Acute pancreatitis has significant morbidity and mortality. Previous studies have raised the possibility that glucagonlike peptide 1 (GLP-1)-based therapies, including a GLP-1 mimetic (exenatide) and a dipeptidyl peptidase 4 inhibitor (sitagliptin phosphate), may increase the risk of acute pancreatitis. Objective: To test whether GLP-1-based therapies such as exenatide and sitagliptin are associated with an increased risk of acute pancreatitis. We used conditional logistic regression to analyze the data.

Program (PDMP) and pill mill laws are among the principal means states use to reduce prescription drug abuse and diversion, yet little high-quality evidence exists regarding their effect. OBJECTIVE To quantify the effect of Florida's PDMP and pill mill laws on overall and high-risk opioid prescribing and use. DESIGN, SETTING, AND PARTICIPANTS We applied comparative interrupted time-series analyses to IMS Health LifeLink LRx data to characterize the effect of PDMP and pill mill law implementation on a closed cohort of prescribers, retail pharmacies, and patients from July 2010 through September 2012 in Florida (intervention state) compared with Georgia (control state). We conducted sensitivity analyses, including varying length of observation and modifying requirements for continuous observation of individuals throughout the study period. MAIN OUTCOMES AND MEASURES Total opioid volume, mean morphine milligram equivalent (MME) per transaction, mean days' supply per transaction, and total number of opioid prescriptions dispensed. Analyses were conducted per prescriber and per patient, in aggregate and after stratifying by volume of baseline opioid prescribing for prescribers and use for patients. RESULTS From July 2010 through September 2012, a cohort of 2.6 million patients, 431 890 prescribers, and 2829 pharmacies was associated with approximately 480 million prescriptions in Florida and Georgia, 7.7% of which were for opioids. Total monthly opioid volume, MME per transaction, days' supply, and prescriptions dispensed were higher in Florida than Georgia before implementation. Florida's laws were associated with statistically significant declines in opioid volume (2.5 kg/mo, P < .05; equivalent to approximately 500 000 5-mg tablets of hydrocodone bitartrate per month) and MME per transaction (0.45 mg/mo, P < .05), without any change in days' supply. Twelve months after implementation, the policies were associated with approximately a 1.4% decrease in opioid prescriptions, 2.5% decrease in opioid volume, and 5.6% decrease in MME per transaction. Reductions were limited to prescribers and patients with the highest baseline opioid prescribing and use. Sensitivity analyses, varying time windows, and enrollment criteria supported the main results. CONCLUSIONS AND RELEVANCE Florida's PDMP and pill mill laws were associated with modest decreases in opioid prescribing and use. Decreases were greatest among prescribers and patients with the highest baseline opioid prescribing and use.

Background Fried et al described a frailty phenotype measured in the Cardiovascular Health Study (CHS). This phenotype is manifest when 3 or more of the following are present: low grip strength, low energy, slowed waking speed, low physical activity, or unintentional weight loss. We sought to approximate frailty phenotype using only administrative claims data in order to enable frailty to be assessed without physical performance measures. Study Design We used the CHS cohort data linked to participants Medicare claims. The reference standard was the frailty phenotype measured at visits 5 and 9. With penalized logistic regression, we developed a parsimonious index for predicting the frailty phenotype using a linear combination of diagnoses, operationalized with claims data. We assessed the predictive validity of frailty index by examining how well it predicted common aging-related outcomes including hospitalization, disability and death. Results There were 4,454 CHS participants from 4 clinical sites. 84% were white, 58% were women and their mean age was 72 years at enrollment. Approximately 11% of the cohort was frail. The model had an area under the ROC curve of 0.75 to concurrently predict a frailty phenotype. This Claims-based Frailty Index (CFI) significantly predicted death [Odds-Ratio 1.84], time to death [Hazard-Ratio 1.71], number of hospital admissions [Incidence Rate-Ratio 1.74], and nursing home admission [OR 1.47] in models adjusted for age and sex. Conclusions Claims data alone can be used to classify individuals as frail and non-frail. The CFI might be used in research with large datasets for confounding adjustment or risk prediction. The indicator might also be used for emergency preparedness for identification of regions enriched with frail individuals.

Background Escalating rates of prescription opioid use and abuse have occurred in the context of efforts to improve the treatment of non-malignant pain. Objectives To characterize the diagnosis and management of non-malignant pain in ambulatory, office-based settings in the United States between 2000 and 2010. Design, setting, and participants Serial cross-sectional and multivariate regression analyses of the National Ambulatory Medical Care Survey (NAMCS), a nationally representative audit of office-based physician visits. Measures (1) Annual visits volume among adults with primary pain symptom or diagnosis; (2) receipt of any pain treatment; and (3) receipt of prescription opioid or non-opioid pharmacologic therapy in visits for new musculoskeletal pain. Results Primary symptoms or diagnoses of pain consistently represented one-fifth of visits, varying little from 2000 through 2010. Among all pain visits, opioid prescribing nearly doubled from 11.3% to 19.6%, whereas non-opioid analgesic prescribing remained unchanged (26%–29% of visits). One-half of new musculoskeletal pain visits resulted in pharmacologic treatment, though the prescribing of non-opioid pharmacotherapies decreased from 38% of visits (2000) to 29% of visits (2010). After adjusting for potentially confounding covariates, few patient, physician or practice characteristics were associated with a prescription opioid rather than a non-opioid analgesic for new musculoskeletal pain, and increases in opioid prescribing generally occurred non-selectively over time. Conclusions Increased opioid prescribing has not been accompanied by similar increases in non-opioid analgesics or the proportion of ambulatory pain patients receiving pharmacologic treatment. Clinical alternatives to prescription opioids may be underutilized as a means of treating ambulatory non-malignant pain.

IMPORTANCE Results of clinical trials suggest that canagliflozin, a sodium-glucose cotransporter 2 (SGLT-2) inhibitor for treating type 2 diabetes, may be associated with lower extremity amputation. OBJECTIVE To quantify the association between the use of oral medication for type 2 diabetes and 5 outcomes (lower extremity amputation, peripheral arterial disease, critical limb ischemia, osteomyelitis, and ulcer). DESIGN, SETTING, AND PARTICIPANTSA retrospective cohort study was conducted using Truven Health MarketScan Commercial Claims and Encounters data on new users between September 1, 2012, and September 30, 2015. The study focused on 2.0 million commercially insured individuals and used propensity score weighting to balance baseline differences among groups. Sensitivity analyses varied statistical models, assessed the effect of combining dipeptidyl peptidase 4 (DPP-4) inhibitors and glucagon-like peptide 1 (GLP-1) agonists as a single referent group, adjusted for baseline use of older oral agents, and included people with baseline amputation.EXPOSURES New use of SGLT-2 inhibitors alone, DPP-4 inhibitors alone, GLP-1 agonists alone, or other antidiabetic agents (sulfonylurea, metformin hydrochloride, or thiazolidinediones). MAIN OUTCOMES AND MEASURES Foot and leg amputation, defined by validated International Classification of Diseases, Ninth Revision and Current Procedural Terminology codes.RESULTS Among 2.0 million potentially eligible individuals, a total of 953 906 (516 046 women and 437 860 men; mean [SD] age, 51.8 [10.9] years) were included in the final analyses, including 39 869 new users of SGLT-2 inhibitors (4.2%), 105 023 new users of DPP-4 inhibitors (11.0%), and 39 120 new users of GLP-1 agonists (4.1%). The median observation time ranged from 99 days for new users of GLP-1 agonists to 127 days for those using metformin, sulfonylureas, and thiazolidinediones, while the crude incident rates ranged from 4.90 per 10 000 person-years for those using metformin, sulfonylureas, and thiazolidinediones to 10.53 per 10 000 person-years for new users of SGLT-2 inhibitors. After propensity score weighting and adjustment for demographics, severity of diabetes, comorbidities, and medications, there was a nonstatistically significant increased risk of amputation associated with new use of SGLT-2 inhibitors compared with DPP-4 inhibitors (adjusted hazard ratio, 1.50; 95% CI, 0.85-2.67) and GLP-1 agonists (adjusted hazard ratio, 1.47; 95% CI, 0.64-3.36). New use of SGLT-2 inhibitors was statistically significantly associated with amputation compared with sulfonylureas, metformin, or thiazolidinediones (adjusted hazard ratio, 2.12; 95% CI, 1.19-3.77). These results persisted in sensitivity analyses.CONCLUSIONS AND RELEVANCE Use of SGLT-2 inhibitors may be associated with increased risk of amputation compared with some oral treatments for type 2 diabetes. Further observational studies are needed with extended follow-up and larger sample sizes.