Required elements for an educational programme for lay exercise instructors in charge of community-based exercise targeting young adults with schizophrenia spectrum disorders - A stakeholder focus group study.

BACKGROUND: Exercise plays a crucial role in addressing the increased cardiometabolic morbidity and premature mortality in people with schizophrenia spectrum disorders. When delivered in community-based settings, exercise may also reduce loneliness, while promoting overall physical activity behaviours. Skilled instructors are essential to deliver effective community-based exercise; however, knowledge about their roles and required training is lacking. We aim to explore various stakeholders' perspectives regarding lay exercise instructors' roles, and the required elements in an educational programme supporting the delivery of community-based exercise for young adults with SSD. METHODS: We used semi-structured homogeneous focus groups with representatives from different stakeholder groups (i.e., including representatives of clinical staff within mental health, physiotherapists, exercise instructors, young adults with schizophrenia spectrum disorders, and relatives of individuals with schizophrenia spectrum disorders) targeted or affected by a community-based exercise intervention. Data were analysed using qualitative content analysis. RESULTS: We conducted six focus groups comprising a total of 30 individuals representing five different stakeholder groups The analysis identified three categories: (i) awareness and understanding of mental illness, i.e., providing basic knowledge to dispel common myths and stigma regarding mental illness (ii) protecting youth identity, i.e., supporting the feeling of being more than just a patient, and (iii) promoting exercise as a shared activity, i.e., a communal pursuit, fostering personal growth among participants, their peers and the instructors. CONCLUSIONS: An educational programme for lay exercise instructors delivering community-based exercise targeting young adults with SSD should empower the instructors to assume the role of guardians of an inclusive exercise culture. Educational elements identified were adapted and integrated into an educational programme implemented and evaluated as a part of the Vega trial. Our results may be transferable to the education of lay workers in mental health care where the aim is to facilitate sustainable, recreational, community-based activities.

Unravelling pituitary tumours in medically treated patients with acromegaly: the impact of systematic MRI reassessment.

BACKGROUND: In acromegaly, the primary tumor is usually found during magnetic resonance imaging (MRI) of the pituitary gland. A remnant tumor after surgery is, however, harder to depict. When a tumor is missed, the remaining option is usually lifelong pharmacological treatment. PURPOSE: To identify tumors by reassessment of all available MRI scans in pharmacologically treated patients, operated or not, and to compare our results with the routine MRI reports. MATERIAL AND METHODS: Adult patients diagnosed with acromegaly and managed at a tertiary care center between 2005 and 2021 and currently on pharmacological treatment were included. MRI scans were evaluated in a standardized manner and classified independently by a radiologist and an endocrinologist into "certain," "suspected," or "no tumor." In case of disagreement, consensus was achieved with a senior neuroradiologist. The results were compared using the clinical radiologists' routine MRI reports. RESULTS: We identified certain and suspected tumors in 29/74 and 36/74 patients, respectively. No tumor was identified in nine patients. In five of these, no MRI contrast agent was given. Discrepancy between our results and the routine MRI reports was found in 31/74 patients (P = 0.01). In 22 patients, the routine reports described no tumor while we identified certain tumors in 2/22 patients and suspected tumors in 13/22 patients. CONCLUSION: In most patients with pharmacologically treated acromegaly, we identified a certain or suspected pituitary tumor. These findings were more frequent compared to the routine MRI reports. Based on our results, patients will be considered for a change in long-term treatment modality.

Mental health promotion and the positive concept of health: Navigating dilemmas.

A prevailing view holds that the main goal of mental health promotion is to maintain and improve positive mental health, which is not merely defined by the absence of mental disorders, but by the presence of certain abilities. There are, however, challenges associated with this view that this paper aims to identify and explore. We start by highlighting three requirements for an ethically and politically justified mental health promotion scheme: (i) using a positive concept of mental health that (ii) respects the neutrality principle while (iii) not being overly permissive. Then, we argue that the WHO's positive concept of health violates (ii), and continue by exploring three philosophical accounts (i.e., Nordenfelt, 1995, 2017; Graham 2010; Wren-Lewis & Alexandrova, 2021) that could potentially provide a solution. We show that these face a dilemma of their own: they either violate (ii) or (iii), and they can rectify one issue only by violating the other. Considering the problems linked to the positive notion of health, the final section explores the alternate route of rejecting proposition (i) and instead embracing a negative concept of health. We argue that this option does not present a more advantageous solution. We conclude by highlighting the necessity for additional research to tackle the challenges we identified.

Absolute risk estimation of new-onset proteinuria in patients with systemic lupus erythematosus: a Danish nationwide cohort study.

OBJECTIVES: Kidney involvement and medical compliance are frequent challenges in systemic lupus erythematosus (SLE). Additional data reporting such as absolute risk estimates may strengthen risk stratification and compliance. This study provides absolute risk estimations of risk of new-onset proteinuria among SLE patients. METHODS: Danish SLE centres provided clinical data on first time observations of proteinuria and other clinical parameters listed in the 1997 American College of Rheumatology Classification Criteria for SLE. Time from first occurring non-renal manifestation to new-onset proteinuria or censoring defined time at risk. Multivariate Cox-regression models were used to identify risk factors for new-onset proteinuria and to calculate risk of proteinuria stratified by risk factor debut age, duration, and sex. RESULTS: The patient population consisted of 586 patients with SLE, mainly Caucasian (94%) women (88%), mean age at inclusion of 34.6 years (standard deviation, SD=14.4 years), observed for a mean of 14.9 years (SD=11.2 years). The cumulative prevalence of proteinuria was 40%. Discoid rash, HR =0.42 (p=0.01) and lymphopenia HR=1.77 (p=0.005) were associated with new-onset proteinuria. Male patients with lymphopenia had the highest predictive risks of proteinuria with a 1-, 5- and 10-year risk of proteinuria ranging from 9-27%, 34-75% and 51-89%, depending on the age at presentation (debut at 20, 30, 40 or 50 years). The corresponding risk profiles for women with lymphopenia were 3-9%, 8-34% and 12-58%, respectively. CONCLUSIONS: Large differences in absolute risk estimates for new-onset proteinuria were identified. The differences may aid risk stratification and patient compliance among high-risk individuals.

Does paid sick leave encourage staying at home? Evidence from the United States during a pandemic.

We study the impact of a temporary U.S. paid sick leave mandate that became effective April 1st, 2020 on self-quarantining, proxied by physical mobility behaviors gleaned from cellular devices. We study this policy using generalized difference-in-differences methods, leveraging pre-policy county-level heterogeneity in the share of workers likely eligible for paid sick leave benefits. We find that the policy leads to increased self-quarantining as proxied by staying home. We also find that COVID-19 confirmed cases decline post-policy.

Value of gym-based group exercise versus usual care for young adults receiving antipsychotic medication: study protocol for the multicenter randomized controlled Vega trial.

BACKGROUND: Exercise is recommended to protect physical health among people with severe mental illness and holds the potential to facilitate long-term recovery. An inclusive exercise community provides an opportunity for life skill training and social connectedness and may reduce the experience of loneliness and internalized stigmatization which together may improve personal recovery. Using a pragmatic randomized design, we aim to examine the effectiveness of a gym-based exercise intervention tailored to young adults in antipsychotic treatment (i.e., Vega Exercise Community) compared to usual care. It is hypothesized that the Vega Exercise Community will be superior to usual care for personal recovery at four months. METHODS: The trial will be conducted at four sites in Denmark from which 400 participants, aged 18 to 35 years, who are in current treatment with antipsychotic medications for the management of schizophrenia spectrum or affective disorders, will be recruited. Participants will be randomized (2:1) to Vega Exercise Community or usual care. Vega Exercise Community includes three weekly group-based exercise sessions hosted in commercial functional training centers delivered by certified Vega instructors. After four months, participants in Vega Exercise Community will be randomized (1:1) to minimal versus extended support with regards to sustained physical activity. Data will be collected at baseline, four, six and 12 months. The primary outcome is personal recovery assessed by Questionnaire about the Process of Recovery at four months. Behavioral symptoms, health-related quality of life, metabolic health, and program costs will be evaluated to further determine the effectiveness and cost-effectiveness of the Vega Exercise Community. Finally, the quality of life and physical and mental health of the participants' primary relative will be evaluated. DISCUSSION: The results of this trial may have important implications for health, sustained physical activity, and recovery for individuals in treatment with antipsychotics. Given the pragmatic design, positive results may readily be implemented by mental health care professionals to promote exercise as an integrated part of treatment of severe mental illness. TRIAL REGISTRATION: Clinical Trials.gov (NCT05461885, initial registration June 29th, 2022). WHO Universal Trial Number (UTN): U1111-1271-9928.

Why caregivers have no autonomy-based reason to respect advance directives in dementia care.

Advance directives (ADs) have for some time been championed by ethicists and patient associations alike as a tool that people newly diagnosed with dementia, or prior to onset, may use to ensure that their future care and treatment are organized in accordance with their interests. The idea is that autonomous people, not yet neurologically affected by dementia, can design directives for their future care that caregivers are morally obligated to respect because they have been designed by autonomous individuals. In this paper, we first criticize the idea that ADs can retain moral authority in severe dementia by arguing that it is paradoxical. Second, we consider two arguments that initially seem to refute this critique of ADs, but we eventually dismiss them. The first argument states that ADs retain moral authority in severe dementia because autonomously formed interests, for example, ADs, can only be appropriately discarded by autonomous persons. This we term the historical autonomy argument. We dismiss it by demonstrating how we, in analog cases, are not obligated to continue to respect autonomously formed interests even though they have been discarded under nonappropriate conditions. The second argument is that ADs can be justified by what we term external interests. While we agree that people with severe dementia plausible can be said to have external interests, we show that ADs cannot express such interests and hence cannot be justified by them. We conclude that none of the discussed arguments support the use of ADs and because of this, the idea of ADs should be reassigned.

The utility of transbronchial lung biopsies to guide the treatment decision in patients with rheumatic inflammatory diseases: a retrospective cross-sectional study.

The role of transbronchial lung biopsies (TBB) in the diagnostic workup of systemic inflammatory rheumatic disease-associated interstitial lung disease (SIRD-ILD) is unclear and TBB is not generally recommended. The study objective was to examine the utility of TBB to guide treatment in a population of patients with SIRD-ILD. All patients from the Department of Rheumatology, Rigshospitalet, Denmark, who had TBB performed, from 2002 to 2016 were identified. Patient demographics as well as smoking status, previous lung disease, pulmonary function test, SIRD-diagnosis, imaging results and immunomodulatory therapy pre- and post-bronchoscopy were obtained. Histology findings were used to dichotomize patients into a high-inflammatory group or a low-inflammatory group. The high-inflammation group primarily consisted of non-specific interstitial pneumonia, organizing pneumonia, lymphocytic infiltrating pneumonia and granulomatous inflammation whereas the low inflammation group primarily consisted of histological findings of usual interstitial pneumonitis and biopsies describing fibrosis and/or sparse unspecific inflammation. Therapeutic consequence was defined as intensification of therapy. Differences in treatment intensification were calculated using a binominal logistic regression model. Ninety-six patients had TBB performed. Biopsies from 55 patients were categorized as high inflammatory and 41 as low inflammatory, respectively. In the high-inflammatory group, 38 (69%) had their therapy intensified compared to 6 (14%) in the low-inflammatory group (Odds ratio 8.0, 95% confidence limits 3.2-20.0, P < 0.001). No procedure-related complications were registered. TBB findings can guide treatment strategy in SIRD-ILD patients with suspected activity in the pulmonary disease. TBB appears safe and could be considered as part of the diagnostic workup.

A prospective examination of health care costs associated with posttraumatic stress disorder diagnostic status and symptom severity among veterans.

Posttraumatic stress disorder (PTSD) is associated with increased health care costs; however, most studies exploring this association use PTSD diagnostic data in administrative records, which can contain inaccurate diagnostic information and be confounded by the quantity of service use. We used a diagnostic interview to determine PTSD diagnostic status and examined associations between PTSD symptom severity and health care costs and utilization, extracted from Veteran Health Administration (VHA) administrative databases. Using a nationwide longitudinal sample of U.S. veterans with and without PTSD (N = 1,377) enrolled in VHA health care, we determined the costs and utilization of mental health and non-mental health outpatient, pharmacy, and inpatient services for 1 year following cohort enrollment. Relative to veterans without PTSD, those with PTSD had higher total health care, B = 0.47; mental health clinic care, B = 0.72; non-mental health clinic care, B = 0.30; and pharmacy costs, B = 0.72, ps < .001. More severe PTSD symptoms were associated with mental health clinic care costs, B = 0.12; non-mental health clinic care costs, B = 0.27; and higher odds of inpatient, B = 0.63, and emergency service use, B = 0.39, p < .001-p = .012. These findings indicate that veterans' PTSD status, determined by a clinician-administered semistructured diagnostic interview, was associated with higher health care costs and increased use of mental health and non-mental health clinic services. The findings also suggest that more severe PTSD is associated with increased costs and utilization, including costly emergency and inpatient utilization.

Patients' Expectations of Physiotherapeutic Treatment for Long-Term Side Effects After Cancer: A Qualitative Study.

OBJECTIVE: This study aims to explore the expectations of physiotherapeutic treatment of long-term side effects (LTSEs) after cancer among patients treated in physiotherapy clinics. METHODS: This a qualitative interview study based on a phenomenological approach. Adult patients with LTSEs after cancer were recruited through The Danish Cancer Society and a private physiotherapy clinic in Denmark. Individual semi-structured interviews were carried out using Microsoft Teams based on an interview guide piloted before the interviews. Interviews were audiotaped and transcribed verbatim. Sampling was conducted with a focus on variation in LTSE. The data were analyzed using Malterud's principles of systematic text condensation and coded in NVivo 12. RESULTS: 2 males and 8 females with an average age of 55.8 years were interviewed for between 40 and 60 minutes from October to November 2020. Four main themes emerged from the interviews1: The importance of the physiotherapist's approach,2 the benefits of meeting patients with similar symptoms,3 the importance of receiving knowledge, and4 patients seeking to maintain their current state more often than aiming to improve their condition. CONCLUSIONS: Patients consulting a physiotherapy clinic with LTSE after cancer prefer the physiotherapist to have knowledge about cancer and to be emphatic. Furthermore, patients prefer to meet like-minded people and expect support to maintain their current condition rather than improve their condition.

Regularization by denoising sub-sampled Newton method for spectral CT multi-material decomposition.

Spectral Computed Tomography (CT) is an emerging technology that enables us to estimate the concentration of basis materials within a scanned object by exploiting different photon energy spectra. In this work, we aim at efficiently solving a model-based maximum-a-posterior problem to reconstruct multi-materials images with application to spectral CT. In particular, we propose to solve a regularized optimization problem based on a plug-in image-denoising function using a randomized second order method. By approximating the Newton step using a sketching of the Hessian of the likelihood function, it is possible to reduce the complexity while retaining the complex prior structure given by the data-driven regularizer. We exploit a non-uniform block sub-sampling of the Hessian with inexact but efficient conjugate gradient updates that require only Jacobian-vector products for denoising term. Finally, we show numerical and experimental results for spectral CT materials decomposition. This article is part of the theme issue 'Synergistic tomographic image reconstruction: part 1'.

Practice-guided public health philosophy.

Although highly relevant, philosophical theory and philosophical competences are rarely integrated in empirical public health research. We suggest a variant of applied philosophy that is valuable for the development and improvement of public health research. We call it practice-guided public health philosophy because: (i) research questions derive from public health challenges, i.e. real-life concerns that relate to the prevention of disease or the promotion of health and well-being, (ii) the ultimate test of success lies within an empirical framework aiming to improve public health practices and (iii) philosophers collaborate very closely with different kinds of empirical researchers in the different stages of the research process. Using examples from current public health projects at the National Institute of Public Health at the University of Southern Denmark, we outline three paradigmatic cases of practice-guided public health philosophy: (i) by using philosophy as an idea generator of empirical research, (ii) by using philosophy as a frame of reference for interpreting ethnographic data and (iii) by using philosophy as an explanatory resource for discussing survey and register data.

Assessment of the cognitive attentional syndrome in children: an adaptation of the CAS-1.

BACKGROUND: Research suggests that the metacognitive model is applicable to clinical child populations. However, few measures related to the model are available for younger age groups. A key concept of the model is the cognitive attentional syndrome (CAS), which encompasses the individual's worry and rumination, maladaptive coping strategies, and metacognitive beliefs. While the CAS has been successfully measured in adults, this has not yet been attempted in children. AIMS: The aim of this study was to adapt a measure of the CAS for use with children and investigate the measure's associations with anxiety, worry, depression and metacognitions. METHODS: Our study included 127 children with anxiety disorders aged 7-13 years. The adult measure of CAS was adapted for use with children and administered at pre- and post-treatment. We examined the correlations between variables and the ability of the CAS measure to explain variance in anxious symptomatology, as well as the measure's sensitivity to treatment change. RESULTS: The adapted measure, CAS-1C, displayed strong associations with overall anxiety, depression, worry and metacognitions. The CAS-1C explained an additional small amount of variance in anxiety and worry symptoms after accounting for metacognitions, which may be due to the measure also assessing thinking styles and coping strategies. Furthermore, the measure displayed sensitivity to treatment change. CONCLUSIONS: The child measure of the CAS is a brief tool for collecting information on metacognitive beliefs and strategies that maintain psychopathology according to the metacognitive model, and it can be used to monitor treatment changes in these components.

Impacts of state COVID-19 reopening policy on human mobility and mixing behavior.

This study quantifies the effect of the 2020 state COVID economic activity reopening policies on daily mobility and mixing behavior, adding to the economic literature on individual responses to public health policy that addresses public contagion risks. We harness cellular device signal data and the timing of reopening plans to provide an assessment of the extent to which human mobility and physical proximity in the United States respond to the reversal of state closure policies. We observe substantial increases in mixing activities, 13.56% at 4 days and 48.65% at 4 weeks, following reopening events. Echoing a theme from the literature on the 2020 closures, mobility outside the home increased on average prior to these state actions. Furthermore, the largest increases in mobility occurred in states that were early adopters of closure measures and hard-hit by the pandemic, suggesting that psychological fatigue is an important barrier to implementation of closure policies extending for prolonged periods of time.

Antibody-Mediated Neutralization of uPA Proteolytic Function Reduces Disease Progression in Mouse Arthritis Models.

Genetic absence of the urokinase-type plasminogen activator (uPA) reduces arthritis progression in the collagen-induced arthritis (CIA) mouse model to an extent just shy of disease abrogation, but this remarkable observation has not been translated into therapeutic intervention. Our aim was to test the potential in mice of an Ab that blocks the proteolytic capacity of uPA in the CIA model and the delayed-type hypersensitivity arthritis model. A second aim was to determine the cellular origins of uPA and the uPA receptor (uPAR) in joint tissue from patients with rheumatoid arthritis. A mAb that neutralizes mouse uPA significantly reduced arthritis progression in the CIA and delayed-type hypersensitivity arthritis models. In the CIA model, the impact of anti-uPA treatment was on par with the effect of blocking TNF-α by etanercept. A pharmacokinetics evaluation of the therapeutic Ab revealed target-mediated drug disposition consistent with a high turnover of endogenous uPA. The cellular expression patterns of uPA and uPAR were characterized by double immunofluorescence in the inflamed synovium from patients with rheumatoid arthritis and compared with synovium from healthy donors. The arthritic synovium showed expression of uPA and uPAR in neutrophils, macrophages, and a fraction of endothelial cells, whereas there was little or no expression in synovium from healthy donors. The data from animal models and human material provide preclinical proof-of-principle that validates uPA as a novel therapeutic target in rheumatic diseases.

HAI-2 stabilizes, inhibits and regulates SEA-cleavage-dependent secretory transport of matriptase.

It has recently been shown that hepatocyte growth factor activator inhibitor-2 (HAI-2) is able to suppress carcinogenesis induced by overexpression of matriptase, as well as cause regression of individual established tumors in a mouse model system. However, the role of HAI-2 is poorly understood. In this study, we describe 3 mutations in the binding loop of the HAI-2 Kunitz domain 1 (K42N, C47F and R48L) that cause a delay in the SEA domain cleavage of matriptase, leading to accumulation of non-SEA domain cleaved matriptase in the endoplasmic reticulum (ER). We suggest that, like other known SEA domains, the matriptase SEA domain auto-cleaves and reflects that correct oligomerization, maturation, and/or folding has been obtained. Our results suggest that the HAI-2 Kunitz domain 1 mutants influence the flux of matriptase to the plasma membrane by affecting the oligomerization, maturation and/or folding of matriptase, and as a result the SEA domain cleavage of matriptase. Two of the HAI-2 Kunitz domain 1 mutants investigated (C47F, R48L and C47F/R48L) also displayed a reduced ability to proteolytically silence matriptase. Hence, HAI-2 separately stabilizes matriptase, regulates the secretory transport, possibly via maturation/oligomerization and inhibits the proteolytic activity of matriptase in the ER, and possible throughout the secretory pathway.

Are current EU policies on GMOs justified?

The European Court of Justice's recent ruling that the new techniques for crop development are to be considered as genetically modified organisms under the European Union's regulations exacerbates the need for a critical evaluation of those regulations. The paper analyzes the regulation from the perspective of moral and political philosophy. It considers whether influential arguments for restrictions of genetically modified organisms provide cogent justifications for the policies that are in place, in particular a pre-release authorization requirement, mandatory labelling, and de facto bans (in the form of withholding or opting out of authorizations). It is argued that arguments pertaining to risk can justify some form of pre-release authorization scheme, although not necessarily the current one, but that neither de facto bans nor mandatory labelling can be justified by reference to common arguments concerning naturalness, agricultural policy (in particular the promotion of organic farming), socio-economic effects, or consumers' right to choose.

PKD Phosphorylation as Novel Pathway of KV11.1 Regulation.

BACKGROUND/AIMS: The voltage-gated potassium channel KV11.1 has been originally cloned from the brain and is expressed in a variety of tissues. The role of phosphorylation for channel function is a matter of debate. In this study, we aimed to elucidate the extent and role of protein kinase D mediated phosphorylation. METHODS: We employed mass spectrometry, whole-cell patch clamp electrophysiology, confocal microscopy, site-directed mutagenesis, and western blotting. RESULTS: Using brain tissue from rat and mouse, we mapped several phosphorylated KV11.1 residues by LC-MS mass spectrometry and identified protein kinase D (PKD1) as possible regulatory kinase. Co-expression of KV11.1 with PKD1 reduced current amplitudes without altering protein levels or surface expression of the channel. Based on LC-MS results from in vivo and HEK293 cell experiments we chose four KV11.1 mutant candidates for further functional analysis. Ablation of the putative PKD phosphorylation site in the mutant S284A increased the maximal current indicating S284 as a main PKD target in KV11.1. CONCLUSIONS: Our data might help mitigating a long-standing controversy in the field regarding PKC regulation of KV11.1. We propose that PKD1 mediates the PKC effects on KV11.1 and we found that PKD targets S284 in the N-terminus of the channel.

Effect of Transient Wave Forcing on the Behavior of Arsenic in a Nearshore Aquifer.

Groundwater-coastal water interactions influence the fate of inorganic chemicals in nearshore aquifers and their flux to receiving coastal waters. This study evaluates the impact of variable wave conditions on the geochemical changes and distribution of mobile arsenic (As) in a nearshore aquifer. Field measurements in a sandy nearshore aquifer on Lake Erie, Canada, are presented with geochemical changes analyzed over a period of high waves. A numerical model of wave-induced groundwater flow dynamics, validated against field data, is used to provide insight into the physical flow processes underlying the observed geochemical changes. Rapid changes in dissolved As, Fe, Mn, and S demonstrate the importance of reactions as well as dynamic transport in controlling the behavior of reactive species, especially those that are redox sensitive. Field data suggest the presence of sediment traps, which under certain hydrological and geochemical conditions may result in a "hot moment" with episodic release of As. The study provides new insight into factors controlling the fate of reactive species in dynamic coastal environments as required to better predict chemical fluxes to coastal waters. Additionally, it highlights the need to pay particular attention to "hot moments" for reaction and transport caused by storms and waves.

Constraints on Formulary Design Under the Affordable Care Act.

I study the effect of prescription drug essential health benefits (EHB) requirements from the Affordable Care Act on prescription drug formularies of health insurance marketplace plans. The EHB regulates the number of drugs covered but leaves other dimensions (cost sharing and utilization management) of the formulary unregulated. Using data on almost all formularies in the country, I demonstrate that requiring insurers to cover one additional drug adds 0.22 drugs (3.3%) to the average formulary, mostly owing to firms increasing the number of drugs covered to comply with the EHB requirement. The EHB requirement also increases the probability that a drug is subject to utilization management and is assigned to a higher (more costly) formulary tier. My results suggest that newly covered drugs are 22.3 percentage points more likely to be subject to utilization management, compared to 36.7% for the average covered drug. Using formularies for Medicare Advantage plans, which are subject to uniform, nationwide benefit design standards, and the formulary status of newly approved drugs that do not satisfy the EHB requirement, I reject the hypotheses that consumer demand or effects on plan entry can explain my results. Copyright © 2017 John Wiley & Sons, Ltd.