Computed tomography-based assessment of sphenoid sinus and sella turcica pneumatization analysis: a retrospective study.

Background: A preoperative three-dimensional examination of the sphenoid sinus anatomy, its pneumatization pattern, and its relevance to neighboring neurovascular constructions is crucial to preventing possible complications. In this study, the aim was to evaluate the relationship between sphenoid sinus pneumatization types and the sella turcica using computed tomography (CT). Methods: CT data from 420 patients referred to the Department of Dentomaxillofacial Radiology were evaluated retrospectively. Sella pneumatization types were classified as conchal, presellar, incomplete sellar, and complete sellar, and they were evaluated. Obtained data were evaluated using the IBM SPSS 25.0 (Armonk, New York, USA) package program. Results: CT images of 420 individuals, including 174 women and 246 men with a mean age of 43.87 ± 17.58 years, were included in the study. When the sella turcica morphologies were evaluated, the most widespread morphological type was irregularity in the posterior part of the dorsum sella, in 51.2% of cases. In addition, a statistically significant correlation was found between the pneumatization of the sphenoid sinus and the morphological types of sella (p < 0.05). Conclusion: In this research endeavor, the predominant observation comprised the complete sellar sphenoid sinus pneumatization type, exhibiting irregularity in the posterior aspect of the dorsum sella, representing one of the sellar types. Notwithstanding, it is imperative to conduct additional investigations to establish the generalizability of the present study's findings.

Glucagon-Like Peptide 1 Receptor Agonists and Risk of Anaphylactic Reaction Among Patients With Type 2 Diabetes: A Multisite Population-Based Cohort Study.

Case reports and a pharmacovigilance analysis have linked glucagon-like peptide 1 receptor agonists (GLP-1 RAs) with anaphylactic reactions, but real-world evidence for this possible association is lacking. Using databases from the United Kingdom (Clinical Practice Research Datalink) and the United States (Medicare, Optum (Optum, Inc., Eden Prairie, Minnesota), and IBM MarketScan (IBM, Armonk, New York)), we employed a new-user, active comparator study design wherein initiators of GLP-1 RAs were compared with 2 different active comparator groups (initiators of dipeptidyl peptidase 4 (DPP-4) inhibitors and initiators of sodium-glucose cotransporter 2 (SGLT-2) inhibitors) between 2007 and 2019. Propensity score fine stratification weighted Cox proportional hazards models were fitted to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for an anaphylactic reaction. Database-specific HRs were pooled using random-effects models. Compared with the use of DPP-4 inhibitors (n = 1,641,520), use of GLP-1 RAs (n = 324,098) generated a modest increase in the HR for anaphylactic reaction, with a wide 95% CI (36.9 per 100,000 person-years vs. 32.1 per 100,000 person-years, respectively; HR = 1.15, 95% CI: 0.94, 1.42). Compared with SGLT-2 inhibitors (n = 366,067), GLP-1 RAs (n = 259,929) were associated with a 38% increased risk of anaphylactic reaction (40.7 per 100,000 person-years vs. 29.4 per 100,000 person-years, respectively; HR = 1.38, 95% CI: 1.02, 1.87). In this large, multisite population-based cohort study, GLP-1 RAs were associated with a modestly increased risk of anaphylactic reaction when compared with DPP-4 inhibitors and SGLT-2 inhibitors.

Linking the Paul Coverdell National Acute Stroke Program to commercial claims to establish a framework for real-world longitudinal stroke research.

BACKGROUND: Non-interventional large-scale research on real-world patients who had a stroke requires the use of multiple data sources ensuring access to longitudinal data from large populations with clinically-detailed information. We sought to establish a framework for longitudinal research on patients hospitalised with stroke by linking information-rich, deidentified inpatient data from the Paul Coverdell National Acute Stroke Program (PCNASP) to commercial and Medicare Advantage longitudinal claims data. METHODS: All stroke admissions in PCNASP between 2008 and 2015 were evaluated for linkage to longitudinal claims from a commercial insurer using an algorithm based on six available common data fields (patient age, gender, admission date, discharge date, discharge diagnosis and state) and a hospital match. We evaluated the linkage quality (via the percentage of unique records in the linked dataset) and the representativeness of the linked population. We also described medical history, stroke severity and patterns of medication use among the PCNASP-claims linked cohort. RESULTS: The linkage produced uniqueness equal to 99.1%. We identified 5644 linked and 98 896 unlinked patients who had an ischaemic stroke hospitalisation in claims data. Linked patients were younger than unlinked (69.7 vs 72.5 years), but otherwise similar by medical history, prestroke medication use or lab values. Stroke severity was mild and most patients were discharged home. Prestroke and discharge use of antihypertensive and statins in the PCNASP were greater than their use as measured by filled prescriptions in claims. CONCLUSIONS: High-quality linkage between the PCNASP and commercial claims data is feasible. This linkage identified differences between reported or recommended versus actual out-of-hospital medication utilisation, highlighting the importance of longitudinal data availability for research aimed to improve the care of patients who had a stroke.

Effectiveness and safety of empagliflozin in routine care patients: Results from the EMPagliflozin compaRative effectIveness and SafEty (EMPRISE) study.

AIM: To investigate effectiveness and safety outcomes among patients with type 2 diabetes (T2D) initiating empagliflozin versus dipeptidyl peptidase-4 (DPP-4) inhibitor treatment across the broad spectrum of cardiovascular risk. METHODS: In a population-based cohort study we identified 39 072 pairs of 1:1 propensity score-matched adult patients with T2D initiating empagliflozin or DPP-4 inhibitors, using data from 2 US commercial insurance databases and Medicare between August 2014 and September 2017. The primary outcomes were a composite of myocardial infarction (MI)/stroke, and hospitalization for heart failure (HHF). Safety outcomes were bone fractures, lower-limb amputations (LLAs), diabetic ketoacidosis (DKA), and acute kidney injury (AKI). We estimated pooled hazard ratios (HRs) and 95% confidence intervals (CIs) adjusting for more than 140 baseline covariates. RESULTS: Study participants had a mean age of 60 years and only 28% had established cardiovascular disease. Compared to DPP-4 inhibitors, empagliflozin was associated with similar risk of MI/stroke (HR 0.99 [95% CI 0.81-1.21]), and lower risk of HHF (HR 0.48 [95% CI 0.35-0.67] and 0.63 [95% CI 0.54-0.74], based on a primary and any heart failure discharge diagnosis, respectively). The HR was 0.52 (95% CI 0.38-0.72) for all-cause mortality (ACM) and 0.83 (95% CI 0.70-0.98) for a composite of MI/stroke/ACM. Empagliflozin was associated with a similar risk of LLA and fractures, an increased risk of DKA (HR 1.71 [95% CI 1.08-2.71]) and a decreased risk of AKI (HR 0.60 [95% CI 0.43-0.85]). CONCLUSIONS: In clinical practice, the initiation of empagliflozin versus a DPP-4 inhibitor was associated with a lower risk of HHF, ACM and MI/stroke/ACM, a similar risk of MI/stroke, and a safety profile consistent with documented information.

Using a Simple Prescription Gap to Determine Warfarin Discontinuation Can Lead to Substantial Misclassification.

BACKGROUND: Warfarin remains widely used and a key comparator in studies of other direct oral anticoagulants. As longer-than-needed warfarin prescriptions are often provided to allow for dosing adjustments according to international normalized ratios (INRs), the common practice of using a short allowable gap between dispensings to define warfarin discontinuation may lead to substantial misclassification of warfarin exposure. We aimed to quantify such misclassification and determine the optimal algorithm to define warfarin discontinuation. METHODS: We linked Medicare claims data from 2007 to 2014 with a multicenter electronic health records system. The study cohort comprised patients ≥65 years with atrial fibrillation and venous thromboembolism initiating warfarin. We compared results when defining warfarin discontinuation by (1) different gaps (3, 7, 14, 30, and 60 days) between dispensings and (2) having a gap ≤60 days or bridging larger gaps if there was INR ordering at least every 42 days (60_INR). Discontinuation was considered misclassified if there was an INR ≥2 within 7 days after the discontinuation date. RESULTS: Among 3,229 patients, a shorter gap resulted in a shorter mean follow-up time (82, 95, 117, 159, 196, and 259 days for gaps of 3, 7, 14, 30, 60, and 60_INR, respectively; p < 0.001). Incorporating INR (60_INR) can reduce misclassification of warfarin discontinuation from 68 to 4% (p < 0.001). The on-treatment risk estimation of clinical endpoints varied significantly by discontinuation definitions. CONCLUSION: Using a short gap between warfarin dispensings to define discontinuation may lead to substantial misclassification, which can be improved by incorporating intervening INR codes.

Three-dimensional semi-automated volumetric assessment of the pulp space of teeth following regenerative dental procedures.

The volumetric change that occurs in the pulp space over time represents a critical measure when it comes to determining the secondary outcomes of regenerative endodontic procedures (REPs). However, to date, only a few studies have investigated the accuracy of the available domain-specialized medical imaging tools with regard to three-dimensional (3D) volumetric assessment. This study sought to compare the accuracy of two different artificial intelligence-based medical imaging programs namely OsiriX MD (v 9.0, Pixmeo SARL, Bernex Switzerland, https://www.osirix-viewer.com ) and 3D Slicer ( http://www.slicer.org ), in terms of estimating the volume of the pulp space following a REP. An Invitro assessment was performed to check the reliability and sensitivity of the two medical imaging programs in use. For the subsequent clinical application, pre- and post-procedure cone beam computed tomography scans of 35 immature permanent teeth with necrotic pulp and periradicular pathosis that had been treated with a cell-homing concept-based REP were processed using the two biomedical DICOM software programs (OsiriX MD and 3D Slicer). The volumetric changes in the teeth's pulp spaces were assessed using semi-automated techniques in both programs. The data were statistically analyzed using t-tests and paired t-tests (P = 0.05). The pulp space volumes measured using both programs revealed a statistically significant decrease in the pulp space volume following the REP (P < 0.05), with no significant difference being found between the two programs (P > 0.05). The mean decreases in the pulp space volumes measured using OsiriX MD and 3D Slicer were 25.06% ± 19.45% and 26.10% ± 18.90%, respectively. The open-source software (3D Slicer) was found to be as accurate as the commercially available software with regard to the volumetric assessment of the post-REP pulp space. This study was the first to demonstrate the step-by-step application of 3D Slicer, a user-friendly and easily accessible open-source multiplatform software program for the segmentation and volume estimation of the pulp spaces of teeth treated with REPs.

Risk of venous thromboembolism associated with methotrexate versus hydroxychloroquine for rheumatoid arthritis: A propensity score-matched cohort study.

AIMS: Patients with rheumatoid arthritis (RA) have an increased risk of venous thromboembolism (VTE), likely related to underlying inflammation. We examined VTE risk associated with two commonly used immunomodulators in RA patients, methotrexate and hydroxychloroquine. METHODS AND RESULTS: Using U.S. Medicare claims data (2008-2017), we identified RA patients (≥65 years) who initiated methotrexate or hydroxychloroquine without prior use of any immunomodulators. The primary outcome was VTE, a composite of pulmonary embolism (PE) or deep vein thrombosis (DVT). Secondary outcomes included PE, DVT, and all-cause mortality. After 1:1 propensity score matching for confounding control, we identified 26,534 pairs of methotrexate and hydroxychloroquine initiators (mean (SD) age 74 (7) years; 79% female). During a total of 56,686 person-years of follow-up, 208 methotrexate and 83 hydroxychloroquine initiators developed VTE. The incidence rate of VTE was higher among methotrexate initiators (6.94/1,000 person-years) than hydroxychloroquine initiators (3.11/1,000 person-years) with a hazard ratio (HR) of 2.26 (95% CI 1.75, 2.91). Methotrexate initiators had a greater risk of PE (HR 3.30, 95% CI 2.28, 4.77) and DVT (HR 1.53, 95% CI 1.07, 2.19) than hydroxychloroquine initiators. All-cause mortality was similar between the two groups (HR 0.91, 95% CI 0.83, 1.00). CONCLUSION: In this large real-world cohort of older RA patients, treatment with methotrexate was associated with a 2-fold increased risk of VTE relative to hydroxychloroquine, although all-cause mortality was similar. Future experimental studies with non-user control groups are needed to determine the causal relationships between the study drugs and VTE and whether methotrexate elevates or hydroxychloroquine reduces the risk of VTE.

Sodium-Glucose Cotransporter-2 Inhibitors Versus Glucagon-like Peptide-1 Receptor Agonists and the Risk for Cardiovascular Outcomes in Routine Care Patients With Diabetes Across Categories of Cardiovascular Disease.

BACKGROUND: Both sodium-glucose cotransporter-2 (SGLT2) inhibitors and glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have shown cardiovascular benefits in placebo-controlled trials of patients with type 2 diabetes (T2D) and established cardiovascular disease (CVD). OBJECTIVE: To evaluate whether SGLT2 inhibitors and GLP-1 RAs are associated with differential cardiovascular benefit among T2D patients with and without CVD. DESIGN: Population-based cohort study. SETTING: Medicare and 2 U.S. commercial claims data sets (April 2013 to December 2017). PARTICIPANTS: 1:1 propensity score-matched adult T2D patients with and without CVD (52 901 and 133 139 matched pairs) initiating SGLT2 inhibitor versus GLP-1 RA therapy. MEASUREMENTS: Primary outcomes were myocardial infarction (MI) or stroke hospitalization and hospitalization for heart failure (HHF). Pooled hazard ratios (HRs) and rate differences (RDs) per 1000 person-years were estimated, with 95% CIs, controlling for 138 preexposure covariates. RESULTS: The initiation of SGLT2 inhibitor versus GLP-1 RA therapy was associated with a slightly lower risk for MI or stroke in patients with CVD (HR, 0.90 [95% CI, 0.82 to 0.98]; RD, -2.47 [CI, -4.45 to -0.50]) but similar risk in those without CVD (HR, 1.07 [CI, 0.97 to 1.18]; RD, 0.38 [CI, -0.30 to 1.07]). The initiation of SGLT2 inhibitor versus GLP-1 RA therapy was associated with reductions in HHF risk regardless of baseline CVD in patients with CVD (HR, 0.71 [CI, 0.64 to 0.79]; RD, -4.97 [CI, -6.55 to -3.39]) and in those without CVD (HR, 0.69 [CI, 0.56 to 0.85]; RD, -0.58 [CI, -0.91 to -0.25]). LIMITATION: Treatment selection was not randomized. CONCLUSION: Use of SGLT2 inhibitors versus GLP-1 RAs was associated with consistent reductions in HHF risk among T2D patients with and without CVD, although the absolute benefit was greater in patients with CVD. There were no large differences in risk for MI or stroke among T2D patients with and without CVD. PRIMARY FUNDING SOURCE: Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School.

Frailty and Clinical Outcomes of Direct Oral Anticoagulants Versus Warfarin in Older Adults With Atrial Fibrillation : A Cohort Study.

BACKGROUND: The role of differing levels of frailty in the choice of oral anticoagulants for older adults with atrial fibrillation (AF) is unclear. OBJECTIVE: To examine the outcomes of direct oral anticoagulants (DOACs) versus warfarin by frailty levels. DESIGN: 1:1 propensity score-matched analysis of Medicare data, 2010 to 2017. SETTING: Community. PATIENTS: Medicare beneficiaries with AF who initiated use of dabigatran, rivaroxaban, apixaban, or warfarin. MEASUREMENTS: Composite end point of death, ischemic stroke, or major bleeding by frailty levels, defined by a claims-based frailty index. RESULTS: In the dabigatran-warfarin cohort (n = 158 730; median follow-up, 72 days), the event rate per 1000 person-years was 63.5 for dabigatran initiators and 65.6 for warfarin initiators (hazard ratio [HR], 0.98 [95% CI, 0.92 to 1.05]; rate difference [RD], -2.2 [CI, -6.5 to 2.1]). For nonfrail, prefrail, and frail persons, HRs were 0.81 (CI, 0.68 to 0.97), 0.98 (CI, 0.90 to 1.08), and 1.09 (CI, 0.96 to 1.23), respectively. In the rivaroxaban-warfarin cohort (n = 275 944; median follow-up, 82 days), the event rate per 1000 person-years was 77.8 for rivaroxaban initiators and 83.7 for warfarin initiators (HR, 0.98 [CI, 0.94 to 1.02]; RD, -5.9 [CI, -9.4 to -2.4]). For nonfrail, prefrail, and frail persons, HRs were 0.88 (CI, 0.77 to 0.99), 1.04 (CI, 0.98 to 1.10), and 0.96 (CI, 0.89 to 1.04), respectively. In the apixaban-warfarin cohort (n = 218 738; median follow-up, 84 days), the event rate per 1000 person-years was 60.1 for apixaban initiators and 92.3 for warfarin initiators (HR, 0.68 [CI, 0.65 to 0.72]; RD, -32.2 [CI, -36.1 to -28.3]). For nonfrail, prefrail, and frail persons, HRs were 0.61 (CI, 0.52 to 0.71), 0.66 (CI, 0.61 to 0.70), and 0.73 (CI, 0.67 to 0.80), respectively. LIMITATIONS: Residual confounding and lack of clinical frailty assessment. CONCLUSION: For older adults with AF, apixaban was associated with lower rates of adverse events across all frailty levels. Dabigatran and rivaroxaban were associated with lower event rates only among nonfrail patients. PRIMARY FUNDING SOURCE: National Institute on Aging.

Comparative Effectiveness and Safety of Sodium-Glucose Cotransporter 2 Inhibitors Versus Glucagon-Like Peptide 1 Receptor Agonists in Older Adults.

OBJECTIVE: Both sodium-glucose cotransporter 2 inhibitors (SGLT2i) and glucagon-like peptide 1 receptor agonists (GLP-1RA) demonstrated cardiovascular benefits in randomized controlled trials of patients with type 2 diabetes (T2D) generally <65 years old and mostly with cardiovascular disease. We aimed to evaluate the comparative effectiveness and safety of SGLT2i and GLP-1RA among real-world older adults. RESEARCH DESIGN AND METHODS: Using Medicare data (April 2013-December 2016), we identified 90,094 propensity score-matched (1:1) T2D patients ≥66 years old initiating SGLT2i or GLP-1RA. Primary outcomes were major adverse cardiovascular events (MACE) (i.e., myocardial infarction, stroke, or cardiovascular death) and hospitalization for heart failure (HHF). Other outcomes included diabetic ketoacidosis (DKA), genital infections, fractures, lower-limb amputations (LLA), acute kidney injury (AKI), severe urinary tract infections, and overall mortality. We estimated hazard ratios (HRs) and rate differences (RDs) per 1,000 person-years, controlling for 140 baseline covariates. RESULTS: Compared with GLP-1RA, SGLT2i initiators had similar MACE risk (HR 0.98 [95% CI 0.87, 1.10]; RD -0.38 [95% CI -2.48, 1.72]) and reduced HHF risk (HR 0.68 [95% CI 0.57, 0.80]; RD -3.23 [95% CI -4.68, -1.77]), over a median follow-up of ∼6 months. They also had 0.7 more DKA events (RD 0.72 [95% CI 0.02, 1.41]), 0.9 more LLA (RD 0.90 [95% CI 0.10, 1.70]), 57.1 more genital infections (RD 57.08 [95% CI 53.45, 60.70]), and 7.1 fewer AKI events (RD -7.05 [95% CI -10.27, -3.83]) per 1,000 person-years. CONCLUSIONS: Among older adults, those taking SGLT2i had similar MACE risk, decreased HHF risk, and increased risk of DKA, LLA, and genital infections versus those taking GLP-1RA.

Evaluation of Risk of Bullous Pemphigoid With Initiation of Dipeptidyl Peptidase-4 Inhibitor vs Second-generation Sulfonylurea.

Importance: Despite several recent reports on the elevated risk of bullous pemphigoid in patients with type 2 diabetes treated with dipeptidyl peptidase-4 (DPP-4) inhibitors, evidence on the absolute risk and comparative safety against other antidiabetics is limited. Objective: To characterize the incidence rate of bullous pemphigoid associated with DPP-4 inhibitor use compared with second-generation sulfonylureas. Design, Setting, and Participants: This cohort study used data from 2 large commercial insurance claims databases (Optum Clinformatics Data Mart from October 17, 2006, to December 31, 2018, and IBM MarketScan Research Database from October 17, 2006, to December 31, 2017) and Medicare data from January 1, 2006, to December 31, 2016. Patients with type 2 diabetes who initiated treatment with DPP-4 inhibitors or second-generation sulfonylurea were included. Main Outcomes and Measures: The primary outcome of the study was bullous pemphigoid, identified using diagnosis codes. After 1:1 propensity score matching, the incidence rates of bullous pemphigoid and the hazard ratios (HRs) with 95% CIs comparing patients who initiated DPP-4 inhibitor and second-generation sulfonylurea therapy were estimated. Subgroup analyses by age, sex, race, and individual DPP-4 agents were performed. The results from each database were pooled using inverse-variance fixed-effects meta-analysis. Results: A total of 1 664 880 patients who initiated DPP-4 inhibitors (51.0% female; mean [SD] age, 63.9 [9.7] years) and sulfonylurea (50.4% female; mean [SD] age, 63.9 [9.9] years) were included. The incidence rate of bullous pemphigoid per 1000 person-years was 0.42 in the DPP-4 inhibitor group vs 0.31 in the sulfonylurea group (HR, 1.42; 95% CI, 1.17-1.72). Higher rates per 1000 person-years for DPP-4 inhibitor vs sulfonylurea groups were seen in those who were 65 years or older (0.79 vs 0.49; HR, 1.62; 95% CI, 1.32-1.99), white (0.93 vs 0.54; HR, 1.70; 95% CI, 1.30-2.24), and treated with linagliptin (1.20 vs 0.55; HR, 1.68; 95% CI, 1.16-2.43). Conclusions and Relevance: This study found that patients who initiated DPP-4 inhibitor therapy had higher risk of bullous pemphigoid than those who initiated second-generation sulfonylurea therapy. Clinicians should be aware of this rare adverse effect of DPP-4 inhibitors in subgroups of patients who are older, white, and linagliptin users.

Rates and Costs of Dispensing Naloxone to Patients at High Risk for Opioid Overdose in the United States, 2014-2018.

INTRODUCTION: Clinical practice guidelines recommend co-prescribing naloxone to patients at high risk of opioid overdose, but few such patients receive naloxone. High costs of naloxone may contribute to limited dispensing. OBJECTIVE: The aim of this study was to evaluate rates and costs of dispensing naloxone to patients receiving opioid prescriptions and at high risk for opioid overdose. METHODS: Using claims data from a large US commercial insurance company, we conducted a retrospective cohort study of new opioid initiators between January 2014 and December 2018. We identified patients at high risk for overdose defined as a diagnosis of opioid use disorder, prior overdose, an opioid prescription of ≥ 50 mg morphine equivalents/day for ≥ 90 days, and/or concurrent benzodiazepine prescriptions. RESULTS: Among 5,292,098 new opioid initiators, 616,444 (12%) met criteria for high risk of overdose during follow-up, and, of those, 3096 (0.5%) were dispensed naloxone. The average copayment was US$24.83 for naloxone (standard deviation [SD] 67.66) versus US$9.74 for the index opioid (SD 19.75). The average deductible was US$6.18 for naloxone (SD 27.32) versus US$3.74 for the index opioid (SD 25.56), with 94% and 88% having deductibles of US$0 for their naloxone and opioid prescriptions, respectively. The average out-of-pocket cost was US$31.01 for naloxone (SD 73.64) versus US$13.48 for the index opioid (SD 34.95). CONCLUSIONS: Rates of dispensing naloxone to high risk patients were extremely low, and prescription costs varied greatly. Since improving naloxone's affordability may increase access, whether naloxone's high cost is associated with low dispensing rates should be evaluated.

Measuring Frailty in Administrative Claims Data: Comparative Performance of Four Claims-Based Frailty Measures in the U.S. Medicare Data.

BACKGROUND: There has been increasing effort to measure frailty in the U.S. Medicare data. The performance of claims-based frailty measures has not been compared. METHODS: This cross-sectional study included 3,097 community-dwelling fee-for-service Medicare beneficiaries (mean age 75.6 years) who participated in the 2008 Health and Retirement Study examination. Four claims-based frailty measures developed by Davidoff, Faurot, Segal, and Kim were compared against frailty phenotype, a deficit-accumulation frailty index (FI), and activities of daily living (ADL) dependence using Spearman correlation coefficients and C-statistics. RESULTS: Claims-based frailty measures were positively associated with frailty phenotype (prevalence in ≤10th vs >90th percentile: 8.0% vs 41.3% for Davidoff; 5.9% vs 53.1% for Faurot; 3.3% vs 48.0% for Segal; 2.9% vs 51.0% for Kim) and FI (mean in ≤10th vs >90th percentile: 0.17 vs 0.33 for Davidoff; 0.13 vs 0.37 for Faurot; 0.12 vs 0.31 for Segal; 0.10 vs 0.37 for Kim). The age and sex-adjusted C-statistics for frailty phenotype for Davidoff, Faurot, Segal, and Kim indices were 0.73, 0.74, 0.73, and 0.78, respectively, and partial correlation coefficients with FI were 0.18, 0.32, 0.26, and 0.55, respectively. The results for ADL dependence were similar (prevalence in ≤10th vs >90th percentile: 3.7% vs 50.5% for Davidoff; 2.3% vs 55.0% for Faurot; 3.0% vs 38.3% for Segal; 2.3% vs 50.8% for Kim). The age and sex-adjusted C-statistics for the indices were 0.79, 0.80, 0.74, and 0.81, respectively. CONCLUSIONS: The choice of a claims-based frailty measure can influence the identification of older adults with frailty and disability in Medicare data.

Risk of admission to hospital for serious infection after initiating tofacitinib versus biologic DMARDs in patients with rheumatoid arthritis: a multidatabase cohort study.

BACKGROUND: The risk of serious infection is a major concern when prescribing a disease-modifying antirheumatic drug (DMARD) for rheumatoid arthritis. Little evidence exists with regard to serious infection risk associated with tofacitinib, a targeted synthetic (ts)DMARD, compared with biologic DMARDs (bDMARDs) among patients with rheumatoid arthritis. We compared the risk of serious infection in patients with rheumatoid arthritis initiating tofacitinib versus one of the seven bDMARDs. METHODS: In this multidatabase cohort study, we identified eight mutually exclusive groups of patients with rheumatoid arthritis initiating tofacitinib or one of the seven bDMARDs using US public (Medicare 20012-15) and private (Optum Clinformatics 2012-18 and IBM MarketScan 2012-17) health insurance programmes. Eligible patients were aged 18 years or older, and had one inpatient visit or two or more outpatient visits (7-365 days apart) for rheumatoid arthritis using International Classification of Diseases 9th and 10th revision codes. The primary outcome was a composite endpoint of admission to hospital for serious infection including bacterial, viral, or opportunistic infection based on the inpatient principal diagnosis code. Secondary outcomes were individual types of serious infections and herpes zoster. We adjusted for more than 60 potential confounders through propensity score-based inverse probability treatment weighting in each database. Database-specific adjusted hazard ratios (aHRs) were combined using a fixed-effects meta-analysis. FINDINGS: We identified 130 718 patients with rheumatoid arthritis across the three databases. During 100 790 person-years of follow-up, 3140 serious infections occurred (crude incidence rate per 100 person-years 3·12, 95% CI 3·01-3·23). The aHR for serious infection associated with tofacitinib was 1·41 (95% CI 1·15-1·73) versus etanercept, 1·20 (0·97-1·49) versus abatacept, 1·23 (0·94-1·62) versus golimumab, and 1·17 (0·89-1·53) versus tocilizumab. The serious infection risk with tofacitinib was similar to adalimumab (1·06, 0·87-1·30) and certolizumab (1·02, 0·80-1·29), and was lower than infliximab (0·81, 0·65-1·00). Tofacitinib was associated with a 2-fold higher risk of herpes zoster versus all bDMARDs. INTERPRETATION: This study found potential differences between tofacitinib and several bDMARDs in the risk of admission to hospital for serious infection, as well as herpes zoster, in patients with rheumatoid arthritis. These results contribute to the evolving understanding of the overall risk-benefit profile of tofacitinib. FUNDING: Division of Pharmacoepidemiology and Pharmacoeconomics, Brigham and Women's Hospital, Harvard Medical School, Harvard University, MA, USA.

Variation in Prescription Drug Prices by Retail Pharmacy Type: A National Cross-sectional Study.

Background: Cash prices for prescription drugs vary widely in the United States. Objective: To describe cash price variation by retail pharmacy type for 10 generic and 6 brand-name drugs throughout the United States and stratified by ZIP code. Design: Cross-sectional study. Setting: Drug pricing data from GoodRx, an online tool for comparing drug prices, representing more than 60 000 U.S. pharmacies (fall 2015). Measurements: Cash prices for a 1-month supply of generic and brand-name drugs were ascertained. Stratified by ZIP code, relative cash prices for groups of generic and brand-name drugs were estimated for big box, grocery-based, small chain, and independent pharmacies compared with a reference group of large chain pharmacies. Results: Across 16 325 ZIP codes, 68 353 unique pharmacy stores contributed cash prices. When stratified by 5-digit ZIP code, the relative cash prices for generic drugs at big box, grocery-based, small chain, and independent pharmacies compared with those at large chain pharmacies were 0.52 (95% CI, 0.51 to 0.53), 0.82 (CI, 0.81 to 0.83), 1.51 (CI, 1.45 to 1.56), and 1.61 (CI, 1.58 to 1.64), respectively. The relative cash prices for brand-name drugs were 0.97 (CI, 0.96 to 0.97), 1.00 (CI, 0.99 to 1.00), 1.06 (CI, 1.05 to 1.08), and 1.03 (CI, 1.02 to 1.04), respectively. Limitation: Results may not reflect current drug prices and do not account for point-of-sale discounts or price matching that may be offered by smaller pharmacies. Conclusion: Compared with large chains, independent pharmacies and small chains had the highest cash prices for generic drugs and big box pharmacies the lowest. Relative differences in cash prices for brand-name drugs were modest across types of retail pharmacies. Primary Funding Source: Arnold Ventures.

Validation of a Claims-Based Frailty Index Against Physical Performance and Adverse Health Outcomes in the Health and Retirement Study.

BACKGROUND: A claims-based frailty index (CFI) was developed based on a deficit-accumulation approach using self-reported health information. This study aimed to independently validate the CFI against physical performance and adverse health outcomes. METHODS: This retrospective cohort study included 3,642 community-dwelling older adults who had at least 1 health care encounter in the year prior to assessments of physical performance in the 2008 Health and Retirement Study wave. A CFI was estimated from Medicare claims data in the past year. Gait speed, grip strength, and the 2-year risk of death, institutionalization, disability, hospitalization, and prolonged (>30 days) skilled nursing facility (SNF) stay were evaluated for CFI categories (robust: <0.15, prefrail: 0.15-0.24, mildly frail: 0.25-0.34, moderate-to-severely frail: ≥0.35). RESULTS: The prevalence of robust, prefrail, mildly frail, and moderate-to-severely frail state was 52.7%, 38.0%, 7.1%, and 2.2%, respectively. Individuals with higher CFI had lower mean gait speed (moderate-to-severely frail vs robust: 0.39 vs 0.78 m/s) and weaker grip strength (19.8 vs 28.5 kg). Higher CFI was associated with death (moderate-to-severely frail vs robust: 46% vs 7%), institutionalization (21% vs 5%), activity of daily living disability (33% vs 9%), instrumental activity of daily living disability (100% vs 22%), hospitalization (79% vs 23%), and prolonged SNF stay (17% vs 2%). The odds ratios per 1-SD (=0.07) difference in CFI were 1.46-2.06 for these outcomes, which remained statistically significant after adjustment for age, sex, and a comorbidity index. CONCLUSION: The CFI is useful to identify individuals with poor physical function and at greater risks of adverse health outcomes in Medicare data.

Predictors of Drug Shortages and Association with Generic Drug Prices: A Retrospective Cohort Study.

BACKGROUND: Prescription drug shortages can disrupt essential patient care and drive up drug prices. OBJECTIVE: To evaluate some predictors of shortages within a large cohort of generic drugs in the United States and to determine the association between drug shortages and changes in generic drug prices. METHODS: This was a retrospective cohort study. Outpatient prescription claims from commercial health plans between 2008 and 2014 were analyzed. Seven years of data were divided into fourteen 6-month periods; the first period was designated as the baseline period. The first model estimated the probability of experiencing a drug shortage using drug-specific competition levels, market sizes, formulations (e.g., capsules), and drug prices as predictors. The second model estimated the percentage change in drug prices from baseline on the basis of drug shortage duration. RESULTS: From 1.3 billion prescription claims, a cohort of 1114 generic drugs was identified. Low-priced generic drugs were at a higher risk for drug shortages compared with medium- and high-priced generic drugs, with odds ratios of 0.60 (95% confidence interval [CI] 0.44-0.82) and 0.72 (95% CI 0.52-0.99), respectively. Compared with periods of no shortage, drug shortages lasting less than 6 months, 6 to 12 months, 12 to 18 months, and at least 18 months had corresponding price increases of 6.0% (95% CI 4.7-7.4), 10.9% (95% CI 8.5-13.4), 14.2% (95% CI 10.6-17.9), and 14.0% (95% CI 9.1-19.2), respectively. CONCLUSIONS: Study findings may not be generalizable to drugs that became generic after 2008 or those commonly used in an inpatient setting. The lowest priced drugs are at a substantially elevated risk of experiencing a drug shortage. Periods of drug shortages were associated with modest increases in drug prices.

Assessment of the fracture resistance of teeth instrumented using 2 rotary and 2 reciprocating files versus the Self-Adjusting File (SAF): An ex vivo comparative study on mandibular premolars.

AIM: Current ex vivo study compared fracture resistance of teeth instrumented using 5 endodontic files, filled with Gutta-percha and AH Plus. MATERIALS AND METHODS: Sixty freshly extracted, single-rooted mandibular premolars were acquired and decoronated to obtain 15 mm segments. These samples were randomly divided into six groups (n = 10). Group 1 served as the control containing untreated samples (without instrumentation or filling). In Groups 2-6, samples were instrumented using rotary (Universal ProTaper and Revo-S), reciprocating (WaveOne and RECIPROC(®)), and self-adjusting file (SAF), respectively. Following instrumentation, the samples were filled by lateral compaction with Gutta-percha and AH Plus. A week later, after the sealer was completely set, a vertical load was applied to the specimen's canal in each group until fracture. The loads required for fracture were recorded, and statistical analysis was performed. RESULTS: The mean fracture load differed significantly among the groups (P < 0.01; one-way ANOVA). Tukey's post-hoc tests revealed that the fracture resistance was similar in the control and SAF groups (P > 0.05) and was significantly higher than that of the 2 rotary and reciprocating groups (P < 0.01). CONCLUSION: The samples instrumented by the SAF exhibited a better fracture resistance.