent ASCVD events were present across sociodemographic factors among very high risk patients. The addition of sociodemographic factors to current definitions of very high risk could reduce health disparities.

Trends in statin utilization among adults with severe peripheral artery disease including critical limb ischemia in an integrated healthcare delivery system.

Evidence suggests that statin therapy in patients with peripheral artery disease (PAD) is beneficial yet use remains suboptimal. We examined trends in statin use, intensity, and discontinuation among adults aged ⩾ 40 years with incident severe PAD and a subset with critical limb ischemia (CLI) between 2002 and 2015 within an integrated healthcare delivery system. Discontinuation of statin therapy was defined as the first 90-day gap in treatment within 1 year following PAD diagnosis. We identified 11,059 patients with incident severe PAD: 31.1% (n = 3442) with CLI and 68.9% (n = 7617) without CLI. Mean (SD) age was 68.6 (11.3) years, 60.5% were male, 54.2% white, 23.2% Hispanic, and 16.2% black. Statin use in the year before diagnosis increased from 50.4% in 2002 to 66.0% in 2015 (CLI: 43.7% to 68.0%; without CLI: 53.1% to 64.2%, respectively). The proportion of patients on high-intensity statins increased from 7.3% in 2002 to 41.9% in 2015 (CLI: 7.2% to 39.4%; without CLI: 7.4% to 44.2%, respectively). Of the 40.5% (n = 4481) who were not on a statin in the year before diagnosis, 13.5% (n = 607) newly initiated therapy within 1 month (CLI: 10.1% (n = 150); without CLI: 15.3% (n = 457)). Following diagnosis, 12.5% (n = 660) discontinued statin therapy within 1 year (CLI: 15.5% (n = 202); without CLI: 11.5% (n = 458)). Although use of statins increased from 2002 to 2015, a substantial proportion of the overall PAD and CLI subpopulation remained untreated with statins, representing a significant treatment gap in a population at high risk for cardiovascular events and adverse limb outcomes.

Complications of Corrective Osteotomies for Extra-Articular Distal Radius Malunion.

PURPOSE: Osteotomy of the distal radius for a fracture malunion is a challenging procedure. The purpose of this study was to review a series of osteotomies to determine the type and risk of complications. METHODS: A retrospective cohort study was performed, including all Kaiser Permanente Southern California patients who were aged 18 years or older between January 1, 2007, and September 25, 2015, and underwent osteotomy for an extra-articular distal radius fracture malunion. Charts were reviewed for demographic data, comorbidities, osteotomy type (hinged vs distraction), implant, and bone graft type. Complications including infection, nonunion, loss of reduction, implant failure, nerve injury, tendon injury, and complex regional pain syndrome were recorded. RESULTS: There were 60 patients who underwent extra-articular osteotomy of the distal radius for malunion during the study period. The mean age was 54 years (range, 21-83 years). There were 24 distraction-type (intervening bone graft) and 36 hinge-type (volar cortical contact maintained) osteotomies. Twenty-five of 60 patients had complications related to the procedure requiring 13 subsequent procedures. There were 7 nonunions and 3 cases of delayed healing at the osteotomy site. One extensor carpi radialis longus tendon laceration resulted from the use of an osteotome. There were 3 delayed extensor pollicis longus (EPL) tendon ruptures after surgery. The distraction-type osteotomy was associated with a greater risk of major complications including nonunion and delayed union. CONCLUSIONS: A complication rate of nearly 50% was observed in distal radius osteotomies. Surgeons should be aware of the risk of injury to, or delayed rupture of the EPL tendon associated with these procedures. The risk of nonunion or delayed union is higher in distraction-type compared with hinge-type osteotomies. Low surgeon volume with this procedure may be a contributing factor to the high rate of complications. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic IV.

Kidney Function Decline in Patients with CKD and Untreated Hepatitis C Infection.

BACKGROUND AND OBJECTIVES: Studies evaluating the role of hepatitis C viral (HCV) infection on the progression of CKD are few and conflicting. Therefore, we evaluated the association of untreated HCV on kidney function decline in patients with stage 3-5 CKD. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: This retrospective cohort study included members of Kaiser Permanente Southern California and Kaiser Permanente Mid-Atlantic States aged ≥18 years, with incident HCV and CKD diagnoses from January 1, 2004 to December 31, 2014. We used generalized estimating equations to compare the rate of change in eGFR between those with HCV and CKD versus CKD alone, adjusting for covariates. Cox proportional hazards models compared the risk of 25% decrease in eGFR and ESKD (defined as progression to eGFR<15 ml/min per 1.73 m2 on two or more occasions, at least 90 days apart) in those with HCV and CKD versus CKD alone, adjusting for covariates. RESULTS: We identified 151,974 patients with CKD only and 1603 patients with HCV and CKD who met the study criteria. The adjusted annual decline of eGFR among patients with HCV and CKD was greater by 0.58 (95% confidence interval [95% CI], 0.31 to 0.84) ml/min per 1.73 m2, compared with that in the CKD-only population (HCV and CKD, -1.61; 95% CI, -1.87 to -1.35 ml/min; CKD only, -1.04; 95% CI, -1.06 to -1.01 ml/min). Adjusted for covariates, the hazard for a 25% decline in eGFR and for ESKD were 1.87 (95% CI, 1.75 to 2.00) and 1.93 (95% CI, 1.64 to 2.27) times higher among those with HCV and CKD, respectively, compared with those with CKD only. CONCLUSIONS: Untreated HCV infection was associated with greater kidney function decline in patients with stage 3-5 CKD.

Trends in Lipid Screening Among Adults in an Integrated Health Care Delivery System, 2009-2015.

BACKGROUND: Lipid screening determines eligibility for statins and other cardiovascular risk reduction interventions. OBJECTIVE: To examine trends in lipid screening among adults aged ≥20 years in a large, multiethnic, integrated health care delivery system in southern California. METHODS: Temporal trends in lipid screening were examined from 2009 to 2015 with an index date of September 30 of each year. Lipid screening was defined as the proportion of eligible members each year who (a) had ever been screened among those aged 20-39 years and (b) had been screened in the previous 6 years for those aged ≥ 40 years. Trends were analyzed by age, gender, and the presence of atherosclerotic cardiovascular disease (ASCVD) or diabetes without ASCVD status. RESULTS: More than 2 million individuals were included each year: 5%-6% had ASCVD (includes those with diabetes), 7%-8% had diabetes without ASCVD, and 87% had neither condition. Among the entire population, lipid screening increased from 79.8% in 2009 to 82.6% in 2015 (P < 0.0001). Among those with ASCVD or diabetes, lipid screening was 99% across all years. Among those without ASCVD or DM, screening increased from 76.9% in 2009 to 80.0% in 2015 (P < 0.0001), with higher screening among women compared with men and lower screening among individuals younger than 55 years. CONCLUSIONS: Consistently high rates of lipid screening were observed among individuals with ASCVD or diabetes. In individuals without these conditions, screening increased over time. However, there is room to further increase screening rates in adults younger than 55 years. DISCLOSURES: This manuscript and research work was supported by a contractual agreement between the Southern California Permanente Medical Group and Regeneron Pharmaceuticals and Sanofi U.S. Researchers from Regeneron and Sanofi collaborated on the study design, interpretation of data, and writing of the manuscript. Ling Grant, Harrison, Chang, Hsu, Cheetham, Wei, and Reynolds are employed by Kaiser Permanente Southern California. Scott is employed by Southern California Permanente Medical Group. Boklage is employed by Regeneron, and Romo-LeTourneau is employed by Sanofi. Preliminary results from this study were presented at the American Heart Association Scientific Sessions; November 12-16, 2016; New Orleans, LA.

Trends in Statin Use 2009-2015 in a Large Integrated Health System: Pre- and Post-2013 ACC/AHA Guideline on Treatment of Blood Cholesterol.

PURPOSE: Implementation of the 2013 ACC/AHA cholesterol treatment guideline is likely to vary by statin benefit group. The aim of this study was to document trends in statin use before and after introduction of the ACC/AHA guideline. METHODS: We conducted a retrospective study with annual cohorts from 2009 to 2015 among members of Kaiser Permanente Southern California aged ≥ 21 years. Members were categorized into four mutually exclusive statin benefit groups: atherosclerotic cardiovascular disease (ASCVD), LDL-C ≥ 190 mg/dL in the last year, diabetes (aged 40-75 years), and 10-year ASCVD risk ≥ 7.5% (aged 40-75 years). RESULTS: The cohorts ranged from 1,993,755 members in 2009 to 2,440,429 in 2015. Approximately 5% of patients had ASCVD, 1% had LDL-C ≥ 190 mg/dL, 6% had diabetes, and 10% had a 10-year ASCVD risk ≥ 7.5% each year. Trends in statin use were stable for adults with ASCVD (2009 78%; 2015 80%), recent LDL-C ≥ 190 mg/dL (2009 45%; 2015 44%), and diabetes (2009 74%; 2015 73%), but increased for patients with 10-year ASCVD risk ≥ 7.5% (2009 36%; 2015 47%). High-intensity statin use also increased 142% and 54% among patients with LDL-C ≥ 190 mg/dL and those with ASCVD ≤ 75 years of age, respectively. Moderate-to-high intensity statin utilization increased over 50% among those with a 10-year ASCVD risk ≥ 7.5%. CONCLUSIONS: Statin use increased substantially among patients with 10-year ASCVD risk ≥ 7.5% and use of appropriate statin dosage increased in each of the four statin benefit groups between 2009 and 2015; however, there is room for improvement.

Unmet Patient Need in Statin Intolerance: the Clinical Characteristics and Management.

PURPOSE: A substantial percentage of patients report intolerance or side effects of statin treatment leading to treatment changes or discontinuation. The purpose of this study was to examine statin therapy changes and subsequent effects on low-density lipoprotein cholesterol (LDL-C) among patients with statin intolerance (SI). METHODS: We identified 45,037 adults from Kaiser Permanente Southern California with SI documented between 2006 and 2012. Changes in statin therapy in the year before and after the SI index date were examined. We categorized patients into those who initiated statin therapy, discontinued, up-titrated, down-titrated, or did not switch therapy. We calculated the percentage change in LDL-C from the year before to the year after SI, and the percentage of patients attaining LDL-C < 100 and < 70 mg/dL. RESULTS: In the year prior to the SI date, 77.8% of patients filled a statin prescription. Following SI, 44.6% had no treatment change, 25.5% discontinued, and 30.0% altered their statin therapy. Of those who altered statin therapy, 52.6% down-titrated and 17.2% up-titrated their dose. Rhabdomyolysis was documented in < 1% of the cohort. The largest changes in LDL-C were experienced by patients who were on a high-intensity statin then discontinued treatment (35.6% increase) and those who initiated a high-intensity statin (25.5% decrease). The proportion of patients achieving LDL-C < 100 mg/dL and LDL-C < 70 mg/dL was the lowest among those who discontinued therapy. CONCLUSIONS: Although adjustments to the statin dosage may be appropriate upon documentation of SI, many of these patients will have high LDL-C. Strategies for LDL-C reduction in patients with SI may be necessary.

Racial and Ethnic Variation in Time to Prostate Biopsy After an Elevated Screening Level of Serum Prostate-specific Antigen.

OBJECTIVE: To examine the racial and ethnic variation in time to prostate biopsy after an elevated screening level of serum prostate-specific antigen (PSA). METHODS: Male members of the Kaiser Permanente of Southern California health plan, 45 years of age or older, with no history of prostate cancer or a prostate biopsy, and at least 1 elevated screening level of serum PSA between January 1, 1998 and December 31, 2007 were retrospectively identified (n = 59,506). All participants were passively followed via electronic health records until their time of prostate biopsy, death, membership disenrollment, or study conclusion (December 31, 2014), whichever was the initial event. Proportional hazard regression analyses were used to estimate the association between time from an elevated screening level of serum PSA to prostate biopsy, adjusting for age, benign prostatic hyperplasia, prostatitis, type 2 diabetes mellitus, hypertension, and Charlson Comorbidity Index score. RESULTS: Median time until biopsy was 0.6 years (214 days), with approximately 41% of participants receiving a prostate biopsy within the study period. Results from the fully adjusted analysis indicated that the non-Hispanic Asian or Pacific Islanders (hazard ratio: 1.10, 95% confidence interval: [1.04, 1.15]) and the non-Hispanic blacks (hazard ratio: 1.04, 95% confidence interval: [1.00, 1.08]) had a slightly shorter time to prostate biopsy after an elevated screening level of serum PSA compared to the non-Hispanic whites. CONCLUSION: These data suggest that, within an integrated healthcare organization, minimal differences exist between racial and ethnic subgroups in their time to prostate biopsy after an elevated screening level of serum PSA.

Trends in Prostate-specific Antigen Screening, Prostate Biopsies, Urology Visits, and Prostate Cancer Treatments From 2000 to 2012.

OBJECTIVE: To determine whether the rates of prostate-specific antigen (PSA) screening, related biopsies and subsequent prostate cancer utilization decreased between 2000 and 2012 in a large, managed care organization. METHODS: Male members of Kaiser Permanente Southern California who were aged ≥40 years and had no history of prostate cancer (N = 15,326) were passively followed through electronic health plan files from January 1, 2000, through December 31, 2012 (N = 1,539,469). The rates of PSA testing, elevated PSA tests, prostate biopsies, prostate cancer treatment (surgery and radiation), and urology visits were calculated per year among eligible men and stratified by age group. RESULTS: A 59% decrease in PSA screening occurred among men aged ≥75 years beginning in 2008, followed by 49% in ages 65-74, 20% in ages 50-64, and 33% in ages 40-49 years in 2009. However, the number of elevated PSA tests remained largely unchanged in all groups except in men aged ≥75 years (45% decrease). Prostate biopsy rates and urology visits remained consistent among elderly men. CONCLUSION: Among men in this managed care setting, although there was a sharp decline in PSA testing among men aged ≥75 years after 2008, prostate biopsy rates remained constant, and subsequent prostate cancer treatment remained highest among men in this age group. These results suggest that the guidelines recommending against PSA and the subsequent provider-targeted interventions implemented in this system resulted in decreased screening across age groups and potentially led to more discriminant screening among those aged ≥75 years.

Variability in date of prostate cancer diagnosis: a comparison of cancer registry, pathology report, and electronic health data sources.

PURPOSE: The date of cancer diagnosis is a critical data element for clinical care and research. Because this date can be abstracted from various data sources, its comparability from source to source is unclear. This study compared the date of diagnosis from multiple sources within the same population of prostate cancer patients. METHODS: We linked cancer registry, pathology report, and electronic health data sources from the Kaiser Permanente Southern California health data systems for a cohort of 22,666 members diagnosed with prostate cancer between 2000 and 2010. The magnitude and direction of the differences in date of diagnosis were assessed for each date pairwise comparison. We reviewed 454 medical records to determine reasons for date discrepancies. RESULTS: Among the date pairwise comparisons, differences in date of diagnosis spanned from 9.6 years earlier to 10 years later than each other. However, the overall median difference ranged from 1 to 16 days, thus suggesting that the vast majority of the date differences were small. Chart review results identified major categories of date discrepancies. CONCLUSIONS: These data demonstrate variability in date of diagnosis across these data sources. This variability may have implications for epidemiologic estimates or patient identification in research studies using different data sources.

Validation of the Osteoporosis-Specific Morisky Medication Adherence Scale in long-term users of bisphosphonates.

PURPOSE: To examine the psychometric properties and validity of the 8-item Osteoporosis-Specific Morisky Medication Adherence Scale (OS-MMAS-8) in postmenopausal women prescribed bisphosphonates (BPs) for at least 15 months. METHODS: A random sample of women aged ≥55 years with osteoporosis prescribed daily or weekly BPs was identified. Pharmacy fill data were extracted to calculate the medication possession ratio (MPR). Eligible women were stratified by low (<0.50), medium (0.50-0.79), or high (≥0.80) MPR, with the a priori goal of recruiting 133 participants in each group. OS-MMAS-8 scores can range from 0 to 8 and were categorized as low (<6), medium (6 to <8), and high (8) adherence. Internal consistency reliability (Cronbach's alpha), test-retest reliability [intraclass correlation coefficients (ICCs)] and convergent validity (correlating OS-MMAS-8 with MPR and other self-reported measures) were assessed. RESULTS: A total of 400 women out of 449 respondents reported that they were still taking their BPs at the time of the survey and completed OS-MMAS-8. Overall, 38.5, 34.3, and 27.3% of participants had low, medium, and high OS-MMAS-8 scores, respectively. The mean (SD) MPRs according to OS-MMAS-8 scores (<6, 6 to <8 and 8) were 56.9 (22.6), 69.0 (24.9), and 76.7 (26.4), respectively. The correlation between OS-MMAS-8 and MPR was 0.36; p < 0.0001. Cronbach's alpha was 0.74, and the ICC was 0.83 (95% CI 0.76-0.88). CONCLUSIONS: OS-MMAS-8 has acceptable psychometric properties for assessing medication adherence in postmenopausal women prescribed therapy for osteoporosis. Additional studies are needed to investigate the psychometric properties of OS-MMAS-8 in other settings and populations.

Phenotypes determined by cluster analysis in severe or difficult-to-treat asthma.

BACKGROUND: Asthma phenotyping can facilitate understanding of disease pathogenesis and potential targeted therapies. OBJECTIVE: To further characterize the distinguishing features of phenotypic groups in difficult-to-treat asthma. METHODS: Children ages 6-11 years (n = 518) and adolescents and adults ages ≥12 years (n = 3612) with severe or difficult-to-treat asthma from The Epidemiology and Natural History of Asthma: Outcomes and Treatment Regimens (TENOR) study were evaluated in this post hoc cluster analysis. Analyzed variables included sex, race, atopy, age of asthma onset, smoking (adolescents and adults), passive smoke exposure (children), obesity, and aspirin sensitivity. Cluster analysis used the hierarchical clustering algorithm with the Ward minimum variance method. The results were compared among clusters by χ(2) analysis; variables with significant (P < .05) differences among clusters were considered as distinguishing feature candidates. Associations among clusters and asthma-related health outcomes were assessed in multivariable analyses by adjusting for socioeconomic status, environmental exposures, and intensity of therapy. RESULTS: Five clusters were identified in each age stratum. Sex, atopic status, and nonwhite race were distinguishing variables in both strata; passive smoke exposure was distinguishing in children and aspirin sensitivity in adolescents and adults. Clusters were not related to outcomes in children, but 2 adult and adolescent clusters distinguished by nonwhite race and aspirin sensitivity manifested poorer quality of life (P < .0001), and the aspirin-sensitive cluster experienced more frequent asthma exacerbations (P < .0001). CONCLUSION: Distinct phenotypes appear to exist in patients with severe or difficult-to-treat asthma, which is related to outcomes in adolescents and adults but not in children. The study of the therapeutic implications of these phenotypes is warranted.

Accuracy and implications of percutaneous renal biopsy in the management of renal masses.

INTRODUCTION: Percutaneous renal biopsy in patients with renal masses is increasing. We investigated the accuracy of percutaneous renal mass biopsy results in patients undergoing evaluation of solid renal masses. METHODS: A retrospective review was performed of patients in the Kaiser Permanente Southern California Region who underwent computed tomography or ultrasound-guided percutaneous renal biopsy of a solid renal mass between January 2005 and December 2009. Patients were stratified by size of mass (≤ 4 cm vs > 4 cm). Initial biopsy results were correlated with final pathology specimens after extirpation. RESULTS: Medical records of 126 patients (129 renal units with 132 biopsies) were reviewed. Initial diagnostic biopsies revealed 87 (66%) malignant, 38 (29%) benign, and 7 (5%) nondiagnostic lesions. Sixty-three patients (50%) ultimately underwent extirpative surgery (23 partial and 40 radical nephrectomies). Of these patients, the diagnostic accuracy of the initial percutaneous renal mass biopsy was 76%, with an overall sensitivity and specificity of 75.4% and 100%, respectively. The biopsy concordance to final histologic tumor subtype was 93%. Larger tumor size (odds ratio [OR], 2.20; 95% confidence interval [CI], 0.55 to 8.88) and increasing number of biopsies (OR, 2.50; 95% CI, 0.59 to 10.69) were associated with increasing accuracy of a biopsy result to predict cancer; however, these associations were not statistically significant. CONCLUSION: Percutaneous renal mass biopsy is diagnostically accurate and has good sensitivity, specificity, and concordance with final pathologic renal cell carcinoma subtype. This diagnostic modality can assist in management of select renal masses as treatment options are expanding.

Racial and ethnic differences in time to treatment for patients with localized prostate cancer.

OBJECTIVE: To investigate the racial/ethnic differences in the time to treatment among patients with prostate cancer. MATERIALS AND METHODS: All 3448 men diagnosed with localized prostate cancer at Kaiser Permanente Southern California from 2006 to 2007 were identified. The patients were passively followed up through their electronic health records until definitive treatment, defined as the first treatment given with curative intent within 1 year of diagnosis. Cox proportional hazard models, with PROC SURVEYPHREG procedures, were used to account for the variability in time to the different treatments within multiple medical centers. RESULTS: The overall median time to treatment was 102 days, with modest differences for whites (100 days), blacks (104 days), and Hispanics (99 days). In the adjusted model, black men had a significantly longer time to surgery (adjusted hazard ratio 0.74, 95% confidence interval 0.56-0.91) compared with white men. Hispanic men (adjusted hazard ratio 1.44, 95% confidence interval 1.07-1.74) experienced significantly shorter times to radiotherapy compared with white men. No difference was found in the time to radiotherapy or brachytherapy for black men relative to white men. CONCLUSION: These data suggest that minimal racial/ethnic differences exist in the time to treatment after the diagnosis of prostate cancer in this equal-access setting. This is encouraging, but does not mean that all men were satisfied with their treatment choice.

Changes in serum prostate-specific antigen levels and the identification of prostate cancer in a large managed care population.

OBJECTIVE: To determine whether the rate of change in total serum prostate-specific antigen (PSA) levels accurately detects prostate cancer and to evaluate whether it adds any predictive value to a single measurement of serum PSA alone, in general practice settings. MATERIALS AND METHODS: A retrospective cohort of 219,388 community-dwelling men, aged ≥45 years, enrolled in the Kaiser Permanente Southern California health plan, with no history of prostate cancer and at least three PSA measurements, were followed from 1 January 1998 to 31 December 2007, for the development of biopsy-confirmed prostate cancer. Annual percent changes in total serum PSA levels were estimated using linear mixed models. The accuracy of prostate cancer prediction was assessed for prostate cancer overall and for aggressive disease (Gleason score ≥7) and compared with that of a single measure of PSA level using area under the receiver-operating characteristic curves (AUCs). RESULTS: The men in this cohort experienced a mean change of 2.9% in PSA levels per year and the rate of change in PSA increased modestly with age (P ≤ 0.001). Annual percent changes in PSA accurately predicted the presence of prostate cancer (AUC = 0.963) and aggressive disease (AUC = 0.955) and had more predictive accuracy for aggressive disease than did a single measurement of PSA alone (AUC = 0.727). CONCLUSIONS: Longitudinal measures of PSA improve the accuracy of aggressive prostate cancer detection when compared with a single measurement of PSA alone. Findings from this study provide insight into the usefulness of PSA velocity as a detection marker for aggressive prostate cancer.

Prostate cancer screening trends in a large, integrated health care system.

BACKGROUND: As the debate over the effectiveness of prostate-specific antigen (PSA) screening for prostate cancer continues, it is increasingly important to understand how PSA screening occurs in general-practice settings. METHODS: We conducted a retrospective cohort study within Kaiser Permanente Southern California, a large integrated health care system. Men aged 35 years and older at baseline, in 1998, were eligible. The proportion of men who underwent PSA screening was estimated and compared across groups defined by patient and physician characteristics. We also evaluated trends in screening across time and serum PSA levels for all subgroups. RESULTS: Of 2,061,047 men, 572,306 (28%) underwent PSA screening from 1998 through 2007. Patterns of PSA screening varied modestly by age, race, and physician. The lowest frequencies of screening occurred among men younger than age 45 years (19%) and men ages 85 years and older (13%). PSA screening was most common among white men (33.5%) and in men seen by physicians of the same race/ethnicity (32%), compared with men with physicians of disparate race/ethnicity (26%, p < 0.001). PSA screening increased over time for all racial/ethnic groups and among men age 75 years and older but decreased over time for men younger than age 75 years old. CONCLUSIONS: Nearly 1 in 4 eligible men underwent PSA screening from 1998 through 2007, and screening varied only modestly by patient and physician characteristics. Estimates of the frequency of PSA screening in general-practice settings can inform the debate and provide useful insight as to how changes in cancer screening guidelines would alter practice patterns in an increasingly integrated health care environment.