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Introduction Randomized controlled trials and real-world data from the USA have shown similar glycemic control with insulin glargine 300 U/ml (Gla-300) and insulin glargine 100 U/ml (Gla-100) and reduced hypoglycemia risk with Gla-300. This real-world study describes the efficacy and safety of Gla-300 and Gla-100 in patients with type 2 diabetes (T2D) in France, Spain, and Germany. Methods This retrospective chart review analysis used anonymized data for adults with T2D switching basal insulin analog (BIA) therapy to Gla-300 or Gla-100, or insulin-naïve patients initiating Gla-300 or Gla-100. Outcomes included change from baseline to 6-month follow-up in glycated hemoglobin A1c (A1C), total and severe hypoglycemia incidences and events, insulin dose, and reasons for BIA choice. Results Six hundred sixty-five physicians (33.8% Spain, 31.7% France, 34.4% Germany) provided chart data for patients switching to Gla-300 (n = 679) or Gla-100 (n = 429) or initiating Gla-300 (n = 719) or Gla-100 (n = 711). After adjustment for baseline characteristics, A1C reductions from baseline were similar for patients switching to Gla-300 or Gla-100 (− 0.87% vs. − 0.93%; p = 0.326) while those switched to Gla-300 vs. Gla-100 had a significantly greater mean reduction in hypoglycemic events (− 1.29 vs. − 0.81 events during 6 months; p = 0.012). Mean insulin doses after titration were 0.43 ± 0.36 and 0.40 ± 0.28 U/kg in Gla-300 and Gla-100 switchers, respectively. Factors that significantly influenced BIA choice included a lower risk of hypoglycemia (for Gla-300) and physician familiarity (for Gla-100). Outcomes for insulin-naïve patients were broadly similar to those of switchers. Conclusions In this real-world European study, patients with T2D who switched therapy to Gla-300 or Gla-100 had improved glycemic control and reduced hypoglycemia at 6 months, with significant hypoglycemia advantages with Gla-300. Electronic Supplementary Material The online version of this article (10.1007/s12325-020-01436-5) contains supplementary material, which is available to authorized users.

Aims To compare 12‐month clinical effectiveness of insulin glargine 300 units/mL (Gla‐300) versus first‐generation basal insulin analogues (BIAs) (insulin glargine 100 units/mL [Gla‐100] or insulin detemir [IDet]) in patients with type 2 diabetes (T2D) who were at high risk of hypoglycaemia and switched from one BIA to a different one (Gla‐300 or Gla‐100/IDet) in a real‐world setting. Methods DELIVER High Risk was a retrospective observational cohort study of 2550 patients with T2D who switched BIA to Gla‐300 (Gla‐300 switchers) and were propensity score‐matched (1:1) to patients who switched to Gla‐100 or IDet (Gla‐100/IDet switchers). Outcomes were change in glycated haemoglobin A1c (HbA1c), attainment of HbA1c goals (, In patients with type 2 diabetes at high risk of hypoglycaemia, risk of inpatient/emergency department‐related hypoglycaemia was significantly lower during 12 months after switching to insulin glargine 300 units/mL, compared with switching to insulin glargine 100 units/mL or insulin detemir.

Following the release of the framework for the Real-World Evidence (RWE) Program, the US Food and Drug Administration (FDA) is actively evaluating and exploring ways to optimize the utility of real-world data (RWD) and RWE to support regulatory decision making. For rare conditions, conducting traditional randomized clinical trials may not always be feasible, and RWD and RWE have played and will continue to play an important role. We use three case examples-cerliponase alfa, asfotase alfa, and uridine triacetate-to illustrate how RWD from disease registries, medical records with chart review, and literature, respectively, have been used to generate RWE to support regulatory decisions for selected rare diseases. These examples highlight the need for improving data reliability and quality in existing data to expand use of RWD and RWE beyond "hard endpoints" and standardizing data collection for outcome measures in patient registries to expand its utility. We also discuss a recent FDA guidance for using RWE in supporting rare disease drug development, including its recommendations about using natural history studies as external control groups for single-arm interventional trials. The external control group needs to be comparable with the treated group. Selection bias and confounding are major concerns because of lack of randomization and unrecognized baseline differences. Use of valid epidemiological approaches can reduce these biases. Lastly, we discuss future directions to expand the use of RWD and RWE to support orphan drug approvals, including the need for including patient experience data as an important source of RWD.

Aims To estimate risk factors associated with early hypoglycaemia and its impact on adherence to and persistence with therapy in Medicare Part D beneficiaries with type 2 diabetes who are initiating basal insulin (BI). Materials and methods This retrospective analysis used a 5% sample of Medicare files from 2007-2013, identifying beneficiaries with type 2 diabetes initiating BI from 1 January 2008 to 31 December 2012. Early hypoglycaemia was defined as ≥1 hypoglycaemic event ≤6 months postindex. Outcomes included medication adherence and persistence over 12- and 36-month follow-up. Multivariable logistic and Cox regression analyses were conducted to examine factors associated with early hypoglycaemia and BI adherence/persistence. Results Of the 14 466 included patients, 1315 (9.1%) experienced hypoglycaemia ≤6 months after initiating BI. Factors associated with early hypoglycaemia were female sex (odds ratio [OR] 1.16 [95% confidence interval [CI] 1.02-1.32]), receipt of a low-income subsidy under Medicare Part D (OR 1.20 [95% CI 1.01-1.43]), high diabetes complication score index (OR 1.08 [95% CI 1.01-1.15]), and hypoglycaemia during the baseline period (OR 4.24 [95% CI 3.63-4.96]). At 12 months, patients with baseline hypoglycaemia were less likely to be adherent to (OR 0.81 [95% CI 0.70-0.93]) and more likely to discontinue (OR 1.33 [95% CI 1.07-1.66]) their insulin therapy. Results were similar at 36 months. Conclusions Within 6 months of BI initiation, almost 1 in 10 Medicare Part D beneficiaries experienced hypoglycaemia. Early hypoglycaemia was associated with decreased adherence to BI treatment over 12- and 36-month follow-up.

Aim To compare the second‐generation basal insulin glargine 300 units/mL (Gla‐300) and first‐generation basal insulins on glycaemic control and hypoglycaemia risk in older adults with type 2 diabetes (T2D). Materials and methods DELIVER 3 was a retrospective observational cohort study of electronic medical records. A total of 1176 older adults (aged ≥ 65 years) with T2D and ≥1 HbA1c value during 6 month baseline and 3 to 6 month follow‐up who switched from basal insulin to Gla‐300 were propensity score‐matched to 1176 older adults who switched to a first‐generation basal insulin [insulin detemir (IDet) or insulin glargine 100 units/mL (Gla‐100)]. Outcomes were follow‐up HbA1c, achievement of HbA1c

Randomized controlled trial (RCT) populations often do not reflect those typically seen in clinical practice. This retrospective, observational cohort study analysed real-world data of people with type 2 diabetes (T2DM) prescribed basal insulin analogues from electronic medical records (EMRs) in the Explorys database, which includes data from 39 integrated healthcare systems in the USA, to determine how representative selected RCTs investigating insulin glargine 300 U/mL (Gla-300) are of T2DM populations in a real-world setting. Applying eligibility criteria derived from the EDITION 1, 2, and 3 (Gla-300 vs 100 U/mL [Gla-100]) and BRIGHT (Gla-300 vs insulin degludec) RCTs, we observed that only 17% (33,345/191,218) of people captured in the real-world database would have been eligible for such trials. Those who were ineligible tended to be older, had more comorbidities and a higher baseline hypoglycaemia rate than the eligible group. Using another large US EMR database (Optum Humedica) as corroboration, we found that 15% (36,285/235,697) would have been eligible to participate in the EDITION/BRIGHT RCTs. Furthermore, only 7% (1734/24,547) would have been eligible for the CONCLUDE (insulin degludec vs Gla-300) RCT. Our findings remind us of the value of real-world data studies, complementing the results of RCTs, and providing additional insights into groups who would typically be excluded from RCTs. This article is protected by copyright. All rights reserved.

DELIVER - High Risk study compared long-term clinical outcomes for patients with T2D and high hypoglycemia risk on first-generation BIs who were switched to Gla-300 or other first-generation BIs (other switchers). Electronic medical record data from the PHIE database were used. Eligible patients (age >18 years) had ≥1 criterion for high hypoglycemia risk (age >64 years; basal-bolus insulin use; renal impairment; uncontrolled baseline A1C; sulfonylurea use; atherosclerotic cardiovascular disease; history indicating high risk, including ≥1 severe hypoglycemic episode (prior 12 months). Endpoints were A1C reduction from baseline to 9-12 months, attainment of A1C goals ( Disclosure S.D. Sullivan: Research Support; Self; Sanofi. N. Freemantle: Advisory Panel; Self; Sanofi. Research Support; Self; Akcea Therapeutics, Allergan, AstraZeneca, Ipsen Biopharmaceuticals, Inc., Sanofi, Takeda Pharmaceutical Company Limited. Speaker’s Bureau; Self; Sanofi. A.A. Menon: None. R. Gupta: None. J. Wu: Employee; Self; Sanofi US. C. Nicholls: Employee; Self; Sanofi. J. Westerbacka: Employee; Self; Sanofi. Stock/Shareholder; Self; Sanofi. T.S. Bailey: Advisory Panel; Self; Abbott. Consultant; Self; Capillary Biomedical, Inc., Eli Lilly and Company, Medtronic, Novo Nordisk Inc., Sanofi. Research Support; Self; Abbott, Ascensia Diabetes Care, Becton, Dickinson and Company, Boehringer Ingelheim Pharmaceuticals, Inc., Calibra Medical, Capillary Biomedical, Inc., Companion Medical, Dance Biopharm Holdings Inc., Dexcom, Inc., Diasome Pharmaceuticals, Inc., Eli Lilly and Company, GlySens Incorporated, Kowa Pharmaceutical Europe Co. Ltd., Lexicon Pharmaceuticals, Inc., Medtronic, Novo Nordisk Inc., POPS! Diabetes Care, POPS! Diabetes Care, Sanofi, Senseonics, vTv Therapeutics, Xeris Pharmaceuticals, Inc., Zealand Pharma A/S. Speaker’s Bureau; Self; Abbott, MannKind Corporation, Medtronic, Novo Nordisk Inc., Sanofi US, Senseonics. Funding Sanofi

RCTs are the gold standard for comparing therapies’ efficacy and safety but can have strict eligibility criteria and may not reflect real-life clinical practice. Electronic medical records such as those from the Predictive Health Intelligence Environment (PHIE) database may be used to assess clinical effectiveness in real-world populations missed by clinical trials. We describe here the proportion and characteristics of patients with T2DM who would have been excluded from RCTs using eligibility criteria adapted from the EDITION 1-3 and BRIGHT trials. Records from people with T2DM, with a basal insulin prescription on the index date (1 March 2015) and ≥1 HbA1c value in the previous 12 months, were evaluated. Exclusion criteria included HbA1c 10.0 %, systolic blood pressure >180 mmHg and/or diastolic blood pressure >95 mmHg, or key comorbidities (e.g., heart failure or stroke) in the previous 12 months. Of 191,218 evaluated records, 157,873 (83%) met ≥1 exclusion criterion; only 33,345 (17%) could have been included in RCTs (Table). Excluded patients were older, with more previous hypoglycemia vs. included patients and were less likely to have HbA1c between 7 and 9 %. This divergence in clinical characteristics and patient numbers highlights the need for real-world studies assessing clinical effectiveness in populations of interest typically excluded from RCTs. Disclosure D. Mauricio: Advisory Panel; Self; Merck Sharp & Dohme Corp., Sanofi. Speaker’s Bureau; Self; Almirall, S.A., Boehringer Ingelheim International GmbH, Lilly Diabetes, Merck Sharp & Dohme Corp., Novo Nordisk A/S, Sanofi, Urgo Medical. J. Westerbacka: Employee; Self; Sanofi. Stock/Shareholder; Self; Sanofi. C. Nicholls: Employee; Self; Sanofi. J. Wu: Employee; Self; Sanofi US. R. Gupta: None. A.A. Menon: None. B. Eliasson: Advisory Panel; Self; Amgen Inc., AstraZeneca, Merck Sharp & Dohme Corp. Speaker’s Bureau; Self; Boehringer Ingelheim International GmbH. Other Relationship; Self; Eli Lilly and Company, Novo Nordisk A/S, Sanofi. Funding Sanofi

Aim To compare glycaemic control, hypoglycaemia and treatment discontinuation of insulin glargine 300 units/mL (Gla‐300) and insulin degludec (IDeg) in a real‐world study of insulin‐naïve adults with type 2 diabetes (T2D). Materials and methods DELIVER Naive D was a retrospective observational study that used electronic medical record data from the IBM Watson Health Explorys database. Insulin‐naïve adults with T2D who started Gla‐300 or IDeg between March 2015 and September 2017 were identified. Patients were active in the system for ≥12 months before and ≥6 months after starting Gla‐300 or IDeg and had HbA1c measurements during 6‐month baseline and 3‐ to 6‐month follow‐up. Outcomes were compared among 1:1 propensity score‐matched cohorts. Results In the matched cohorts (n = 638 each), the mean age was 59 years, approximately 53% were male, and mean HbA1c was 9.67% (82 mmol/mol). Mean (SD) HbA1c decreases were comparable in the Gla‐300 and IDeg cohorts (−1.67% [2.22] and −1.58% [2.20]; P = 0.51), as were HbA1c target attainment [

The US Food and Drug Administration (FDA) Amendments Act of 2007 granted the FDA new authorities to enhance drug safety by requiring application holders to submit a proposed Risk Evaluation and Mitigation Strategy (REMS). A REMS is a required risk management plan that uses tools beyond the package insert. REMS elements may include a medication guide and patient package insert for patients and a communication plan focused on health care professionals. Elements to assure safe use (ETASUs) are put in place to mitigate a specific known serious risk when other less restrictive elements of a REMS are not sufficient to mitigate such risk. An implementation system is required for an REMS that includes the ETASUs. With approximately eight years of experience with REMS programs, many health care settings have created systems to manage REMS and also to integrate REMS into their practice settings. At the same time, there are issues associated with the development and implementation of REMS. In 2011, FDA created the REMS Integration Initiative to develop guidance on how to apply statutory criteria to determine when a REMS is required, to improve standardization and assessment of REMS, and to improve integration of REMS into the existing healthcare system. A key component of the REMS Integration Initiative is stakeholder outreach to better understand how existing REMS programs are working and to identify opportunities for improvement. This review attempts to share our company's experience with the REMS program, and to provide updates on FDA's efforts to improve REMS communication, to standardize REMS process, to reduce REMS program burdens and to build a common REMS platform.

The objectives of the study were to estimate the incidence of Wernicke's encephalopathy (WE) and cardiac disorders among patients with myeloproliferative neoplasms (MPN), and compare it with those without MPN. A total of 39,761 MPN patients were identified from the US Marketscan database. Approximately 27% of them were 65+ years of age, and 51% were male. Patients with MPN had higher rates of WE, compared to those without MPN (MPN vs. non-MPN: 1.09 vs. 0.39/1000 person-year, adjusted HR=2.19, 95%CI 1.43–3.34). Patients with MPN also had higher rates of cardiac events (congestive heart failure: MPN vs. non-MPN: 9.27 vs. 3.70/1000 person-year, adjusted HR=1.64, 95%CI 1.42–1.88; acute myocardial infarction: MPN vs. non-MPN: 10.45 vs. 5.02/1000 person-year, adjusted HR=1.44, 95%CI 1.27, 1.63; cardiac arrhythmia: MPN vs. non-MPN: 106.5 vs. 53.9/1000 person-year, adjusted HR=1.42, 95%CI 1.36–1.48). Physicians who care for patients with MPN should be aware of increased risk of WE and cardiac disorders in this population.

Purpose. To evaluate potential cost savings, trial data were used to determine the clinical outcomes for i.v. ertapenem given once daily and i.v. piperacillin–tazobactam given every six hours daily in treating diabetic foot infections. Methods. A cost-minimization analysis (CMA) was conducted on the drug-dosing data of the subset of patients enrolled in a recent double-blind randomized trial who were treated solely as inpatients and were clinically evaluable at fi nal assessment ( n = 99). Cost per dose was calculated from (a) average hospital acquisition price per dose for ertapenem ($40.52) or piperacillin–tazobactam ($13.58), (b) average U.S. wages and benefi ts for labor, based on nine published time-and-motion studies of i.v. antibiotic preparation and administration ($3.10), and (c) consumable supplies, using a 40% discount off the manufacturer list price ($2.90). For each patient, the actual number of antibiotic doses given was multiplied by total cost per dose. Results. There were no significant differences between antibiotic groups with respect to patient demographics, percentage with a severe wound, and mean days of i.v. therapy. Compared with piperacillin–tazobactam, patients treated with ertapenem received significantly fewer mean doses (25.5 versus 7.5; p < 0.0001) and lower antibiotic-related costs ($502.76 versus $355.55, respectively; p < 0.001). The $147.21 difference between groups accounts for approximately 3% of total hospital Medicare reimbursements for these infections. Conclusion. A CMA of treatment of diabetic foot infections showed that, compared with piperacillin–tazobactam given four times daily i.v., ertapenem given once daily i.v. was associated with lower drug acquisition and supply costs and less time and labor devoted to preparation and administration of i.v. therapy.

Hepatocellular carcinoma (HCC) is a major disease worldwide. There were 782,000 estimated new cases globallyin 2012 with the majority (76%) occurring in Asia, especially China. Although the etiologies are similar, the prevalence ofeach HCC risk factor varies in different geographic regions. In China, hepatitis B virus (HBV) infection is the major causeof HCC, whereas in Japan, US and Europe, hepatitis C virus (HCV) infection predominates. With the epidemic of obesityand diabetes, non-alcoholic fatty liver disease (NAFLD), especially its more aggressive form non-alcoholic steatohepatitis(NASH), has now become a major contributor to HCC. It is anticipated that NAFLD/NASH is likely to overtake viralhepatitis as the leading contributor to HCC in the future. Prior success in reducing HCC cases through hepatitis Bimmunization program and effective HBV treatments is likely to be offset by rising significance of NASH-associated HCC.In view of this, appropriate measures such as aggressive monitoring clinical course and prognoses of patients with HCCfrom NASH, studying pathogenesis and mechanism by which NASH promotes HCC, and developing novel intervention andtreatment strategy for these patients would be important to address this important public health challenge.

Background: When using inpatient claims data to identify hospitalizations in supplemental Medicare beneficiaries, e.g., in the MarketScan database, there is a concern that the coverage of hospitalizations in such inpatient claims may be incomplete. However, whether hospitalizations are covered by inpatient claims or not, they incur professional charges that are recorded in the professional claims data in the MarketScan Medicare database. In the context of identifying hospitalizations that might be related to heart failure (HF) in dronedarone users, we compared different approaches to identify such hospitalizations. Objective: To assess the impact of using professional claims in addition to inpatient claims on identifying hospitalizations that might be related to HF. Methods: A total of 20,834 dronedarone users who were supplemental Medicare beneficiaries between July 2009 (launch date in US) and December 2012 were identified in the MarketScan database. The hospitalizations that might be related to HF within 30 days prior to initiating dronedarone were identified by searching (1) inpatient claims and (2) both inpatient and professional claims using related ICD-9-CM diagnosis codes for HF and Current Procedural Terminology codes for hospitalizations. Results: A total of 1,162 patients who had HF hospitalizations within 30 days prior to initiating dronedarone were identified by searching inpatient claims between July 2009 and December 2012. Supplementing with professional claims identified an additional 177 patients who had HF hospitalizations, increasing the total number to 1,339. Therefore, 13.2% (177/1,399) of the patients who had HF hospitalizations could only be identified in professional claims. Thus, the prevalence of hospitalizations that might be related to HF within 30 days prior to initiating dronedarone was 5.6% (1,162/20,834; 95% confidence interval (CI): 5.3 - 5.9%) when hospitalizations were identified using inpatient claims alone. Adding professional claims in the search algorithm, the prevalence of HF hospitalizations was 6.4% (1,339/20,834, 95% CI: 6.1 - 6.8%). Conclusions: Using professional claims, in addition to inpatient claims, can improve the identification of hospitalizations that might be related to HF.

Background A dronedarone utilization study using US MarketScan and InVision Data Mart databases was conducted to estimate the prevalence of the following: (1) dronedarone use in contraindicated patients with worsening heart failure (HF) or hospitalization for HF within 1 month before dronedarone prescription; (2) concomitant prescribing of contraindicated drugs; and (3) recommended creatinine testing after dronedarone initiation among dronedarone users. Methods In this retrospective cohort study, data in the MarketScan database between July 20, 2009, and December 31, 2011, and in the InVision Data Mart database between July 20, 2009, and March 31, 2012, were analyzed. The study population included patients who received ≥1 dronedarone prescription during the study period. The following variables were reported: worsening of or hospitalization for HF, concomitant prescribing of potent cytochrome P450 CYP 3A4 inhibitors or QT-prolonging drugs, and creatinine testing. Results There were 31,408 and 7025 dronedarone users identified in the MarketScan and InVision Data Mart databases, respectively. Approximately 86% to 90% of patients had a diagnosis of atrial fibrillation in each database. In the MarketScan database, 40% were women and 54% were aged ≥65 years. In the InVision Data Mart database, 31% were women and 32% were aged ≥65 years. The corresponding prevalence of worsening or hospitalization for HF was 6.4% (95% CI, 6.2–6.7) and 4.7% (95% CI, 4.2–5.2) in each database, respectively. The corresponding estimates of concomitant prescribing of potent cytochrome P450 CYP 3A4 inhibitors and QT-prolonging drugs within 30 days before initiation or refilling of dronedarone were 2.0% (95% CI, 1.8–2.1) and 10.0% (95% CI, 9.7–10.4), respectively, in the MarketScan database, and 2.3% (95% CI, 2.0–2.7) and 11.2% (95% CI, 10.5–12.0) in the InVision Data Mart database. More than 50% of patients in each database had serum creatinine tests conducted after dronedarone initiation. Conclusions The results of the present analysis based on a long-term follow-up (nearly 3 years) were consistent with the previous findings that dronedarone has mostly been used appropriately in compliance with US prescribing in the target populations.

Antipsychotic drug therapy is the cornerstone of treatment of persons with schizophrenia. Because most antipsychotics are metabolized by the hepatic cytochrome P450 system, concomitant use of an antipsychotic and medications that are competitively metabolized by the same system may cause a potentially harmful drug-drug interaction. This study used a large state's Medicaid claims database to examine the proportion of patients exposed to such interactions and the risk factors associated with exposure.Claims from January 2000 through December 2003 for adult patients with a diagnosis of schizophrenia and at least one prescription for an antipsychotic (N=27,909) were examined for pairs of medications identified as potentially causing moderate or severe adverse drug effects. Logistic regression models were estimated to determine potential risk factors associated with exposure to the interaction pairs.A total of 6,417 (23%) patients were exposed to 14,213 potentially harmful interactions; 4,725 patients had at least one exposure from the same pharmacy, and 4,032 patients were exposed by the same physician. The greatest number of exposures (N=1,353) to potentially harmful combinations involved olanzapine and haloperidol. Patients prescribed risperidone were most likely to be exposed to an interaction (13.1%), followed by patients prescribed olanzapine (10.3%), quetiapine (3.3%), and clozapine (3.2%). A higher risk of exposure was associated with being female (odds ratio [OR]=.94), being white (OR=1.43), having depression (OR=1.21), or having impulse-control disorder (OR=1.98).Interventions by physicians and pharmacies to reduce the prescribing and dispensing of potentially harmful pairs of medications to patients with schizophrenia are recommended.

Background A reporting association of risperidone with pituitary tumors has been observed. Because such tumors are highly prevalent, there may be other reasons why they were revealed in association with risperidone treatment. We assessed two potential explanations: disproportionately more prolactin assessment and head/brain imaging in risperidone-treated patients vs patients treated with other antipsychotics. Methods Treatment episodes with risperidone, clozapine, olanzapine, quetiapine, ziprasidone, aripiprazole, haloperidol, perphenazine and 'other typical' antipsychotics were identified in two databases (large commercial, Medicaid). Comparisons used proportional hazards regression to determine whether prolactin testing was disproportionate with risperidone, regardless of prior potentially prolactin-related adverse events (PPAEs). Logistic regression determined whether magnetic resonance imaging (MRI)/computed tomography (CT) were disproportionate in risperidone-treated patients vs other patients, regardless of hyperprolactinemia or PPAEs. In each regression, the 'other typical' antipsychotic category served as the comparator. Regression models controlled for age, gender, and other factors. Results Altogether, 197,926 treatment episodes were analyzed (63,878 risperidone). Among patients with or without preceding PPAEs, risperidone treatment was associated with a significantly greater likelihood of prolactin assessment (hazard ratio (HR) 1.34, 95% confidence interval (CI) = 1.09 to 1.66, p = 0.007). Among patients with hyperprolactinemia or PPAEs, those treated with risperidone (odds ratio (OR) 1.66, 95% CI 1.23 to 2.23, p = 0.001) or ziprasidone (OR 1.66, 95% CI 1.06 to 2.62, p = 0.028) had a higher likelihood of MRI/CT. Conclusion Risperidone-treated patients are more likely to undergo prolactin assessment regardless of prior PPAEs, and more likely to undergo MRI/CT in association with hyperprolactinemia or PPAEs. Thus, a predisposition for more evaluations in risperidone-treated patients may contribute to disproportionate identification and reporting of prevalent pituitary adenoma.

The majority of clinical outcome assessments developed for generalized anxiety disorder (GAD) may not efficiently and sensitively reflect heterogeneous symptom clusters from a patient perspective. The Patient-Rated Troubling Symptoms Scale for Anxiety (PaRTS-A) instrument was developed to provide an individualized assessment of patient relevant GAD symptoms.The objective of this analysis was to evaluate the psychometric characteristics of the PaRTS-A.Data were taken from a 6-week clinical trial evaluating the efficacy of adjunctive risperidone therapy in GAD patients undergoing standard treatment. Patients completed the PaRTS-A, the Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q), and the Sheehan Disability Scale (SDS) as well as impressions of improvement. Physicians completed the Hamilton Anxiety Rating Scale (HAM-A). A instrument characteristics were assessed through statistical tests of reliability, reproducibility, construct and discriminant validity, and responsiveness.In the item response theory (IRT) analysis, the PaRTS-A items fit into a single construct of anxiety. Internal consistency reliability exceeded 0.70. The PaRTS-A total score was moderately correlated with the Q-LES-Q and the SDS. The PaRTS-A distinguished between patients with high and low HAM-A scores (p0.001). The PaRTS-A was responsive to changes in clinical status and the minimal important difference was identified.The PaRTS-A provides a unique patient-rated assessment of anxiety symptoms. The instrument may provide clinicians with useful information regarding patient's self-rated anxiety disorder symptoms and the hierarchy of symptoms that they considered most troubling. Our analysis suggests that the PaRTS-A is an internally consistent, valid, and responsive instrument that may be a beneficial adjunct to other instruments in clinical trials.

To assess differences in the number of days hospitalized among schizophrenic patients receiving paliperidone extended-release (paliperidone ER) during the open-label extension (OLE) phases, compared to a similar time period prior to the screening for entry into the double-blind (DB) trials conducted in the United States.Mental health-related hospital days during the 52 weeks before entering the DB trials and during the OLE phases were compared. The mean number of hospital days per person per year in the pre- and post-periods was calculated and the statistical significance of pre-post differences was assessed using bootstrap resampling methods. Total person-years were also calculated for the pre- and post-periods to account for different lengths of observation.Patients' (n=215) mean (+/-SD) age was 41.2 (+/-11.0) years; most were male (73.0%); and black (52.1 vs. 45.1% white). The mean (+/-SD) paliperidone ER treatment duration during the OLE phase was 167.0 (+/-145.0) days and the mean (+/-SD) daily dose was 10.5 (+/-2.0) mg. Overall, paliperidone ER patients spent an average (+/-SD) of 13.2 (+/-1.6) and 3.1 (+/-0.7) hospital days per person-year in the pre-and post-periods, respectively (mean +/-SD change 10.0+/-1.8, 95% CI 6.5, 13.4, p0.001). Using the 2007 Federal Per Diem Base Rate (i.e., $595.09 per day), this reduction in hospital days would result in an average (+/-SD) cost savings of $5951 (+/-1071) per person per year.Patients had significantly fewer hospital days in the OLE phase compared to the 1-year period prior to entering the DB trial. Paliperidone ER may play a role in reducing mental health-related hospital days and associated costs. Important study limitations include the lack of a control group, the pre-post design comparing historical data with data collected in the trials which could create a bias due to the mismatch in settings, and patients having more frequent contact with treating physicians and investigators during the trial period, which could favor the outcomes in the OLE phase. Further studies are needed to confirm these findings.

There is little published research addressing how the 2003 Infectious Diseases Society of America (IDSA) guidelines for empiric therapy of community-acquired pneumonia (CAP) are implemented in clinical practice.This study was designed to describe antibiotic treatment patterns among patients with CAP treated in ambulatory settings in light of the IDSA guidelines.Health insurance claims data from a large managed care organization with -30 million enrollees located in geographically diverse regions of the United States were analyzed. Patientsor =18 years of age with CAP who received a prescription for any antibiotic in an ambulatory setting during 2004 were identified via International Classification of Diseases, Ninth Revision, Clinical Modification codes for diagnosis (481-486). Recent antibiotic use was defined as receipt of any antibiotics90 days before the date of diagnosis. Antibiotics were identified through National Drug Codes and from outpatient medical claims data with the use of J codes. Individuals were classified, per IDSA guidelines, as previously healthy without recent antibiotic use (group 1); previously healthy with recent antibiotic use (group 2); with comorbidities and without recent antibiotic use (group 3); and with comorbidities and recent antibiotic use (group 4). The guideline adherence was calculated using the number of patients receiving recommended treatment divided by the total number of patients in each group.Of 34,342 patients identified, 76.5% had no reported comorbidities. Among group-1 patients, 52.0% received the recommended empiric therapy (macrolide or doxycycline). In group-2 patients, 42.5% received the recommended therapy (respiratory quinolone alone or advanced-generation macrolide plus amoxicillin or amoxicillin-clavulanate). A high rate of compliance with recommended empiric therapy (advanced-generation macrolides or respiratory quinolones) was observed in group-3 patients (81.5%). In group-4 patients, 43.4% received the recommended therapy (respiratory quinolone or advanced-generation macrolide plus ss-lactam). Patients whose therapy was adherent with the guidelines had fewer respiratory-infection-related hospital admissions within 30 days after initiation of antibiotic treatment (overall, relative risk = 0.81 [95% CI, 0.71-0.94]).Although these data reflect a period shortly after the 2003 IDSA guidelines were published, they suggest that there is room for improvement with regard to choice of empiric antibiotic therapy among these patients with CAP treated in ambulatory settings.

Background :Wernicke’s encephalopathy (WE) is an acute neuropsychiatric syndrome resulting from thiamine deficiency. This neurological deterioration is potentially dangerous because it predisposes the patient to hypothermia and decreased immunity. Cancer patients are at high risk of WE due to chronic malnutrition, chemotherapy-induced nausea and vomiting, and consumption of thiamine by rapidly growing tumors. Very little published research addresses the risk of WE in patients with myeloproliferative neoplasm (MPN). Objectives: To estimate the incidence of WE among patients with MPN, and compare it with those without MPN. Methods: Patients with a diagnosis of MPN, including polycythemia vera (PV), essential thrombocythemia (ET) and primary myelofibrosis (PMF) were identified from 1/1/2003 to 03/31/2013 using the US MarketScan database. The control cohort consisted of a random sample matched to the MPN cohort by age and gender in a 1:1 ratio. Diagnosis of WE was ascertained using ICD-9-CM 265.0, 265.1, 291.1, 294.0 or J code J3411. The two study cohorts were followed for WE from the index date. Cox proportional hazards modeling was used to compare the rates between two cohorts and also control for confounding variables. Results: A total of 39,761 MPN patients, including PV (51%), ET (42%), post-PV MF (0.2%), post-ET MF (1%), and PMF (2.8%) were identified. Approximately 27% of them were > 65 years of age, and 51% were male. Patients with MPN had higher rates of WE, compared to those without MPN (MPN vs. non-MPN: 1.09 vs. 0.39/1000 person-year, hazard ratio = 2.19, 95% confidence interval 1.43-3.34). The incidence rate of WE was higher in males (male vs. female: 0.93 vs. 0.55/1000 person-year). No specific pattern was observed in age subgroups for both cohorts (e.g. MPN: age 70 = 0 vs. 0.85 vs. 1.09 vs. 1.16 vs. 0.72 vs. 0.86/1000 person-year). Conclusions: Patients with MPN had higher incidence rates of WE, compared to those without MPN. Given the potentially dangerous outcomes associated with WE, physicians who care for patients with MPN should be aware of the risk of WE in this population. Disclosures Wu: Sanofi: Employment. Mirza:Sanofi: Employment. Partisano:Sanofi: Employment. Gallagher:Sanofi: Postdoctoral Fellow Other. Vaze:Sanofi: Employment. Zhang:Sanofi: Employment. Gallagher:Sanofi: Employment. Lin:Sanofi: Employment. Juhaeri:Sanofi: Employment.