Three Essays on Potentially Inappropriate Antidepressant Use among Older Adults in Office-based Outpatient Settings

University of Minnesota Ph.D. dissertation. April 2017. Major: Social and Administrative Pharmacy. Advisor: Jon Schommer. 1 computer file (PDF); viii, 149 pages.The use of antidepressants has recently increased over time in older adults aged 65 and over. While potentially inappropriate antidepressants (PIAs) are medications that should be avoided as they carry greater risks of harm than potential benefits, relatively little is known about the patterns of PIA use among older adults. Furthermore, no study has yet assessed the impact of the recent policy initiative of depression screening on the PIA use. This dissertation project addresses these literature gaps, and aims at promoting clinical and policy efforts to improve patient safety in older adults prescribed antidepressants in their ambulatory care visits

Imaginary Worlds: The Status of Modeled Quality Adjusted Life Year Claims for New Oral Anticoagulants in Atrial Fibrillation Published Between January 2012 and February 2016

The purpose of this commentary is to evaluate modeled quality adjusted life year claims (QALYs) for new oral anticoagulants (NOACs) published in the period from January 2012 to February 2016. The focus of this commentary is to assess whether or not the modeled claims meet the standards of normal science in supporting falsification and replication. A systematic and consensus review by the authors identified a total of 23 cost-utility NOACs evaluations along with four single technology appraisals undertaken by the National Institute for Health and Care Excellence (NICE) in the UK. Each study was evaluated in terms of four criteria: (i) did the study generate evaluable claims (ii) id the authors attempt to generate evaluable claims (iii) did the authors suggest how the claims might be evaluated and (iv) did the authors caution readers as to the implications of generating non-evaluable projections or claims for credibility in health system decision making? None of the 23 studies assessed or the four NICE single technology appraisals met any of the four assessment criteria. None of the studies presented projections or claims in a form suitable for empirical evaluation. None could support falsification or replication. They failed the standards associated with the scientific method. Failure to meet the standards of normal science meant that the studies, from a formulary assessment perspective, are not credible. The claims made were either impossible to verify, or if potentially verifiable, were not presented in a testable form. There was no basis for assessing whether the claims were right or even if they were wrong. This lack of scientific credibility is a major concern. In particular, the choice of a lifetime cost-utility framework for assessing the NOACs against warfarin and against each other effectively precludes any experimental assessment. If medical economics is to advance through the formulation and testing of hypotheses, then editors of journals should consider whether or not to set standards for the acceptance of publications to include the requirement for testable claims and the results of claims assessment. If this is not acceptable, then it should be made clear that published modeled claims and simulations are simply imaginary worlds or thought experiments. Editors cannot sit back and assume that at some time in the future non-testable projections will possibly be evaluated. Conflict of Interest None   Type: Commentar

Imaginary Worlds: The Status of Simulation Modeling in Claims for Cost-Effectiveness In Diabetes Mellitus

Over the past 20 years a number of simulations or models have been developed as a basis for tracking and evaluating the impact of pharmacological and other interventions in type 1 and type 2 diabetes mellitus. These models have typically tracked the natural course of these diseases generating long-term composite claims for cost-effectiveness. These claims can extend over the lifetime of the modeled patient cohort. Set against the standards of normal science, however, these claims lack credibility. The claims presented are all too often either immune to failure or are presented in a form that is non-testable. As such they fail to meet the key experimental requirements of falsification and replication. Unfortunately, there is a continuing belief that long-term or lifetime models are essential to decision-making. This is misplaced. The purpose of this review is to argue that there is a pressing need to reconsider the needs of health system decision makers and focus on modeled or simulated claims that are meaningful, testable, reportable and replicable in evaluating interventions in diabetes mellitus.   Type: Commentar

More Imaginary Worlds: A Systematic Review of the Status of Modeled Cost-Effectiveness Claims Published in the Journal of Medical Economics from January 2016 to December 2016

In 2016 a review of modeled cost-effectiveness studies published in the Journal of Medical Economics between January 2015 and December 2015 was presented in INNOVATIONS in Pharmacy. The purpose of this review, together with similar reviews for studies published in calendar 2015 in Value in Health and Pharmacoeconomics, was to consider whether these modeled claims for cost-effectiveness met the standards of normal science: were the claims made credible, evaluable and replicable? A total of 32 studies were identified. None of the studies presented their claims or projections in an evaluable form and none suggested how they might be evaluated. None met the standards of normal science. The claims made for cost-effectiveness were either impossible to verify, or if potentially verifiable, were not presented in an evaluable form. The studies lacked credibility. There was no basis for assessing whether the claims were right or even if they were wrong. The purpose of the present review which covers cost-effectiveness studies published in the Journal of Medical Economics between January 2016 and December 2016 is to revisit this question of the credibility of the claims made against the standards of normal science. A total of 40 cost-effectiveness studies were identified. Although 14 had a timeframe of 5 years or less and hand the potential to provide short-term evaluable claims, none addressed the issue of claims evaluation and the possible protocols that would support empirical assessment. Of the balance, 19 presented results as unevaluable lifetime modeled claims. The conclusions from the 2016 review remain unchanged.   Type: Commentar

Imaginary Worlds: A Systematic Review of the Status of Modeled Cost-Effectiveness Claims Published in the Journal of Medical Economics from January 2015 to December 2015

The purpose of this review is to evaluate the credibility of modeled claims for cost-effectiveness studies published in the Journal of Medical Economics (JME) in the period January 2015 to December 2015. Credibility is assessed in terms of the standards of normal science. Are the claims made capable of falsification and replication? Following the PRISMA-P recommendations, abstracts of all papers published in the JME were evaluated by both authors independently against a MeSH terms checklist: cost, cost-effectiveness, cost-utility, outcomes, QALY and Markov. A total of 32 studies were identified. A systematic review of each study was then evaluated. The consensus was that all studies be included in the review. Each study was judged against four criteria: (i) Is the model capable of generating evaluable claims? (ii) did the author(s) attempt to generate evaluable claims? (iii) did the author(s) suggested how the claims might be evaluated? and (iv) did the author(s) caution readers as to the implications of generating non-evaluable clams for the credibility of the analysis? None of the studies presented their claims or projections in an evaluable form and none suggested how they might be evaluated. None met the standards of normal science. The claims made for cost-effectiveness were either impossible to verify, or if potentially verifiable, were not presented in an evaluable form. The studies lacked credibility. There was no basis for assessing whether the claims were right or even if they were wrong. The JME is not alone. As part of an ongoing systematic review program, covering the leading journals and focusing on chronic condition areas, it is clear that the majority of cost-effectiveness papers also fail the test of credibility. Of course, it might be that the consensus opinion among practitioners is that non-evaluable projections are acceptable. Evidence is not discovered, but is constructed through models and simulations. This lack of scientific credibility is a major concern. If medical economics is to advance through the formulation and testing of hypotheses, then editors of journals should consider whether or not to set standards for the acceptance of publications to include the requirement for evaluable claims and the results of claims assessment. If this is not acceptable, then it should be made clear that published papers are simply imaginary worlds or thought experiments.   Type: Commentar

Imaginary Worlds: The Status of Modeled Economic Evaluation Claims Published in Value in Health January 2015 to December 2015

The purpose of this paper is to assess the extent to which modeled or simulated cost-effectiveness claims published in Value in Health in 2015 meet the standards of normal science. To meet these standards, modeled or simulated claims must be credible. They must be capable of empirical evaluation and replication. If these standards are not met then such claims run the risk of being labeled as pseudoscience. Following a systematic review of all publications in Value in Health, 16 papers were identified. Of these 14 presented a cost-per-QALY analysis, with 9 presenting their claims for comparative effectiveness in a lifetime cost-per-QALY framework. With the focus of the assessment on whether or not these studies generated testable claims, none of the studies met this standard. They were best seen as thought experiments or imaginary worlds. Recipients of such claims can of course, on the one hand, reject them outright as not meeting accepted standards in normal science. After all, QALYs are never collected by health care systems and are unlikely to be collected. This means that the outcome metrics are untestable and may never have been intended to be tested. On the other hand, if the recipient believes that the model or simulation provides a sufficient correspondence to reality then the claims made are necessarily entailed. The issue of testing is irrelevant to the belief in the credibility of the claims. The modeled or simulated claims are immune to failure. The review concluded that none of the claims presented were in a testable form and that while 7 (at most) of the studies had the potential to generate testable claims, the rest were immune to failure. In the absence of testable claims, the studies reviewed are most appropriately characterized as imaginary worlds or thought experiments.   Type: Commentar

The Imaginary Worlds of ISPOR: Modeled Cost-Effectiveness Claims Published in Value in Health from January 2016 to December 2016

In 2016, a review of modeled cost-effectiveness studies published in Value in Health between January 2015 and December 2015 was presented. The purpose of the review was to consider whether these modeled claims for cost-effectiveness met the standards of normal science: were the claims made credible, evaluable and replicable? The review concluded that none of the 16 studies assessed met this standard. They should be seen as thought experiments; the construction of imaginary worlds which should be categorized as pseudoscience. The reader, or health care decision maker, would have had no idea, and would never know, whether the claims were right, wrong or misleading. Similar reviews were undertaken in Pharmacoeconomics and the Journal of Medical Economics and came to the same conclusion. The purpose of this second review is to consider the modeled claims published in Value in Health between January 2016 and December 2016, applying the same criteria. Unfortunately, for those who subscribe to the standards of normal science, we must come to the same conclusion. Of the 13 economic evaluations reviewed, 12 simulated claims that were immune to failure. The model structures ensured that the claims were neither evaluable nor replicable. They were categorized as pseudoscience; they failed to meet the standards of normal science. Five of these studies were supported by manufacturers and all supported the manufacturer’s product. Three systematic reviews were also evaluated. Once again, there was a failure to consider meeting the standards of normal science in presenting modeled claims for cost-effectiveness.   Type: Commentar

Comparison of industry payments to psychiatrists and psychiatric advanced practice clinicians in the USA, 2021: A cross-sectional study

Objectives: To compare industry payment patterns among US psychiatrists and psychiatric advanced practice clinicians (APCs) and determine how scope of practice laws has influenced these patterns. Design: Cross-sectional study. Setting: This study used the publicly available US Centers for Medicare and Medicaid Services Sunshine Act Open Payment database and the National Plan and Provider Enumeration System (NPPES) database for the year 2021. Participants: All psychiatrists and psychiatric APCs (subdivided into nurse practitioners (NPs) and clinical nurse specialists (CNSs)) included in either database. Primary and secondary outcome measures: Number and percentage of clinicians receiving industry payments and value of payments received. Total payments and number of transactions by type of payment, payment source and clinician type were also evaluated. Results: A total of 85 053 psychiatric clinicians (61 011 psychiatrists (71.7%), 21 895 NPs (25.7%), 2147 CNSs (2.5%)) were reviewed; 16 240 (26.6%) psychiatrists received non-research payment from industry, compared with 10 802 (49.3%) NPs and 231 (10.7%) CNSs (p United States Dollars (US) $) 100 (33.9$ 1000 (5.3% vs 4.1%; IRR, 1.29 (1.20 to 1.38); p US$ 10 000 (0.4% vs 1.0%; IRR, 0.39 (0.31 to 0.49); p Conclusions: Psychiatric NPs were nearly two times as likely to receive industry payments as psychiatrists, while psychiatric CNSs were less than half as likely to receive payment. Stricter scope of practice laws increases the likelihood of psychiatric NPs receiving payment, the opposite of what was found in a recent specialty agnostic study.</p

Longitudinal Patterns of Strengths Among Youth with Psychiatric Disorders: A Latent Profile Transition Analysis

A better understanding of variability in the strengths of youth with psychiatric disorders is critical as a strength-based approach can lead to recovery. This study aimed to identify subgroups of strengths among youth with mental disorders and determine whether subgroups changes were associated with mental health recovery. Youth with mental disorders (N = 2228) from a statewide database were identified in the state fiscal year of 2019. Using the latent profile analysis and latent transition analysis, we identified three strength profiles (i.e., essential, usable, and buildable). Over 90% of youth sustained or developed strengths over time. Positive transitions were associated with mental health recovery, symptom reduction, and personal recovery. Buildable strengths supported youth’s personal recovery independent of improving mental health needs. The findings suggest that subgroups of strengths may be a promising source for planning and tracking youth’s progress and guiding clinicians to more efficiently allocate community-based resources

Mid-life Leukocyte Telomere Length and Dementia Risk: An Observational and Mendelian Randomization Study of 435,046 UK Biobank Participants

Telomere attrition is one of biological aging hallmarks and may be intervened to target multiple aging-related diseases, including Alzheimer\u27s disease and Alzheimer\u27s disease related dementias (AD/ADRD). The objective of this study was to assess associations of leukocyte telomere length (TL) with AD/ADRD and early markers of AD/ADRD, including cognitive performance and brain magnetic resonance imaging (MRI) phenotypes. Data from European-ancestry participants in the UK Biobank (n = 435,046) were used to evaluate whether mid-life leukocyte TL is associated with incident AD/ADRD over a mean follow-up of 12.2 years. In a subsample without AD/ADRD and with brain imaging data (n = 43,390), we associated TL with brain MRI phenotypes related to AD or vascular dementia pathology. Longer TL was associated with a lower risk of incident AD/ADRD (adjusted Hazard Ratio [aHR] per SD = 0.93, 95% CI 0.90–0.96, p = 3.37 × 10−7). Longer TL also was associated with better cognitive performance in specific cognitive domains, larger hippocampus volume, lower total volume of white matter hyperintensities, and higher fractional anisotropy and lower mean diffusivity in the fornix. In conclusion, longer TL is inversely associated with AD/ADRD, cognitive impairment, and brain structural lesions toward the development of AD/ADRD. However, the relationships between genetically determined TL and the outcomes above were not statistically significant based on the results from Mendelian randomization analysis results. Our findings add to the literature of prioritizing risk for AD/ADRD. The causality needs to be ascertained in mechanistic studies