The Long-Term Care Data Cooperative: The Next Generation of Data Integration.

Despite important advances in the linkage of residents' Medicare claims and Minimum Data Set (MDS) information, the data infrastructure for long-term care remains inadequate for public health surveillance and clinical research. It is widely known that the evidence base supporting treatment decisions for older nursing home residents is scant as residents are systematically excluded from clinical trials. Electronic health records (EHRs) hold the promise to improve this population's representation in clinical research, especially with the more timely and detailed clinical information available in EHRs that are lacking in claims and MDS. The COVID-19 pandemic shined a spotlight on the data gap in nursing homes. To address this need, the National Institute on Aging funded the Long-Term Care (LTC) Data Cooperative, a collaboration among providers and stakeholders in academia, government, and the private sector. The LTC Data Cooperative assembles residents' EHRs from major specialty vendors and facilitates linkage of these data with Medicare claims to create a comprehensive, longitudinal patient record. These data serve 4 key purposes: (1) health care operations and population health analytics; (2) public health surveillance; (3) observational, comparative effectiveness research; and (4) clinical research studies, including provider and patient recruitment into Phase 3 and Phase 4 randomized trials. Federally funded researchers wanting to conduct pragmatic trials can now enroll their partnering sites in this Cooperative to more easily access the clinical data needed to close the evidence gaps in LTC. Linkage to Medicare data facilitates tracking patients' long-term outcomes after being discharged back to the community. As of August 2022, nearly 1000 nursing homes have joined, feedback reports to facilities are being piloted, algorithms for identifying infections are being tested, and proposals for use of the data have been reviewed and approved. This emerging EHR system is a substantial innovation in the richness and timeliness of the data infrastructure of the nursing home population.

Effects of dipeptidyl peptidase-4 inhibitors and sulphonylureas on cognitive and physical function in nursing home residents.

AIMS: Dipeptidyl peptidase-4 inhibitors (DPP4Is) may mitigate hypoglycaemia-mediated declines in cognitive and physical functioning compared with sulphonylureas (SUs), yet comparative studies are unavailable among older adults, particularly nursing home (NH) residents. We evaluated the effects of DPP4Is versus SUs on cognitive and physical functioning among NH residents. MATERIALS AND METHODS: This new-user cohort study included long-stay NH residents aged ≥65 years from the 2007-2010 national US Minimum Data Set (MDS) clinical assessments and linked Medicare claims. We measured cognitive decline from the validated 6-point MDS Cognitive Performance Scale, functional decline from the validated 28-point MDS Activities of Daily Living scale, and hospitalizations or emergency department visits for altered mental status from Medicare claims. We compared 180-day outcomes in residents who initiated a DPP4I versus SU after 1:1 propensity score matching using Cox regression models. RESULTS: The matched cohort (N = 1784) had a mean ± SD age of 80 ± 8 years and 73% were women. Approximately 46% had no or mild cognitive impairment and 35% had no or mild functional impairment before treatment initiation. Compared with SU users, DPP4I users had lower 180-day rates of cognitive decline [hazard ratio (HR) = 0.61, 95% confidence interval (CI) 0.31-1.19], altered mental status events (HR = 0.71, 95% CI 0.39-1.27), and functional decline (HR = 0.89, 95% CI 0.51-1.56), but estimates were imprecise. CONCLUSIONS: Rates of cognitive and functional decline may be reduced among older NH residents using DPP4Is compared with SUs, but larger studies with greater statistical power should resolve the remaining uncertainty by providing more precise effect estimates.

Comparative safety of dipeptidyl peptidase-4 inhibitors and sulfonylureas among frail older adults.

BACKGROUND: Studies comparing dipeptidyl peptidase-4 inhibitors (DPP4Is) to sulfonylureas (SUs) are unavailable for frail older adults, especially nursing home (NH) residents. We examined the effects of DPP4Is versus SUs on severe adverse glycemic events, cardiovascular events, and death among NH residents. METHODS: We conducted a national retrospective cohort study of long-stay NH residents aged ≥65 years using 2008-2010 national US Minimum Data Set clinical assessment data and linked Medicare claims. Exposure was new DPP4I versus new SU use assessed via Medicare Part D drug claims. One-year outcomes were severe hypoglycemia, severe hyperglycemia, acute myocardial infarction (AMI), heart failure (HF), major adverse cardiovascular events plus HF (MACE+HF), and death. We compared outcomes after propensity score matching using Cox proportional hazards regression models. RESULTS: The cohort (N = 2016) had a mean (SD) age of 81 (8.1) years and was 72% female. Compared with SU users, DPP4I users had a lower 1-year rate of severe hypoglycemic events (HR = 0.57, 95% CI 0.34-0.94), but statistically similar rates of severe hyperglycemic events (HR = 0.94, 95% CI 0.52-1.72), AMI (HR = 0.76, 95% CI 0.44-1.30), HF (HR = 1.01, 95% CI 0.79-1.30), MACE+HF (HR = 0.90, 95% CI 0.72-1.12), and death (HR = 0.97, 95% CI 0.86-1.10). CONCLUSIONS: DPP4Is should be a preferred treatment option over SUs for NH residents and other frail older adults given the importance of avoiding hypoglycemia.

Risk of Thyroid Cancer Associated with Use of Liraglutide and Other Antidiabetic Drugs in a US Commercially Insured Population.

BACKGROUND: Quantify association between the glucagon-like peptide-1 receptor agonist liraglutide and risk of thyroid cancer (TC) compared to other antidiabetics. PATIENTS AND METHODS: Initiators of liraglutide, exenatide, metformin, pioglitazone or groups of dipeptidyl peptidase-4 inhibitors or sulfonylureas were identified in a US health plan (2010-2014) and followed for a median of 17 months. Thyroid cancer cases during follow-up were identified via a validated algorithm. Incidence rates of TC among liraglutide and comparators were assessed using relative risks estimated within propensity score-matched cohorts using intention to treat (ITT) and time on drug analyses. Latency effects and potential surveillance bias were evaluated. RESULTS: Relative risks from ITT analyses ranged from 1.00 (95% confidence interval (CI) 0.56-1.79) versus metformin to 1.70 (95% CI 1.03-2.81) versus all comparators excluding exenatide. Effect estimates from latency analyses were slightly attenuated. Time on drug analyses suggested no increased risk for either longer duration or higher cumulative dose of liraglutide. Medical record review found 85% were papillary or a follicular variant of papillary or both; 46% were microcarcinomas (≤10 millimeters), which were more prevalent in the liraglutide cohort (67% versus 43% in all comparators). CONCLUSION: Relative risks were elevated for several comparisons, which should be interpreted cautiously because of potential residual confounding and surveillance bias. Liraglutide cases had smaller thyroid nodules and shorter time-to-diagnosis, suggesting increased surveillance for TC among liraglutide initiators, especially shortly after the drug´s approval. After adjusting the primary analyses (ITT) for latency, no significant elevated risk of TC was observed among liraglutide initiators.

Development and Validation of a Risk Prediction Model for Cesarean Delivery After Labor Induction.

Objective: The goal of the study was to develop and validate a prediction model for cesarean delivery after labor induction that included factors known before the start of induction, unlike prior studies that focused on characteristics at the time of induction. Materials and Methods: Using 17,370 term labor inductions without documented medical indications occurring at 14 U.S. hospitals, 2007-2012, we created and evaluated a model predicting cesarean delivery. We assessed model calibration and discrimination, and we used bootstrapping for internal validation. We externally validated the model by using 2122 labor inductions from a hospital not included in the development cohort. Results: The model contained eight variables-gestational age, maternal race, parity, maternal age, obesity, fibroids, excessive fetal growth, and history of herpes-and was well calibrated with good risk stratification at the extremes of predicted probability. The model had an area under the curve (AUC) for the receiver operating characteristic curve of 0.82 (95% confidence interval 0.81-0.83), and it performed well on internal validation. The AUC in the external validation cohort was 0.82. Conclusion: This prediction model can help providers estimate a woman's risk of cesarean delivery when planning a labor induction.

Liraglutide use and evaluation of pancreatic outcomes in a US commercially insured population.

AIMS: Both acute pancreatitis (AP) and pancreatic cancer (PC) have been areas of focus for studies of incretin drugs. This 5-year prospective cohort study aimed to quantify possible associations between liraglutide and risk of AP and PC as compared to other antidiabetic drugs (ADs). MATERIALS AND METHODS: Patients initiating liraglutide or other ADs who were enrolled in a US health plan (2010-2014) were included. Comparisons of AP and PC incidence rates were made between matched cohorts of liraglutide initiators and initiators of other ADs. Adjudicated AP cases and algorithm-based PC cases were identified. Propensity score-matched intention-to-treat (ITT) and time-on-drug (TOD) analyses were completed using Poisson regression. A latency analysis was performed for PC. RESULTS: Median follow-up was 405 days for AP cohorts (9995 liraglutide, 1:1 matched to all comparators) and 503 days for PC cohorts (35 163 liraglutide, 1:1 matched to all comparators). In the primary AP analysis, "current" use of liraglutide was not significantly associated with elevated risk across comparators (all comparators relative risk [RR] = 1.2; 95% confidence interval [CI], 0.6-2.3). ITT results were similar where, in the primary analysis, no RRs were significantly associated with PC (all comparators RR = 0.7; 95% CI, 0.3-1.4); latency and TOD analyses did not alter findings. There was no evidence of a dose-response effect. CONCLUSIONS: Liraglutide was not associated with an increased risk of AP or PC, although risk estimates were more variable for AP, and numbers of cases for both outcomes were limited because of the rarity of outcomes.

Exenatide use and incidence of pancreatic and thyroid cancer: A retrospective cohort study.

A retrospective cohort study, supplemented with a nested case-control study, was performed using two administrative databases from commercial health plans in the United States to compare the incidence of pancreatic and thyroid cancer among users of exenatide versus other antidiabetic drugs (OADs). Patients with type 2 diabetes who initiated exenatide or OADs between 1 June 2005 and 30 June 2015 were included. Pancreatic and thyroid cancers were identified using chart-validated algorithms in the cohort study. Cases in the nested case-control study were chart-confirmed pancreatic or thyroid cancers, and controls were sampled using risk-set sampling. The time-fixed analyses comparing 33 629 exenatide initiators with 49 317 propensity-score-matched OAD initiators yielded hazard ratios of 0.76 (95% confidence interval [CI] 0.47-1.21) for pancreatic cancer and 1.46 (95% CI 0.98-2.19) for thyroid cancer. Results in the time-dependent analyses by cumulative duration or dose were similar. Nested case-control analyses yielded rate ratios of 0.61 (95%CI, 0.37-1.00) for pancreatic cancer and 0.89 (95% CI, 0.64-1.24) for thyroid cancer. This observational study suggested exenatide use was not associated with an increased risk of pancreatic or thyroid cancer.

Is there an association between liraglutide use and female breast cancer in a real-world setting?

BACKGROUND: Liraglutide is a human glucagon-like peptide-1 receptor agonist approved for treatment of adults with type 2 diabetes mellitus at a maximum dose of 1.8 mg/day (Victoza®) and more recently at 3.0 mg/day for weight management (Saxenda®). During the evaluation of liraglutide for approval in weight management, a minor imbalance in the numbers of reported breast neoplasms was observed, motivating the present study. Our objective was to quantify the association between liraglutide and incidence of breast cancer (BC) among women in a real-world setting. PATIENTS AND METHODS: Women initiating liraglutide or other antidiabetic therapies and who were enrolled in a large US health plan (2010-2014) were included. Comparisons of BC incidence rates were made between matched cohorts of initiators of liraglutide and cohorts of initiators of exenatide, metformin, pioglitazone, sulfonylureas, and dipeptidyl peptidase-4 inhibitors separately and as two "all comparators" groupings: with or without exenatide. Women with two or more claims with BC diagnosis codes within 61days of each other were identified as possible cases, with additional confirmation by clinician review of comprehensive claims listings. Propensity score matched intention-to-treat (ITT) and time-on-drug (TOD) analyses were completed via Poisson regression. A latency analysis was performed. RESULTS: Relative risks for BC for liraglutide vs comparators from the ITT analyses ranged from 0.90 (95% CI: 0.67-1.22) for both the "all comparator" and "all comparator except exenatide" cohorts to 1.46 (95% CI: 0.96-2.22) relative to exenatide. Latency analyses excluding the first year of follow-up yielded slightly attenuated point estimates. The TOD analyses of cumulative use of liraglutide suggested no increased risk of BC. CONCLUSION: Neither the ITT (overall or latency analysis) nor cumulative TOD analyses suggested an elevated risk of BC among liraglutide initiators. Short length of follow-up and the potential for confounding by unmeasured factors limit the full assessment of long-term risk.

Outcomes of "diabetes-friendly" vs "diabetes-unfriendly" ß-blockers in older nursing home residents with diabetes after acute myocardial infarction.

AIMS: To assess whether nursing home (NH) residents with type 2 diabetes mellitus (T2D) preferentially received "T2D-friendly" (vs "T2D-unfriendly") ß-blockers after acute myocardial infarction (AMI), and to evaluate the comparative effects of the two groups of ß-blockers. MATERIALS AND METHODS: This new-user retrospective cohort study of NH residents with AMI from May 2007 to March 2010 used national data from the Minimum Data Set and Medicare system. T2D-friendly ß-blockers were those hypothesized to increase peripheral glucose uptake through vasodilation: carvedilol, nebivolol and labetalol. Primary outcomes were hospitalizations for hypoglycaemia and hyperglycaemia in the 90 days after AMI. Secondary outcomes were functional decline, death, all-cause re-hospitalization and fracture hospitalization. We compared outcomes using binomial and multinomial logistic regression models after propensity score matching. RESULTS: Of 2855 NH residents with T2D, 29% initiated a T2D-friendly ß-blocker vs 24% of 6098 without T2D (P < 0.001). For primary outcomes among residents with T2D, T2D-friendly vs T2D-unfriendly ß-blockers were associated with a reduction in hospitalized hyperglycaemia (odds ratio [OR] 0.45, 95% confidence interval [CI] 0.21-0.97), but unassociated with hypoglycaemia (OR 2.05, 95% CI 0.82-5.10). For secondary outcomes, T2D-friendly ß-blockers were associated with a greater rate of re-hospitalization (OR 1.26, 95% CI 1.01-1.57), but not death (OR 1.06, 95% CI 0.85-1.32), functional decline (OR 0.91, 95% CI 0.70-1.19), or fracture (OR 1.69, 95% CI 0.40-7.08). CONCLUSIONS: In older NH residents with T2D, T2D-friendly ß-blocker use was associated with a lower rate of hospitalization for hyperglycaemia, but a higher rate of all-cause re-hospitalization.

Effectiveness and Tolerability of Therapy With Once-Weekly Exenatide Versus Basal Insulin Among Injectable-Naive Patients With Type 2 Diabetes in a Real-World Setting in the United States.

A propensity-matched cohort study compared injectable-naive patients with type 2 diabetes initiating exenatide once weekly (EQW) or basal insulin (BI), from 2012 through 2015, within a U.S. electronic health record database. A1C and weight were obtained as observed or multiply imputed values at baseline and quarterly for 1 year (Q1-Q4). Hypoglycemia and gastrointestinal symptoms were identified using diagnostic codes and clinical notes. EQW (n = 2,008) and BI (n = 4,016) cohorts were comparable at baseline (mean A1C and weight: EQW, 8.3% and 107.5 kg, respectively; BI, 8.5% and 107.9 kg, respectively). A1C declined in Q2: -0.69 and -0.50 percentage points for EQW and BI, respectively, with little further change in year 1. The EQW cohort lost 0.9 kg in Q1 and 1.9 kg by the end of the year; no weight change was observed in the BI cohort. Among EQW and BI cohorts, 25.9% and 14.3% achieved both glycemic control and weight loss, respectively. In the EQW and BI cohorts, the incidence of hypoglycemia per 1,000 person-years was 52.5 and 65.7, respectively. The incidence of nausea was greater among EQW relative to BI initiators (relative rate 1.18). EQW offers an advantage compared to BI in achieving glycemic control and weight loss and a lower incidence of hypoglycemia, but is associated with greater risk of gastrointestinal symptoms.

Predictive values of diagnostic codes for identifying serious hypocalcemia and dermatologic adverse events among women with postmenopausal osteoporosis in a commercial health plan database.

BACKGROUND: Post-marketing safety studies of medicines often rely on administrative claims databases to identify adverse outcomes following drug exposure. Valid ascertainment of outcomes is essential for accurate results. We aim to quantify the validity of diagnostic codes for serious hypocalcemia and dermatologic adverse events from insurance claims data among women with postmenopausal osteoporosis (PMO). METHODS: We identified potential cases of serious hypocalcemia and dermatologic events through ICD-9 diagnosis codes among women with PMO within claims from a large US healthcare insurer (June 2005-May 2010). A physician adjudicated potential hypocalcemic and dermatologic events identified from the primary position on emergency department (ED) or inpatient claims through medical record review. Positive predictive values (PPVs) and 95% confidence intervals (CIs) quantified the fraction of potential cases that were confirmed. RESULTS: Among 165,729 patients with PMO, medical charts were obtained for 40 of 55 (73%) potential hypocalcemia cases; 16 were confirmed (PPV 40%, 95% CI 25-57%). The PPV was higher for ED than inpatient claims (82 vs. 24%). Among 265 potential dermatologic events (primarily urticaria or rash), we obtained 184 (69%) charts and confirmed 128 (PPV 70%, 95% CI 62-76%). The PPV was higher for ED than inpatient claims (77 vs. 39%). CONCLUSION: Diagnostic codes for hypocalcemia and dermatologic events may be sufficient to identify events giving rise to emergency care, but are less accurate for identifying events within hospitalizations.

Safety study of live, oral human rotavirus vaccine: A cohort study in United States health insurance plans.

As part of a regulatory commitment for post-licensure safety monitoring of live, oral human rotavirus vaccine (RV1), this study compared the incidence rates (IR) of intussusception, acute lower respiratory tract infection (LRTI) hospitalization, Kawasaki disease, convulsion, and mortality in RV1 recipients versus inactivated poliovirus vaccine (IPV) recipients in concurrent (cIPV) and recent historical (hIPV) comparison cohorts. Vaccine recipients were identified in 2 claims databases from August 2008 - June 2013 (RV1 and cIPV) and January 2004 - July 2008 (hIPV). Outcomes were identified in the 0-59 days following the first 2 vaccine doses. Intussusception, Kawasaki disease, and convulsion were confirmed via medical record review. Outcome IRs were estimated. Incidence rate ratios (IRRs) were obtained from Poisson regression models. A post-hoc self-controlled case series (SCCS) analysis compared convulsion IRs in a 0-7 day post-vaccination period to a 15-30 day post-vaccination period. We identified 57,931 RV1, 173,384 cIPV, and 159,344 hIPV recipients. No increased risks for intussusception, LRTI, Kawasaki disease, or mortality were observed. The convulsion IRRs were elevated following RV1 Dose 1 (cIPV: 2.07, 95% confidence interval [CI]: 1.27 - 3.38; hIPV: 2.05, 95% CI: 1.24 - 3.38), a finding which is inconclusive as it was observed in only one of the claims databases. The IRR following RV1 Dose 1 in the SCCS analysis lacked precision (2.40, 95% CI: 0.73 - 7.86). No increased convulsion risk was observed following RV1 Dose 2. Overall, this study supports the favorable safety profile of RV1. Continued monitoring for safety signals through routine surveillance is needed to ensure vaccine safety.

Age, Sex, and Dose Effects of Nonbenzodiazepine Hypnotics on Hip Fracture in Nursing Home Residents.

OBJECTIVE: The Food and Drug Administration recommends a reduced dose of nonbenzodiazepine hypnotics in women, yet little is known about the age-, sex-, and dose-specific effects of these drugs on risk of hip fracture, especially among nursing home (NH) residents. We estimated the age-, sex-, and dose-specific effects of nonbenzodiazepine hypnotics on the rate of hip fracture among NH residents. DESIGN AND SETTING: Case-crossover study in US NHs. PARTICIPANTS: A total of 691 women and 179 men with hip fracture sampled from all US long-stay NH residents. MEASUREMENTS: Measures of patient characteristics were obtained from linked Medicare and the Minimum Data Set (2007-2008). The outcome was hospitalization for hip fracture with surgical repair. We estimated rate ratios (RRs) and 95% confidence intervals (CIs) from conditional logistic regression models for nonbenzodiazepine hypnotics (vs nonuse) comparing 0 to 29 days before hip fracture (hazard period) with 60 to 89 and 120 to 149 days before hip fracture (control periods). We stratified analyses by age, sex, and dose. RESULTS: The average RR of hip fracture was 1.7 (95% CI 1.5-1.9) for any use. The RR of hip fracture was higher for residents aged ≥90 years vs <70 years (2.2 vs 1.3); however, the CIs overlapped. No differences in the effect of the hypnotic on risk of hip fracture were evident by sex. Point estimates for hip fracture were greater with high-dose versus low-dose hypnotics (RR 1.9 vs 1.6 for any use), but these differences were highly compatible with chance. CONCLUSIONS: The rate of hip fracture in NH residents due to use of nonbenzodiazepine hypnotics was greater among older patients than among younger patients and, possibly, with higher doses than with lower doses. When clinicians are prescribing a nonbenzodiazepine hypnotic to any NH resident, doses of these drugs should be kept as low as possible, especially among those with advanced age.

Effectiveness and tolerability of therapy with exenatide once weekly vs basal insulin among injectable-drug-naïve elderly or renal impaired patients with type 2 diabetes in the United States.

AIM: To evaluate the effectiveness and tolerability of exenatide once weekly (EQW) compared with basal insulin (BI) among injectable-drug-naïve patients with type 2 diabetes mellitus (T2DM) who are elderly or have renal impairment (RI). MATERIALS AND METHODS: Initiators of EQW and BI with T2DM were identified for the period 2012 to 2015 within a US electronic health record database and matched by propensity score. Matched EQW and BI initiators aged ≥65 years or who had RI were compared. Data on weight, glycated haemoglobin (HbA1c), estimated glomerular filtration rate (eGFR), blood pressure and lipids were obtained at baseline and quarterly (Q1-Q4) or semi-annually for 1 year after drug initiation. Hypoglycaemia and gastrointestinal symptoms were identified using diagnosis codes and data abstracted from clinical notes. RESULTS: Among patients aged ≥65 years, HbA1c changed by -0.50 and -0.31 percentage points from baseline to Q4 for EQW and BI initiators, respectively. Weight changed by -1.6 kg among EQW initiators compared with 0.2 kg among BI initiators. Compared with BI initiators, EQW initiators had a 1.45-fold increased risk of nausea and vomiting. Among patients with RI, HbA1c changed by -0.58 and -0.33 percentage points from baseline to Q4 for EQW and BI initiators, respectively. Weight changed by -1.9 kg for EQW initiators while BI initiators had no change in weight. EQW initiators had a 1.28-fold increased risk of constipation and diarrhoea compared with BI initiators. CONCLUSION: Regardless of age or renal function, the benefits of EQW relative to BI treatment are improved glycaemic control and increased weight loss, which should be weighed against the increased risk of gastrointestinal symptoms.

Secondary Prevention Medication Use After Myocardial Infarction in U.S. Nursing Home Residents.

BACKGROUND/OBJECTIVES: Secondary prevention medications are recommended for older adults after acute myocardial infarction (AMI), but little is known about whether nursing home (NH) residents receive these medications. The objective was to evaluate new use of secondary prevention medications after AMI in NH residents who were previously nonusers and to evaluate what factors were associated with use. DESIGN: Retrospective cohort using linked national Minimum Data Set assessments; Online Survey, Certification and Reporting records; and Medicare claims. SETTING: U.S. NHs. PARTICIPANTS: National cohort of 11,192 NH residents aged 65 and older who were hospitalized for an AMI between May 2007 and March 2010, had no beta-blocker or statin use for 4 months or longer before the hospitalization, and survived 14 days or more after NH readmission. MEASUREMENTS: The outcome was the number of secondary prevention medications initiated within 30 days of NH readmission. RESULTS: Thirty-seven percent of residents had no secondary prevention medications initiated after AMI, 41% had 1 initiated, and 22% had 2 initiated. After covariate adjustment, fewer secondary prevention medications were used in older residents (proportional odds ratio (POR) = 0.48, 95% confidence interval (CI)  = 0.40-0.57 for ≥95 vs 65-74); women (POR = 0.88, 95% CI = 0.80-0.96);and those with a do-not-resuscitate (DNR) order (POR = 0.90, 95% CI = 0.83-0.98), functional impairment (dependent or totally dependent vs independent to limited assistance, POR = 0.77, 95% CI = 0.69-0.86), and cognitive impairment (moderate to severe vs no impairment, POR = 0.79, 95% CI = 0.70-0.89). CONCLUSION: More than one-third of older NH residents in the United States do not have any secondary prevention medications initiated after AMI, with fewer medications initiated in older residents; women; and those with, DNR orders, poor physical function, and cognitive impairment. A lack of evidence about the safety and effectiveness of secondary preventions medications in the NH population and unmeasured person-centered goals of care are plausible explanations for these findings.

Tolerability and Effectiveness of Exenatide Once Weekly Relative to Basal Insulin Among Type 2 Diabetes Patients of Different Races in Routine Care.

INTRODUCTION: Analyses of efficacy and tolerability of pharmacologic interventions are based on clinical trials that often include predominately white populations, in part because of challenges associated with recruitment and retention of racial/ethnically diverse study populations. Using real-world electronic health record (EHR) data, we sought to evaluate the tolerability and effectiveness of exenatide once weekly (EQW), overall and relative to basal insulin (BI), according to race. METHODS: Patients with type 2 diabetes initiating EQW or BI between 2012 and 2015 were selected from the Optum EHR Research Database, a system pooling data from dozens of hospitals throughout the US. Measures of HbA1c, weight, and body mass index (BMI) were summarized at initiation and quarterly in the first year afterwards. Occurrences of gastrointestinal (GI) symptoms and hypoglycemia were identified by diagnostic codes and clinical notes, and incidence rates (IR) and relative rates (RR) were calculated. RESULTS: Overall, 4907 white patients (mean age = 57 years) and 454 African American patients (mean age = 53 years) were included. The percent change in HbA1c from initiation through 9-12 months was similar for white and African American patients [EQW-White: -6.89 (95% CI: -8.29, -5.50), EQW-African American: -5.99 (95% CI: -10.33, -1.65), BI-White: -4.68 (95% CI: -5.51, -3.86), BI-African American: -3.11 (95% CI: -5.37, -0.85)]. For EQW, percent change in weight was -1.73 (95% CI: -2.45, -1.02) for white patients and -1.11 (95% CI: -3.02, -0.81) for African American patients. No weight loss was observed among BI initiators. Relative to BI initiators, EQW initiators had lower rates of hypoglycemia [White RR: 0.82 (95% CI: 0.66, 1.01), African American RR: 0.59 (95% CI: 0.26, 1.34)]. GI symptoms were increased in white EQW initiators. CONCLUSIONS: Treatment with EQW, relative to BI, was associated with larger reductions in HbA1c and weight and reduced risk of hypoglycemia, effects that were not different for white and African American patients. FUNDING: AstraZeneca, Gothenburg, Sweden.

Metformin Safety Warnings and Diabetes Drug Prescribing Patterns for Older Nursing Home Residents.

OBJECTIVE: Diabetes mellitus is common in US nursing homes (NHs), and the mainstay treatment, metformin, has US Food and Drug Administration (FDA) boxed warnings indicating safety concerns in those with advanced age, heart failure, or renal disease. Little is known about treatment selection in this setting, especially for metformin. We quantified the determinants of initiating sulfonylureas over metformin with the aim of understanding the impact of FDA-labeled boxed warnings in older NH residents. DESIGN AND SETTING: National retrospective cohort in US NHs. PARTICIPANTS: Long-stay NH residents age ≥65 years who initiated metformin or sulfonylurea monotherapy following a period of ≥6 months with no glucose-lowering treatment use between 2008 and 2010 (n = 7295). MEASUREMENTS: Measures of patient characteristics were obtained from linked national Minimum Data Set assessments; Online Survey, Certification and Reporting (OSCAR) records; and Medicare claims. Odds ratios (ORs) comparing patient characteristics and treatment initiation were estimated using univariable and multivariable multilevel logistic regression models with NH random intercepts. RESULTS: Of the 7295 residents in the study population, 3066 (42%) initiated metformin and 4229 (58%) initiated a sulfonylurea. In multivariable analysis, several factors were associated with sulfonylurea initiation over metformin initiation, including heart failure (odds ratio [OR] 1.2, 95% confidence interval [CI] 1.1-1.4) and renal disease (OR 2.1, 95% CI 1.7-2.5). Compared with those aged 65 to <75 years, residents 75 to <85 (OR 1.3, 95% CI 1.2-1.5), 85 to <95 (OR 2.0, 95% CI 1.7-2.3), and ≥95 (OR 4.3, 95% CI 3.2-5.8) years were more likely to initiate sulfonylureas over metformin. CONCLUSIONS: In response to FDA warnings, providers initiated NH residents on a drug class with a known, common adverse event (hypoglycemia with sulfonylureas) over one with tenuous evidence of a rare adverse event (lactic acidosis with metformin).

Performance of claims-based algorithms for identifying incident thyroid cancer in commercial health plan enrollees receiving antidiabetic drug therapies.

BACKGROUND: Thyroid cancer incidence is increasing in the United States (US) and many other countries. The objective of this study was to develop and evaluate algorithms using administrative medical claims data for identification of incident thyroid cancer. METHODS: This effort was part of a prospective cohort study of adults initiating therapy on antidiabetic drugs and used administrative data from a large commercial health insurer in the US. Patients had at least 6 months of continuous enrollment prior to initiation during 2009-2013, with follow-up through March, 2014 or until disenrollment. Potential incident thyroid cancers were identified using International Classification of Diseases, 9th Revision (ICD-9) diagnosis code 193 (malignant neoplasm of the thyroid gland). Medical records were adjudicated by a thyroid cancer specialist. Several clinical variables (e.g., hospitalization, treatments) were considered as predictors of case status. Positive predictive values (PPVs) and 95% confidence intervals (CIs) were calculated to evaluate the performance of two primary algorithms. RESULTS: Charts were requested for 170 patients, 150 (88%) were received and 141 (80%) had sufficient information to adjudicate. Of the 141 potential cases identified using ≥1 ICD-9 diagnosis code 193, 72 were confirmed as incident thyroid cancer (PPV of 51% (95% CI 43-60%)). Adding the requirement for thyroid surgery increased the PPV to 68% (95% CI 58-77%); including the presence of other therapies (chemotherapy, radio-iodine therapy) had no impact. When cases were required to have thyroid surgery during follow-up and ≥2 ICD-9 193 codes within 90 days of this surgery, the PPV was 91% (95% CI 81-96%); 62 (82%) of the true cases were identified and 63 (91%) of the non-cases were removed from consideration by the algorithm as potential cases. CONCLUSIONS: These findings suggest a significant degree of misclassification results from relying only on ICD-9 diagnosis codes to detect thyroid cancer. An administrative claims-based algorithm was developed that performed well to identify true incident thyroid cancer cases.

Hypoglycaemia seriousness and weight gain as determinants of cardiovascular disease outcomes among sulfonylurea users.

AIMS: Certain treatments for type 2 diabetes mellitus cause hypoglycaemia and weight gain, and thus might counteract the benefits of intensive glucose control. We quantify the association of cardiovascular disease (CVD) outcomes with hypoglycaemia and weight gain among patients with type 2 diabetes treated with sulfonylureas. MATERIALS AND METHODS: This cohort study included patients from January 2009 through December 2014 who were selected from within a deidentified nationwide electronic health records repository, including multiple provider networks and electronic medical records systems. Hypoglycaemia measures from structured data fields and free text clinical notes were categorized as serious or non-serious. Covariate adjusted Poisson regression analysis was used to assess the association between frequency of hypoglycaemia (by severity), or magnitude of weight change, and incidence of acute myocardial infarction (AMI), congestive heart failure (CHF) and stroke. RESULTS: Among 143 635 eligible patients, we observed 5669 cases of AMI, 14 109 incident cases of CHF and 7017 cases of stroke. Overall incidence rates were 1.53, 4.26 and 1.92 per 100 person-years for AMI, CHF and stroke, respectively. The associations between overall hypoglycaemia and each of the CVD outcomes were positive, with stronger associations observed for serious hypoglycaemia and attenuated or null associations observed for non-serious hypoglycaemia. Weight change exhibited a U-shaped association with increased risks associated with both weight loss and weight gain relative to stable weight. CONCLUSIONS: This study provides evidence of increased CVD risk associated with hypoglycaemia, especially with serious hypoglycaemia events. While associations were attenuated with non-serious hypoglycaemia, the results were suggestive of a potential increased risk.

Frequency and Predictors of Analgesic Prescribing in U.S. Nursing Home Residents with Persistent Pain.

OBJECTIVES: To quantify prescription analgesic use of elderly nursing home (NH) residents with persistent noncancer pain and to identify individual and facility traits associated with no treatment. DESIGN: Cross-sectional study. SETTING: Linked Minimum Data Set (MDS) assessments; Online Survey, Certification and Reporting (OSCAR) records; and Medicare Part D claims. PARTICIPANTS: Individuals aged 65 and older with persistent noncancer pain were identified from a cross-section of all long-stay U.S. NH residents with an MDS assessment and Medicare Part D enrollment in 2008, excluding those who were terminally ill, those with Alzheimer's disease, and those with the most-severe cognitive impairment. MEASUREMENTS: Residents with moderate to severe daily pain on consecutive assessments at least 90 days apart constituted the cohort with persistent pain. Part D dispensing for an opioid or nonsteroidal anti-inflammatory drug (NSAID) within 30 days of persistent pain onset was identified. Information on resident and facility characteristics was obtained from MDS and OSCAR records. Associations between resident and facility attributes and pain treatment were estimated using multilevel mixed-effects logistic regression analyses. RESULTS: Of the study sample of 18,526 residents with persistent pain, 3,094 (16.7%) did not receive prescription analgesics, 12,815 (69.2%) received a prescription opioid, 485 (2.6%) received a prescription NSAID, and 2,132 (11.5%) received a prescription opioid and NSAID. After adjusting for potentially confounding covariates, residents who were older (≥95, odds ratio (OR) = 2.06, 95% confidence interval (CI) = 1.70-2.49), more cognitively impaired (moderately severe cognitive impairment, OR = 2.12, 95% CI = 1.71-2.62), or black (OR = 1.20, 95% CI = 1.03-1.39) or Asian (OR = 1.97, 95% CI = 1.22-3.20) were less likely to receive a prescription analgesic. CONCLUSION: Through 2008, pain remained undertreated in NHs, especially in certain subpopulations, including cognitively impaired and older residents. Changes in pain management practice and policies may be necessary to target these vulnerable residents.