Background: Overactive bladder (OAB) is a common non-motor symptom of Parkinson disease (PD), often treated with antimuscarinics or beta-3 agonists. There is lack of evidence to guide OAB management in PD.Objectives: To assess the comparative safety of antimuscarinics versus beta-3 agonists for OAB treatment in PD.Methods: We employed a new-user, active-comparator cohort study design. We included Medicare beneficiaries age >= 65 years with PD who were new users of either antimuscarinic or beta-3 agonist. The primary outcome was any acute care encounter (i.e., non-elective hospitalization or emergency department visit) within 90 days of OAB drug initiation. The main secondary outcome was a composite measure of acute care encounters for anticholinergic related adverse events (AEs). Matching on high-dimensional propensity score (hdPS) was used to address potential confounding. We used Cox proportional hazards models to examine the association between OAB drug category and outcomes. We repeated analyses for 30- and 180-day follow-up periods.Results: We identified 27,091 individuals meeting inclusion criteria (mean age: 77.8 years). After hdPS matching, antimuscarinic users had increased risks for any acute care encounter (hazard ratio [HR] 1.23, 95% confidence interval [CI] 1.12-1.37) and encounters for anticholinergic related AEs (HR 1.18, 95% CI 1.04-1.34) compared to beta-3 agonist users. Similar associations were observed for sensitivity analyses.Conclusions: Among persons with PD, anticholinergic initiation was associated with a higher risk of acute care encounters compared with beta-3 agonist initiation. The long-term safety of anticholinergic vs. beta-3 agonist therapy in the PD population should be evaluated in a prospective study.

Objective: To describe fall risk-increasing drug (FRID) use before and after an unintentional traumatic injury or fall-related fracture and examine the extent to which hospital encounters affect medication prescribing in individuals with Parkinson disease (PD). Background: Individuals with PD are at increased risk of falls and fractures. FRIDs represent a major modifiable factor that can potentially reduce the risk of subsequent events. Design/Methods: We identified persons with PD hospitalized for injury or fracture and matched each person to up to 4 individuals with PD who were hospitalized for other reasons using 2013–2017 U.S. Medicare data. A difference-in-difference design was used to compare FRID dispensing before and after hospitalization between the two groups. We examined the changes in standardized daily doses of FRIDs in the two groups upon hospital admission and at 3-, 6-, and 12-months post-discharge, adjusting for covariates. Exploratory analyses were performed to evaluate potential medication discontinuation and tapering following discharge. Results: We identified 9,437 persons with PD who had a qualifying hospitalization for injury or fracture and 32,487 matched individuals. While both groups experienced reductions in standardized daily doses of FRIDs, the differences in dose reductions were minimal (−1.94, 95% CI [−2.05, −1.82] in the injury group vs. −1.91, 95% CI [−1.97, −1.84] in the non-injury group; p=0.66 at 12 months). Over 40% of subjects discontinued FRIDs at 3 months in both groups, and ~2/3 to 3/4 of these sustained discontinuations through one year. Conclusions: There were no clinically significant differences in FRID dose reductions pre- to post-hospitalization between PD individuals with injury or fracture versus those without. More efforts are needed to enhance deprescribing practices during transition of care, especially after a sentinel event, to prevent subsequent unintentional injuries or fractures. Disclosure: The institution of Dr. Pham Nguyen has received research support from National Institute of Health. The institution of Dr. Pham Nguyen has received research support from National Institute of Health. Dr. Gray has nothing to disclose. Mr. Newcomb has nothing to disclose. Miss Liu has nothing to disclose. The institution of Dr. Hamedani has received research support from Michael J. Fox Foundation. The institution of Dr. Hamedani has received research support from NIH. The institution of Dr. Hamedani has received research support from Biogen. The institution of Dr. Hamedani has received research support from Biohaven. Dr. Hennessy has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Biogen. Dr. Hennessy has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Intercept Pharmaceuticals. Dr. Hennessy has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Medullary Thyroid Cancer Consortium. Dr. Hennessy has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Provention Bio, Inc. Dr. Hennessy has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Bluebird bio, Inc. Dr. Hennessy has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Amylyx Pharmaceuticals. Dr. Hennessy has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Ipsen Bioscence Inc.. The institution of Dr. Hennessy has received research support from US Food and Drug Administration. The institution of Dr. Hennessy has received research support from US National Institutes of Health. The institution of Dr. Hennessy has received research support from US Centers for Disease Control and Prevention. Dr. Wright Willis has received personal compensation in the range of $0-$499 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Pharmacoepidemiology and Drug Safety. The institution of Dr. Wright Willis has received research support from NIH. The institution of Dr. Wright Willis has received research support from NIA. The institution of Dr. Wright Willis has received research support from Biogen. The institution of Dr. Wright Willis has received research support from Parkinson Foundation. The institution of Dr. Wright Willis has received research support from Arcadia.

Background: Parkinson disease (PD) patients are at increased risk of serious injury, such as fall-related fractures. Prescription medications are a modifiable factor for injury risk.Objectives: To determine the extent to which a serious injury requiring hospitalization affects prescribing of potentially inappropriate medications (PIMs) among older adults with PD. Methods: We conducted a quasi-experimental difference-in-difference (DID) study using 2013-2017 Medicare data. The cohort consisted of beneficiaries with PD hospitalized for injury versus for other reasons. PIMs were classified into PD and injury-relevant categories (CNS-active PIMs, PD motor symptom PIMs, PD non-motor symptom PIMs, PIMs that reduce bone mineral density). We estimated mean standardized daily doses (SDDs) of medications within each PIM category before and at 3, 6, and 12 months after hospitalization. We used generalized linear regression models to compare changes in mean SDDs for each PIM category between the injury and non-injury group at each timepoint, adjusting for biological, clinical and social determinants of health variables. Results: Both groups discontinued PIMs and/or reduced PIM doses after hospitalization. There were no between -group differences in mean SDD changes, after covariate adjustment, for any PIM category, except for the CNS-active PIMs category at 3 months (DID p-value = 0.00) and for the category of PIMs that reduce bone mineral density at all timepoints (DID p-values = 0.02, 0.04, 0.02 at 3, 6, and 12 months).Conclusions: Similar patterns of PIM among persons with PD after hospitalization for serious injury versus for other reasons may represent a missed opportunity to deprescribe high-risk medications during care transitions.

ObjectiveTo evaluate the risk of serious adverse events among patients with type 2 diabetes mellitus initiating saxagliptin compared with oral antidiabetic drugs (OADs) in classes other than dipeptidyl peptidase-4 (DPP-4) inhibitors.Research design and methodsCohort studies using 2009–2014 data from two UK medical record data sources (Clinical Practice Research Datalink, The Health Improvement Network) and two USA claims-based data sources (HealthCore Integrated Research Database, Medicare). All eligible adult patients newly prescribed saxagliptin (n=110 740) and random samples of up to 10 matched initiators of non-DPP-4 inhibitor OADs within each data source were selected (n=913 384). Outcomes were hospitalized major adverse cardiovascular events (MACE), acute kidney injury (AKI), acute liver failure (ALF), infections, and severe hypersensitivity events, evaluated using diagnostic coding algorithms and medical records. Cox regression was used to determine HRs with 95% CIs for each outcome. Meta-analyses across data sources were performed for each outcome as feasible.ResultsThere were no increased incidence rates or risk of MACE, AKI, ALF, infection, or severe hypersensitivity reactions among saxagliptin initiators compared with other OAD initiators within any data source. Meta-analyses demonstrated a reduced risk of hospitalization/death from MACE (HR 0.91, 95% CI 0.85 to 0.97) and no increased risk of hospitalization for infection (HR 0.97, 95% CI 0.93 to 1.02) or AKI (HR 0.99, 95% CI 0.88 to 1.11) associated with saxagliptin initiation. ALF and hypersensitivity events were too rare to permit meta-analysis.ConclusionsSaxagliptin initiation was not associated with increased risk of MACE, infection, AKI, ALF, or severe hypersensitivity reactions in clinical practice settings.Trial registration numberNCT01086280,NCT01086293,NCT01086319,NCT01086306, andNCT01377935; Results.

Background. The risk of hepatotoxicity with antiretroviral therapy (ART) remains unknown. We determined the comparative risk of acute liver injury (ALI) for antiretroviral drugs, classes, and regimens, by viral hepatitis status.Methods. We followed a cohort of 10 083 human immunodeficiency virus (HIV)-infected persons in Kaiser Permanente Northern California (n = 2099) from 2004 to 2010 and the Veterans Aging Cohort Study (n = 7984) from 2004 to 2012. Within the first year of ART, we determined occurrence of (1) liver aminotransferases >200 U/L and (2) severe ALI (coagulopathy with hyper-bilirubinemia). We used Cox regression to determine hazard ratios (HRs) with 95% confidence intervals (CIs) of endpoints among initiators of nucleos(t) ide analogue combinations, antiretroviral classes, and ART regimens, all stratified by viral hepatitis status.Results. Liver aminotransferases >200 U/L developed in 206 (2%) persons and occurred more frequently among HIV/viral hepatitis-coinfected than HIV-monoinfected persons (116.1 vs 20.7 events/1000 person-years; P <.001). No evidence of differential risk was found between initiators of abacavir/lamivudine versus tenofovir/emtricitabine among coinfected (HR, 0.68; 95% CI,.29-1.57) or HIV-monoinfected (HR, 1.19; 95% CI,.47-2.97) groups. Coinfected patients had a higher risk of aminotransferases >200 U/L after initiation with a protease inhibitor than nonnucleoside reverse-transcriptase inhibitor (HR, 2.01; 95% CI, 1.36-2.96). Severe ALI (30 events; 0.3%) occurred more frequently in coinfected persons (15.9 vs 3.1 events/1000 person-years; P <.001) but was too uncommon to evaluate in adjusted analyses.Conclusions. Within the year after ART initiation, aminotransferase elevations were infrequently observed and rarely led to severe ALI. Protease inhibitor use was associated with a higher risk of aminotransferase elevations among viral hepatitis-coinfected patients.

BACKGROUND & AIMS: Despite recent attention to differences in access to livers for transplantation, research has focused on patients already on the wait list. We analyzed data from a large administrative database that represents the entire US population, and state Medicaid data, to identify factors associated with differences in access to wait lists for liver transplantation.METHODS: We performed a retrospective cohort study of transplant-eligible patients with end-stage liver disease using the HealthCore Integrated Research Database (2006-2014; n = 16,824) and Medicaid data from 5 states (2002-2009; California, Florida, New York, Ohio, and Pennsylvania; n = 67,706). Transplant-eligible patients had decompensated cirrhosis, hepatocellular carcinoma (HCC), and/or liver synthetic dysfunction, based on validated International Classification of Diseases, Ninth Revision-based algorithms and data from laboratory studies. Placement on the wait list was determined through linkage with the Organ Procurement and Transplantation Network database.RESULTS: In an unadjusted analysis of the HealthCore database, we found that 29% of patients with HCC were placed on the 2-year wait list (95% confidence interval [CI], 25.4%-33.0%) compared with 11.9% of patients with stage 4 cirrhosis (ascites) (95% CI, 11.0%-12.9%) and 12.6% of patients with stage 5 cirrhosis (ascites and variceal bleeding) (95% CI, 9.4%-15.2%). Among patients with each stage of cirrhosis, those with HCC were significantly more likely to be placed on the wait list; adjusted subhazard ratios ranged from 1.7 (for patients with stage 5 cirrhosis and HCC vs those without HCC) to 5.8 (for patients with stage 1 cirrhosis with HCC vs those without HCC). Medicaid beneficiaries with HCC were also more likely to be placed on the transplant wait list, compared with patients with decompensated cirrhosis, with a subhazard ratio of 2.34 (95% CI, 2.20-2.49). Local organ supply and wait list level demand were not associated with placement on the wait list.CONCLUSIONS: In an analysis of US healthcare databases, we found patients with HCC to be more likely to be placed on liver transplant wait lists than patients with decompensated cirrhosis. Previously reported reductions in access to transplant care for wait-listed patients with decompensated cirrhosis underestimate the magnitude of this difference.

PURPOSE:Primary immunodeficiency diseases (PID) are a rare group of disorders with a wide array of clinical presentations. The absence of validated methods to identify these diseases in electronic databases has limited understanding of their epidemiology and the impact of drug therapies on outcomes. We measured the positive predictive values (PPVs) of ICD-9 diagnoses for identifying PID within US Medicaid.METHODS:We identified Medicaid patients from California, Florida, New York, Ohio, and Pennsylvania with PID ICD-9 diagnoses (common variable immunodeficiency [279.06], X-linked agammaglobulinemia [279.04], hyper-immunoglobulin M syndrome [279.05], Wiskott Aldrich Syndrome [279.12]) recorded at least twice from 1999 to 2007. Outpatient records were reviewed by a clinical immunologist to adjudicate diagnoses. PPVs with 95% confidence intervals (CIs) for confirmed outcomes were determined for individual ICD-9 diagnoses and combinations of diagnoses and Current Procedural Terminology codes for a quantitative immunoglobulin test (82784) or immunoglobulin infusion (96365).RESULTS:Among 83 patients with PID ICD-9 diagnoses, 16 were adjudicated as having the condition (PPV, 19.3%; 95% CI, 11.4-29.4%). Individual ICD-9 diagnoses had low PPVs (range, 16.7-33.3%). Requiring procedural codes for quantitative immunoglobulins or intravenous immunoglobulin did not increase PPVs of these diagnoses (range, 11.1-41.7%). An X-linked agammaglobulinemia diagnosis plus intravenous immunoglobulin had the highest PPV among the algorithms evaluated (PPV, 41.7%; 95% CI, 15.1-72.3%).CONCLUSIONS:Algorithms comprising PID ICD-9 diagnoses and procedures for quantitative immunoglobulin tests and immunoglobulin infusion had low PPVs for adjudicated diagnoses in Medicaid. Alternative data sources should be evaluated to study the epidemiology of these diseases.

Non-AIDS defining malignancies, particularly colorectal cancer (CRC), may be more prevalent among persons living with HIV (PLWH). Further, PLWH may be less likely to receive CRC screening (CRCS). We studied the epidemiology of CRC and CRCS patterns in PLWH and HIV-uninfected persons in a large US Medicaid population. We performed a matched cohort study examining CRC incidence in 2006 and CRCS between 1999 and 2007. Study participants were continuously enrolled in the Medicaid programs of California, Florida, New York, Ohio, and Pennsylvania. All PLWH enrollees were matched to five randomly sampled HIV-uninfected enrollees on 5-year age group, gender, and state. Adjusted odds ratios (AORs) for incident CRC (adjusted for comorbidity index) and the presence of CRCS (adjusted for comorbidity index and years in the data-set) among PLWH compared to HIV-uninfected enrollees were calculated. PLWH were not more likely to be diagnosed with CRC after adjusting for comorbidity index (unadjusted OR: 1.73, 95% confidence interval [CI]: 1.37-2.19; AOR 1.29; 95% CI: 0.98-1.70). While CRCS rates were low overall, PLWH were more likely to have received CRCS in unadjusted analyses (35.8% vs. 33.7%; OR 1.10, 95% CI: 1.07-1.13). This relationship was reversed after adjusting for comorbidity index and years in the data-set (AOR: 0.80, 95% CI: 0.77-0.83). Limitations of the study include a focus on the Medicaid population, an inability to detect fecal occult blood tests (FOBT), and having half of patients between 50 and 55 years of age. In conclusion, PLWH were not more likely to be diagnosed with CRC, but in adjusted analyses, were less likely to have received CRCS. As we showed a low rate of CRCS overall in this Medicaid population, researchers, clinicians, and policy-makers should improve access to and uptake of CRCS among all Medicaid patients, and particularly among PLWH.