Elevated Serum Androstenedione Level in a Patient With Ectopic Adrenocorticotropic Hormone Syndrome.

Background/Objective: Ectopic Cushing syndrome can be challenging to diagnose when its presentation is atypical. Herein, we highlight features of ectopic adrenocorticotropic hormone (ACTH) syndrome in a patient with worsening hypertension, hypokalemia, ACTH-dependent hypercortisolism, and disproportionate elevation in serum androstenedione levels. Case Report: A 59-year-old woman presented with rapidly progressing hypertension, severe hypokalemia, confusion, and weakness. Her medical history included well-controlled hypertension receiving amlodipine 5 mg/day, which worsened 3 months prior to admission requiring losartan and spironolactone therapy, with twice daily potassium supplementation. Physical examination was notable for bruising, muscle wasting, thin extremities, facial fullness, and abdominal adiposity despite body mass index 17 kg/m2. Laboratory evaluation showed potassium 2.6 mEq/L (3.5-5.3), morning cortisol >50 mcg/dL (8-25), 24-hour urine cortisol 8369 mcg/day (<50), ACTH 308 pg/mL (<46), androstenedione 398 ng/dL (20-75), dehydroepiandrosterone sulfate 48 mcg/dL (≤430), and testosterone 11 ng/dL (≤4.5) levels. A 3.8-cm carcinoid right lung tumor was identified, and resection was performed with clean margins. Cortisol, androstenedione, and potassium levels rapidly normalized postoperatively and blood pressure returned to baseline, well-controlled on amlodipine. Discussion: Our case illustrates disproportionate elevation in androstenedione levels despite normal dehydroepiandrosterone sulfate and testosterone in a woman with ectopic ACTH syndrome. Limited reports have observed similar discordance in androgen profiles in ectopic versus pituitary ACTH hypersecretion, potentially attributable to differential activation of androgen biosynthesis. Conclusion: Adrenal androgen assessment may help differentiate pituitary versus ectopic ACTH secretion in which androstenedione is elevated, but studies are needed to determine whether disproportionate androstenedione elevation reliably predicts the origin of ACTH excess.

Reducing Cardiovascular Risk for Patients With Diabetes: An Evidence-Based, Population Health Management Program.

ABSTRACT: Those with diabetes are at an increased risk of cardiovascular disease (CVD). Safety net clinics serve populations that bear a significant burden of disease and disparities and are a key setting in which to focus on reducing CVD. An integrated health system provided funding and technical assistance (TA) to safety net organizations (community health centers and public hospitals) in Northern California to decrease the risk of cardiovascular events for patients with diabetes. This was a program called Preventing Heart Attacks and Strokes Everyday (PHASE), which combined an evidence-based medication protocol with population health management and team-based care strategies. The TA supported organizations by sharing best practices, providing quality improvement coaching, and facilitating peer learning. A mixed-methods evaluation found that organizations involved in PHASE improved rates of blood pressure control and cardioprotective medication prescriptions for patients with diabetes. They made progress on these measures through strategies such as leveraging team-based care, providing education on evidence-based protocols, and using data to drive improvements. The evaluation concluded that financially supporting and providing focused TA to safety net organizations can help them build capacity and leverage their strengths to improve outcomes and potentially decrease the risk of heart attacks and strokes in communities.

Treatment Patterns and Blood Pressure Control With Initiation of Combination Versus Monotherapy Antihypertensive Regimens.

Many patients with hypertension require 2 or more drug classes to achieve their blood pressure (BP) goal. We compared antihypertensive medication treatment patterns and BP control between patients who initiated combination therapy versus monotherapy. We identified adults with hypertension enrolled in a US integrated healthcare system who initiated antihypertensive medication between 2008 and 2014. Patient demographics, clinical characteristics, antihypertensive medication, and BP were extracted from electronic health records. Antihypertensive medication patterns and multivariable adjusted prevalence ratios (PRs) of achieving the 2017 American College of Cardiology/American Heart Association guideline-recommended BP <130/80 mm Hg were evaluated for 2 years following treatment initiation. Of 135 971 patients, 43% initiated antihypertensive combination therapy (35% ACE [angiotensin converting enzyme] inhibitor (ACEI)-thiazide diuretics; 8% with other combinations) and 57% initiated monotherapy (22% ACEIs; 16% thiazide diuretics; 11% ß blockers; 8% calcium channel blockers). After multivariable adjustment including premedication BP levels, patients who initiated ACEI-thiazide diuretic combination therapy were more likely to achieve BP <130/80 mm Hg compared with their counterparts who initiated monotherapy with ACEI (PR, 1.10 [95% CI, 1.08-1.12]), thiazide diuretic (PR, 1.21 [95% CI, 1.18-1.24]), ß blocker (PR, 1.17 [95% CI, 1.14-1.20]), or calcium channel blocker (PR, 1.25 [95% CI, 1.22-1.29]). Compared with initiating monotherapy, patients initiating ACEI-thiazide diuretic combination therapy were more likely to achieve BP goals.

Inpatient-outpatient shared electronic health records: telemedicine and laboratory follow-up after hospital discharge.

OBJECTIVES: Continuity of patient information across settings can improve transitions after hospital discharge, but outpatient clinicians often have limited access to complete information from recent hospitalizations. We examined whether providers' timely access to clinical information through shared inpatient-outpatient electronic health records (EHRs) was associated with follow-up visits, return emergency department (ED) visits, or readmissions after hospital discharge in patients with diabetes. STUDY DESIGN: Stepped-wedge observational study. METHODS: As an integrated delivery system staggered implementation of a shared inpatient-outpatient EHR, we studied 241,510 hospital discharges in patients with diabetes (2005-2011), examining rates of outpatient follow-up office visits, telemedicine (phone visits and asynchronous secure messages), laboratory tests, and return ED visits or readmissions (as adverse events). We used multivariate logistic regression adjusting for time trends, patient characteristics, and medical center and accounting for patient clustering to calculate adjusted follow-up rates. RESULTS: For patients with diabetes, provider use of a shared inpatient-outpatient EHR was associated with a statistically significant shift toward follow-up delivered through a combination of telemedicine and outpatient laboratory tests, without a traditional in-person visit (from 22.9% with an outpatient-only EHR to 27.0% with a shared inpatient-outpatient EHR; P < .05). We found no statistically significant differences in 30-day return ED visits (odds ratio, 1.02; 95% CI, 0.96-1.09) or readmissions (odds ratio, 0.98; 95% CI, 0.91-1.06) with the shared EHR compared with the outpatient-only EHR. CONCLUSIONS: Real-time clinical information availability during transitions between health care settings, along with robust telemedicine access, may shift the method of care delivery without adversely affecting patient health outcomes. Efforts to expand interoperability and information exchange may support follow-up care efficiency.

Cumulative Adherence to Secondary Prevention Guidelines and Mortality After Acute Myocardial Infarction.

Background The survival benefit associated with cumulative adherence to multiple clinical and lifestyle-related guideline recommendations for secondary prevention after acute myocardial infarction (AMI) is not well established. Methods and Results We examined adults with AMI (mean age 68 years; 64% men) surviving at least 30 (N=25 778) or 90  (N=24 200) days after discharge in a large integrated healthcare system in Northern California from 2008 to 2014. The association between all-cause death and adherence to 6 or 7 secondary prevention guideline recommendations including medical treatment (prescriptions for ß-blockers, renin-angiotensin-aldosterone system inhibitors, lipid medications, and antiplatelet medications), risk factor control (blood pressure <140/90 mm Hg and low-density lipoprotein cholesterol <100 mg/dL), and lifestyle approaches (not smoking) at 30 or 90 days after AMI was evaluated with Cox proportional hazard models. To allow patients time to achieve low-density lipoprotein cholesterol <100 mg/dL, this metric was examined only among those alive 90 days after AMI. Overall guideline adherence was high (35% and 34% met 5 or 6 guidelines at 30 days; and 31% and 23% met 6 or 7 at 90 days, respectively). Greater guideline adherence was independently associated with lower mortality (hazard ratio, 0.57 [95% CI, 0.49-0.66] for those meeting 7 and hazard ratio, 0.69 [95% CI, 0.61-0.78] for those meeting 6 guidelines versus 0 to 3 guidelines in 90-day models, with similar results in the 30-day models), with significantly lower mortality per each additional guideline recommendation achieved. Conclusions In a large community-based population, cumulative adherence to guideline-recommended medical therapy, risk factor control, and lifestyle changes after AMI was associated with improved long-term survival. Full adherence was associated with the greatest survival benefit.

Comparative Trends in Heart Disease, Stroke, and All-Cause Mortality in the United States and a Large Integrated Healthcare Delivery System.

OBJECTIVES: Heart disease and stroke remain among the leading causes of death nationally. We examined whether differences in recent trends in heart disease, stroke, and total mortality exist in the United States and Kaiser Permanente Northern California (KPNC), a large integrated healthcare delivery system. METHODS: The main outcome measures were comparisons of US and KPNC total, age-specific, and sex-specific changes from 2000 to 2015 in mortality rates from heart disease, coronary heart disease, stroke, and all causes. The Centers for Disease Control and Prevention Wide-Ranging Online Data for Epidemiologic Research data system was used to determine US mortality rates. Mortality rates for KPNC were determined from health system, Social Security vital status, and state death certificate databases. RESULTS: Declines in age-adjusted mortality rates were noted in KPNC and the United States for heart disease (36.3% in KPNC vs 34.6% in the United States), coronary heart disease (51.0% vs 47.9%), stroke (45.5% vs 38.2%), and all-cause mortality (16.8% vs 15.6%). However, steeper declines were noted in KPNC than the United States among those aged 45 to 65 years for heart disease (48.3% KPNC vs 23.6% United States), coronary heart disease (55.6% vs 35.9%), stroke (55.8% vs 26.0%), and all-cause mortality (31.5% vs 9.1%). Sex-specific changes were generally similar. CONCLUSIONS: Despite significant declines in heart disease and stroke mortality, there remains an improvement gap nationally among those aged less than 65 years when compared with a large integrated healthcare delivery system. Interventions to improve cardiovascular mortality in the vulnerable middle-aged population may play a key role in closing this gap.

Improved Cardiovascular Risk Factors Control Associated with a Large-Scale Population Management Program Among Diabetes Patients.

BACKGROUND: Optimal cardiovascular risk factors control among individuals with diabetes remains a challenge. We evaluated changes in glucose, lipid, and blood pressure control among diabetes patients after implementation of a large-scale population management program, known as Preventing Heart Attacks and Strokes Everyday, at Kaiser Permanente Northern California (KPNC), during 2004-2013. METHODS: We used National Committee for Quality Assurance Healthcare Effectiveness Data and Information Set cut points to identify prevalence of poor glycemic (hemoglobin A1c > 9%) control, good lipid control (low-density lipoprotein cholesterol < 100 mg/dL), and good blood pressure control (blood pressure < 140/90 mm Hg) in each year (N range = 98,345 to 122,177 over the entire period). We assessed trends in risk factor control based on Joinpoint regression and average annual percentage change (AAPC) compared with published National Committee for Quality Assurance Healthcare Effectiveness Data and Information Set commercial rates. RESULTS: We found that the prevalence of poor glycemic control (hemoglobin A1c > 9%) declined in both KPNC and nationally, but was statistically significant only in KPNC (AAPC = -4.8; P < .05). The prevalence of good lipid control (low-density lipoprotein cholesterol < 100 mg/dL) increased significantly in KPNC (47% to 71%; AAPC = +4.3; P < .05), but there was no significant improvement nationally (40% to 44%; AAPC = +1.4; P = .2). The prevalence of blood pressure control (<140/90 mm Hg) was higher in KPNC (77% to 82%; AAPC = +1.1; P < .05) versus nationally (57% to 62%; AAPC = +1.9; P < .05) during the reported years 2007-2013. CONCLUSIONS: Relative to national benchmarks, a substantially greater improvement in risk factor control among adults with diabetes was observed after implementation of a comprehensive population management program.

Accuracy of the Atherosclerotic Cardiovascular Risk Equation in a Large Contemporary, Multiethnic Population.

BACKGROUND: The accuracy of the 2013 American College of Cardiology/American Heart Association (ACC/AHA) Pooled Cohort Risk Equation for atherosclerotic cardiovascular disease (ASCVD) events in contemporary and ethnically diverse populations is not well understood. OBJECTIVES: The goal of this study was to evaluate the accuracy of the 2013 ACC/AHA Pooled Cohort Risk Equation within a large, multiethnic population in clinical care. METHODS: The target population for consideration of cholesterol-lowering therapy in a large, integrated health care delivery system population was identified in 2008 and followed up through 2013. The main analyses excluded those with known ASCVD, diabetes mellitus, low-density lipoprotein cholesterol levels <70 or ≥190 mg/dl, prior lipid-lowering therapy use, or incomplete 5-year follow-up. Patient characteristics were obtained from electronic medical records, and ASCVD events were ascertained by using validated algorithms for hospitalization databases and death certificates. We compared predicted versus observed 5-year ASCVD risk, overall and according to sex and race/ethnicity. We additionally examined predicted versus observed risk in patients with diabetes mellitus. RESULTS: Among 307,591 eligible adults without diabetes between 40 and 75 years of age, 22,283 were black, 52,917 were Asian/Pacific Islander, and 18,745 were Hispanic. We observed 2,061 ASCVD events during 1,515,142 person-years. In each 5-year predicted ASCVD risk category, observed 5-year ASCVD risk was substantially lower: 0.20% for predicted risk <2.50%; 0.65% for predicted risk 2.50% to <3.75%; 0.90% for predicted risk 3.75% to <5.00%; and 1.85% for predicted risk ≥5.00% (C statistic: 0.74). Similar ASCVD risk overestimation and poor calibration with moderate discrimination (C statistic: 0.68 to 0.74) were observed in sex, racial/ethnic, and socioeconomic status subgroups, and in sensitivity analyses among patients receiving statins for primary prevention. Calibration among 4,242 eligible adults with diabetes was improved, but discrimination was worse (C statistic: 0.64). CONCLUSIONS: In a large, contemporary "real-world" population, the ACC/AHA Pooled Cohort Risk Equation substantially overestimated actual 5-year risk in adults without diabetes, overall and across sociodemographic subgroups.

Ethnic Differences in Risk of Coronary Heart Disease in a Large Contemporary Population.

INTRODUCTION: Racial/ethnic differences in diabetes and cardiovascular disease are well documented, but disease estimates are often confounded by differences in access to quality health care. The objective of this study was to evaluate the ethnic differences in risk of future coronary heart disease in patient populations stratified by status of diabetes mellitus and prior coronary heart disease among those with uniform access to care in an integrated healthcare delivery system in Northern California. METHODS: A cohort was constructed consisting of 1,344,899 members with self-reported race/ethnicity, aged 30-90 years, and followed from 2002 through 2012. Cox proportional hazard regression models were specified to estimate race/ethnicity-specific hazard ratios for coronary heart disease (with whites as the reference category) separately in four clinical risk categories: (1) no diabetes with no prior coronary heart disease; (2) no diabetes with prior coronary heart disease; (3) diabetes with no prior coronary heart disease; and (4) diabetes with prior coronary heart disease. Analyses were performed in 2015. RESULTS: The median follow-up was 10 years (10,980,800 person-years). Compared with whites, blacks, Latinos, and Asians generally had lower risk of coronary heart disease across all clinical risk categories, with the exception of blacks with prior coronary heart disease and no diabetes having higher risk than whites. Findings were not substantively altered after multivariate adjustments. CONCLUSIONS: Identification of health outcomes in a system with uniform access to care reveals residual racial/ethnic differences and point to opportunities to improve health in specific subgroups and to improve health equity.

Diabetes and Prior Coronary Heart Disease are Not Necessarily Risk Equivalent for Future Coronary Heart Disease Events.

BACKGROUND: For more than a decade, the presence of diabetes has been considered a coronary heart disease (CHD) "risk equivalent". OBJECTIVE: The objective of this study was to revisit the concept of risk equivalence by comparing the risk of subsequent CHD events among individuals with or without history of diabetes or CHD in a large contemporary real-world cohort over a period of 10 years (2002 to 2011). DESIGN: Population-based prospective cohort analysis. PARTICIPANTS: We studied a cohort of 1,586,061 adult members (ages 30-90 years) of Kaiser Permanente Northern California, an integrated health care delivery system. MAIN MEASUREMENTS: We calculated hazard ratios (HRs) from Cox proportional hazard models for CHD among four fixed cohorts, defined by prevalent (baseline) risk group: no history of diabetes or CHD (None), prior CHD alone (CHD), diabetes alone (DM), and diabetes and prior CHD (DM + CHD). KEY RESULTS: We observed 80,012 new CHD events over the follow-up period (~10,980,800 person-years). After multivariable adjustment, the HRs (reference: None) for new CHD events were as follows: CHD alone, 2.8 (95% CI, 2.7-2.85); DM alone 1.7 (95% CI, 1.66-1.74); DM + CHD, 3.9 (95% CI, 3.8-4.0). Individuals with diabetes alone had significantly lower risk of CHD across all age and sex strata compared to those with CHD alone (12.2 versus 22.5 per 1000 person-years). The risk of future CHD for patients with a history of either DM or CHD was similar only among those with diabetes of long duration (≥10 years). CONCLUSIONS: Not all individuals with diabetes should be unconditionally assumed to be a risk equivalent of those with prior CHD.

Implementation of an outpatient electronic health record and emergency department visits, hospitalizations, and office visits among patients with diabetes.

IMPORTANCE: The US federal government is spending billions of dollars in physician incentives to encourage the meaningful use of electronic health records (EHRs). Although the use of EHRs has potential to improve patient health outcomes, the existing evidence has been limited and inconsistent. OBJECTIVE: To examine the association between implementing a commercially available outpatient EHR and emergency department (ED) visits, hospitalizations, and office visits for patients with diabetes mellitus. DESIGN, SETTING, AND POPULATION: Staggered EHR implementation across outpatient clinics in an integrated delivery system (Kaiser Permanente Northern California) between 2005 and 2008 created an opportunity for studying changes associated with EHR use. Among a population-based sample of 169,711 patients with diabetes between 2004 and 2009, we analyzed 4,997,585 person-months before EHR implementation and 4,648,572 person-months after an EHR was being used by patients' physicians. MAIN OUTCOMES AND MEASURES: We examined the association between EHR use and unfavorable clinical events (ED visits and hospitalizations) and office visit use among patients with diabetes, using multivariable regression with patient-level fixed-effect analyses and adjustment for trends over time. RESULTS: In multivariable analyses, use of the EHR was associated with a statistically significantly decreased number of ED visits, 28.80 fewer visits per 1000 patients annually (95% CI, 20.28 to 37.32), from a mean of 519.12 visits per 1000 patients annually without using the EHR to 490.32 per 1000 patients when using the EHR. The EHR was also associated with 13.10 fewer hospitalizations per 1000 patients annually (95% CI, 7.37 to 18.82), from a mean of 251.60 hospitalizations per 1000 patients annually with no EHR to 238.50 per 1000 patients annually when using the EHR. There were similar statistically significant reductions in nonelective hospitalizations (10.92 fewer per 1000 patients annually) and hospitalizations for ambulatory care-sensitive conditions (7.08 fewer per 1000 patients annually). There was no statistically significant association between EHR use and office visit rates. CONCLUSIONS AND RELEVANCE: Among patients with diabetes, use of an outpatient EHR in an integrated delivery system was associated with modest reductions in ED visits and hospitalizations but not office visit rates. Further studies are needed to quantify the association of EHR use with changes in costs.

Improved blood pressure control associated with a large-scale hypertension program.

IMPORTANCE: Hypertension control for large populations remains a major challenge. OBJECTIVE: To describe a large-scale hypertension program in Northern California and to compare rates of hypertension control in that program with statewide and national estimates. DESIGN, SETTING, AND PATIENTS: The Kaiser Permanente Northern California (KPNC) hypertension program included a multifaceted approach to blood pressure control. Patients identified as having hypertension within an integrated health care delivery system in Northern California from 2001-2009 were included. The comparison group comprised insured patients in California between 2006-2009 who were included in the Healthcare Effectiveness Data and Information Set (HEDIS) commercial measurement by California health insurance plans participating in the National Committee for Quality Assurance (NCQA) quality measure reporting process. A secondary comparison group was included to obtain the reported national mean NCQA HEDIS commercial rates of hypertension control between 2001-2009 from health plans that participated in the NCQA HEDIS quality measure reporting process. MAIN OUTCOMES AND MEASURES: Hypertension control as defined by NCQA HEDIS. RESULTS: The KPNC hypertension registry included 349,937 patients when established in 2001 and increased to 652,763 by 2009. The NCQA HEDIS commercial measurement for hypertension control within KPNC increased from 43.6% (95% CI, 39.4%-48.6%) to 80.4% (95% CI, 75.6%-84.4%) during the study period (P < .001 for trend). In contrast, the national mean NCQA HEDIS commercial measurement increased from 55.4% to 64.1%. California mean NCQA HEDIS commercial rates of hypertension were similar to those reported nationally from 2006-2009 (63.4% to 69.4%). CONCLUSIONS AND RELEVANCE: Among adults diagnosed with hypertension, implementation of a large-scale hypertension program was associated with a significant increase in hypertension control compared with state and national control rates. Key elements of the program included a comprehensive hypertension registry, development and sharing of performance metrics, evidence-based guidelines, medical assistant visits for blood pressure measurement, and single-pill combination pharmacotherapy.