Approach to Multimorbidity Burden Classification and Outcomes in Older Adults With Heart Failure.

BACKGROUND: The optimal approach to classifying multimorbidity burden in assessing treatment-associated outcomes using real-world data remains uncertain. We assessed whether 2 measurement approaches to characterize multimorbidity influenced observed associations of ß-blocker use with outcomes in adults with heart failure (HF). METHODS: We conducted a retrospective study on adults with HF from 4 integrated health care delivery systems. Multimorbidity burden was characterized by either (1) simple counts of chronic conditions or (2) a weighted multiple chronic conditions score using data from electronic health records. We assessed the impact of these 2 approaches to characterizing multimorbidity on associations between exposure to ß-blockers and subsequent all-cause death, hospitalization for HF, and hospitalization for any cause. RESULTS: The study population characterized by a count of chronic conditions included 9988 adults with HF who had a mean (SD) age of 76.4 (12.5) years, with 48.7% women and 24.7% racial/ethnic minorities. The cohort characterized by weighted multiple chronic conditions included 10,082 adults with HF who had a mean (SD) age of 76.4 (12.4) years, 48.9% women, and 25.5% racial/ethnic minorities. The multivariable associations of risks of death or hospitalizations for HF or for any cause associated with incident ß-blocker use were similar regardless of how multimorbidity burden was characterized. CONCLUSIONS: Simple counts of chronic conditions performed similarly to a weighted multimorbidity score in predicting outcomes using real-world data to examine clinical outcomes associated with ß-blocker therapy in HF. Our findings challenge conventional wisdom that more complex measures of multimorbidity are always necessary to characterize patients in observational studies examining therapy-associated outcomes.

"I really had somebody in my corner." Patient experiences with a pharmacist-led opioid tapering program.

BACKGROUND: Opioid tapering has been identified as an effective strategy to prevent the dangers associated with long-term opioid therapy for patients with chronic pain. However, many patients are resistant to tapering, and conversations about tapering can be challenging for health care providers. Pharmacists can play a role in supporting both providers and patients with the process of opioid tapering. OBJECTIVE: Qualitatively describe patient experiences with a unique phone-based and pharmacy-led opioid tapering program implemented within an integrated health care system. METHODS: In-depth telephone interviews with patients who completed the program were recorded, transcribed, and analyzed. Themes were identified through a constant comparative approach. RESULTS: We completed 25 interviews; 80% of patients were women (20), with a mean age of 58 years, and 72% (18) had been using opioids for pain management for 10 or more years. Most (60%) described a positive and satisfying experience with the tapering program. Strengths of the program reported by patients included a patient-centered and compassionate taper approach, flexible taper pace, easy access to knowledgeable pharmacist advocates, and resultant improvements in quality of life (e.g., increased energy). Challenges reported included: unhelpful or difficult-to-access nonpharmacological pain management options, negative quality of life impacts (e.g., inability to exercise), and lack of choice in the taper process. At the end of tapering, most patients (72%) described their pain as reduced or manageable rather than worse and expressed willingness to use the program in the future if a need should arise. CONCLUSIONS: Patients in a pharmacist-led opioid tapering program appreciated the program's individualized approach to care and access to pharmacist' expertise. Most interviewed patients successfully reduced their opioid use and recommended that the program should continue as an offered service. To improve the program, patients suggested increased personalization of the taper process and additional support for withdrawal symptoms and nonpharmacological pain management.

Costs and Cost-Effectiveness of Implementing a Digital Diabetes Prevention Program in a Large, Integrated Health System.

BackgroundThe Diabetes Prevention Program (DPP) has been translated into digital formats. We report an economic evaluation of a digital DPP implemented in a large, integrated health care system. MethodsPatients (n = 4148) were invited to participate in digital DPP based on clinical characteristics (HbA1c 5.7%-6.4% and body mass index ≥ 30 kg/m2) assessed using electronic medical record data. Using a propensity score we matched (1:1) enrolled and not enrolled patients for a total of 784. We identified high-risk patients (ie, above the 50th percentile of risk; n = 202) by calculating each patient's 2-year of developing diabetes. We report the cost of the intervention and the costs of medical care over 12- and 24-month follow-up, and the incremental cost-effectiveness ratio as the cost per additional kilogram weight loss at 24 months. ResultsAt 12 months, enrolled patients had lower total costs ($6,926, 95% CI $5,681-$8,171) than not enrolled patients ($7,538, 95% CI $6,293-$8,783). This pattern attenuated slightly at 24 months (enrolled = $16,255, 95% CI $14,097-$18,412; not enrolled = $16,688, 95% CI $14,531-$18,846). We found an incremental cost-effectiveness ratio of $81.92 per additional kilogram weight loss. For high-risk patients, the digital DPP group had, on average, lower costs and greater weight loss. We found a 55% chance of the digital DPP program being cost-effective at a willingness-to-pay of $150 per additional kilogram of weight loss; at the same willingness-to-pay, there is a 60% chance in the high-risk subgroup. Limitations include the nonrandomized design and potential volunteer bias. ConclusionDigital DPP had a favorable cost-effectiveness profile compared to other lifestyle interventions.

A Primary Care-Based Cognitive Behavioral Therapy Intervention for Long-Term Opioid Users With Chronic Pain : A Randomized Pragmatic Trial.

BACKGROUND: Chronic pain is common, disabling, and costly. Few clinical trials have examined cognitive behavioral therapy (CBT) interventions embedded in primary care settings to improve chronic pain among those receiving long-term opioid therapy. OBJECTIVE: To determine the effectiveness of a group-based CBT intervention for chronic pain. DESIGN: Pragmatic, cluster randomized controlled trial. (ClinicalTrials.gov: NCT02113592). SETTING: Kaiser Permanente health care systems in Georgia, Hawaii, and the Northwest. PARTICIPANTS: Adults (aged ≥18 years) with mixed chronic pain conditions receiving long-term opioid therapy. INTERVENTION: A CBT intervention teaching pain self-management skills in 12 weekly, 90-minute groups delivered by an interdisciplinary team (behaviorist, nurse, physical therapist, and pharmacist) versus usual care. MEASUREMENTS: Self-reported pain impact (primary outcome, as measured by the PEGS scale [pain intensity and interference with enjoyment of life, general activity, and sleep]) was assessed quarterly over 12 months. Pain-related disability, satisfaction with care, and opioid and benzodiazepine use based on electronic health care data were secondary outcomes. RESULTS: A total of 850 patients participated, representing 106 clusters of primary care providers (mean age, 60.3 years; 67.4% women); 816 (96.0%) completed follow-up assessments. Intervention patients sustained larger reductions on all self-reported outcomes from baseline to 12-month follow-up; the change in PEGS score was -0.434 point (95% CI, -0.690 to -0.178 point) for pain impact, and the change in pain-related disability was -0.060 point (CI, -0.084 to -0.035 point). At 6 months, intervention patients reported higher satisfaction with primary care (difference, 0.230 point [CI, 0.053 to 0.406 point]) and pain services (difference, 0.336 point [CI, 0.129 to 0.543 point]). Benzodiazepine use decreased more in the intervention group (absolute risk difference, -0.055 [CI, -0.099 to -0.011]), but opioid use did not differ significantly between groups. LIMITATION: The inclusion of only patients with insurance in large integrated health care systems limited generalizability, and the clinical effect of change in scores is unclear. CONCLUSION: Primary care-based CBT, using frontline clinicians, produced modest but sustained reductions in measures of pain and pain-related disability compared with usual care but did not reduce use of opioid medication. PRIMARY FUNDING SOURCE: National Institutes of Health.

"We Need to Taper." Interviews with Clinicians and Pharmacists About Use of a Pharmacy-Led Opioid Tapering Program.

OBJECTIVE: To identify factors that influence or interfere with referrals by primary care providers (PCPs) to a pharmacist-led telephone-based program to assist patients undergoing opioid tapering. The Support Team Onsite Resource for Management of Pain (STORM) program provides individualized patient care and supports PCPs in managing opioid tapers. DESIGN: Qualitative interviews were conducted with referring PCPs and STORM staff. Interview guides addressed concepts from the RE-AIM framework, focusing on issues affecting referral to the STORM program. SETTING: An integrated healthcare system (HCS) in the Northwest United States. SUBJECTS: Thirty-five interviews were conducted with 20 PCPs and 15 STORM staff. METHODS: Constant comparative analysis was used to identify key themes from interviews. A codebook was developed based on interview data and a qualitative software program was used for coding, iterative review, and content analysis. Representative quotes illustrate identified themes. RESULTS: Use of the STORM opioid tapering program was influenced by PCP, patient, and HCS considerations. Factors motivating use of STORM included lack of PCP time to support chronic pain patients requiring opioid tapering and the perception that STORM is a valued partner in patient care. Impediments to referral included PCP confidence in managing opioid tapering, patient resistance to tapering, forgetting about program availability, and PCP resistance to evolving guidelines regarding opioid tapering goals. CONCLUSIONS: PCPs recognized that STORM supported patient safety and reduced clinician burden. Utilization of the program could be improved through ongoing PCP education about the service and consistent co-location of STORM pharmacists within primary care clinics.

Evaluating the Implementation of Digital and In-Person Diabetes Prevention Program in a Large, Integrated Health System: Natural Experiment Study Design.

INTRODUCTION: Implementation of a Diabetes Prevention Program (DPP) in both in-person and digital health-care settings has been increasing. The purpose of this article is to describe the protocol of a mixed-methods, natural experiment study designed to evaluate the implementation of DPP in a large, integrated health system. METHODS: Kaiser Permanente Northwest patients who were 19 to 75 years with prediabetes (hemoglobin A1c or glycated hemoglobin, 5.7-6.4) and obesity (body mass index ≥ 30 kg/m2) were invited, via the Kaiser Permanente Northwest patient portal, to participate in the digital (n = 4124) and in-person (n = 2669) DPP during 2016 through 2018. Primary (weight) and secondary (hemoglobin A1c or glycated hemoglobin level) outcome data will be obtained from electronic health records. A cost-effectiveness analysis as well as qualitative interviews with patients (enrolled and not enrolled in the DPP) and stakeholders will be conducted to examine further implementation, acceptability, and sustainability. CONCLUSION: The mixed-methods, natural experiment design we will use to evaluate Kaiser Permanente Northwest's implementation of the digital and in-person DPP builds on existing evidence related to the effectiveness of these two DPP delivery modes and will contribute new knowledge related to best practices for implementing and sustaining the DPP within large health systems over the long term.

Noncardiac-Related Morbidity, Mobility Limitation, and Outcomes in Older Adults With Heart Failure.

BACKGROUND: To examine the individual and combined associations of noncardiac-related conditions and mobility limitation with morbidity and mortality in adults with heart failure (HF). METHODS: We conducted a retrospective cohort study in a large, diverse group of adults with HF from five U.S. integrated healthcare delivery systems. We characterized patients with respect to the presence of noncardiac conditions (<3 vs ≥3) and/or mobility impairment (defined by the use/nonuse of a wheelchair, cane, or walker), categorizing them into four subgroups. Outcomes included all-cause death and hospitalizations for HF or any cause. RESULTS: Among 114,553 adults diagnosed with HF (mean age: 73 years old, 46% women), compared with <3 noncardiac conditions/no mobility limitation, adjusted hazard ratios (HR) for all-cause death among those with <3 noncardiac conditions/mobility limitation, ≥3 noncardiac conditions/no mobility limitation, ≥3 noncardiac conditions/mobility limitation (vs) were 1.40 (95% CI, 1.31-1.51), 1.72 (95% CI, 1.69-1.75), and 1.93 (95% CI, 1.85-2.01), respectively. We did not observe an increased risk of any-cause or HF-related hospitalization related to the presence of mobility limitation among those with a greater burden of noncardiac multimorbidity. Consistent findings regarding mortality were observed within groups defined according to age, gender, and HF type (preserved, reduced, mid-range ejection fraction), with the most prominent impact of mobility limitation in those <65 years of age. CONCLUSIONS: There is an additive association of mobility limitation, beyond the burden of noncardiac multimorbidity, on mortality for patients with HF, and especially prominent in younger patients.

Balancing Adherence and Expense: The Cost-Effectiveness of Two-Sample vs One-Sample Fecal Immunochemical Test.

Colorectal cancer (CRC) causes more than 50,000 deaths each year in the United States but early detection through screening yields survival gains; those diagnosed with early stage disease have a 5-year survival greater than 90%, compared to 12% for those diagnosed with late stage disease. Using data from a large integrated health system, this study evaluates the cost-effectiveness of fecal immunochemical testing (FIT), a common CRC screening tool. A probabilistic decision-analytic model was used to examine the costs and outcomes of positive test results from a 1-FIT regimen compared with a 2-FIT regimen. The authors compared 5 diagnostic cutoffs of hemoglobin concentration for each test (for a total of 10 screening options). The principal outcome from the analysis was the cost per additional advanced neoplasia (AN) detected. The authors also estimated the number of cancers detected and life-years gained from detecting AN. The following costs were included: program management of the screening program, patient identification, FIT kits and their processing, and diagnostic colonoscopy following a positive FIT. Per-person costs ranged from $33 (1-FIT at 150ng/ml) to $92 (2-FIT at 50ng/ml) across screening options. Depending on willingness to pay, the 1-FIT 50 ng/ml and the 2-FIT 50 ng/ml are the dominant strategies with cost-effectiveness of $11,198 and $28,389, respectively, for an additional AN detected. The estimates of cancers avoided per 1000 screens ranged from 1.46 to 4.86, depending on the strategy and the assumptions of AN to cancer progression.

Interdisciplinary team-based care for patients with chronic pain on long-term opioid treatment in primary care (PPACT) - Protocol for a pragmatic cluster randomized trial.

BACKGROUND: Chronic pain is one of the most common, disabling, and expensive public health problems in the United States. Interdisciplinary pain management treatments that employ behavioral approaches have been successful in helping patients with chronic pain reduce symptoms and regain functioning. However, most patients lack access to such treatments. We are conducting a pragmatic clinical trial to test the hypothesis that patients who receive an interdisciplinary biopsychosocial intervention, the Pain Program for Active Coping and Training (PPACT), at their primary care clinic will have a greater reduction in pain impact in the year following than patients receiving usual care. METHODS/DESIGN: This is an effectiveness-implementation hybrid pragmatic clinical trial in which we randomize clusters of primary care providers and their patients with chronic pain who are on long-term opioid therapy to 1) receive an interdisciplinary behavioral intervention in conjunction with their current health care or 2) continue with current health care services. Our primary outcome is pain impact (a composite of pain intensity and pain-related interference) measured using the PEG, a validated three-item assessment. Secondary outcomes include pain-related disability, patient satisfaction, opioids dispensed and health care utilization. An economic evaluation assesses the resources and costs necessary to deliver the intervention and its cost-effectiveness compared with usual care. A formative evaluation employs mixed methods to understand the context for implementation in the participating health care systems. DISCUSSION: This trial will inform the feasibility of implementing interdisciplinary behavioral approaches to pain management in the primary care setting, potentially providing a more effective, safer, and more satisfactory alternative to opioid-based chronic pain treatment. Clinical Trials Registration Number: NCT02113592.

Comparison of Inappropriate Shocks and Other Health Outcomes Between Single- and Dual-Chamber Implantable Cardioverter-Defibrillators for Primary Prevention of Sudden Cardiac Death: Results From the Cardiovascular Research Network Longitudinal Study of Implantable Cardioverter-Defibrillators.

BACKGROUND: In US clinical practice, many patients who undergo placement of an implantable cardioverter-defibrillator (ICD) for primary prevention of sudden cardiac death receive dual-chamber devices. The superiority of dual-chamber over single-chamber devices in reducing the risk of inappropriate ICD shocks in clinical practice has not been established. The objective of this study was to compare risk of adverse outcomes, including inappropriate shocks, between single- and dual-chamber ICDs for primary prevention. METHODS AND RESULTS: We identified patients receiving a single- or dual-chamber ICD for primary prevention who did not have an indication for pacing from 15 hospitals within 7 integrated health delivery systems in the Longitudinal Study of Implantable Cardioverter-Defibrillators from 2006 to 2009. The primary outcome was time to first inappropriate shock. ICD shocks were adjudicated for appropriateness. Other outcomes included all-cause hospitalization, heart failure hospitalization, and death. Patient, clinician, and hospital-level factors were accounted for using propensity score weighting methods. Among 1042 patients without pacing indications, 54.0% (n=563) received a single-chamber device and 46.0% (n=479) received a dual-chamber device. In a propensity-weighted analysis, device type was not significantly associated with inappropriate shock (hazard ratio, 0.91; 95% confidence interval, 0.59-1.38 [P=0.65]), all-cause hospitalization (hazard ratio, 1.03; 95% confidence interval, 0.87-1.21 [P=0.76]), heart failure hospitalization (hazard ratio, 0.93; 95% confidence interval, 0.72-1.21 [P=0.59]), or death (hazard ratio, 1.19; 95% confidence interval, 0.93-1.53 [P=0.17]). CONCLUSIONS: Among patients who received an ICD for primary prevention without indications for pacing, dual-chamber devices were not associated with lower risk of inappropriate shock or differences in hospitalization or death compared with single-chamber devices. This study does not justify the use of dual-chamber devices to minimize inappropriate shocks.

Use of Risk Models to Predict Death in the Next Year Among Individual Ambulatory Patients With Heart Failure.

Importance: The clinical practice guidelines for heart failure recommend the use of validated risk models to estimate prognosis. Understanding how well models identify individuals who will die in the next year informs decision making for advanced treatments and hospice. Objective: To quantify how risk models calculated in routine practice estimate more than 50% 1-year mortality among ambulatory patients with heart failure who die in the subsequent year. Design, Setting, and Participants: Ambulatory adults with heart failure from 3 integrated health systems were enrolled between 2005 and 2008. The probability of death was estimated using the Seattle Heart Failure Model (SHFM) and the Meta-Analysis Global Group in Chronic Heart Failure (MAGGIC) risk calculator. Baseline covariates were collected from electronic health records. Missing covariates were imputed. Estimated mortality was compared with actual mortality at both population and individual levels. Main Outcomes and Measures: One-year mortality. Results: Among 10 930 patients with heart failure, the median age was 77 years, and 48.0% of these patients were female. In the year after study enrollment, 1661 patients died (15.9% by life-table analysis). At the population level, 1-year predicted mortality among the cohort was 9.7% for the SHFM (C statistic of 0.66) and 17.5% for the MAGGIC risk calculator (C statistic of 0.69). At the individual level, the SHFM predicted a more than 50% probability of dying in the next year for 8 of the 1661 patients who died (sensitivity for 1-year death was 0.5%) and for 5 patients who lived at least a year (positive predictive value, 61.5%). The MAGGIC risk calculator predicted a more than 50% probability of dying in the next year for 52 of the 1661 patients who died (sensitivity, 3.1%) and for 63 patients who lived at least a year (positive predictive value, 45.2%). Conversely, the SHFM estimated that 8496 patients (77.8%) had a less than 15% probability of dying at 1 year, yet this lower-risk end of the score range captured nearly two-thirds of deaths (n = 997); similarly, the MAGGIC risk calculator estimated a probability of dying of less than 25% for the majority of patients who died at 1 year (n = 914). Conclusions and Relevance: Although heart failure risk models perform reasonably well at the population level, they do not reliably predict which individual patients will die in the next year.

Risk factors for adverse outcomes by left ventricular ejection fraction in a contemporary heart failure population.

BACKGROUND: Although heart failure (HF) is a syndrome with important differences in response to therapy by left ventricular ejection fraction (LVEF), existing risk stratification models typically group all HF patients together. The relative importance of common predictor variables for important clinical outcomes across strata of LVEF is relatively unknown. METHODS AND RESULTS: We identified all members with HF between 2005 and 2008 from 4 integrated healthcare systems in the Cardiovascular Research Network. LVEF was categorized as preserved (LVEF ≥ 50% or normal), borderline (41%-49% or mildly reduced), and reduced (≤ 40% or moderately to severely reduced). We used Cox regression models to identify independent predictors of death and hospitalization by LVEF category. Among 30094 ambulatory adults with HF, mean age was 74 years and 46% were women. LVEF was preserved in 49.5%, borderline in 16.2%, and reduced in 34.3% of patients. During a median follow-up of 1.8 years (interquartile range, 0.8-3.1), 8060 (26.8%) patients died, 8108 (26.9%) were hospitalized for HF, and 20272 (67.4%) were hospitalized for any reason. In multivariable models, nearly all tested covariates performed similarly across LVEF strata for the outcome of death from any cause, as well as for HF-related and all-cause hospitalizations. CONCLUSIONS: We found that in a large, diverse contemporary HF population, risk assessment was strikingly similar across all LVEF categories. These data suggest that, although many HF therapies are uniquely applied to patients with reduced LVEF, individual prognostic factor performance does not seem to be significantly related to level of left ventricular systolic function.

Hypertension management: rationale for triple therapy based on mechanisms of action.

An estimated 25% of patients will require 3 antihypertensive agents to achieve blood pressure (BP) control; combination therapy is thus an important strategy in hypertension treatment. This review discusses the triple-therapy combination of an angiotensin receptor blocker (ARB) or direct renin antagonist (DRI) with a calcium channel blocker (CCB) and a diuretic, with a focus on mechanisms of action. Multiple physiologic pathways contribute to hypertension. Combining antihypertensive agents not only better targets the underlying pathways, but also helps blunt compensatory responses that may be triggered by single-agent therapy. DRIs and ARBs target the renin-angiotensin-aldosterone system (RAAS) at the initial and final steps, respectively, and both classes lower BP by reducing the effects of angiotensin-2; however, ARBs may trigger a compensatory increase in renin activity. Dihydropyridine CCBs target L-type calcium channels and lower BP through potent vasodilation, but can trigger compensatory activation of the sympathetic nervous system (SNS) and RAAS. Thiazide diuretics lower BP initially through sodium depletion and plasma volume reduction, followed by total peripheral resistance reduction, but can also trigger compensatory activation of the SNS and RAAS. The combination of an agent targeting the RAAS with a CCB and diuretic is rational, and triple combinations of valsartan/amlodipine/hydrochlorothiazide, olmesartan/amlodipine/hydrochlorothiazide, and aliskiren/amlodipine/hydrochlorothiazide have demonstrated greater effectiveness compared with their respective dual-component combinations. In addition, single-pill, fixed-dose combinations can address barriers to BP control including clinical inertia and poor adherence. Fixed-dose antihypertensive combination products capitalize on complementary mechanisms of action and have been shown to result in improved BP control.

Automated telephone calls to enhance colorectal cancer screening: economic analysis.

OBJECTIVES: To estimate the cost-effectiveness of an automated telephone intervention for colorectal cancer screening from a managed care perspective, using data from a pragmatic randomized controlled trial. METHODS: Intervention patients received calls for fecal occult blood testing (FOBT) screening. We searched patients' electronic medical records for any screening (defined as FOBT, flexible sigmoidoscopy, double-contrast barium enema, or colonoscopy) during follow-up. Intervention costs included project implementation and management, telephone calls, patient identification, and tracking. Screening costs included FOBT (kits, mailing, and processing) and any completed screening tests during follow-up. We estimated the incremental cost-effectiveness ratio (ICER) of the cost per additional screen. RESULTS: At 6 months, average costs for intervention and control patients were $37 (25% screened) and $34 (19% screened), respectively. The ICER at 6 months was $42 per additional screen, less than half what other studies have reported. Cost-effectiveness probability was 0.49, 0.84, and 0.99 for willingness-to-pay thresholds of $40, $100, and $200, respectively. Similar results were seen at 9 months. A greater increase in FOBT testing was seen for patients aged >70 years (45/100 intervention, 33/100 control) compared with younger patients (25/100 intervention, 21/100 control). The intervention was dominant for patients aged >70 years and was $73 per additional screen for younger patients. It increased screening rates by about 6% and costs by $3 per patient. CONCLUSIONS: At willingness to pay of $100 or more per additional screening test, an automated telephone reminder intervention can be an optimal use of resources.

Diabetes and drug-associated hyperkalemia: effect of potassium monitoring.

BACKGROUND: Renin-angiotensin-aldosterone system (RAAS) inhibitors are associated with hyperkalemia, but there is little evidence demonstrating patients who receive potassium monitoring have a lower rate of hyperkalemia. OBJECTIVE: To evaluate the association between potassium monitoring and serious hyperkalemia-associated adverse outcomes among patients with diabetes newly initiating RAAS inhibitor therapy. DESIGN: Retrospective observational study. PARTICIPANTS: Patients with diabetes without end-stage renal disease initiating RAAS inhibitor therapy between 2001 and 2006 at three integrated health care systems. MEASUREMENTS: Potassium monitoring and first hyperkalemia-associated adverse event during the initial year of therapy. Hyperkalemia-associated adverse events included hospitalizations, emergency department visits or deaths within 24 h of hyperkalemia diagnosis and/or diagnostic potassium >or=6 mmol/l. Incidence rates were calculated in person-years (p-y). We used inverse probability propensity score weighting to adjust for differences between patients with and without monitoring; Poisson regression was used to obtain adjusted relative risks. RESULTS: A total of 19,391 of 27,355 patients (71%) received potassium monitoring. Serious hyperkalemia-associated events occurred at an incidence rate of 10.2 per 1,000 p-y. Compared to patients without monitoring, adjusted relative risk of hyperkalemia-associated adverse events among all patients with monitoring was 0.50 (0.37, 0.66); in the subset of patients who also had chronic kidney disease (n = 2,176), adjusted relative risk was 0.29 (0.18, 0.46). CONCLUSIONS: Patients prescribed RAAS inhibitors who have both diabetes and chronic kidney disease and receive potassium monitoring are less likely to experience a serious hyperkalemia-associated adverse event compared to similar patients who did not receive potassium monitoring. This evidence supports existing consensus-based guidelines.

Predicting the risk of hyperkalemia in patients with chronic kidney disease starting lisinopril.

PURPOSE: Angiotensin-converting enzyme (ACE) inhibitors are recommended for patients with chronic kidney disease (CKD) because they slow disease progression. But physicians' concerns about the risk of hyperkalemia (elevated serum potassium level), a potentially fatal adverse effect, may limit optimal management with ACE-inhibitors. We synthesized known predictors of hyperkalemia into a prognostic risk score to predict the risk of hyperkalemia. METHODS: We assembled a retrospective cohort of adult patients with possible CKD (at least one estimated glomerular filtration rate (eGFR) value less than 60 ml/min/1.73 m(2)) who started an ACE-inhibitor (i.e., incident users) between 1998 and 2006 at a health maintenance organization. We followed patients for hyperkalemia: (1) potassium value >5.5 mmol/L; or (2) diagnosis code for hyperkalemia. Cox regression synthesized a priori predictors recorded in the electronic medical record into a risk score. RESULTS: We followed 5171 patients and 145 experienced hyperkalemia, a 90-day risk of 2.8%. Predictors included: age, eGFR, diabetes, heart failure, potassium supplements, potassium-sparing diuretics, and a high dose for the ACE-inhibitor (lisinopril). The risk score separated high-risk patients (top quintile, observed risk of 6.9%) from low-risk patients (bottom quintile, observed risk of 0.7%). Predicted and observed risks agreed within 1% for each quintile. The risk increased gradually in relation to declining eGFR with no apparent threshold for contraindicating ACE-inhibitors. CONCLUSIONS: The risk score separated high-risk patients (who may need more intensive laboratory monitoring) from low-risk patients. The risk score should be validated in other populations before it is ready for use in clinical practice.

Outcomes predicted by phosphorous in chronic kidney disease: a retrospective CKD-inception cohort study.

BACKGROUND: The impact of secondary hyperparathyroidism on morbidity and mortality among patients with chronic kidney disease (CKD) is unclear. METHODS: We conducted a retrospective cohort study to investigate the relationship between CKD and serum phosphorous. Through clinical databases at a large health maintenance organization, we identified a dynamic CKD inception cohort between 1997 and 2004, with stage 3-5 kidney disease with subsequent phosphorous measurement; the patients were followed up for up to 5 years for outcomes of mortality, cardiovascular mortality, cardiovascular hospitalizations and renal replacement therapy (RRT; dialysis or transplant). Survival analysis with time-varying covariables for phosphorous and renal function estimated the relationship between phosphorous level and outcomes, adjusting for potential confounding variables. RESULTS: A total of 930 patients with complete data were included in our analysis; they had a higher disease burden than excluded patients. Phosphorous did not predict overall or cardiovascular mortality, or cardiovascular hospitalizations. The rate of RRT increased significantly with the level of phosphorous, even when controlling for renal function. CONCLUSIONS: Contrary to some previous reports, we did not find evidence of increased mortality with phosphorous, but did find that increased levels of phosphorous are related to excess rates of RRT. Our work does not suggest that controlling phosphorous will lower the risk of RRT; our work motivates randomized controlled trials to investigate the clinical value of such interventions.

Increasingly restrictive definitions of hyperkalemia outcomes in a database study: effect on incidence estimates.

PURPOSE: To determine the incidence of hyperkalemia-associated adverse outcomes among ambulatory patients with diabetes newly initiating renin-angiotensin-aldosterone system (RAAS) inhibitor therapy and to examine to what extent increasingly restrictive definitions of hyperkalemia-associated outcomes influenced incidence estimates. METHODS: Retrospective cohort study of 27 355 individuals with diabetes who were new users of RAAS inhibitors at three integrated healthcare systems. RESULTS: Using the least restrictive definition of hyperkalemia-associated outcome, an ambulatory visit (AV), inpatient hospitalization (IP), or emergency department (ED) visit co-occurring within 7 days of coded hyperkalemia diagnosis and/or potassium concentration of > or =5.5 mmol/L, the incidence rate of hyperkalemia was 30.1 per 1000 person-years (p-y). Restricting to only IP or ED visits co-occurring within 24 hours of coded diagnosis and/or potassium > or =6 mmol/L, the incidence rate was 10.2 per 1000 p-y. When this latter definition was further restricted by removing available potassium laboratory values, the incidence rate declined to 9.5 per 1000 p-y. CONCLUSIONS: Modifying the definition of hyperkalemia-associated outcome resulted in up to threefold differences in incidence rate estimates. Our results demonstrate the value of including potassium laboratory results and AVs in identifying hyperkalemia from electronic data. Comparing incidence estimates across published studies requires consideration of differences in outcome definitions.

Adherence to K/DOQI bone metabolism guidelines.

OBJECTIVE: Guidelines for the treatment of patients with chronic kidney disease recommend laboratory testing of markers of bone metabolism, including intact parathyroid hormone, calcium, and phosphorus. The authors sought to evaluate the concordance of contemporary clinical practice with treatment recommendations. Trends were evaluated (2002 to 2005) in testing for bone metabolism in patients with chronic kidney disease, and the relation between bone metabolism markers, severity of chronic kidney disease, and cardiovascular hospitalizations were examined. DESIGN: Retrospective cohort. SETTING: Large United States health-maintenance organization. PATIENTS: Chronic kidney disease. RESULTS: Little variation was found in testing rates over time. Testing frequency was positively correlated with severity of kidney disease, referral to nephrology, and test type (annual testing was most likely for intact parathyroid hormone, and least likely for calcium). Patients with higher intact parathyroid hormone values had a greater risk of cardiovascular-related hospitalization; after adjusting for potential confounders, those with an intact parathyroid hormone value of 200 and greater had a relative risk of 2.16 (95% confidence interval, 1.09 to 4.29). CONCLUSIONS: This study supports the hypothesized association between disorders of bone metabolism and cardiovascular disease, but it does not address whether increased testing for disorders of bone metabolism will improve outcomes for patients with chronic kidney disease. Nor does our analysis imply that controlling parathyroid hormone will prevent cardiovascular hospitalizations. Future studies should more fully explore those critical clinical questions.

The Cardiovascular Research Network: a new paradigm for cardiovascular quality and outcomes research.

BACKGROUND: A clear need exists for a more systematic understanding of the epidemiology, diagnosis, and management of cardiovascular diseases. More robust data are also needed on how well clinical trials are translated into contemporary community practice and the associated resource use, costs, and outcomes. METHODS AND RESULTS: The National Heart, Lung, and Blood Institute recently established the Cardiovascular Research Network, which represents a new paradigm to evaluate the epidemiology, quality of care, and outcomes of cardiovascular disease and to conduct future clinical trials using a community-based model. The network includes 15 geographically distributed health plans with dedicated research centers, National Heart, Lung, and Blood Institute representatives, and an external collaboration and advisory committee. Cardiovascular research network sites bring complementary content and methodological expertise and a diverse population of approximately 11 million individuals treated through various health care delivery models. Each site's rich electronic databases (eg, sociodemographic characteristics, inpatient and outpatient diagnoses and procedures, pharmacy, laboratory, and cost data) are being mapped to create a standardized virtual data warehouse to facilitate rapid and efficient large-scale research studies. Initial projects focus on (1) hypertension recognition and management, (2) quality and outcomes of warfarin therapy, and (3) use, outcomes, and costs of implantable cardioverter defibrillators. CONCLUSIONS: The Cardiovascular Research Network represents a new paradigm in the approach to cardiovascular quality of care and outcomes research among community-based populations. Its unique ability to characterize longitudinally large, diverse populations will yield novel insights into contemporary disease and risk factor surveillance, management, outcomes, and costs. The Cardiovascular Research Network aims to become the national research partner of choice for efforts to improve the prevention, diagnosis, treatment, and outcomes of cardiovascular diseases.