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.

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.

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.

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.

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.

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.

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.

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.

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.

Disparities in Discontinuing Rosiglitazone Following the 2007 FDA Safety Alert.

BACKGROUND: Responsiveness to the Food and Drug Administration (FDA) rosiglitazone safety alert, issued on May 21, 2007, has not been examined among vulnerable subpopulations of the elderly. OBJECTIVE: To compare time to discontinuation of rosiglitazone after the safety alert between black and white elderly persons, and across sociodemographic and economic subgroups. RESEARCH DESIGN: A cohort study. SUBJECTS: Medicare fee-for-service enrollees in 2007 who were established users of rosiglitazone identified from a 20% national sample of pharmacy claims. MEASURES: Outcome of interest was time to discontinuation of rosiglitazone after the May alert. We modeled the number of days following the warning to the end of the days' supply for the last rosiglitazone claim during the study period (May 21, 2007-December 31, 2007) using multivariable proportional hazards models. RESULTS: More than 67% of enrollees discontinued rosiglitazone within six months of the advisory. In adjusted analysis, white enrollees (hazard ratio=0.90; 95% confidence interval, 0.86-0.94) discontinued rosiglitazone later than the comparison group of black enrollees. Enrollees with a history of low personal income also discontinued later than their comparison group (hazard ratio=0.84; 95% confidence interval, 0.81-0.87). There were no observed differences across quintiles of area-level socioeconomic status. CONCLUSIONS: White race and a history of low personal income modestly predicted later discontinuation of rosiglitazone after the FDA's safety advisory in 2007. The impact of FDA advisories can vary among sociodemographic groups. Policymakers should continue to monitor whether risk management policies reach their intended populations.

Prescriber and pharmacy variation in patient adherence to five medication classes measured using implementation during persistent episodes.

PURPOSE: The objective of this study was to determine the fraction of variance in patient-level medication adherence accounted for by prescribers and pharmacies. METHODS: We used prescription drug claims paid between January 2010 and July 2011 to a national pharmacy benefits manager to define implementation during persistent episodes. Patients in Massachusetts or Rhode Island covered by Blue Cross Blue Shield of Rhode Island and their prescribers were included. Five drug classes were analyzed: angiotensin converting enzyme (ACE) inhibitors, antihyperglycemics (ANHGs), drugs for prostatic hyperplasia (PH), statins, and levothyroxine (THYR). We performed mixed models with random intercepts (drug, patient, prescriber, and pharmacy) and examined the fraction of variance explained at each level using intraclass correlations. RESULTS: Overall implementation ranged from 87 to 91%. The fraction of the explained variance in implementation to ACEs, ANHG, PH, statins, and THYR accounted for by prescribers was 16.4%, 12.6%, 14.6%, 15.6%, and 15% respectively; and for pharmacies 20.4%, 20%, 15.2%, 10.6%, and 9.4%, respectively. CONCLUSIONS: Prescriber and pharmacy effects accounted for a substantial amount of the explained variance in implementation across all five drug classes. Adherence interventions for chronic conditions that target prescribers and pharmacies, in addition to patients, could be effective and efficient. Copyright © 2016 John Wiley & Sons, Ltd.

Validation of current procedural terminology codes for rotavirus vaccination among infants in two commercially insured US populations.

PURPOSE: We validated procedure codes used in health insurance claims for reimbursement of rotavirus vaccination by comparing claims for monovalent live-attenuated human rotavirus vaccine (RV1) and live, oral pentavalent rotavirus vaccine (RV5) to medical records. METHODS: Using administrative data from two commercially insured United States populations, we randomly sampled vaccination claims for RV1 and RV5 from a cohort of infants aged less than 1 year from an ongoing post-licensure safety study of rotavirus vaccines. The codes for RV1 and RV5 found in claims were confirmed through medical record review. The positive predictive value (PPV) of the Current Procedural Terminology codes for RV1 and RV5 was calculated as the number of medical record-confirmed vaccinations divided by the number of medical records obtained. RESULTS: Medical record review confirmed 92 of 104 RV1 vaccination claims (PPV: 88.5%; 95% CI: 80.7-93.9%) and 98 of 113 RV5 vaccination claims (PPV: 86.7%; 95% CI: 79.1-92.4%). Among the 217 medical records abstracted, only three (1.4%) of vaccinations were misclassified in claims-all were RV5 misclassified as RV1. The medical records corresponding to 9 RV1 and 15 RV5 claims contained insufficient information to classify the type of rotavirus vaccine. CONCLUSIONS: Misclassification of rotavirus vaccines is infrequent within claims. The PPVs reported here are conservative estimates as those with insufficient information in the medical records were assumed to be incorrectly coded in the claims. Copyright © 2016 John Wiley & Sons, Ltd.

Patterns of Lipid Lowering Therapy among Children Ages 8-20 Years.

OBJECTIVES: Pediatric guidelines in 2008 and 2011 recommended lipid lowering therapy in children ≥ 8 years of age with high-risk cardiovascular conditions, such as familial hypercholesterolemia (FH). Our objective was to describe the patterns and predictors of lipid lowering therapy initiation in commercially insured children between 2005 and 2010. STUDY DESIGN: Using commercial health plan data on children ages 8-20 years from 2004-2010, we estimated rates of lipid lowering therapy initiation overall and stratified by age. Using a nested case-control design, we used multivariable logistic regression to identify temporal, demographic, clinical, and health utilization characteristics associated with lipid lowering therapy initiation. RESULTS: Among >13 million children, 665 initiated lipid lowering therapy for an incidence rate 2.6/100,000 person-years (PY). Incidence rates were highest in 2005 (4.1/100,000 PY) and 2008 (3.9/100,000 PY), with no discernable secular trend. Rates of lipid lowering therapy initiation were significantly greater in children ≥ 15 years of age (OR 2.9 [95% CI 5.2-13.0]), males (2.1 [1.7-2.4]), and those with a diagnosis of FH (165.2 [129.0-211.6]), other dyslipidemia (175.5 [143.2-215.3]), diabetes type I (7.7 [4.7-12.4]), diabetes type II (13.6 [8.5-21.7]), hypertension (8.1 [4.9-13.3]), obesity (7.8 [4.7-12.7]), and ≥ 5 outpatient visits (1.5 [1.2-1.7]), and children with dispensing of ≥ 2 nonlipid lowering therapy prescriptions were less likely to initiate lipid lowering therapy (0.2 [0.2-0.3]). CONCLUSIONS: Despite new guidelines, lipid lowering therapy initiation in children is low and has not increased through 2010. Although diagnosis of FH and other dyslipidemias was associated with higher probability of lipid lowering therapy initiation, our findings suggest lipid lowering therapy is underutilized in this population given the prevalence of these disorders.

Hepatic outcomes among adults taking duloxetine: a retrospective cohort study in a US health care claims database.

BACKGROUND: Hepatic injury has been reported following duloxetine use. This study further examines the hepatic safety of duloxetine in a large US health insurance database. METHODS: In this propensity score-matched cohort analysis in a US commercially insured population (01 August 2004 to 31 December 2010), we compared individuals with depression and without liver disease who initiated duloxetine to comparators (venlafaxine or selective serotonin reuptake inhibitors [SSRIs], and individuals with pharmacologically untreated depression). We estimated incidence rates (IR) and 95 % confidence intervals (CI) for medical record-confirmed hepatic-related death, liver failure, and other clinically significant hepatic injury. RESULTS: Among 30,844 duloxetine initiators, 21,000 were matched to venlafaxine initiators, 28,479 to SSRI initiators, and 22,714 to untreated patients. There were no cases of hepatic-related death or liver failure. IRs of other clinically significant hepatic injury without documented alternate etiologies were higher but not statistically significant among duloxetine initiators compared to initiators of venlafaxine (0.7/1000 person-years [PY] [95 % CI: 0.2 - 1.5] vs. 0.0/1000 PY [95 % CI: 0.0 - 0.3]) and SSRIs (0.4/1000 PY [95 % CI: 0.1 - 1.0] vs. 0.0/1000 PY [95 % CI: 0.0 - 0.3]). IRs were similar among duloxetine and untreated patients (0.5/1000 PY [95 % CI: 0.1 - 1.3] vs. 0.5/1000 PY [95 % CI: 0.1 - 1.5]). When hepatic outcomes were considered irrespective of alternate etiologies, similar results were observed. CONCLUSIONS: Our findings, while not statistically significant, may suggest a higher incidence of hepatic injury other than hepatic-related death or liver failure among duloxetine initiators compared to venlafaxine and possibly SSRIs, but not untreated patients. These differences remain consistent with chance, and an elevated risk cannot be ruled in or out.

A cross-sectional study of the identification of prevalent asthma and chronic obstructive pulmonary disease among initiators of long-acting ß-agonists in health insurance claims data.

BACKGROUND: Claims data are potentially useful for identifying long-acting ß-agonist (LABA) use by patients with asthma, a practice that is associated with increased mortality. We evaluated the accuracy of claims data for classifying prevalent asthma and chronic obstructive pulmonary disease (COPD) among initiators of LABAs. METHODS: This study included adult LABA initiators during 2005-2008 in a US commercial health plan. Diagnosis codes from the 6 months before LABA initiation identified potential asthma or COPD and a physician adjudicated case status using abstracted medical records. We estimated the positive predictive value (PPV) and 95% confidence intervals (CI) of covariate patterns for identifying asthma and COPD. RESULTS: We sought 520 medical records at random from 225,079 LABA initiators and received 370 (71%). The PPV for at least one asthma claim was 74% (CI 63-82), and decreased as age increased. Having at least one COPD claim resulted in a PPV of 82% (CI 72-89), and of over 90% among older patients, men, and recipients of inhaled anticholinergic drugs. Only 2% (CI 0.2-7.6) of patients with a claim for COPD alone were found to have both COPD and asthma, while 9% (CI 4-16) had asthma only. Twenty-one percent (CI 14-30) of patients with claims for both diagnoses had both conditions. Among patients with no asthma or COPD claims, 62% (CI 50-72) had no confirmed diagnosis and 29% (CI 19-39) had confirmed asthma. CONCLUSIONS: Subsets of patients with asthma, COPD, and both conditions can be identified and differentiated using claims data, although categorization of the remaining patients is infeasible. Safety surveillance for off-label use of LABAs must account for this limitation.

Underreporting high-risk prescribing among Medicare Advantage plans: a cross-sectional analysis.

BACKGROUND: Although Medicare Advantage plans are required to report clinical performance using Healthcare Effectiveness Data and Information Set (HEDIS) quality indicators, the accuracy of plan-reported performance rates is unknown. OBJECTIVE: To compare calculated and reported rates of high-risk prescribing among Medicare Advantage plans. DESIGN: Cross-sectional comparison. SETTING: 172 Medicare Advantage plans. PATIENTS: A random sample of beneficiaries in 172 Medicare Advantage plans in 2006 (n = 177,227) and 2007 (n = 173,655). MEASUREMENTS: Plan-reported HEDIS rates of high-risk prescribing among elderly persons were compared with rates calculated from Medicare Advantage plans' Part D claims by using the same measure specifications and source population. RESULTS: The mean rate of high-risk prescribing derived from Part D claims was 26.9% (95% CI, 25.9% to 28.0%), whereas the mean plan-reported rate was 21.1% (CI, 20.0% to 22.3%). Approximately 95% of plans underreported rates of high-risk prescribing relative to calculated rates derived from Part D claims. The differences in the calculated and reported rates negatively affected quality rankings for the plans that most accurately reported rates. For example, the 9 plans that reported rates of high-risk prescribing within 1 percentage point of calculated rates were ranked 43.4 positions lower when reported rates were used instead of calculated rates. Among 103,680 individuals present in both the sample of Part D claims and HEDIS data in 2006, Medicare Advantage plans incorrectly excluded 10.3% as ineligible for the HEDIS high-risk prescribing measure. Among those correctly included in the high-risk prescribing denominator, the reported rate of high-risk prescribing was 21.9% and the calculated rate was 26.2%. LIMITATION: A single quality measure was assessed. CONCLUSION: Medicare Advantage plans underreport rates of high-risk prescribing, suggesting a role for routine audits to ensure the validity of publicly reported quality measures. PRIMARY FUNDING SOURCE: Health Assessment Lab and National Institute on Aging.

Vaccine discontinuation and switching following regulatory interventions in response to rotavirus vaccine contamination with porcine circovirus DNA fragments.

PURPOSE: The Food and Drug Administration temporarily suspended monovalent rotavirus vaccine (RV1) use following discovery of contamination with porcine circovirus fragments and subsequently announced similar contamination of the pentavalent rotavirus vaccine (RV5) but recommended continued use of the product. We assessed the utilization of these vaccines in relation to the announcements. METHODS: Using claims submitted to a commercial health insurer for administration of RV1 and RV5, we estimated the number of administrations of the vaccines and the extent of switching between RV1 and RV5. Procedure codes on submitted claims identified vaccine administrations among infants ≤ 1 year old through 16 June 2010. Among infants who received a first dose of vaccine before the corresponding announcement, and whose second dose was anticipated following the announcement, we estimated the number who received no second dose of rotavirus vaccine. RESULTS: There were 31 178 RV1 initiators and 514 357 RV5 initiators. We observed a 93% reduction in RV1 doses in the month following the recommended suspension of use, coupled with extensive switching to RV5 (90% of subsequent doses) and a reduction in second RV1 doses (from 35.5% incomplete to 40.9%). There was a 15% increase in number of RV5 administrations following announcement of its contamination, with little switching to RV1 but with a possible decrease in completion. CONCLUSIONS: Recommended suspension of RV1 use led to a substantial decrease in use and extensive switching to RV5. The announcement that RV5 was similarly contaminated, but without a corresponding recommendation to suspend use, had little effect on use.

Linkage of routinely collected oncology clinical data with health insurance claims data--an example with aromatase inhibitors, tamoxifen, and all-cause mortality.

PURPOSE: Studies of cancer based solely on health insurance claims data typically lack information on cancer clinical characteristics that are strong predictors of treatment and prognosis. Our objective was to evaluate routinely collected cancer clinical data for adjustment of confounding using an example evaluation of mortality associated with aromatase inhibitors and tamoxifen. METHODS: This cohort study identified women with breast cancer from 2008 through 2010 using health insurance claims data linked to clinical information on stage at diagnosis, current clinical status, histology, and other clinical markers. Estimated mortality rates (MRs) and 95% confidence intervals (CI) were compared between users of aromatase inhibitors or tamoxifen, adjusted for claims-identified covariates and additionally for the clinical variables using propensity scores and proportional hazards regression models. RESULTS: The overall (n = 7974) estimated MR was 69/1000 person-years (95%CI = 62-76 person-years), 308/1000 person-years (95% CI = 273-345 person-years) for women with metastasis, and 12/1000 person-years (95%CI = 8-16 person-years) for women without active cancer. Propensity score matching of aromatase inhibitor users (n = 777) with tamoxifen users (n = 535) removed many, but not all, covariate imbalances. The hazard ratios (HRs) of all-cause mortality comparing users of aromatase inhibitors with tamoxifen users ranged from 1.0 to 1.6, with the HR most similar to previous clinical trials (0.87) coming from the claims-only analysis. CONCLUSIONS: We were able to address potential unmeasured confounders by linking clinical information to the claims data; however, there was no apparent improvement in confounding control in the chosen example. Conditioning eligibility on the clinical data restricted the sample size substantially.

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.

Stratum-specific positive predictive values of claims for acute pancreatitis among commercial health insurance plan enrollees with diabetes mellitus.

PURPOSE: To estimate the positive predictive value (PPV) of claims for acute pancreatitis among initiators of antihyperglycemic drugs in commercial health insurance claims data. METHODS: As part of a systematic study of the occurrence of acute pancreatitis among antihyperglycemic drug initiators (N=260,255) within a large US health insurer's claims database, we identified potential cases of acute pancreatitis and confirmed them through medical record review. Potential cases had an International Classification of Diseases, 9th revision diagnosis code for acute pancreatitis (577.0) associated with an inpatient or emergency department claim. We sought 860 medical records to confirm potential cases and received 585 (70%), which were reviewed by a clinical adjudication committee. We estimated the PPV and 95% confidence intervals (CI) of claims for these medical records and a subset that had the diagnosis code listed in the first position of an inpatient claim. RESULTS: The PPV was 0.50 (95% CI 0.44-0.53) for an acute pancreatitis diagnosis code in any position and 0.60 (95% CI 0.55-0.65) if in the first position of an inpatient claim. The estimated PPV varied across strata defined by patient characteristics and was generally lower within strata where potential risk factors for acute pancreatitis were present. CONCLUSIONS: These data indicate that health insurance claims-based identification of acute pancreatitis might overestimate actual cases and introduce appreciable bias, usually toward the null. Further case confirmation or relative risk correction may be necessary to address potential bias.