Development and validation of algorithms to identify acute diverticulitis.

PURPOSE: The objectives of this study were to develop and validate algorithms to accurately identify patients with diverticulitis using electronic medical records (EMRs). METHODS: Using Kaiser Permanente Southern California's EMRs of adults (≥18 years) with International Classification of Diseases, Clinical Modifications, Ninth Revision diagnosis codes of diverticulitis (562.11, 562.13) between 1 January 2008 and 31 August 2009, we generated random samples for pilot (N = 692) and validation (N = 1502) respectively. Both samples were stratified by inpatient (IP), emergency department (ED), and outpatient (OP) care settings. We developed and validated several algorithms using EMR data on diverticulitis diagnosis code, antibiotics, computed tomography, diverticulosis history, pain medication and/or pain diagnosis, and excluding patients with infections and/or conditions that could mimic diverticulitis. Evidence of diverticulitis was confirmed through manual chart review. Agreement between EMR algorithm and manual chart confirmation was evaluated using sensitivity and positive predictive value (PPV). RESULTS: Both samples were similar in socio-demographics and clinical symptoms. An algorithm based on diverticulitis diagnosis code with antibiotic prescription dispensed within 7 days of diagnosis date, performed well overall. In the validation sample, sensitivity and PPV were (84.6, 98.2%), (95.8, 98.1%), and (91.8, 82.6%) for OP, ED, and IP, respectively. CONCLUSION: Using antibiotic prescriptions to supplement diagnostic codes improved the accuracy of case identification for diverticulitis, but results varied by care setting.

Impact of mental health comorbidities on health care utilization and expenditure in a large US managed care adult population with ADHD.

OBJECTIVE: To estimate the health resource use (HRU) and expenditure of adult patients with attention deficit/hyperactivity disorder (ADHD) subsequently diagnosed with one or more mental health (MH) comorbidities. METHODS: Using Kaiser Permanente Southern California electronic medical records (January 1, 2006, to December 31, 2009), we identified adults with at least one ADHD diagnosis and at least two subsequent prescriptions fills for ADHD medication. The date of first MH comorbidity diagnosis after the index ADHD diagnosis was defined as the index transition date. Continuous eligibility 12 months before and after the index transition date was required. For patients with multiple transitions (≥2), the post-transition period reflected the 12 months after the second transition. HRU for all-cause inpatient, outpatient, emergency department, behavioral therapy, overall prescription fill counts, and ADHD-specific prescription fill counts and mean patient expenditure (2010 US $) were estimated. Generalized estimating equations were used to evaluate differences in HRU and expenditure between the pre- and post-transition periods, respectively. RESULTS: Of the 3809 patients with ADHD identified, 989 (26%) had at least one transition (n = 357 single and n = 632 multiple). From the pre- to the post-transition period, for single transition cohort, all HRU increased significantly except for behavioral therapy. In the multiple transition cohort, all HRU increased significantly. Total expenditure increased by mean ± SE of $1822 ± $306 and $4432 ± $301 (both P < 0.0001) in the single and multiple transition cohorts, respectively. CONCLUSIONS: Twenty-six percent of patients with ADHD transitioned to MH comorbid diagnoses. Increased HRU and expenditure were associated with MH transitions. Identifying of patients with ADHD at risk for MH comorbidities may help to improve their outcomes.

Germline mutations in PALB2 in African-American breast cancer cases.

Breast cancer incidence is lower in African Americans than in Caucasian Americans. However, African-American women have higher breast cancer mortality rates and tend to be diagnosed with earlier-onset disease. Identifying factors correlated to the racial/ethnic variation in the epidemiology of breast cancer may provide better understanding of the more aggressive disease at diagnosis. Truncating germline mutations in PALB2 have been identified in approximately 1% of early-onset and/or familial breast cancer cases. To date, PALB2 mutation testing has not been performed in African-American breast cancer cases. We screened for germline mutations in PALB2 in 139 African-American breast cases by denaturing high-performance liquid chromatography and direct sequencing. Twelve variants were identified in these cases and none caused truncation of the protein. Three missense variants, including two rare variants (P8L and T300I) and one common variant (P210L), were predicted to be pathogenic, and were located in a coiled-coil domain of PALB2 required for RAD51- and BRCA1-binding. We investigated and found no significant association between the P210L variant and breast cancer risk in a small case-control study of African-American women. This study adds to the literature that PALB2 mutations, although rare, appear to play a role in breast cancer in all populations investigated to date.

Mitochondrial DNA G10398A variant is not associated with breast cancer in African-American women.

Mitochondria play important roles in cellular energy production, free radical generation, and apoptosis. In a previous report, the mitochondrial DNA (mtDNA) G10398A (Thr-->Ala) polymorphism was associated with breast cancer risk in African-American women [Cancer Res 2005;65:8028-33]. We sought to replicate the association by genotyping the G10398A polymorphism in multiple established population-based case-control studies of breast cancer in African-American women. The 10398A allele was not significantly associated with risk in any of the studies: San Francisco (542 cases, 282 controls, odds ratio OR = 1.73, 95% confidence interval CI = 0.87-3.47, P = 0.12); Multiethnic Cohort (391 cases, 460 controls, OR = 1.08, 95% CI = 0.62-1.86, P = 0.79); and CARE and LIFE (524 cases, 236 controls, OR = 0.81, 95% CI = 0.43-1.52, P = 0.50). With data pooled across the studies (1,456 cases and 978 controls), no significant association was observed with the 10398A allele (OR = 1.14, 95% CI = 0.80-1.62, P = 0.47, test for heterogeneity = 0.30). In analysis of advanced breast cancer cases (n = 674), there was also no significant association (OR = 1.18, 95% CI = 0.76-1.82, P = 0.46). Our results do not support the hypothesis that the mtDNA G10398A polymorphism is, as has previously been reported, a marker of breast cancer risk in African Americans.

Transforming growth factor beta facilitates beta-TrCP-mediated degradation of Cdc25A in a Smad3-dependent manner.

Ubiquitin-dependent degradation of Cdc25A is a major mechanism for damage-induced S-phase checkpoint. Two ubiquitin ligases, the Skp1-cullin-beta-TrCP (SCFbeta-TrCP) complex and the anaphase-promoting complex (APCCdh1), are involved in Cdc25A degradation. Here we demonstrate that the transforming growth factor beta (TGF-beta)-Smad3 pathway promotes SCF(beta-TrCP)-mediated Cdc25A ubiquitination. Cells treated with TGF-beta, as well as cells transfected with Smad3 or a constitutively active type I TGF-beta receptor, exhibit increased ubiquitination and markedly shortened half-lives of Cdc25A. Furthermore, Cdc25A is stabilized in cells transfected with Smad3 small interfering RNA (siRNA) and cells from Smad3-null mice. TGF-beta-induced ubiquitination is associated with Cdc25A phosphorylation at the beta-TrCP docking site (DS82G motif) and physical association of Cdc25A with Smad3 and beta-TrCP. Cdc25A mutant proteins deficient in DS82G phosphorylation are resistant to TGF-beta-Smad3-induced degradation, whereas a Cdc25A mutant protein defective in APCCdh1 recognition undergoes efficient degradation. Smad3 siRNA inhibits beta-TrCP-Cdc25A interaction and Cdc25A degradation in response to TGF-beta. beta-TrCP2 siRNA also inhibits Smad3-induced Cdc25A degradation. In contrast, Cdh1 siRNA had no effect on Cdc25A down-regulation by Smad3. These data suggest that Smad3 plays a key role in the regulation of Cdc25A ubiquitination by SCFbeta-TrCP and that Cdc25A stabilization observed in various cancers could be associated with defects in the TGF-beta-Smad3 pathway.

The impact of patient-centered medical homes on safety net clinics.

OBJECTIVES: To evaluate the impact of moving to a patient-centered medical home (PCMH) model in safety net clinics in a managed Medicaid plan. STUDY DESIGN: Quasi-experimental, difference-in-differences design. METHODS: The study examined whether the PCMH model reduced emergency department (ED) use and whether the growth in the seniors and people with disabilities (SPDs) population crowds out lower-cost populations. The study compared 7 PCMH safety net clinics (22,870 members) in late 2011 in the greater Los Angeles area with 110 general safety net clinics (143,530 members) between January 2011 and December 2013. During the time from 2011 to 2012, California began transitioning SPDs from fee-for-service Medicaid into managed care systems under a federal waiver. RESULTS: Among clinics with less than 10% SPD membership, a PCMH model was associated with more office visits and less ED use. In particular, PCMH clinics-relative to non-PCMH clinics-reduced ED visits by an average of 70 visits per 1000 members per year (PTMPY) and reduced avoidable ED visits by 20 visits PTMPY. Neither the change in office visits nor ED visits was evident in clinics with SPD membership greater than 10%. CONCLUSIONS: Adopting a PCMH model in safety net practices can effectively reduce ED use and increase the use of office visits among Medicaid patients. However, the beneficial effects of the PCMH model can be muted by a sudden influx of high-need users.

Medication adherence and attrition to biologic treatment in rheumatoid arthritis patients.

PURPOSE: The objectives of this study were to assess medication adherence rate and attrition rate in first-time adalimumab (ADA) or etanercept (ETA) users in rheumatoid arthritis (RA) patients. This study also identified the risk factors associated with nonadherence and treatment abandonment. METHODS: This was a retrospective study with a 2-year follow-up. A total 2151 adult RA patients (18 years of age and older) who initiated ADA or ETA treatment in the Kaiser Permanente Southern California health plan between 2002 and 2009 were identified. Among those on treatment in the first year, continuous treatment receipt was determined by having at least 1 medication refill in the second year; otherwise treatment was considered as abandoned. Medication adherence was measured through proportion of days covered (PDC) and compared between patients continuously on treatment and those abandoning treatment. Risk factors of nonadherence (PDC <80%) and treatment abandonment were estimated by a multinomial logistic regression model. FINDINGS: Patients who abandoned treatment had significantly lower PDC (37.3%) and lower average number of refills (5.1) than adherers (PDC = 88.8%; average number of refills = 12.4) and nonadherers (PDC = 53.3%; average refills = 8.2). Age, African Americans (odds ratio [OR], 1.49; 95% CI, 1.03-2.17), corticosteroids use (OR, 0.80; 95% CI, 0.63-0.98), and history of physical/occupational therapy (OR = 0.66; 95% CI, 0.46-0.93) were associated with nonadherence, whereas having a comorbidity (OR, 1.24; 95% CI, 1.01-1.57) was associated with treatment abandonment. The difference in PDC between ADA and ETA was no longer statistically significant after excluding the treatment abandonment group. A higher proportion of ADA users abandoned treatment than ETA users (42.9% vs 32.2%). IMPLICATIONS: Taking into account treatment abandonment when measuring medication adherence in ADA and ETA use in RA patients can provide a fair and clinically meaningful view of patients' medication-taking behavior.

Response rates of three modes of survey administration and survey preferences of rheumatoid arthritis patients.

OBJECTIVE: To compare survey response rates and preferences for 3 modes of survey administration in rheumatoid arthritis (RA) patients. METHODS: Adult RA patients were identified from Kaiser Permanente Southern California's electronic medical records. One hundred patients each were randomly assigned to telephone, mail with followup letter, and mail with followup telephone call as modes of survey administration. Respondents completed a 7-page survey (in English or Spanish) that included the Health Assessment Questionnaire disability index and pain scale, EuroQol 5-dimensions, and generic questions on preferences and sociodemographics. Response rates were based on the number of completed surveys received from the total number of patients contacted (n = 295; 5 were ineligible). RESULTS: The mean ± SD age of the cohort was 61 ± 12.3 years, with the majority being women (141 [85%] of 166). Of the 3 modes of survey administration, telephone (63 [64%] of 99) had the highest response rate, followed by mail with followup telephone call (55 [56%] of 98) and mail with followup letter (48 [49%] of 98). When asked about preference over administration mode, 57% (95 of 166) preferred to complete the survey by mail, followed by telephone (27 [16%] of 166) and internet (17 [10%] of 166). CONCLUSION: When asked about their choice of survey administration mode for reporting their health status, the majority of RA patients in this study had a strong preference for a mail survey as compared to a telephone interview. However, the response rate in the telephone administration mode of survey was the highest between the 3 modes of administration that were compared. Future studies in RA can achieve better response using telephone over mail-in surveys.

Prevalence and incidence of adult attention deficit/hyperactivity disorder in a large managed care population.

OBJECTIVES: To estimate longitudinal trends in prevalence and incidence rates of adult ADHD 2006-2009. RESEARCH DESIGN AND METHODS: Kaiser Permanente Southern California (KPSC) electronic medical records were analyzed to assess prevalence and incidence rates for adult ADHD. Trends over time were estimated and compared using three case definitions (ADHD diagnosis only [DX], ADHD DX and ≥2 FDA-approved ADHD prescriptions [DX + RX], and ADHD DX and ≥1 behavioral therapy visit [DX + BT]). MAIN OUTCOME MEASURES: Prevalence and incidence rates of adult ADHD. RESULTS: Prevalence ranged from 151 (DX + RX) to 312 (DX) cases per 100,000 members in 2006, increasing to 239 (DX + RX) and 415 (DX) cases in 2009. Prevalence based on DX + BT declined from 185 in 2006 to 94 cases per 100,000 in 2009. In 2006, incidence ranged from 15 (DX + BT) to 68 (DX) cases per 100,000 person-years. Incidence rates remained stable throughout the study period. Stratified analyses based on DX + RX revealed only slight variations by gender, but sharp differences by age, with younger adults demonstrating a higher prevalence overall as well as dramatic increases over the study period. Prevalence was highest among Caucasians, increasing substantially across all race groups over time. LIMITATIONS: A limitation of this study is that incidence rates may not be representative of new cases if diagnoses existed prior to enrollment in KPSC. Similarly, prevalence rates may be affected if patients sought care outside of the health plan. CONCLUSIONS: Adult ADHD prevalence in this managed care organization appears low, but showed increasing prevalence and incidence rates over time.

Acute colonic diverticulitis: diagnostic evidence, demographic and clinical features in three practice settings.

BACKGROUND AND AIMS: Diverticulitis is often diagnosed in outpatients, yet little evidence exists on diagnostic evidence and demographic/clinical features in various practice settings. We assessed variation in clinical characteristics and diagnostic evidence in inpatients, outpatients, and emergency department cases and effects of demographic and clinical variables on presentation features. METHODS: In a retrospective cohort study of 1749 patients in an integrated health care system, we compared presenting features and computed tomography findings by practice setting and assessed independent effects of demographic and clinical factors on presenting features. RESULTS: Inpatients were older and more often underweight/normal weight and lacked a diverticulitis past history and had more comorbidities than other patients. Outpatients were most often Hispanic/Latino. The classical triad (abdominal pain, fever, leukocytosis) occurred in 78 (38.6%) inpatients, 29 (5.2%) outpatients and 34 (10.7%) emergency department cases. Computed tomography was performed on 196 (94.4%) inpatients, 110 (9.2%) outpatients and 296 (87.6%) emergency department cases and was diagnostic in 153 (78.6%) inpatients, 62 (56.4%) outpatients and 243 (82.1%) emergency department cases. Multiple variables affected presenting features. Notably, female sex had lower odds for the presence of the triad features (odds ratio [95% CI], 0.65 [0.45-0.94], P<0.05) and increased odds of vomiting (1.78 [1.26-2.53], P<0.01). Patients in age group 56 to 65 and 66 or older had decreased odds of fever (0.67 [0.46-0.98], P<0.05) and 0.46 [0.26-0.81], P<0.01), respectively, while > / =1 co-morbidity increased the odds of observing the triad (1.88 [1.26-2.81], P<0.01). CONCLUSION: There was little objective evidence for physician-diagnosed diverticulitis in most outpatients. Demographic and clinical characteristics vary among settings and independently affect presenting features.

Racial/ethnic differences in the use of biologic disease-modifying antirheumatic drugs among California Medicaid rheumatoid arthritis patients.

OBJECTIVE: To assess racial/ethnic differences in the use of biologic disease-modifying antirheumatic drugs (DMARDs) among California Medicaid (Medi-Cal) rheumatoid arthritis (RA) patients. METHODS: Medi-Cal patient level data for 5,385 DMARD recipients between ages 18 and 100 years with at least 1 diagnosis of RA (International Classification of Disease, Ninth Revision, Clinical Modification code 714.xx) and the use of 1 DMARD between January 1, 1998 and December 31, 2005 were collected. The outcome of interest was the choice of either standard DMARDs (methotrexate, lefluonomide, hydroxychloroquine, and sulfasalazine) or biologic DMARDs (adalimumab, etanercept, anakinra, and infliximab). A univariate analysis and logistic regression model were applied to examine the association of the choice of DMARD among different racial/ethnic groups. RESULTS: In the univariate analysis, biologic DMARD use was significantly associated with race/ethnicity (P < 0.001). In the multivariate logistic regression model, after adjusting for age, sex, insurance coverage, 12 comorbid conditions, RA-related drug prescription, RA-related inpatient stay, and rehabilitation visits, African Americans had 53% lower odds of receiving biologic DMARDs as compared to whites, whereas Hispanics had 36% increased odds of receiving biologic DMARDs as compared to whites. CONCLUSION: In this Medi-Cal population, with its racial diversity and relatively homogenous socioeconomic status and health care benefits, racial/ethnic differences were found in RA patients receiving biologic DMARDs.