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Introduction: Early in COVID‐19, continuing professional development (CPD) providers quickly made decisions about program content, design, funding and technology. Although experiences during an earlier pandemic cautioned providers to make disaster plans, CPD was not entirely prepared for this event. We sought to better understand how CPD organisations make decisions about CPD strategy and operations during a crisis. Methods: This is a descriptive qualitative research study of decision making in two organisations: CPD at the University of Toronto (UofT) and the US‐based Society for Academic Continuing Medical Education (SACME). In March 2021, using purposive and snowball sampling, we invited faculty and staff who held leadership positions to participate in semi‐structured interviews. The interview focused on the individual's role and organisation, their decision‐making process and reflections on how their units had changed because of COVID‐19. Transcripts were reviewed, coded and analysed using thematic analysis. We used Mazmanian et al.'s Ecological Framework as a further conceptual tool. Results: We conducted eight interviews from UofT and five from SACME. We identified that decision making during the pandemic occurred over four phases of reactions and impact from COVID‐19, including shutdown, pivot, transition and the 'new reality'. The decision‐making ability of CPD organisations changed throughout the pandemic, ranging from having little or no independent decision‐making ability early on to having considerable control over choosing appropriate pathways forward. Decision making was strongly influenced by the creativity, adaptability and flexibility of the CPD community and the need for social connection. Conclusions: This adds to literature on the changes CPD organisations faced due to COVID‐19, emphasising CPD organisations' adaptability in making decisions. Applying the Ecological Framework further demonstrates the importance of time to decision‐making processes and the relational aspect of CPD. To face future crises, CPD will need to embrace creative, flexible and socially connected solutions. Future scholarship could explore an organisation's ability to rapidly adapt to better prepare for future crises. Using CPD organizations's response to the covid crisis, Paton et al. demonstrate the importance of time and relations as a means to embrace creative, flexible, and socially connected solutions in future. [ABSTRACT FROM AUTHOR]

Introduction: Electronic health record (EHR) discontinuity (missing out-of-network encounters) can lead to information bias. We sought to construct an algorithm that identifies high EHR-continuity among oncology patients.Methods: Using a linked Medicare-EHR database and regression, we sought to 1) measure how often Medicare claims for outpatient encounters were substantiated by visits recorded in the EHR, and 2) predict continuity ratio, defined as the yearly proportion of outpatient encounters reported to Medicare that were captured by EHR data. The prediction model...s performance was evaluated with the coefficient of determination and Spearman...s correlation. We quantified variable misclassification by decile of continuity ratio using standardized difference and sensitivity.Results: A total of 79,678 subjects met all eligibility criteria. Predicted and observed continuity was highly correlated (σSpearman=0.86). On average across all variables measured, MSD was reduced by a factor of 1/7th and sensitivity was improved 35-fold comparing subjects in the highest vs. lowest decile of CR.Conclusion: In the oncology population, restricting EHR-based study cohorts to subjects with high continuity may reduce misclassification without greatly impacting representativeness. Further work is needed to elucidate the best manner of implementing continuity prediction rules in cohort studies. [ABSTRACT FROM AUTHOR]

Objective: To determine whether sodium-glucose cotransporter 2 (SGLT2) inhibitors, compared with glucagon-like peptide 1 receptor agonists (GLP-1RAs) or dipeptidyl peptidase 4 (DPP-4) inhibitors, are associated with an increased risk of early bladder cancer events.Research Design and Methods: We conducted a multisite, population-based, new-user, active comparator cohort study using the U.K. Clinical Practice Research Datalink, Medicare fee-for-service, Optum's de-identifed Clinformatics Data Mart Database (CDM), and MarketScan Health databases from January 2013 through December 2020. We assembled two cohorts of adults with type 2 diabetes initiating 1) SGLT2 inhibitors or GLP-1RAs and 2) SGLT2 inhibitors or DPP-4 inhibitors. Cox proportional hazards models were fit to estimate hazard ratios (HRs) and 95% CIs of incident bladder cancer. The models were weighted using propensity score fine stratification. Site-specific HRs were pooled using random-effects models.Results: SGLT2 inhibitor (n = 453,560) and GLP-1RA (n = 375,997) users had a median follow-up ranging from 1.5 to 2.2 years. Overall, SGLT2 inhibitors were not associated with an increased risk of bladder cancer compared with GLP-1RAs (HR 0.90, 95% CI 0.81-1.00). Similarly, when compared with DPP-4 inhibitors (n = 853,186), SGLT2 inhibitors (n = 347,059) were not associated with an increased risk of bladder cancer (HR 0.99, 95% CI 0.91-1.09) over a median follow-up ranging from 1.6 to 2.6 years. Results were consistent across sensitivity analyses.Conclusions: Contrary to previous randomized controlled trials, these findings indicate that the use of SGLT2 inhibitors is not associated with an increased risk of bladder cancer compared with GLP-1RAs or DPP-4 inhibitors. This should provide reassurance on the short-term effects of SGLT2 inhibitors on bladder cancer incidence. [ABSTRACT FROM AUTHOR]

Background: The use of electronic health records (EHR) data to assess drug effectiveness in clinical oncology practice is of great interest to regulators, clinicians, and payers. However, the utility of EHR data in clinical effectiveness studies may be limited by missing data, unmeasured confounding, and imperfect outcome surveillance. This study sought to emulate and compare the results of a randomized controlled trial investigating the efficacy of palbociclib with fulvestrant vs letrozole in advanced breast cancer. Methods: This was a cohort study using longitudinal EHR data derived from outpatient oncology practices in the United States. Eligibility criteria from the PARSIFAL trial were emulated as closely as possible. Patients were included if they had hormone-positive, human epidermal growth factor receptor – 2 (HER-2) negative metastatic breast cancer and had no record of prior treatment for metastatic disease. Patients initiating first-line treatment with palbociclib and fulvestrant following their first record of metastasis were compared to those initiating palbociclib and letrozole on the same day. Treatments were ascertained by oncology medication ordering records in the data source. The primary outcome was death as recorded in the oncologists' EHR systems. Results: There were 1886 eligible women in the study cohort. Although the 3-year survival was meaningfully lower in clinical practice (59%) compared to the randomized trial (78%), the relative effect size was a hazard ratio (HR) of 1.07 (95% CI: 0.86– 1.35), similar to the randomized trial (HR = 1.00; 95% CI: 0.68– 1.48). Conclusion: Despite common challenges encountered in EHR-based studies, it is possible to achieve similar conclusions to emulated randomized trials with the application of analytic approaches that address missing data, confounding, and selection bias. This is a promising finding in light of other emulations and ongoing efforts to improve data from clinical practice and causal analytics. [ABSTRACT FROM AUTHOR]

The durability of immune responses after COVID-19 vaccination will drive long-term vaccine effectiveness across settings and may differ by vaccine type. To determine durability of protection of COVID-19 vaccines (BNT162b2, mRNA-1273, and Ad26.COV2.S) following primary vaccination in the United States, a matched case-control study was conducted in three cohorts between 1 January and 7 September 2021 using de-identified data from a database covering 168 million lives. Odds ratios (ORs) for developing outcomes of interest (breakthrough SARS-CoV-2 infection, hospitalization, or intensive care unit admission) were determined for each vaccine (no direct comparisons). In total, 17,017,435 individuals were identified. Relative to the baseline, stable protection was observed for Ad26.COV2.S against infections (OR [95% confidence interval (CI)], 1.31 [1.18–1.47]) and hospitalizations (OR [95% CI], 1.25 [0.86–1.80]). Relative to the baseline, protection waned over time against infections for BNT162b2 (OR [95% CI], 2.20 [2.01–2.40]) and mRNA-1273 (OR [95% CI], 2.07 [1.87–2.29]) and against hospitalizations for BNT162b2 (OR [95% CI], 2.38 [1.79–3.17]). Baseline protection remained stable for intensive care unit admissions for all three vaccines. Calculated baseline VE was consistent with published literature. This study suggests that the three vaccines in three separate populations may have different durability profiles. [ABSTRACT FROM AUTHOR]

Background: Evidence on the risk for cardiovascular events associated with use of first-line sodium-glucose cotransporter-2 inhibitors (SGLT-2i) compared with metformin is limited.Objective: To assess cardiovascular outcomes among adults with type 2 diabetes (T2D) who initiated first-line treatment with SGLT-2i versus metformin.Design: Population-based cohort study.Setting: Claims data from 2 large U.S. commercial and Medicare databases (April 2013 to March 2020).Participants: Patients with T2D aged 18 years and older (>65 years in Medicare) initiating treatment with SGLT-2i or metformin during April 2013 to March 2020, without any use of antidiabetic medications before cohort entry, were identified. After 1:2 propensity score matching in each database, pooled hazard ratios (HRs) and 95% CIs were reported.Intervention: First-line SGLT-2i (canagliflozin, empagliflozin, or dapagliflozin) or metformin.Measurements: Primary outcomes were a composite of hospitalization for myocardial infarction (MI), hospitalization for ischemic or hemorrhagic stroke or all-cause mortality (MI/stroke/mortality), and a composite of hospitalization for heart failure (HHF) or all-cause mortality (HHF/mortality). Safety outcomes including genital infections were assessed.Results: Among 8613 first-line SGLT-2i initiators matched to 17 226 metformin initiators, SGLT-2i initiators had a similar risk for MI/stroke/mortality (HR, 0.96; 95% CI, 0.77 to 1.19) and a lower risk for HHF/mortality (HR, 0.80; CI, 0.66 to 0.97) during a mean follow-up of 12 months. Initiators receiving SGLT-2i showed a lower risk for HHF (HR, 0.78; CI, 0.63 to 0.97), a numerically lower risk for MI (HR, 0.70; CI, 0.48 to 1.00), and similar risk for stroke, mortality, and MI/stroke/HHF/mortality compared with metformin. Initiators receiving SGLT-2i had a higher risk for genital infections (HR, 2.19; CI, 1.91 to 2.51) and otherwise similar safety as those receiving metformin.Limitation: Treatment selection was not randomized.Conclusion: As first-line T2D treatment, initiators receiving SGLT-2i showed a similar risk for MI/stroke/mortality, lower risk for HHF/mortality and HHF, and a similar safety profile except for an increased risk for genital infections compared with those receiving metformin.Primary Funding Source: Brigham and Women's Hospital and Harvard Medical School. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Aim: To assess the trends in the prescribing of antiobesity medications and the characteristics of patients recently initiating antiobesity drugs. Materials and Methods: We conducted a population‐based cohort study using claims data from commercial health insurances in the United States. Patients initiating an antiobesity drug between January 2004 and December 2018 were included. Trends in the utilization of antiobesity medications were plotted by year, as a proportion of any antiobesity treatment, and as initiation rates per 100 000. Descriptive statistics were used to summarize the characteristics of antiobesity initiators. Results: From 2004 to 2018, 626 216 patients started an antiobesity medication (two per 100 000). Phentermine was the most frequently prescribed (50% in 2018). In recent years (2015‐2018), among 227 692 patients who initiated an antiobesity drug, 51% started phentermine, 19% naltrexone‐bupropion, and 13% liraglutide 3.0 mg. Compared to other agents, the use of liraglutide 3.0 mg increased between 2015 and 2018. The average age of initiators was 45 years, 81% of initiators were female, 32% had hypertension, 25% had dyslipidaemia, and 6% had type 2 diabetes. Time on treatment was generally short (mean 81 days). Conclusion: The overall use of antiobesity medications remained low over the past 15 years and phentermine was the preferred antiobesity agent. Although the use of potentially safer antiobesity agents, for example, liraglutide 3.0 mg, has increased in recent years, phentermine remained the most frequently prescribed agent among middle‐aged adults with a moderate burden of comorbidities. [ABSTRACT FROM AUTHOR]

Aim: To reproduce and correct studies on bariatric surgery and the reduction in major adverse cardiovascular events (MACE) among patients with obesity and type 2 diabetes (T2D). Methods: We used electronic healthcare records (EHR) from in and outpatient facilities around the United States to identify a cohort of patients with T2D, aged 18 to 80 years and with a body mass index (BMI) of 30 kg/m2 or higher undergoing bariatric surgery. We compared against hip/knee arthroplasty to establish an active comparison group that reduced bias from differential information and confounding. The main outcome was six‐point MACE. Pre‐exposure characteristics were adjusted in propensity score (PS) models with 1:2 matching plus high‐dimensional PS matching. Results: After a range of exclusions, the final cohort included 344 bariatric surgery patients (65% female; mean age 58 years) and 551 PS‐matched patients undergoing arthroplasty (65% female; 59 years). Median follow‐up was 2.5 years in both groups. Bariatric surgery patients showed a sustained 20% weight reduction and an HbA1c reduction by 1% point. We found no benefits of bariatric surgery for six‐point MACE (HR = 0.99; 95% CI 0.76‐1.30). We observed known increases in risks for vitamin B12 deficiency anaemia (HR = 3.06; 1.10‐8.49) and cholelithiasis (HR = 1.72; 0.94‐3.13). Conclusions: This real‐world evidence study found reductions in HbA1c and BMI following bariatric surgery similar to trials, and no meaningful cardiovascular benefit compatible with the underpowered trials but in contrast to earlier EHR studies. We showed how information bias typical in EHR analyses and confounding may cause substantial bias. [ABSTRACT FROM AUTHOR]

Assessments of clinical evidence vary between regulators and health technology assessment bodies, but precise differences remain unclear. To compare uncertainties raised on the clinical evidence of approved drugs, we analyzed assessments of regulators and health technology assessment (HTA) bodies in the United States and Europe. We found that US and European regulators report uncertainties related to safety for almost all drugs (85–94%), whereas HTA bodies reported these less (53–59%). By contrast, HTA bodies raised uncertainties related to effects against relevant comparators for almost all drugs (88–100%), whereas this was infrequently addressed by regulators (12–32%). Regulators as well as HTA bodies reported uncertainties related to the patient population for 60–95% of drugs. The patterns of regulator‐HTA misalignment were comparable between the United States and Europe. Our results indicate that increased coordination between these complementary organizations is necessary to facilitate the collection of necessary evidence in an efficient and timely manner. [ABSTRACT FROM AUTHOR]

Healthcare database analyses (claims, electronic health records) have been identified by various regulatory initiatives, including the 21st Century Cures Act and Prescription Drug User Fee Act ("PDUFA"), as useful supplements to randomized clinical trials to generate evidence on the effectiveness, harm, and value of medical products in routine care. Specific applications include accelerated drug approval pathways and secondary indications for approved medical products. Such real-world data ("RWD") analyses reflect how medical products impact health outside a highly controlled research environment. A constant stream of data from the routine operation of modern healthcare systems that can be analyzed in rapid cycles enables incremental evidence development for regulatory decision-making. Key evidentiary needs by regulators include 1) monitoring of medication performance in routine care, including the effectiveness, safety and value; 2) identifying new patient strata in which a drug may have added value or unacceptable harms; and 3) monitoring targeted utilization. Four broad requirements have been proposed to enable successful regulatory decision-making based on healthcare database analyses (collectively, "MVET"): Meaningful evidence that provides relevant and context-informed evidence sufficient for interpretation, drawing conclusions, and making decisions; valid evidence that meets scientific and technical quality standards to allow causal interpretations; expedited evidence that provides incremental evidence that is synchronized with the decision-making process; and transparent evidence that is audible, reproducible, robust, and ultimately trusted by decision-makers. Evidence generation systems that satisfy MVET requirements to a high degree will contribute to effective regulatory decision-making. Rapid-cycle analytics of healthcare databases is maturing at a time when regulatory overhaul increasingly demands such evidence. Governance, regulations, and data quality are catching up as the utility of this resource is demonstrated in multiple contexts. [ABSTRACT FROM AUTHOR]

Background: Although echinocandins are generally well tolerated, there is little information on the frequency with which renal and hepatic adverse effects occur during use of micafungin or other parenteral antifungal (PAF) agents in clinical practice.Methods: MYCOS is a multicentre cohort study of adult and paediatric patients who received micafungin or other PAFs between 2005 and 2012 at seven tertiary care hospitals from six centres in the USA. PAF cohort controls were selected through propensity score (PS) matching to micafungin recipients using clinical characteristics, other treatments, procedures and hospital service where PAF treatment was initiated. Analysis was restricted to patients without chronic liver and kidney conditions at the time of cohort entry. Treatment-emergent hepatic and renal injury was documented by changes in liver enzymes or estimated glomerular filtration rate through 30 days following completion of PAF treatment. Comparisons were quantified using the HR from a proportional hazards analysis.Results: There were 2970 micafungin recipients PS matched to 6726 recipients of comparator PAFs. Balance was achieved in all baseline covariates between treatment groups. There were similar rates of hepatic injury (micafungin, 13 events per 100 patients and other PAF, 12 per 100; HR = 0.99; 95% CI 0.86-1.14) and lower rates of renal injury (micafungin, 63 events per 100 patients and other PAF, 65 per 100; HR = 0.93; 95% CI 0.87-0.99) for micafungin recipients versus PAF comparators.Conclusion: For a wide spectrum of underlying conditions, we observed no increase in liver injury by micafungin and possibly a reduced risk of renal dysfunction in comparison with other PAF medications. [ABSTRACT FROM AUTHOR]

Objective: Dipeptidyl peptidase-4 (DPP4), also known as CD26, is a transmembrane glycoprotein that has a costimulatory function in the immune response. DPP4 inhibitors (DPP4i) are oral glucose-lowering drugs for type 2 diabetes mellitus (T2DM). This study evaluated the risk of incident rheumatoid arthritis (RA) and other autoimmune diseases (AD) such as systemic lupus erythematosus, psoriasis, multiple sclerosis and inflammatory bowel disease, associated with DPP4i in patients with T2DM.Methods: Using US insurance claims data (2005-2012), we conducted a population-based cohort study that included initiators of combination therapy with DPP4i (DPP4i plus metformin) and non-DPP4i (non-DPP4i plus metformin). RA and other AD were identified with ≥2 diagnoses and ≥1 dispensing for AD-specific immunomodulating drugs or steroids. Composite AD includes RA or other AD. Propensity score (PS)-stratified Cox proportional hazards models compared the risk of AD in DPP4i initiators versus non-DPP4i, controlling for potential confounders.Results: After asymmetric trimming on the PS, 73 928 patients with T2DM starting DPP4i combination therapy and 163 062 starting non-DPP4i combination therapy were selected. Risks of incident RA and composite AD were lower in the DPP4i group versus non-DPP4i with the PS-stratified HR of 0.66 (95% CI 0.44 to 0.99) for RA, 0.73 (0.51 to 1.03) for other AD and 0.68 (95% CI 0.52 to 0.89) for composite AD.Conclusions: In this large cohort of diabetic patients, those initiating DPP4i combination therapy appear to have a decreased risk of incident AD including RA compared with those initiating non-DPP4i combination therapy. These results may suggest possible pharmacological pathways for prevention or treatment of AD. [ABSTRACT FROM AUTHOR]

Background: When the US FDA approves a new prescription drug there is still a great deal remaining to be learned about the safe and proper use of that product. When new information addressing these topics emerges post-approval, the FDA may issue a Drug Safety Communication (DSC) to alert patients and physicians. The effectiveness of the communication-how drug safety messaging conveyed in FDA DSCs changes patient or prescriber behavior-may depend on multiple factors, including the way physicians and patients learn about the information, their understanding of the issues conveyed, and their perception of the importance of the information. In 2013, the FDA issued two DSCs addressing critical new warnings related to products containing the sedative/hypnotic zolpidem.Objective: In this article, we describe a core set of research initiatives that can be used to study how zolpidem-related DSCs affected subsequent physician and patient decision making.Methods: These research initiatives include analyzing drug utilization patterns and related health outcomes; comparing zolpidem-containing products against a comparator with similar indications [eszopiclone (Lunesta)] not covered by the 2013 DSCs; and surveying patients and qualitatively evaluating the dissemination of information regarding these drugs in traditional and social-media channels.Conclusions: Using an integrated, multidisciplinary approach, we can obtain information that can be used to optimize regulatory communications by seeking to understand the impact of the information contained in FDA risk communications. [ABSTRACT FROM AUTHOR]

Objectives To determine whether adjustment for prognostic indices specifically developed for nursing home ( NH) populations affect the magnitude of previously observed associations between mortality and conventional and atypical antipsychotics. Design Cohort study. Setting A merged data set of Medicaid, Medicare, Minimum Data Set ( MDS), Online Survey Certification and Reporting system, and National Death Index for 2001 to 2005. Participants Dual-eligible individuals aged 65 and older who initiated antipsychotic treatment in a NH (N = 75,445). Measurements Three mortality risk scores (Mortality Risk Index Score, Revised MDS Mortality Risk Index, Advanced Dementia Prognostic Tool) were derived for each participant using baseline MDS data, and their performance was assessed using c-statistics and goodness-of-fit tests. The effect of adjusting for these indices in addition to propensity scores ( PSs) on the association between antipsychotic medication and mortality was evaluated using Cox models with and without adjustment for risk scores. Results Each risk score showed moderate discrimination for 6-month mortality, with c-statistics ranging from 0.61 to 0.63. There was no evidence of lack of fit. Imbalances in risk scores between conventional and atypical antipsychotic users, suggesting potential confounding, were much lower within PS deciles than the imbalances in the full cohort. Accounting for each score in the Cox model did not change the relative risk estimates: 2.24 with PS-only adjustment versus 2.20, 2.20, and 2.22 after further adjustment for the three risk scores. Conclusion Although causality cannot be proven based on nonrandomized studies, this study adds to the body of evidence rejecting explanations other than causality for the greater mortality risk associated with conventional antipsychotics than with atypical antipsychotics. [ABSTRACT FROM AUTHOR]

An introduction is presented in which the authors discuss an article in the issue dealing with nontrial evidence in U.S. medical decision making and statistical approaches to adjust analyses of observational studies, and it mentions design thinking, causal questions, and misleading evidence.

Antipsychotic drugs are used to treat dementia-related symptoms in older adults, and observational studies show higher risks of death and stroke associated with the use of first-generation antipsychotic drugs (FGAs) compared with second-generation antipsychotic drugs (SGAs). However, the extent to which stroke explains the differential mortality risk between FGA use and SGA use in older adults is unclear. We followed those who initiated use of antipsychotic drugs (9,777 FGA users and 21,164 SGA users) aged 65 years or older, and who were enrolled in Medicare and either the New Jersey or Pennsylvania pharmacy assistance program during 1994 to 2005, over 180 days for the outcomes of stroke and death. We estimated direct and indirect effects by comparing 180-day mortality risks associated with the use of FGAs versus SGAs as mediated by stroke on the risk ratio scale, as well as the proportion mediated on the risk difference scale. FGA use was associated with marginally higher risks of stroke (risk ratio =1.24, 95% confidence interval (CI): 1.01, 1.53) and death (risk ratio = 1.15, 95% CI: 1.08, 1.22) compared with SGA use, but stroke explained little (2.7%) of the observed difference in mortality risk. The indirect effect was null (risk ratio = 1.004, 95% CI: 1.000, 1.008), and the direct effect was equal to the total effect of antipsychotic drug type (FGA vs. SGA) on mortality risk (risk ratio = 1.15, 95% CI: 1.08, 1.22). These results suggest that the difference in mortality risk between users of FGAs and SGAs may develop mostly through pathways that do not involve stroke. [ABSTRACT FROM PUBLISHER]

Objective To evaluate the effect of anesthesia type on the risk of in-hospital mortality among adults undergoing hip fracture surgery in the United States. Design Retrospective cohort study. Setting Premier research database, United States. Participants 73 284 adults undergoing hip fracture surgery on hospital day 2 or greater between 2007 and 2011. Of those, 61 554 (84.0%) received general anesthesia, 6939 (9.5%) regional anesthesia, and 4791 (6.5%) combined general and regional anesthesia. Main outcome measure In-hospital all cause mortality. Results In-hospital deaths occurred in 1362 (2.2%) patients receiving general anesthesia, 144 (2.1%) receiving regional anesthesia, and 115 (2.4%) receiving combined anesthesia. In the multivariable adjusted analysis, when compared with general anesthesia the mortality risk did not differ significantly between regional anesthesia (risk ratio 0.93, 95% confidence interval 0.78 to 1.11) or combined anesthesia (1.00, 0.82 to 1.22). A mixed effects analysis accounting for differences between hospitals produced similar results: compared with general anesthesia the risk from regional anesthesia was 0.91 (0.75 to 1.10) and from combined anesthesia was 0.98 (0.79 to 1.21). Findings were also consistent in subgroup analyses. Conclusions In this large nationwide sample of hospital admissions, mortality risk did not differ significantly by anesthesia type among patients undergoing hip fracture surgery. Our results suggest that if the previously posited beneficial effect of regional anesthesia on short term mortality exists, it is likely to be more modest than previously reported. [ABSTRACT FROM AUTHOR]

Objectives. We assessed the relationship between individual characteristics and receipt of oseltamivir (Tamiflu) in the United States during the HI NI pandemic and other flu seasons. Methods. In a cohort of individuals enrolled in pharmacy benefit plans, we used a multivariate logistic regression model to measure associations between subscriber characteristics and filling a prescription for oseltamivir during 3 flu seasons (October 2006-May 2007, October 2007-May 2008, and October 2008- May 2010), In 19 states with county-level influenza rates reported, we controlled for disease burden. Results. Approximately 56 million subscribers throughout the United States were included in 1 or more study periods. During pandemic flu, beneficiaries in the highest income category had 97% greater odds of receiving oseltamivir than those in the lowest category (P<.001). After we controlled for disease burden, subscribers in the 2 highest income categories had 2.18 and 1.72 times the odds of receiving oseltamivir compared with those in the lowest category (P< .001 for both). Conclusions. Income was a stronger predictor of oseltamivir receipt than prevalence of influenza. These findings corroborate concerns about equity of treatment in pandemics, and they call for improved approaches to distributing potentially life-saving treatments. [ABSTRACT FROM AUTHOR]

Objectives To compare the risk of major medical events in nursing home residents newly initiated on conventional or atypical antipsychotic medications ( APMs). Design Cohort study, using linked Medicaid, Medicare, Minimum Data Set, and Online Survey Certification and Reporting data. Propensity score-adjusted proportional hazards models were used to compare risks for medical events at a class and individual drug level. Setting Nursing homes in 45 U.S. states. Participants Eighty-three thousand nine hundred fifty-nine Medicaid-eligible residents aged 65 and older who initiated APM treatment after nursing home admission in 2001 to 2005. Measurements Hospitalization for myocardial infarction, cerebrovascular events, serious bacterial infections, and hip fracture within 180 days of treatment initiation. Results Risks of bacterial infections (hazard ratio ( HR) = 1.25, 95% confidence interval ( CI) = 1.05-1.49) and possibly myocardial infarction ( HR = 1.23, 95% CI = 0.81-1.86) and hip fracture ( HR = 1.29, 95% CI = 0.95-1.76) were higher, and risks of cerebrovascular events ( HR = 0.82, 95% CI = 0.65-1.02) were lower in participants initiating conventional APMs than in those initiating atypical APMs. Little variation existed between individual atypical APMs, except for a somewhat lower risk of cerebrovascular events with olanzapine ( HR = 0.91, 95% CI = 0.81-1.02) and quetiapine ( HR = 0.89, 95% CI = 0.79-1.02) and a lower risk of bacterial infections ( HR = 0.83, 95% CI = 0.73-0.94) and possibly a higher risk of hip fracture ( HR = 1.17, 95% CI = 0.96-1.43) with quetiapine than with risperidone. Dose-response relationships were observed for all events ( HR = 1.12, 95% CI = 1.05-1.19 for high vs low dose for all events combined). Conclusion These associations underscore the importance of carefully selecting the specific APM and dose and monitoring their safety, especially in nursing home residents who have an array of medical illnesses and are undergoing complex medication regimens. [ABSTRACT FROM AUTHOR]

Selective prescribing of conventional antipsychotic medication (APM) to frailer patients is thought to have led to overestimation of the association with mortality in pharmacoepidemiologic studies relying on claims data. The authors assessed the validity of different analytic techniques to address such confounding. The cohort included 82,012 persons initiating APM use after admission to a nursing home in 45 states with 2001–2005 Medicaid/Medicare data, linked to clinical data (Minimum Data Set) and institutional characteristics. The authors compared the association between APM class and 180-day mortality with multivariate outcome modeling, propensity score (PS) adjustment, and instrumental variables. The unadjusted risk difference (per 100 patients) of 10.6 (95% confidence interval (CI): 9.4, 11.7) comparing use of conventional medication with atypical APM was reduced to 7.8 (95% CI: 6.6, 9.0) and 7.0 (95% CI: 5.8, 8.2) after PS adjustment and high-dimensional PS (hdPS) adjustment, respectively. Results were similar in analyses limited to claims-based Medicaid /Medicare variables (risk difference = 8.2 for PS, 7.1 for hdPS). Instrumental-variable estimates were imprecise (risk difference = 8.8, 95% CI: −1.3, 19.0) because of the weak instrument. These results suggest that residual confounding has a relatively small impact on the effect estimate and that hdPS methods based on claims alone provide estimates at least as good as those from conventional analyses using claims enriched with clinical information. [ABSTRACT FROM AUTHOR]

Background: Nations are struggling to expand access to essential medications while curbing rising health and drug spending. While the US government's Medicare Part D drug insurance benefit expanded elderly citizens' access to drugs, it also includes a controversial period called the ''coverage gap'' during which beneficiaries are fully responsible for drug costs. We examined the impact of entering the coverage gap on drug discontinuation, switching to another drug for the same indication, and drug adherence. While increased discontinuation of and adherence to essential medications is a regrettable response, increased switching to less expensive but therapeutically interchangeable medications is a positive response to minimize costs. Methods and Findings: We followed 663,850 Medicare beneficiaries enrolled in Part D or retiree drug plans with prescription and health claims in 2006 and/or 2007 to determine who reached the gap spending threshold, n=217,131 (33%). In multivariate Cox proportional hazards models, we compared drug discontinuation and switching rates in selected drug classes after reaching the threshold between all 1,993 who had no financial assistance during the coverage gap (exposed) versus 9,965 multivariate propensity score-matched comparators with financial assistance (unexposed). Multivariate logistic regressions compared drug adherence (≤80% versus .80% of days covered). Beneficiaries reached the gap spending threshold on average 222 d ±79. At the drug level, exposed beneficiaries were twice as likely to discontinue (hazard ratio [HR] = 2.00, 95% confidence interval [CI] 1.64-2.43) but less likely to switch a drug (HR = 0.60, 0.46-0.78) after reaching the threshold. Gap-exposed beneficiaries were slightly more likely to have reduced adherence (OR = 1.07, 0.98-1.18). Conclusions: A lack of financial assistance after reaching the gap spending threshold was associated with a doubling in discontinuing essential medications but not switching drugs in 2006 and 2007. Blunt cost-containment features such as the coverage gap have an adverse impact on drug utilization that may conceivably affect health outcomes. [ABSTRACT FROM AUTHOR]

The article discusses a study which compared the risk of newly recorded diabetes mellitus (DM) among those diagnosed with rheumatoid arthritis (RA) or psoriasis based on use of disease-modifying antirheumatic drugs (DMARD). It notes that the study was conducted in the context of health insurance programs in Canada and in the U.S. The categories of drug regimens used in the study are tumor necrosis factor (TNF) inhibitors with or without DMARDs, methotrexate without TNF inhibitors, hydroxychloroquine without TNF inhibitors and nonbiologic DMARDs. Findings showed that the multivariate adjusted hazard ratios for DM were 0.62 for TNF inhibitors, 0.77 for methotrexate and 0.54 for hydroxychloroquine.

Background: Picking up prescriptions is an essential but previously unstudied component of adherence for patients who use retail pharmacies. Understanding the epidemiology and correlates of prescription abandonment may have an important effect on health care quality. Objective: To evaluate the rates and correlates of prescription abandonment. Design: Cross-sectional cohort study. Setting: One large retail pharmacy chain and one large pharmacy benefits manager (PBM) in the United States. Measurements: Prescriptions bottled at the retail pharmacy chain between 1 July 2008 and 30 September 2008 by patients insured by the PBM were identified. Pharmacy data were used to identify medications that were bottled and either dispensed or returned to stock (RTS) or abandoned. Data from the PBM were used to identify previous or subsequent dispensing at any pharmacy. The first (index) prescription in a class for each patient was assigned to 1 of 3 mutually exclusive outcomes: filled, RTS, or RTS with fill (in the 30 days after abandonment, the patient purchased a prescription for a medication in the same medication class at any pharmacy). Outcome rates were assessed by drug class, and generalized estimating equations were used to assess patient, neighborhood, insurance, and prescription characteristics associated with abandonment. Results: 10 349 139 index prescriptions were filled by 5 249 380 patients. Overall, 3.27% of index prescriptions were abandoned; 1.77% were RTS and 1.50% were RTS with fill. Patients were least likely to abandon opiate prescriptions. Prescriptions with copayments of $40 to $50 and prescriptions costing more than $50 were 3.40 times and 4.68 times more likely, respectively, to be abandoned than prescriptions with no copayment (P < 0.001 for both comparisons). New users of medications had a 2.74 times greater probability of abandonment than prevalent users (P < 0.001), and prescriptions delivered electronically were 1.64 times more likely to be abandoned than those that were not electronic (P < 0.001). Limitation: The study included mainly insured patients and analyzed data collected during the summer months only. Conclusion: Although prescription abandonment represents a small component of medication nonadherence, the correlates to abandonment highlight important opportunities to intervene and thereby improve medication taking. [ABSTRACT FROM AUTHOR]

The article presents a study on the risk of suicides and suicide attempts related to antidepressant medications. The study uses the population-based health care utilization data of all British Columbian residents 18 years and older between January 1, 1997 and December 31, 2005. The study found no variation in event rates between antidepressant agents, suggesting that the U.S. Food and Drug Administration's (FDA's) decision to treat all antidepressants equal in its advisory was appropriate.

The article presents a study comparing rural with urban Medicare beneficiaries in the U.S. in their willingness to undergo joint replacement surgery. It is stated that arthritis is the leading cause of disability in the U.S. but differences in cultures may affect healthcare utilization. It notes that the study used a Centers for Medicare and Medicaid Services file. It also mentions that the study found that rural Medicare beneficiaries are more likely to undergo surgery.

Background: Head lice are a common infection in school-age children worldwide. Several authorities in the US have recommended different treatments and school policies in order to control this disease. Recent concerns of emerging lice resistance worldwide raise the necessity to reassess the current recommendations. Objective: To perform a cost-effectiveness analysis (from the US caregiver perspective) of three head lice treatments commonly used in the US, permethrin 1%, malathion 0.5% and the lice comb, in order to evaluate the cost effectiveness of different treatments in the current era, and to explore the effect of different factors in this analysis. Methods: We used a decision-tree model to represent the costs and effectiveness of the different treatment strategies. A patient/caregiver perspective was applied, with a time horizon of 2 weeks. Probabilities of treatment success or failure of the three treatments were based on the literature. Effectiveness was measured as the successful eradication of head lice, and costs - including the costs of the treatment, the physician co-pay and the costs of days out of school - were calculated. One-way and multi-way analyses were performed using decision analysis software (Treeage Pro Healthcare 2008). Results: Combing was dominated by permethrin 1%. The incremental costeffectiveness ratio of malathion 0.5% versus permethrin 1% was $US161.75 per cure. For caregivers whose willingness to pay is <$US161.75 per cure, permethrin 1% is the most cost-effective option. For those with a willingness to pay of ≥$US161.75 per cure malathion 1% may offer the highest net monetary benefit. Twenty percent of the uncertainty in the model is due to variation in permethrin 1% resistance, and approximately 73% of the total variability of the model is attributed to the number of days the student has to be out of school because of the school's policy. Conclusions: Our study suggests that permethrin 1% was the most costeffective treatment for those with a willingness to pay of <$US162 per cure. Sensitivity of lice to permethrin and the specific school head lice policy had major effects on themodel. Thus, informing communities in a given geographical area about the degree of head lice resistance and sensitivity is necessary in order for the public to make a rational decision regarding treatment. Schools' head lice policies have a major effect on the cost of head lice treatments. [ABSTRACT FROM AUTHOR]

Background: Adjusting for large numbers of covariates ascertained from patients' health care claims data may improve control of confounding, as these variables may collectively be proxies for unobserved factors. Here, we develop and test an algorithm that empirically identifies candidate covariates, prioritizes covariates, and integrates them into a propensity-score-based confounder adjustment model.Methods: We developed a multistep algorithm to implement high-dimensional proxy adjustment in claims data. Steps include (1) identifying data dimensions, eg, diagnoses, procedures, and medications; (2) empirically identifying candidate covariates; (3) assessing recurrence of codes; (4) prioritizing covariates; (5) selecting covariates for adjustment; (6) estimating the exposure propensity score; and (7) estimating an outcome model. This algorithm was tested in Medicare claims data, including a study on the effect of Cox-2 inhibitors on reduced gastric toxicity compared with nonselective nonsteroidal anti-inflammatory drugs (NSAIDs).Results: In a population of 49,653 new users of Cox-2 inhibitors or nonselective NSAIDs, a crude relative risk (RR) for upper GI toxicity (RR = 1.09 [95% confidence interval = 0.91-1.30]) was initially observed. Adjusting for 15 predefined covariates resulted in a possible gastroprotective effect (0.94 [0.78-1.12]). A gastroprotective effect became stronger when adjusting for an additional 500 algorithm-derived covariates (0.88 [0.73-1.06]). Results of a study on the effect of statin on reduced mortality were similar. Using the algorithm adjustment confirmed a null finding between influenza vaccination and hip fracture (1.02 [0.85-1.21]).Conclusions: In typical pharmacoepidemiologic studies, the proposed high-dimensional propensity score resulted in improved effect estimates compared with adjustment limited to predefined covariates, when benchmarked against results expected from randomized trials. [ABSTRACT FROM AUTHOR]

This study evaluates the effect of Medicare Part D among seniors who previously lacked drug coverage, using time-trend analyses of patient-level dispensing data from three pharmacy chains. Of 114,766 seniors without drug benefits, 55 percent initiated drug insurance under Part D. After the penalty-free Part D enrollment period, use of statins, clopidogrel, and proton pump inhibitors stabilized at levels ranging from 11 percent to 37 percent above the trend that would have been expected if Part D had not been implemented. Patients reaching the Part D coverage gap (12 percent) experienced a decrease in essential medication use ranging from 5.7 percentage points per month for warfarin to 6.3 percentage points for statins. [ABSTRACT FROM AUTHOR]

OBJECTIVES: To evaluate medication use, out-of-pocket spending, and medication switching during the transition period for patients dually eligible for Medicaid and Medicare (dual eligibles). DESIGN: Time-trend analysis, using segmented linear regression. SETTING: Patient-level pharmacy dispensing data from January 2005 to December 2006 from a large pharmacy chain with stores in 34 states. PARTICIPANTS: Dual eligibles aged 65 and older. MEASUREMENTS: Changes in utilization, patient copayments, and medication switching were analyzed using interrupted time trend analyses. Utilization and spending were evaluated for five study drugs: clopidogrel, proton pump inhibitors (PPIs), warfarin, and statins (essential drugs covered by Part D plans) and benzodiazepines (not covered through Part D but potentially covered through Medicaid). RESULTS: Drug use for 13,032 dual eligibles was evaluated. There was no significant effect of the transition to Medicare Part D on use of all study drugs, including the uncovered benzodiazepines. Cumulative reductions were seen in copayments for all covered drugs after implementation of Part D, ranging from 25% annually for PPIs to 53% for warfarin, but there was a larger increase in copayments, 91% annually, for benzodiazepines after the transition. The rate of switching medications was 3.0 times as great for the PPIs after implementation of Part D than before implementation, but there was no significant change in the other study drug classes. CONCLUSION: These findings in a single, large pharmacy chain indicate that the transition plan for dual eligibles led to less medication discontinuation and switching than many had expected. The substantially greater cost sharing for benzodiazepines highlights the importance of implementing a thoughtful transition plan when executing such a national policy. [ABSTRACT FROM AUTHOR]

Background: The government is prohibited from directly negotiating drug prices for Medicare Part D, resulting in substantial policy debate. However, the government has an established mechanism for setting prices with pharmaceutical manufacturers for certain other federal programs--the Federal Supply Schedule (FSS).Objective: To estimate how much could be saved nationwide if prices equivalent to the 2006 FSS were achieved for the top 200 drug formulations dispensed to seniors.Design/setting: Cross-sectional analysis of drug utilization patterns and costs from the nationally representative Medical Expenditure Panel Surveys (MEPS), 2003-2004, and the 2006 FSS.Participants: Seniors who filled a prescription for any of these common drugs (n = 6,135 individuals).Measures: Prescription expenditures were obtained from MEPS, and a price/unit was calculated in 2006 dollars. This price/unit was compared to the 2006 FSS, and a savings/unit was calculated and summed across the observed units dispensed in MEPS.Results: The potential annual savings with FSS prices would be $21.9 billion [95% confidence interval (CI), $21.1 billion to $22.8 billion]. If FSS prices were substituted for only the top ten drugs, the annual savings would be $5.9 billion (95% CI, $5.7 billion, $6.1 billion).Conclusions: Extension of existing price setting mechanisms to Medicare could save tens of billions of dollars if prices similar to those already achieved by other federal programs could be reached. Whether or not this is a political or economic possibility, the magnitude of these savings cannot be ignored. [ABSTRACT FROM AUTHOR]

Physicians and insurers need to weigh the effectiveness of new drugs against existing therapeutics in routine care to make decisions about treatment and formularies. Because Food and Drug Administration (FDA) approval of most new drugs requires demonstrating efficacy and safety against placebo, there is limited interest by manufacturers in conducting such head-to-head trials. Comparative effectiveness research seeks to provide head-to-head comparisons of treatment outcomes in routine care. Health-care utilization databases record drug use and selected health outcomes for large populations in a timely way and reflect routine care, and therefore may be the preferred data source for comparative effectiveness research. Confounding caused by selective prescribing based on indication, severity, and prognosis threatens the validity of non-randomized database studies that often have limited details on clinical information. Several recent developments may bring the field closer to acceptable validity, including approaches that exploit the concepts of proxy variables using high-dimensional propensity scores, within-patient variation of drug exposure using crossover designs, and between-provider variation in prescribing preference using instrumental variable (IV) analyses.Clinical Pharmacology & Therapeutics (2007) 82, 143–156. doi:10.1038/sj.clpt.6100249; published online 6 June 2007 [ABSTRACT FROM AUTHOR]

Objective: The performance of standard comorbidity scores to control confounding is poorly defined in health care utilization data across elderly populations. We sought to evaluate and rank the performance of comorbidity scores across selected U.S. and Canadian elderly populations using health care utilization databases.Design: Cross-population validation study.Participants: Study participants were residents age 65 years or older who had prescription drug coverage through state-funded programs selected from several large health care utilization databases available to the investigators: British Columbia, BC (N = 141,161), New Jersey, NJ (N = 235,881), and Pennsylvania, PA (N = 230,913).Measurements: We calculated 6 commonly used comorbidity scores for all subjects during the baseline year (1994 for NJ and PA, and 1995 for BC). These included scores based on diagnoses (Romano, Deyo, D'Hoore, Ghali) and prescription drugs (CDS-1, CDS-2). The study outcome was 1-year mortality. The performance of scores was measured by c-statistics derived from multivariate logistic regression that included age and gender.Main Results: Across these 4 large elderly populations, we found the same rank order of performance in predicting 1-year mortality after including age and gender in each model: Romano (c-statistic 0.754 to 0.771), Deyo (c-statistic 0.753 to 0.768), D'Hoore (c-statistic 0.745 to 0.760), Ghali (c-statistic 0.733 to 0.745), CDS-1 (c-statistic 0.689 to 0.738), CDS-2 (c-statistic 0.677 to 0.718), and age and gender alone (c-statistic 0.664 to 0.681). Performance was improved by an average of 6% by adding the number of different prescription drugs received during the past year.Conclusions: Performance ranking of 6 frequently used comorbidity scores was consistent across selected elderly populations. We recommend that investigators use these performance data as one important factor when selecting a comorbidity score for epidemiologic analyses of health care utilization data. [ABSTRACT FROM AUTHOR]

The performance of standard comorbidity scores to control confounding is poorly defined in health care utilization data across elderly populations. We sought to evaluate and rank the performance of comorbidity scores across selected U.S. and Canadian elderly populations using health care utilization databases. Cross-population validation study. Study participants were residents age 65 years or older who had prescription drug coverage through state-funded programs selected from several large health care utilization databases available to the investigators: British Columbia, BC ( N = 141,161), New Jersey, NJ ( N = 235,881), and Pennsylvania, PA ( N = 230,913). We calculated 6 commonly used comorbidity scores for all subjects during the baseline year (1994 for NJ and PA, and 1995 for BC). These included scores based on diagnoses (Romano, Deyo, D’Hoore, Ghali) and prescription drugs (CDS-1, CDS-2). The study outcome was 1-year mortality. The performance of scores was measured by c-statistics derived from multivariate logistic regression that included age and gender. Across these 4 large elderly populations, we found the same rank order of performance in predicting 1-year mortality after including age and gender in each model: Romano (c-statistic 0.754 to 0.771), Deyo (c-statistic 0.753 to 0.768), D’Hoore (c-statistic 0.745 to 0.760), Ghali (c-statistic 0.733 to 0.745), CDS-1 (c-statistic 0.689 to 0.738), CDS-2 (c-statistic 0.677 to 0.718), and age and gender alone (c-statistic 0.664 to 0.681). Performance was improved by an average of 6% by adding the number of different prescription drugs received during the past year. Performance ranking of 6 frequently used comorbidity scores was consistent across selected elderly populations. We recommend that investigators use these performance data as one important factor when selecting a comorbidity score for epidemiologic analyses of health care utilization data. J GEN INTERN MED 2004;19:444– 450. [ABSTRACT FROM AUTHOR]

Objective. To define and improve the performance of existing comorbidity scores in predicting mortality in Medicare enrollees. Data Sources. Study participants were two Medicare populations who had complete drug coverage either through Medicaid or a statewide pharmacy assistance program: New Jersey Medicare enrollees (N[sub NJ]=235,881) and Pennsylvania Medicare enrollees (N[sub PA]=230,913). Study Design. Frequently used comorbidity scores were computed for all subjects during the baseline year (January 1, 1994, to December 31, 1994, and one year later in Pennsylvania). The study outcome was one-year mortality during the following year. Performance of scores was measured with the c-statistic derived from multivariate logistic regression models. Empirical weights were derived in the New Jersey population and the performance of scores with new weights was validated in the Pennsylvania population. Principal Findings. A score based on ICD-9-diagnoses (Romano) performed 60 percent better than one based on patterns of medication use (Chronic Disease Score, or CDS-1) (c=0.771 vs. c=0.703). The performance of the Romano score was further improved slightly by inclusion of the number of different prescription drugs used during the past year. Modeling the 17 conditions included in the Romano score as separate binary indicators increased its performance by 8 percent (c=0.781). We derived elderly-specific weights for these scores in the New Jersey sample, including negative weights for the use of some drugs, for example, lipid lowering drugs. Applying these weights, the performance of Romano and CDS-1 scores improved in an independent validation sample of Pennsylvania Medicare enrollees by 8.3 percent and 43 percent compared to the scores with the original weights. When we added an indicator of nursing home residency, age, and gender, the Romano score reached a performance of c=0.80. Conclusions. We conclude that in epidemiologic studies of the elderly, a modified diagnosis-based score using empirically derived weights provides improved adjustment for comorbidity and enhances the validity of findings. [ABSTRACT FROM AUTHOR]

The article presents information on a study, which examined differences among obstetricians, family physicians and certified nurse-midwives in the patterns of obstetric care provided to low-risk patients in the United States. Obstetric care is one of the most important health services in the United States; accounting for over 10% of hospital discharges. Despite the large number of babies delivered annually, substantial controversy exists over what constitutes optimal management of pregnancy. This controversy applies not only to the management of major complications that arise in pregnancy, but also to how to care for the healthy woman with a low-risk pregnancy. The results suggest that certified nurse-midwives in urban Washington State have a different approach to intrapartum care than their physician colleagues. Certified nurse-midwives were much less likely to use a variety of technological tools to monitor or modify the course of labor, Patients of certified nurse-midwives were less likely to be continuously electronically monitored during labor, to receive oxytocin to induce or augment labor, or to be given epidural anesthesia.

A reprint of the article "Managing Drug-Risk Information: What to Do With All Those New Numbers," by Jerry Avorn and Sebastian Schneeweiss, which appeared in the July 27, 2009 issue of the "New England Journal of Medicine" is presented. The authors discusses the decision of the U.S. Food and Drug Administration (FDA) to rely on individual case report analysis submitted by pharmaceutical companies and health care professionals. They say that this thing continues despite the improved availability of information on clinical outcomes and medication use.

Background: Breast cancer treatment has changed tremendously over the last decades. In addition, the use of mammography screening for early detection has increased strongly. To evaluate the impact of these developments, long-term trends in incidence, mortality, stage distribution and survival were investigated for Germany and the United States (US). Methods: Using population-based cancer registry data, long-term incidence and mortality trends (1975–2015), shifts in stage distributions (1998–2015), and trends in five-year relative survival (1979–2015) were estimated. Additionally, trends in five-year relative survival after standardization for stage were explored (2004–2015). Results: Age-standardized breast cancer incidence rates were much higher in the US than in Germany in all periods, whereas age-standardized mortality began to lower in the US from the 1990s on. The largest and increasing differences were observed for patients aged 70+ years with a 19% lower incidence but 45% higher mortality in Germany in 2015. For this age group, large differences in stage distributions were observed, with 29% (Germany) compared to 15% (US) stage III and IV patients. Age-standardized five-year relative survival increased strongly between 1979–1983 and 2013–2015 in Germany (+17% units) and the US (+19% units) but was 9% units lower in German patients aged 70+ years in 2013–2015. This difference was entirely explained by differences in stage distributions. Conclusions: Overall, our results are in line with a later uptake and less extensive utilization of mammography screening in Germany. Further studies and efforts are highly needed to further explore and overcome the increased breast cancer mortality among elderly women in Germany. [ABSTRACT FROM AUTHOR]

The article focuses on the challenges faced by the current health care system of the U. S. in the treatment of the growing number of elderly patients with severe mental illness (SMI). SMI patients include those with schizophrenia, other psychotic-spectrum disorders, bipolar disorder and treatment-refractory severe depression. According to Stephen J. Bartels, M. D., M. S., there are two main challenges: One is providing rehabilitation and associated skills that will enhance their ability to live in the community and improve their health behaviors and the other is to address the high rates of medical comorbidity, which appears to be associated with poor health care habits and poor health care.

Medication synchronization programs based in pharmacies simplify the refill process by enabling patients to pick up all of their medications on a single visit. This can be especially important for improving medication adherence in patients with complex chronic diseases. We evaluated the impact of two synchronization programs on adherence, cardiovascular events, and resource use among Medicare beneficiaries treated between 2011 and 2014 for two or more chronic conditions--at least one of which was hypertension, hyperlipidemia, or diabetes. Among nearly 23,000 patients matched by propensity score, the mean proportion of days covered (a measure of medication adherence) for the control group of patients without a synchronization program was 0.84 compared to 0.87 for synchronized patients--a gain of 3 percentage points. Adherence improvement in synchronized versus control patients was three times greater in patients with low baseline adherence, compared to those with higher baseline adherence. Rates of hospitalization and emergency department visits and rates of outpatient visits were 9 percent and 3 percent lower in the synchronized group compared to the control group, respectively, while cardiovascular event rates were similar. Synchronization programs were associated with improved adherence for patients with cardiovascular disease, especially those with low baseline adherence. [ABSTRACT FROM AUTHOR]

Background: Over the past five years, selective cyclooxygenase-2 inhibitors (coxibs) have accounted for a growing proportion of prescriptions for nonsteroidal antiinflammatory drugs (NSAIDs). To control these expenses, many state Medicaid programs have implemented prior-authorization requirements before coxibs can be prescribed. We evaluated the effect of such programs on the use of coxibs by Medicaid beneficiaries. Methods: We surveyed state Medicaid agencies to determine whether prescription of coxibs required prior authorization and, if so, the criteria for authorization. For each program, we compared these criteria with evidence-based recommendations for prescribing of coxibs. Using data for all filled prescriptions in 50 state Medicaid programs from 1999 through the end of 2003, we calculated the proportion of defined daily doses of NSAIDs accounted for by coxibs. Time-series analyses were used to measure the changes in prescription patterns after the implementation of each prior-authorization program. Results: By 2001, coxibs accounted for half of all NSAID doses covered by Medicaid. This proportion varied widely according to the state in 2003, from a low of 11 percent to a high of 70 percent of all NSAID doses. Twenty-two states implemented prior-authorization programs for coxibs during the study period. Overall, the implementation of such programs reduced the proportion of NSAID doses made up by coxibs by 15.0 percent (95 percent confidence interval, 10.9 to 19.2 percent), corresponding to a decrease of $10.28 (95 percent confidence interval, $7.56 to $13.00) in spending per NSAID prescription. The effect of such programs was not influenced by the degree to which a prior-authorization program incorporated evidence-based prescribing recommendations. Conclusions: The use of coxibs and spending on NSAIDs varies widely by state and declined substantially after the implementation of prior-authorization programs. Determining whether these reductions are clinically appropriate will have important implications for the development of rational drug-reimbursement policies. N Engl J Med 2004;351:2187-94. [ABSTRACT FROM AUTHOR]

Background: The EMPA-REG OUTCOME trial (Empagliflozin Cardiovascular Outcome Event Trial in Type 2 diabetes Mellitus Patients) showed that empagliflozin, a sodium-glucose cotransporter-2 inhibitor, reduces the risk of hospitalization for heart failure (HHF) by 35%, on top of standard of care in patients with type 2 diabetes mellitus (T2D) and established cardiovascular disease. The EMPRISE (Empagliflozin Comparative Effectiveness and Safety) study aims to assess empagliflozin's effectiveness, safety, and healthcare utilization in routine care from August 2014 through September 2019. In this first interim analysis, we investigated the risk of HHF among T2D patients initiating empagliflozin versus sitagliptin, a dipeptidyl peptidase-4 inhibitor.Methods: Within 2 commercial and 1 federal (Medicare) claims data sources in the United States, we identified a 1:1 propensity score-matched cohort of T2D patients ≥18 years old initiating empagliflozin or sitagliptin from August 2014 through September 2016. The HHF outcome was defined as a HF discharge diagnosis in the primary position (HHF-specific); a broader definition was based on a HF discharge diagnosis in any position (HHF-broad). Hazard ratios (HRs) and 95% CIs were estimated controlling for over 140 baseline characteristics in each data source and pooled by fixed-effects meta-analysis.Results: After propensity-score matching, we identified 16,443 patient pairs who initiated empagliflozin or sitagliptin. Average age was approximately 59 years, almost 54% of the participants were males, and approximately 25% had records of existing cardiovascular disease. Compared with sitagliptin, the initiation of empagliflozin decreased the risk of HHF-specific by 50% (HR, 0.50; 95% CI, 0.28-0.91), and the risk of HHF-broad by 49% (HR, 0.51;95% CI, 0.39-0.68), over a mean follow-up of 5.3 months. The results were consistent in patients with and without baseline cardiovascular disease, and for empagliflozin at both the 10- and 25-mg daily doses; analyses comparing empagliflozin versus the dipeptidyl peptidase-4 inhibitor class, and comparing sodium-glucose cotransporter-2 inhibitor versus dipeptidyl peptidase-4 inhibitor classes also produced consistent findings.Conclusions: The first interim analysis from EMPRISE showed that compared with sitagliptin, the initiation of empagliflozin was associated with a decreased risk of HHF among patients with T2D as treated in routine care, with and without a history of cardiovascular disease.Clinical Trial Registration: URL: https://www.clinicaltrials.gov . Unique identifier: NCT03363464. [ABSTRACT FROM AUTHOR]