E. Margaret Warton

Language Barriers, Physician-Patient Language Concordance, and Glycemic Control Among Insured Latinos with Diabetes: The Diabetes Study of Northern California (DISTANCE)

ABSTRACTBACKGROUNDA significant proportion of US Latinos with diabetes have limited English proficiency (LEP). Whether language barriers in health care contribute to poor glycemic control is unknown.OBJECTIVETo assess the association between limited English proficiency (LEP) and glycemic control and whether this association is modified by having a language-concordant physician.DESIGNCross-sectional, observational study using data from the 2005–2006 Diabetes Study of Northern California (DISTANCE). Patients received care in a managed care setting with interpreter services and self-reported their English language ability and the Spanish language ability of their physician. Outcome was poor glycemic control (glycosylated hemoglobin A1c > 9%).KEY RESULTSThe unadjusted percentage of patients with poor glycemic control was similar among Latino patients with LEP (n = 510) and Latino English-speakers (n = 2,683), and higher in both groups than in whites (n = 3,545) (21% vs 18% vs. 10%, p < 0.005). This relationship differed significantly by patient-provider language concordance (p < 0.01 for interaction). LEP patients with language-discordant physicians (n = 115) were more likely than LEP patients with language-concordant physicians (n = 137) to have poor glycemic control (27.8% vs 16.1% p = 0.02). After controlling for potential demographic and clinical confounders, LEP Latinos with language-concordant physicians had similar odds of poor glycemic control as Latino English speakers (OR 0.89; CI 0.53–1.49), whereas LEP Latinos with language-discordant physicians had greater odds of poor control than Latino English speakers (OR 1.76; CI 1.04–2.97). Among LEP Latinos, having a language discordant physician was associated with significantly poorer glycemic control (OR 1.98; CI 1.03–3.80).CONCLUSIONSLanguage barriers contribute to health disparities among Latinos with diabetes. Limited English proficiency is an independent predictor for poor glycemic control among insured US Latinos with diabetes, an association not observed when care is provided by language-concordant physicians. Future research should determine if strategies to increase language-concordant care improve glycemic control among US Latinos with LEP.

HbA1c and Risk of Severe Hypoglycemia in Type 2 Diabetes: The Diabetes and Aging Study

OBJECTIVE We examined the association between HbA1c level and self-reported severe hypoglycemia in patients with type 2 diabetes. RESEARCH DESIGN AND METHODS Type 2 diabetic patients in a large, integrated healthcare system, who were 30–77 years of age and treated with glucose-lowering therapy, were asked about severe hypoglycemia requiring assistance in the year prior to the Diabetes Study of Northern California survey conducted in 2005–2006 (62% response rate). The main exposure of interest was the last HbA1c level collected in the year preceding the observation period. Poisson regression models adjusted for selected demographic and clinical variables were specified to evaluate the relative risk (RR) of severe hypoglycemia across HbA1c levels. We also tested whether the HbA1c-hypoglycemia association differed across potential effect modifiers (age, diabetes duration, and category of diabetes medication). RESULTS Among 9,094 eligible survey respondents (mean age 59.5 ± 9.8 years, mean HbA1c 7.5 ± 1.5%), 985 (10.8%) reported experiencing severe hypoglycemia. Across HbA1c levels, rates of hypoglycemia were 9.3–13.8%. Compared with those with HbA1c of 7–7.9%, the RR of hypoglycemia was 1.25 (95% CI 0.99–1.57), 1.01 (0.87–1.18), 0.99 (0.82–1.20), and 1.16 (0.97–1.38) among those with HbA1c <6, 6–6.9, 8–8.9, and ≥9%, respectively, in a fully adjusted model. Age, diabetes duration, and category of diabetes medication did not significantly modify the HbA1c-hypoglycemia relationship. CONCLUSIONS Severe hypoglycemia was common among patients with type 2 diabetes across all levels of glycemic control. Risk tended to be higher in patients with either near-normal glycemia or very poor glycemic control.

HIV Infection Status, Immunodeficiency, and the Incidence of Non-Melanoma Skin Cancer

Background The incidence of non-melanoma skin cancers (NMSCs), including basal cell (BCC) or squamous cell carcinoma (SCC), is not well documented among HIV-positive (HIV(+)) individuals. Methods We identified 6560 HIV(+) and 36 821 HIV-negative (HIV(-)) non-Hispanic white adults who were enrolled and followed up in Kaiser Permanente Northern California from 1996 to 2008. The first biopsy-proven NMSCs diagnosed during follow-up were identified from pathology records. Poisson models estimated rate ratios that compared HIV(+) (overall and stratified by recent CD4 T-cell counts and serum HIV RNA levels) with HIV(-) subjects and were adjusted for age, sex, smoking history, obesity diagnosis history, and census-based household income. Sensitivity analyses were adjusted for outpatient visits (ie, a proxy for screening). All statistical tests were two-sided. Results The NMSC incidence rate was 1426 and 766 per 100 000 person-years for HIV(+) and HIV(-) individuals, respectively, which corresponds with an adjusted rate ratio of 2.1 (95% confidence interval [CI] = 1.9 to 2.3). Similarly, the adjusted rate ratio for HIV(+) vs HIV(-) subjects was 2.6 (95% CI = 2.1 to 3.2) for SCCs, and it was 2.1 (95% CI = 1.8 to 2.3) for BCCs. There was a statistically significant trend of higher rate ratios with lower recent CD4 counts among HIV(+) subjects compared with HIV(-) subjects for SCCs (P trend < .001). Adjustment for number of outpatient visits did not affect the results. Conclusion HIV(+) subjects had a twofold higher incidence rate of NMSCs compared with HIV(-) subjects. SCCs but not BCCs were associated with immunodeficiency.

Systemic Immune Suppression Predicts Diminished Merkel Cell Carcinoma–Specific Survival Independent of Stage

Merkel cell carcinoma (MCC) is an aggressive cutaneous malignancy linked to a contributory virus (Merkel cell polyomavirus/MCPyV). Multiple epidemiologic studies have established an increased incidence of MCC among persons with systemic immune suppression. Several forms of immune suppression are associated with increased MCC incidence, including hematologic malignancies, HIV/AIDS, and immunosuppressive medications for autoimmune disease or transplant. Indeed, immune suppressed persons represent approximately 10% of the MCC patients, a significant over-representation relative to the general population. We hypothesized that immune suppressed patients may have a poorer MCC-specific prognosis and examined a cohort of 471 patients with a combined follow-up of 1427 years (median 2.1 years). Immune suppressed persons (n=41) demonstrated reduced MCC-specific survival (40% at 3 years) compared to persons with no known systemic immune suppression (n=430; 74% MCC-specific survival at 3 years). By competing risk regression analysis, immune suppression was a stage-independent predictor of worsened MCC-specific survival (hazard ratio 3.8, p < 0.01). Immune-suppressed persons thus have both an increased chance of developing MCC and poorer MCC-specific survival. It may be appropriate to follow these higher-risk individuals more closely, and, when clinically feasible, there may be benefit of diminishing iatrogenic systemic immune suppression.Merkel cell carcinoma (MCC) is an aggressive cutaneous malignancy linked to a contributory virus (Merkel cell polyomavirus). Multiple epidemiologic studies have established an increased incidence of MCC among persons with systemic immune suppression. Several forms of immune suppression are associated with increased MCC incidence, including hematologic malignancies, HIV/AIDS, and immunosuppressive medications for autoimmune disease or transplant. Indeed, immune-suppressed individuals represent ∼10% of MCC patients, a significant overrepresentation relative to the general population. We hypothesized that immune-suppressed patients may have a poorer MCC-specific prognosis and examined a cohort of 471 patients with a combined follow-up of 1,427 years (median 2.1 years). Immune-suppressed patients (n=41) demonstrated reduced MCC-specific survival (40% at 3 years) compared with patients with no known systemic immune suppression (n=430; 74% MCC-specific survival at 3 years). By competing risk regression analysis, immune suppression was a stage-independent predictor of worsened MCC-specific survival (hazard ratio 3.8, P<0.01). Thus, immune-suppressed individuals have both an increased chance of developing MCC and poorer MCC-specific survival. It may be appropriate to follow these higher-risk individuals more closely, and, when clinically feasible, there may be a benefit of diminishing iatrogenic systemic immune suppression.

Place matters: neighborhood deprivation and cardiometabolic risk factors in the Diabetes Study of Northern California (DISTANCE).

While neighborhood deprivation is associated with prevalence of chronic diseases, it is not well understood whether neighborhood deprivation is also associated with cardiometabolic risk factors among adults with chronic disease. Subjects (n = 19,804) from the Diabetes Study of Northern California (DISTANCE) cohort study, an ethnically-stratified, random sample of members of Kaiser Permanente Northern California (KPNC), an integrated managed care consortium, with type 2 diabetes who completed a survey between 2005 and 2007 and who lived in a 19 county study area were included in the analyses. We estimated the association between a validated neighborhood deprivation index (NDI) and four cardiometabolic risk factors: body mass index (BMI = kg/m2), glycosylated hemoglobin (A1c), low density lipoproteins (LDL) and systolic blood pressure (SBP) using multi-level models. Outcomes were modeled in their continuous form and as binary indicators of poor control (severe obesity: BMI ≥35, poor glycemic control: A1c ≥9%, hypercholesterolemia: LDL ≥130 mg/dL, and hypertension: SBP ≥140 mmHg). BMI, A1c and SBP increased monotonically across quartiles of NDI (p < 0.001 in each case); however, LDL was significantly associated with NDI only when comparing the most to the least deprived quartile. NDI remained significantly associated with BMI and A1c after adjusting for individual level factors including income and education. A linear trend (p < 0.001) was observed in the relative risk ratios for dichotomous indicators of severe obesity, poor glycemic control, and 2 or more poorly controlled cardiometabolic risk factors across NDI quartile. In adjusted models, higher levels of neighborhood deprivation were positively associated with indicators of cardiometabolic risk among adults with diabetes, suggesting that neighborhood level deprivation may influence individual outcomes. However, longitudinal data are needed to test the causal direction of these relationships.

The impact of limited English proficiency and physician language concordance on reports of clinical interactions among patients with diabetes: The DISTANCE study

OBJECTIVE To assess the association of limited English proficiency (LEP) and physician language concordance with patient reports of clinical interactions. METHODS Cross-sectional survey of 8638 Kaiser Permanente Northern California patients with diabetes. Patient responses were used to define English proficiency and physician language concordance. Quality of clinical interactions was based on 5 questions drawn from validated scales on communication, 2 on trust, and 3 on discrimination. RESULTS Respondents included 8116 English-proficient and 522 LEP patients. Among LEP patients, 210 were language concordant and 153 were language discordant. In fully adjusted models, LEP patients were more likely than English-proficient patients to report suboptimal interactions on 3 out of 10 outcomes, including 1 communication and 2 discrimination items. In separate analyses, LEP-discordant patients were more likely than English-proficient patients to report suboptimal clinician-patient interactions on 7 out of 10 outcomes, including 2 communication, 2 trust, and 3 discrimination items. In contrast, LEP-concordant patients reported similar interactions to English-proficient patients. CONCLUSIONS Reports of suboptimal interactions among patients with LEP were more common among those with language-discordant physicians. PRACTICE IMPLICATIONS Expanding access to language concordant physicians may improve clinical interactions among patients with LEP. Quality and performance assessments should consider physician-patient language concordance.

Effect of Host, Tumor, Diagnostic, and Treatment Variables on Outcomes in a Large Cohort With Merkel Cell Carcinoma

IMPORTANCE Merkel cell carcinoma (MCC) is a rare, aggressive, neuroendocrine-derived skin cancer with high rates of recurrence and associated mortality. Few published studies have used comprehensive patient data and long-term follow-up to examine factors that predict MCC outcomes. OBJECTIVE To characterize MCC in a large defined-population cohort and analyze predictors of disease recurrence and survival. SETTING, DESIGN, AND PARTICIPANTS Retrospective cohort study of 218 patients with MCC from the cancer registry of Kaiser Permanente Northern California, a large integrated health care delivery system. Patients were diagnosed as having MCC and followed up from January 1, 1995, through December 31, 2009. We examined host (age, sex, race, and immunosuppression), tumor (anatomic site, size, and extent), diagnostic (results of imaging and pathologic nodal evaluation), and treatment (surgery, radiation therapy, and chemotherapy) variables for their association with MCC outcomes. EXPOSURE Host, tumor, diagnostic, and treatment factors. MAIN OUTCOMES AND MEASURES Recurrence (locoregional and distant) of MCC and patient survival (overall and MCC specific). RESULTS We estimated adjusted hazard ratios (AHRs) and 95% CIs for outcomes using Cox proportional hazards regression models. After adjustment for host, tumor, diagnostic, and treatment variables, tumor extent (categorized as local, regional, and distant) remained significantly associated with all outcomes. Immunosuppression was associated with higher MCC-specific mortality (AHR, 4.9 [95% CI, 1.7-14.4]), and an unknown primary site was associated with a lower risk for distant metastasis (0.1 [0.0-0.7]) and improved survival (0.4 [0.2-0.9]). Pathological nodal evaluation was associated with a lower risk for metastasis (AHR, 0.2 [95% CI, 0.0-1.0]) and improved survival. Radiation treatment was associated with a decreased risk for locoregional recurrence (AHR, 0.3 [95% CI, 0.1-0.6]), whereas chemotherapy was not associated with any alteration in outcomes. CONCLUSIONS AND RELEVANCE Tumor site and extent, results of pathologic nodal evaluation, and the presence of radiation treatment were associated with MCC recurrence. Immunosuppression, tumor extent, and results of pathologic nodal evaluation were associated with MCC-specific survival, whereas chemotherapy was not associated with any outcomes. Our findings may help to inform diagnostic and therapeutic management of MCCs.

CD8+ lymphocyte intratumoral infiltration as a stage-independent predictor of Merkel cell carcinoma survival: a population-based study.

OBJECTIVES Intratumoral CD8+ lymphocytes (IT-CD8s) have shown promise as a prognostic indicator for Merkel cell carcinoma (MCC). We tested whether IT-CD8s predict survival among a population-based MCC cohort. METHODS One hundred thirty-seven MCC cases that had not previously been analyzed for IT-CD8s were studied. RESULTS Three-year MCC-specific survival rates were 56%, 72%, and 100% for patients with absent (n = 46), low (n = 85), and moderate or strong (n = 6) IT-CD8s, respectively. Increased IT-CD8s were associated with improved MCC-specific survival in a multivariate competing risk-regression analysis including stage, age, and sex (hazard ratio [HR] = 0.5; 95% confidence interval [CI] = 0.3-0.9). Although a similar trend was observed for overall survival, statistical significance was not reached (HR = 0.8; 95% CI = 0.6-1.0), likely because of the high rate of non-MCC deaths among older patients. CONCLUSIONS This study of prospectively captured MCC cases supports the concept that cellular immunity is important in MCC outcome and that CD8+ lymphocyte infiltration adds prognostic information to conventional staging.

Antihypertensive drugs and lip cancer in non-Hispanic whites

BACKGROUND In screening pharmaceuticals for possible carcinogenic effects we noted an association between lip cancer risk and the photosensitizing antihypertensive drugs hydrochlorothiazide and nifedipine. In this study, we further characterized the risk of lip cancer associated with these and other commonly used antihypertensive drugs. METHODS In a comprehensive medical care program, we evaluated prescriptions dispensed and cancer occurrence from August 1, 1994, to February 29, 2008. We identified 712 patients with lip cancer (cases) and 22,904 comparison individuals (controls) matched for age, sex, and cohort year of entry in the susceptible group, non-Hispanic whites. We determined use, at least 2 years before diagnosis or control index date, of the commonly prescribed diuretics hydrochlorothiazide and hydrochlorothiazide combined with triamterene, the angiotensin-converting enzyme inhibitor lisinopril, the calcium channel blocker nifedipine, and the β-adrenergic blocker atenolol, the only nonphotosensitizer agent studied. We analyzed the use of each drug exclusively and regardless of use of the others, and focused on duration of use. Conditional logistic regression was used for analysis of matched case-control sets, with control for cigarette smoking. RESULTS At least a 5-year supply of a drug yielded the following odds ratios (95% CIs), respectively, compared with no use: hydrochlorothiazide, 4.22 (2.82-6.31); hydrochlorothiazide-triamterene, 2.82 (1.74-4.55); lisinopril, 1.42 (0.95-2.13); nifedipine, 2.50 (1.29-4.84); and atenolol, 1.93 (1.29-2.91). When the other drugs were excluded, the odds ratio for atenolol was reduced to 0.54 (0.07-4.08). CONCLUSION These data support an increased risk of lip cancer in non-Hispanic whites receiving treatment for hypertension with long-term use of photosensitizing drugs.

The effect of bariatric surgery on psychiatric course among patients with bipolar disorder

Bariatric surgery is the most effective therapy for severe obesity. People with bipolar disorder have increased risk of obesity, yet are sometimes considered ineligible for bariatric surgery due to their bipolar disorder diagnosis. This study aimed to determine if bariatric surgery alters psychiatric course among stable patients with bipolar disorder.