OBJECTIVE: Some preclinical in vivo studies and limited human data suggest a possible increased risk of bladder cancer with pioglitazone therapy. This is an interim report of an ongoing cohort study ...examining the association between pioglitazone therapy and the risk of bladder cancer in patients with diabetes. RESEARCH DESIGN AND METHODS: This study includes 193,099 patients in the Kaiser Permanente Northern California diabetes registry who were ≥40 years of age between 1997 and 2002. Those with prior bladder cancer were excluded. Ever use of each diabetes medication (defined as two or more prescriptions within 6 months) was treated as a time-dependent variable. Cox regression-generated hazard ratios (HRs) compared pioglitazone use with nonpioglitazone use adjusted for age, sex, race/ethnicity, diabetes medications, A1C, heart failure, household income, renal function, other bladder conditions, and smoking. RESULTS: The group treated with pioglitazone comprised 30,173 patients. There were 90 cases of bladder cancer among pioglitazone users and 791 cases of bladder cancer among nonpioglitazone users. Overall, ever use of pioglitazone was not associated with risk of bladder cancer (HR 1.2 95% CI 0.9-1.5), with similar results in men and women (test for interaction P = 0.8). However, in the a priori category of >24 months of therapy, there was an increased risk (1.4 1.03-2.0). Ninety-five percent of cancers diagnosed among pioglitazone users were detected at early stage. CONCLUSIONS: In this cohort of patients with diabetes, short-term use of pioglitazone was not associated with an increased incidence of bladder cancer, but use for more than 2 years was weakly associated with increased risk.
Although acute hypoglycemia may be associated with cognitive impairment in children with type 1 diabetes, no studies to date have evaluated whether hypoglycemia is a risk factor for dementia in older ...patients with type 2 diabetes.
To determine if hypoglycemic episodes severe enough to require hospitalization are associated with an increased risk of dementia in a population of older patients with type 2 diabetes followed up for 27 years.
A longitudinal cohort study from 1980-2007 of 16,667 patients with a mean age of 65 years and type 2 diabetes who are members of an integrated health care delivery system in northern California.
Hypoglycemic events from 1980-2002 were collected and reviewed using hospital discharge and emergency department diagnoses. Cohort members with no prior diagnoses of dementia, mild cognitive impairment, or general memory complaints as of January 1, 2003, were followed up for a dementia diagnosis through January 15, 2007. Dementia risk was examined using Cox proportional hazard regression models, adjusted for age, sex, race/ethnicity, education, body mass index, duration of diabetes, 7-year mean glycated hemoglobin, diabetes treatment, duration of insulin use, hyperlipidemia, hypertension, cardiovascular disease, stroke, transient cerebral ischemia, and end-stage renal disease.
At least 1 episode of hypoglycemia was diagnosed in 1465 patients (8.8%) and dementia was diagnosed in 1822 patients (11%) during follow-up; 250 patients had both dementia and at least 1 episode of hypoglycemia (16.95%). Compared with patients with no hypoglycemia, patients with single or multiple episodes had a graded increase in risk with fully adjusted hazard ratios (HRs): for 1 episode (HR, 1.26; 95% confidence interval CI, 1.10-1.49); 2 episodes (HR, 1.80; 95% CI, 1.37-2.36); and 3 or more episodes (HR, 1.94; 95% CI, 1.42-2.64). The attributable risk of dementia between individuals with and without a history of hypoglycemia was 2.39% per year (95% CI, 1.72%-3.01%). Results were not attenuated when medical utilization rates, length of health plan membership, or time since initial diabetes diagnosis were added to the model. When examining emergency department admissions for hypoglycemia for association with risk of dementia (535 episodes), results were similar (compared with patients with 0 episodes) with fully adjusted HRs: for 1 episode (HR, 1.42; 95% CI, 1.12-1.78) and for 2 or more episodes (HR, 2.36; 95% CI, 1.57-3.55).
Among older patients with type 2 diabetes, a history of severe hypoglycemic episodes was associated with a greater risk of dementia. Whether minor hypoglycemic episodes increase risk of dementia is unknown.
Abstract Introduction Reducing racial/ethnic disparities is a primary objective of the National Alzheimer's Plan (NAPA), yet direct comparisons within large samples representing diversity of the ...United States are lacking. Methods Dementia incidence from January 1, 2000 to December 31, 2013 and a 25-year cumulative risk in 274,283 health care members aged 64+ (n = 18,778 African-American, n = 4543 American Indian/Alaska Native AIAN, n = 21,000 Latino, n = 440 Pacific Islander, n = 206,490 white, n = 23,032 Asian-Americans). Cox proportional hazard models were adjusted for age, sex, medical utilization, and comorbidities. Results Dementia incidence (n = 59,555) was highest for African-Americans (26.6/1000 person-years) and AIANs (22.2/1000 person-years); intermediate for Latinos (19.6/1000 person-years), Pacific Islanders (19.6/1000 person-years), and whites (19.3/1000 person-years) and lowest among Asian-Americans (15.2/1000 person-years). Risk was 65% greater for African-Americans (hazard ratio = 1.65; 95% confidence interval = 1.58–1.72) versus Asian-Americans. Cumulative 25-year risk at age 65 was as follows: 38% African-Americans, 35% AIANs, 32% Latino, 25% Pacific Islanders, 30% white, and 28% Asian-Americans. Discussion Dementia rates varied over 60% between groups, providing a comprehensive benchmark for the NAPA goal of reducing disparities.
There are limited data on the risk of pulmonary disease in patients with diabetes. The aim of this study was to evaluate and compare the incidence of asthma, chronic obstructive pulmonary disease ...(COPD), pulmonary fibrosis, pneumonia, and lung cancer in patients with and without a diagnosis of diabetes.
We conducted a retrospective, longitudinal cohort study using the electronic records of a large health plan in northern California. Age and sex data were available for all cohort members (n = 1,811,228). Data on confounders were available for a subcohort that responded to surveys (n = 121,886), among whom Cox proportional hazards regression models were fit.
Age- and sex-adjusted incidence rates and 95% CIs were calculated for members with and without diabetes in the full cohort and the subcohort. No difference was observed for lung cancer, but the incidence of asthma, COPD, fibrosis, and pneumonia was significantly higher in those members with a diagnosis of diabetes. These differences remained significant in regression models adjusted for age, sex, race/ethnicity, smoking, BMI, education, alcohol consumption, and outpatient visits (asthma hazard ratio HR 1.08 95% CI 1.03-1.12, COPD HR 1.22 1.15-1.28, pulmonary fibrosis HR 1.54 1.31-1.81, and pneumonia HR 1.92 1.84-1.99). The risk of pneumonia and COPD increased significantly with increasing A1C.
Individuals with diabetes are at increased risk of several pulmonary conditions (asthma, COPD, fibrosis, and pneumonia) but not lung cancer. This increased risk may be a consequence of declining lung function in patients with diabetes.
Abstract Introduction Post-traumatic stress disorder (PTSD) is associated with an increased risk of dementia in male veterans, but little is known in females and civilians. Methods PTSD and ...comorbidities were abstracted from medical records from 1/1/1996 to 12/31/2001. Dementia incidence from 1/1/2002 to 12/31/2014 in 499,844 health care members aged 60+ years over an average of 8.2 years. Cox proportional hazard models were adjusted for age, demographics, and comorbidities. Results PTSD was associated with increased risk of dementia over an average of 8 years of follow-up (females: hazard ratio HR = 1.59, 95% confidence interval CI = 1.30–1.95; males: HR = 1.96, 95% CI = 1.51–2.55). There was a two-fold risk of dementia in those with both PTSD and depression (females: HR = 2.08; 95% CI = 1.66–2.59; males: HR = 2.06; 95% CI = 1.47–2.91) versus those without. Discussion PTSD was a risk factor for dementia in both sexes, with a heightened risk in those with comorbid depression.
Background: The timely onset of stage II lactogenesis (OL) is important for successful breastfeeding and newborn health. Several risk factors for delayed OL are common in women with a history of ...gestational diabetes mellitus (GDM), which may affect their chances for successful breastfeeding outcomes.Objective: We investigated the prevalence and risk factors associated with delayed OL in a racially and ethnically diverse cohort of postpartum women with recent GDM.Design: We analyzed data collected in the Study of Women, Infant Feeding and Type 2 Diabetes After GDM Pregnancy (SWIFT), which is a prospective cohort of women diagnosed with GDM who delivered at Kaiser Permanente Northern California hospitals from 2008 to 2011. At 6–9 wk postpartum, delayed OL was assessed by maternal report of breast fullness and defined as occurring after 72 h postpartum. We obtained data on prenatal course and postdelivery infant feeding practices from electronic medical records and in-person surveys. We used multivariable logistic regression models to estimate associations of delayed OL with prenatal, delivery, and postnatal characteristics.Results: The analysis included 883 SWIFT participants who initiated breastfeeding and did not have diabetes at 6–9 wk postpartum. Delayed OL was reported by 33% of women and was associated with prepregnancy obesity (OR: 1.56; 95% CI: 1.07, 2.29), older maternal age (OR: 1.05; 95% CI: 1.01, 1.08), insulin GDM treatment (OR: 3.11; 95% CI: 1.37, 7.05), and suboptimal in-hospital breastfeeding (OR: 1.65; 95% CI: 1.20, 2.26). A higher gestational age was associated with decreased odds of delayed OL but only in multiparous mothers (OR: 0.79; 95% CI: 0.67, 0.94).Conclusions: One-third of women with recent GDM experienced delayed OL. Maternal obesity, insulin treatment, and suboptimal in-hospital breastfeeding were key risk factors for delayed OL. Early breastfeeding support for GDM women with these risk factors may be needed to ensure successful lactation. This trial was registered at clinicaltrials.gov as NCT01967030.
OBJECTIVE: To explore whether treatment with pioglitazone was associated with risk of incident cancer at the 10 most common sites (prostate, female breast, lung/bronchus, endometrial, colon, ...non-Hodgkin lymphoma NHL, pancreas, kidney/renal pelvis, rectal, and melanoma). RESEARCH DESIGN AND METHODS: A cohort study of 252,467 patients aged ≥40 years from the Kaiser Permanente Northern California Diabetes Registry was conducted. All prescriptions for diabetes medications were identified by pharmacy records. Cox proportional hazards models were used to examine the association between risk of incident cancer and ever use, duration, dose, and time since initiation of pioglitazone (modeled as time-dependent variables). RESULTS: In models adjusted for age, sex, year of cohort entry, race/ethnicity, income, smoking, glycemic control, diabetes duration, creatinine levels, congestive heart failure, and use of other diabetes medications, the hazard ratio (HR) for each cancer associated with ever use of pioglitazone ranged from 0.7 to 1.3, with all 95% CIs including 1.0. There was a suggestion of an increased risk of melanoma (HR 1.3 95% CI 0.9-2.0) and NHL (1.3 1.0-1.8) and a decreased risk of kidney/renal pelvis cancers (0.7 0.4-1.1) associated with ever use of pioglitazone. These associations were unaltered with increasing dose, duration, or time since first use. CONCLUSIONS: We found no clear evidence of an association between use of pioglitazone and risk of the incident cancers examined. Because the maximum duration of follow-up was fewer than 6 years after the initiation of pioglitazone, longer-term studies are needed.
Although risk factors for indoor falls among older individuals have been well studied, little is known about the etiology of outdoor falls. We examined risk factors for outdoor falls among ...middle-aged and older adults.
We analyzed data on the most recent fall during the past year among participants aged 45 years and older in the control group (N=2193) of a case-control study of fractures. The study was conducted at 5 Northern California Kaiser Permanente Medical Centers between 1996 and 2001.
Falls occurred outdoors more often than indoors among most age groups. Study participants who reported more leisure-time physical activity had a higher risk for outdoor falls, and participants who were in poorer health had a greater risk for indoor falls. Most outdoor falls (73%) were precipitated by environmental factors, such as uneven surfaces and tripping or slipping on objects, and usually occurred on sidewalks, curbs, and streets. Walking (47.3%) was the most common fall-related activity.
Outdoor falls among adults aged 45 years and older were frequently attributable to modifiable environmental factors. With the widespread promotion of active lifestyles among older people, improvements in their outdoor environment are urgently needed.
It is unknown if a survival gap remains between HIV-infected and HIV-uninfected individuals with access to care.
We conducted a cohort study within Kaiser Permanente California during 1996-2011, ...using abridged life tables to estimate the expected years of life remaining ("life expectancy") at age 20.
Among 24,768 HIV-infected and 257,600 HIV-uninfected individuals, there were 2229 and 4970 deaths, with mortality rates of 1827 and 326 per 100,000 person-years, respectively. In 1996-1997, life expectancies at age 20 for HIV-infected and HIV-uninfected individuals were 19.1 and 63.4 years, respectively, corresponding with a gap of 44.3 years (95% confidence interval: 38.4 to 50.2). Life expectancy at age 20 for HIV-infected individuals increased to 47.1 years in 2008 and 53.1 years by 2011, narrowing the gap to 11.8 years (8.9-14.8 years) in 2011. In 2008-2011, life expectancies at age 20 for HIV-infected individuals ranged from a low of 45.8 years for blacks and 46.0 years for those with a history of injection drug use to a high of 52.2 years for Hispanics. HIV-infected individuals who initiated antiretroviral therapy with CD4 ≥500 cells per microliter had a life expectancy at age 20 of 54.5 years in 2008-2011, narrowing the gap relative to HIV-uninfected individuals to 7.9 years (5.1-10.6 years). For these HIV-infected individuals, the gap narrowed further in subgroups with no history of hepatitis B or C infection, smoking, drug/alcohol abuse, or any of these risk factors.
Even with early treatment and access to care, an 8-year gap in life expectancy remains for HIV-infected compared with HIV-uninfected individuals.
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