Pragmatic evaluation of events and benefits of lipid lowering in older adults (PREVENTABLE): Trial design and rationale.

Whether initiation of statins could increase survival free of dementia and disability in adults aged ≥75 years is unknown. PREVENTABLE, a double-blind, placebo-controlled randomized pragmatic clinical trial, will compare high-intensity statin therapy (atorvastatin 40 mg) with placebo in 20,000 community-dwelling adults aged ≥75 years without cardiovascular disease, disability, or dementia at baseline. Exclusion criteria include statin use in the prior year or for >5 years and inability to take a statin. Potential participants are identified using computable phenotypes derived from the electronic health record and local referrals from the community. Participants will undergo baseline cognitive testing, with physical testing and a blinded lipid panel if feasible. Cognitive testing and disability screening will be conducted annually. Multiple data sources will be queried for cardiovascular events, dementia, and disability; survival is site-reported and supplemented by a National Death Index search. The primary outcome is survival free of new dementia or persisting disability. Co-secondary outcomes are a composite of cardiovascular death, hospitalization for unstable angina or myocardial infarction, heart failure, stroke, or coronary revascularization; and a composite of mild cognitive impairment or dementia. Ancillary studies will offer mechanistic insights into the effects of statins on key outcomes. Biorepository samples are obtained and stored for future study. These results will inform the benefit of statins for increasing survival free of dementia and disability among older adults. This is a pioneering pragmatic study testing important questions with low participant burden to align with the needs of the growing population of older adults.

Preoperative opioid use and postoperative pain associated with surgical readmissions.

BACKGROUND: The extent of preoperative opioid utilization and the relationship with pain-related readmissions are not well understood. METHODS: VA Surgical Quality Improvement Program data on general, vascular, and orthopedic surgeries (2007-2014) were merged with pharmacy data to evaluate preoperative opioid use and pain-related readmissions. Opioid use in the 6-month preoperative period was categorized as none, infrequent, frequent, and daily. RESULTS: In the six-month preoperative period, 65.7% had no opioid use, 16.7% had infrequent use, 6.3% frequent use, and 11.4% were daily opioid users. Adjusted odds of pain-related readmission were higher for opioid-exposed groups vs the opioid-naïve group: infrequent (OR 1.17; 95% CI:1.04-1.31), frequent (OR 1.28; 95% CI:1.08-1.52), and daily (OR 1.49; 95% CI:1.27-1.74). Among preoperative opioid users, those with a pain-related readmission had higher daily preoperative oral morphine equivalents (mean 44.5 vs. 36.1, p < 0.001). CONCLUSIONS: Patients using opioids preoperatively experienced higher rates of pain-related readmissions, which increased with frequency and dosage of opioid exposure.

Association Between Preoperative Proteinuria and Postoperative Acute Kidney Injury and Readmission.

Importance: Proteinuria indicates renal dysfunction and is a risk factor for morbidity among medical patients, but less is understood among surgical populations. There is a paucity of studies investigating how preoperative proteinuria is associated with surgical outcomes, including postoperative acute kidney injury (AKI) and readmission. Objective: To assess preoperative urine protein levels as a biomarker for adverse surgical outcomes. Design, Setting, and Participants: A retrospective, population-based study was conducted in a cohort of patients with and without known preoperative renal dysfunction undergoing elective inpatient surgery performed at 119 Veterans Affairs facilities from October 1, 2007, to September 30, 2014. Data analysis was conducted from April 4 to December 1, 2016. Preoperative dialysis, septic, cardiac, ophthalmology, transplantation, and urologic cases were excluded. Exposures: Preoperative proteinuria as assessed by urinalysis using the closest value within 6 months of surgery: negative (0 mg/dL), trace (15-29 mg/dL), 1+ (30-100 mg/dL), 2+ (101-300 mg/dL), 3+ (301-1000 mg/dL), and 4+ (>1000 mg/dL). Main Outcomes and Measures: Primary outcome was postoperative predischarge AKI and 30-day postdischarge unplanned readmission. Secondary outcomes included any 30-day postoperative outcome. Results: Of 346 676 surgeries, 153 767 met inclusion criteria, with the majority including orthopedic (37%), general (29%), and vascular procedures (14%). Evidence of proteinuria was shown in 43.8% of the population (trace: 20.6%, 1+: 16.0%, 2+: 5.5%, 3+: 1.6%) with 20.4%, 14.9%, 4.3%, and 0.9%, respectively, of the patients having a normal preoperative estimated glomerular filtration rate (eGFR). In unadjusted analysis, preoperative proteinuria was significantly associated with postoperative AKI (negative: 8.6%, trace: 12%, 1+: 14.5%, 2+: 21.2%, 3+: 27.6%; P < .001) and readmission (9.3%, 11.3%, 13.3%, 15.8%, 17.5%, respectively, P < .001). After adjustment, preoperative proteinuria was associated with postoperative AKI in a dose-dependent relationship (trace: odds ratio [OR], 1.2; 95% CI, 1.1-1.3, to 3+: OR, 2.0; 95% CI, 1.8-2.2) and 30-day unplanned readmission (trace: OR, 1.0; 95% CI, 1.0-1.1, to 3+: OR, 1.3; 95% CI, 1.1-1.4). Preoperative proteinuria was associated with AKI independent of eGFR. Conclusions and Relevance: Proteinuria was associated with postoperative AKI and 30-day unplanned readmission independent of preoperative eGFR. Simple urine assessment for proteinuria may identify patients at higher risk of AKI and readmission to guide perioperative management.

Clinical Outcomes by Race and Ethnicity in the Systolic Blood Pressure Intervention Trial (SPRINT): A Randomized Clinical Trial.

BACKGROUND: The Systolic Blood Pressure Intervention Trial (SPRINT) showed that targeting a systolic blood pressure (SBP) of ≤ 120 mm Hg (intensive treatment) reduced cardiovascular disease (CVD) events compared to SBP of ≤ 140 mm Hg (standard treatment); however, it is unclear if this effect is similar in all racial/ethnic groups. METHODS: We analyzed SPRINT data within non-Hispanic White (NHW), non-Hispanic Black (NHB), and Hispanic subgroups to address this question. High-risk nondiabetic hypertensive patients (N = 9,361; 30% NHB; 11% Hispanic) 50 years and older were randomly assigned to intensive or standard treatment. Primary outcome was a composite of the first occurrence of a myocardial infarction, acute coronary syndrome, stroke, decompensated heart failure, or CVD death. RESULTS: Average postbaseline SBP was similar among NHW, NHB, and Hispanics in both treatment arms. Hazard ratios (HRs) (95% confidence interval) (intensive vs. standard treatment groups) for primary outcome were 0.70 (0.57-0.86), 0.71 (0.51-0.98), 0.62 (0.33-1.15) (interaction P value = 0.85) in NHW, NHB, and Hispanics. CVD mortality HRs were 0.49 (0.29-0.81), 0.77 (0.37-1.57), and 0.17 (0.01-1.08). All-cause mortality HRs were 0.61 (0.47-0.80), 0.92 (0.63-1.35), and 1.58 (0.73-3.62), respectively. A test for differences among racial/ethnic groups in the effect of treatment assignment on all-cause mortality was not significant (Hommel-adjusted P value = 0.062) after adjustment for multiple comparisons. CONCLUSION: Targeting a SBP goal of ≤ 120 mm Hg compared to ≤ 140 mm Hg led to similar SBP control and was associated with similar benefits and risks among all racial ethnic groups, though NHBs required an average of ~0.3 more medications. CLINICAL TRIALS REGISTRATION: Trial Number NCT01206062, ClinicalTrials.gov Identifier at https://clinicaltrials.gov/ct2/show/NCT01206062.

Primary care physician decision making regarding severe obesity treatment and bariatric surgery: a qualitative study.

BACKGROUND: Less than 1% of severely obese US adults undergo bariatric surgery annually. It is critical to understand the factors that contribute to its utilization. OBJECTIVES: To understand how primary care physicians (PCPs) make decisions regarding severe obesity treatment and bariatric surgery referral. SETTING: Focus groups with PCPs practicing in small, medium, and large cities in Wisconsin. METHODS: PCPs were asked to discuss prioritization of treatment for a severely obese patient with multiple co-morbidities and considerations regarding bariatric surgery referral. Focus group sessions were analyzed by using a directed approach to content analysis. A taxonomy of consensus codes was developed. Code summaries were created and representative quotes identified. RESULTS: Sixteen PCPs participated in 3 focus groups. Four treatment prioritization approaches were identified: (1) treat the disease that is easiest to address; (2) treat the disease that is perceived as the most dangerous; (3) let the patient set the agenda; and (4) address obesity first because it is the common denominator underlying other co-morbid conditions. Only the latter approach placed emphasis on obesity treatment. Five factors made PCPs hesitate to refer patients for bariatric surgery: (1) wanting to "do no harm"; (2) questioning the long-term effectiveness of bariatric surgery; (3) limited knowledge about bariatric surgery; (4) not wanting to recommend bariatric surgery too early; and (5) not knowing if insurance would cover bariatric surgery. CONCLUSION: Decision making by PCPs for severely obese patients seems to underprioritize obesity treatment and overestimate bariatric surgery risks. This could be addressed with PCP education and improvements in communication between PCPs and bariatric surgeons.

Fracture risk in nursing home residents initiating antipsychotic medications.

OBJECTIVES: To determine whether antipsychotic medication initiation is associated with subsequent fracture in nursing home residents, whether fracture rates differ between users of first- and second-generation antipsychotics, and whether fracture rates differ between users of haloperidol, risperidone, olanzapine, and quetiapine. DESIGN: Time-to-event analyses were conducted in a retrospective cohort using linked Medicaid; Medicare; Minimum Data Set; and Online Survey, Certification, and Reporting data sets. SETTING: Nursing homes in California, Florida, Missouri, New Jersey, and Pennsylvania. PARTICIPANTS: Nursing home residents aged ≥ 65. MEASUREMENTS: Fracture outcomes (any fracture; hip fracture) in users of first- and second-generation anti-psychotic and specifically users of haloperidol, risperidone, olanzapine, and quetiapine. Comparisons incorporated propensity scores that included individual- (demographic characteristics, comorbidity, diagnoses, weight, fall history, concomitant medications, cognitive performance, physical function, aggressive behavior) and facility- (nursing home size, ownership factors, staffing levels) level variables. RESULTS: Of 8,262 subjects (in 4,131 pairs), 4.3% suffered any fracture during observation, with 1% having a hip fracture during an average follow-up period of 93 ± 71 days (range 1-293 days). Antipsychotic initiation was associated with any fracture (hazard ratio (HR) = 1.39, P = .004) and hip fracture (HR = 1.76, P = .02). The highest risk was found for hip fracture when antipsychotic use was adjusted for dose (HR = 2.96, P = .008), but no differences in time to fracture were found between first- and second-generation agents or between individual drugs. CONCLUSION: Antipsychotic initiation is associated with fracture in nursing home residents, but risk does not differ between commonly used antipsychotics.