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This study aimed to examine the reasons underlying treatment changes among pediatric patients with attention-deficit/hyperactivity disorder (ADHD).Data were obtained through online medical chart abstraction (08/2021-09/2021). Eligible patients with ADHD had initiated a treatment regimen at ages 6-17 and within 1-5 years of chart abstraction. Reasons contributing to treatment changes were analyzed for a randomly selected treatment episode. ADHD/treatment-related complication rate was also described. Results were reported overall and among children (ages 6-12) and adolescents (ages 13-17), separately. Physicians' perspective on adherence among their child, adolescent, and adult patients was assessed through an online survey.A total of 156 physicians abstracted 434 patient charts (235 children + 199 adolescents). Mean patient age was 11.3 years, and 68.7% were male. Inadequate/suboptimal symptom management was the most common reason for treatment discontinuation (50/83 [60.2%]), add-on (17/21 [81.0%]), and dose increase (189/237 [79.7%]). Patient/parent/family attitude/dislike of medication and ADHD/treatment-related complications were common reasons for treatment discontinuation, add-on, switch, and dose decrease. Overall, 42.4% of patients had ≥ 1 documented ADHD/treatment-related complication, insomnia/sleep disturbances being the most common (9.7%). Among patients with ≥ 1 complication, 75.5% reported the experience/fear of complications had a negative impact on their treatment adherence. Results were similar among children and adolescents. Physicians reported taking actions toward patients' non-adherence by further educating patients, closer monitoring, and changing the prescribed ADHD medication.Lack of effectiveness and ADHD/treatment-related complications are important reasons for treatment changes among children and adolescents with ADHD, highlighting the need for more effective and tolerable treatments to mitigate the burden of ADHD.

BACKGROUND A new class of interventions called digital therapeutics (DTx) is emerging and shows promise in the treatment of a spectrum of medical disorders and diseases. DTx are software-based interventions which could deliver unprecedented portability and scalability for patients. Their adoption and implementation were accelerated by the need for remote care during the COVID-19 pandemic, and awareness about their utility grew among health care providers, payers, and regulators. Yet, despite increasing clinical evidence that DTx can prevent, manage, or treat chronic conditions and disorders, the digital nature of these technologies creates a new set of challenges to evaluating their cost-effectiveness. As a result, little is known regarding the capacity of DTx to provide economic value to payers, providers, and health systems. OBJECTIVE This study aims to systematically review and summarize published evidence regarding the cost-effectiveness of clinical-grade mobile application-based DTx, as well as explore factors affecting such evaluations. METHODS A systematic review of economic evaluations of clinical-grade mobile application-based DTx was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines. Major electronic databases (including PubMed, Cochrane Library, and Web of Science) were searched for eligible studies published from inception to October 28, 2022. Two independent reviewers evaluated the eligibility of all retrieved articles for inclusion. The methodological quality and risk of bias were assessed for included studies. RESULTS The search yielded 11,228 abstracts, of which 18 studies are included in this review. Of the 18 studies, 7 (39%) are non-randomized studies-based economic evaluations, 6 (33%) are model-based evaluations and 5 (28%) are randomized clinical trials-based evaluations. Twelve of the studies (67%) used a payer perspective for the economic analysis, while the rest (33%) used a societal perspective. Thirteen of the studies (72%) conducted a full economic evaluation, and 12 of those (92%) found the DTx intervention under assessment to be cost-effective; one study (8%) found the intervention to be cost-effective in only one of the three countries of study. The remaining 5 studies (28%), which focused on a partial economic evaluation, found the DTx intervention under assessment to be cost-saving. Across the 18 studies included in this review, health care resource utilization was the most often reported cost impacting the DTx economic value of the DTx interventions (16/18, 89%), followed by the cost of the pharmaceutical treatment (12/18, 67%). The participants’ baseline characteristics was the most often reported factors influencing DTx economic impact in 12 of the studies (67%). By way of limitations, qualitative deficits in methodology and significant potential biases, including risks of performance bias and of selection bias in participant recruitment, were identified across some of the studies. CONCLUSIONS This systematic review supports the thesis that DTx interventions have potential economic benefits. However, the distinctive nature of DTx creates a new set of challenges to evaluating such novel technologies, which were not consistently addressed across studies. To provide evidence of economic impact, which is required for DTx adoption and deployment, further evaluations leveraging more comprehensive and standardized economic analyses across settings will be necessary. CLINICALTRIAL PROSPERO Registration No. CRD42022358616

To provide a comprehensive evaluation of the economic burden associated with attention-deficit/hyperactivity disorder (ADHD) among children and adolescents from a US societal perspective.Direct healthcare costs of children (5-11 years) and adolescents (12-17 years) with ADHD were obtained using claims data from the IBM MarketScan Research Databases (01/01/2017-12/31/2018). Direct non-healthcare and indirect costs were estimated based on literature and government publications. Each cost component was estimated using a prevalence-based approach, with per-patient costs extrapolated to the national level.The total annual societal excess costs associated with ADHD were estimated at $19.4 billion among children ($6,799 per child) and $13.8 billion among adolescents ($8,349 per adolescent). Education costs contributed to approximately half of the total excess costs in both populations ($11.6 billion [59.9%] in children; $6.7 billion [48.8%] in adolescents). Other major contributors to the overall burden were direct healthcare costs ($5.0 billion [25.9%] in children; $4.0 billion [29.0%] in adolescents) and caregiving costs ($2.7 billion [14.1%] in children; $1.6 billion [11.5%] in adolescents).Cost estimates were calculated based on available literature and/or governmental publications due to the absence of a single data source for all costs associated with ADHD. Thus, the quality of cost estimates is limited by the accuracy of available data as well as the study populations and methodologies used by different studies.ADHD in children and adolescents is associated with a substantial economic burden that is largely driven by education costs, followed by direct healthcare costs and caregiver costs. Improved intervention strategies and policies may reduce the clinical and economic burden of ADHD in these populations.

BACKGROUND: Attention-deficit/hyperactivity disorder (ADHD) is associated with substantial clinical burden as individuals transition to adulthood, including higher rates of comorbidities, mortality, incarceration, and psychiatric hospitalizations than in individuals without ADHD. These higher rates likely contribute to substantial economic burden as well. OBJECTIVE: To provide a comprehensive evaluation of the economic burden associated with ADHD in the US adult population. METHODS: Direct health care costs were obtained by using claims data from the IBM MarketScan Research Databases (January 1, 2017, through December 31, 2018). Direct non-health care costs and indirect costs were estimated on the basis of the literature and government publications. Excess costs incurred by adults with ADHD during 2018 were evaluated from a societal perspective; per-patient costs were extrapolated to the national level. RESULTS: An estimated 8.7 million adults live with ADHD in the United States, resulting in a total societal excess cost attributable to ADHD of $122.8 billion ($14,092 per adult). Excess costs of unemployment ($66.8 billion; 54.4%) comprised the largest proportion of the total, followed by productivity loss ($28.8 billion; 23.4%) and health care services ($14.3 billion; 11.6%). CONCLUSIONS: ADHD in adults is associated with substantial economic burden. DISCLOSURES: This study was funded by Otsuka Pharmaceutical Development & Commercialization, Inc. (Otsuka). The study sponsor contributed to and approved the study design, participated in the interpretation of data, and reviewed and approved the manuscript. Schein is an employee of Otsuka. Gagnon-Sanschagrin, Davidson, Kinkead, Cloutier, Guerin, and Lefebvre are employees of Analysis Group, Inc., a consulting company that provided paid consulting services to Otsuka to develop and conduct this study and write the manuscript. Adler has received research support from Shire/Takeda, Sunovion, and Otsuka; consulting fees from Bracket, Shire/Takeda, Sunovion, Otsuka, the State University of New York (SUNY), the National Football League (NFL), and Major League Baseball (MLB); and royalty payments (as inventor) from New York University (NYU) for license of adult ADHD scales and training materials. Childress has received research support from Allergan, Takeda/Shire, Emalex, Akili, Ironshore, Arbor, Aevi Genomic Medicine, Neos Therapeutics, Otsuka, Pfizer, Purdue, Rhodes, Sunovion, Tris, KemPharm, Supernus, and the US Food and Drug Administration; was on the advisory board of Takeda/Shire, Akili, Arbor, Cingulate, Ironshore, Neos Therapeutics, Otsuka, Pfizer, Purdue, Adlon, Rhodes, Sunovion, Tris, Supernus, and Corium; received consulting fees from Arbor, Ironshore, Neos Therapeutics, Purdue, Rhodes, Sunovion, Tris, KemPharm, Supernus, Corium, Jazz, and Tulex Pharma; received speaker fees from Takeda/Shire, Arbor, Ironshore, Neos Therapeutics, Pfizer, Tris, and Supernus; and received writing support from Takeda/Shire, Arbor, Ironshore, Neos Therapeutics, Pfizer, Purdue, Rhodes, Sunovion, and Tris. Part of the material in this study was presented as a poster at the International Society for Pharmacoeconomics and Outcomes Research (ISPOR) 2021 Virtual Meeting; May 17-20, 2021.

Background The risk of invasive extraintestinal pathogenic Escherichia coli disease (IED) increases with age and can lead to severe outcomes, including sepsis and death. Aim To describe the clinical outcomes of IED in older adults in the United States (US). Methods The Premier Healthcare Database (10/01/2015-03/31/2020) was used to identify IED encounters among patients ≥ 60 years old. The index encounter was defined as the first encounter with a positive E. coli culture in a normally sterile body site (Group 1) or a positive E. coli culture in urine with signs of sepsis (Group 2), in the absence of other pathogens. Outcomes included medical resource utilization, antibiotic use, IED recurrence, and in-hospital death, and were descriptively reported during the index encounter and over the subsequent year. Results Overall, 19,773 patients with IED were included (mean age: 76.8 years; 67.4% female; 82.1% white). Approximately half of index encounters were from Group 1 (51.8%), and the vast majority of patients had community-onset IED (94.3%). Most index encounters led to inpatient hospitalization (96.5%; mean duration: 6.9 days) and 32.4% required transfer to an intensive care unit (mean duration: 3.7 days). During the index encounter, patients received a mean [SD] of 2.9 [1.4] antibiotic agents, and 30.1% received ≥ 4 agents. The 3 most prevalent antibiotics received were ceftriaxone (66.2%), vancomycin (36.3%), and piperacillin (35.0%; Fig 1). The majority of E. coli isolates showed resistance to ≥ 1 antibiotic category (61.7%), and 34.4% were classified as multi-drug resistant (i.e., ≥ 3 categories). Following discharge, 34.8% of patients were transferred to a skilled nursing/intermediate care facility. In-hospital death reached 6.8% during the index encounter and increased to 10.9% 1-year post-index (Fig 2). One-year post-index, 2.4% of patients had an IED recurrence and 36.8% were readmitted to the hospital for any reason (Fig 3). Conclusion Our findings suggest that IED is a severe disease that is associated with substantial burden and far-reaching consequences beyond the initial encounter. These findings emphasize the need for increased awareness and surveillance of IED and its consequences and the potential benefit of preventative measures. Disclosures Elie Saade, MD, Janssen: Grant/Research Support|Pfizer: Board Member|Pfizer: Grant/Research Support|Sanofi Pasteur: Grant/Research Support|Sanofi Pasteur: Speaking/lecture fees, travel reimbursement|Seqirus: Grant/Research Support Jeroen Geurtsen, PhD, Janssen: Employee of Janssen Vaccines & Prevention BV Bryan Baugh, MD, Janssen Research & Development LLC: Employee|Janssen Research & Development LLC: Stocks/Bonds Antoine El Khoury, PhD, Janssen: Employee of Janssen Global Services, LLC. Nnanya Kalu, PhD, Janssen: Employee of Janssen Scientific Affairs, LLC. Marjolaine Gauthier-Loiselle, PhD, Janssen: Advisor/Consultant|Janssen: Advisor/Consultant Rebecca Bungay, MScPH, Janssen: Employees of Analysis Group, Inc. which has received consultancy fees from Janssen Scientific Affairs, LLC for the conduct of this studies. Martin Cloutier, MSc, Janssen: Employees of Analysis Group, Inc. which has received consultancy fees from Janssen Scientific Affairs, LLC for the conduct of this studies. Luis Hernandez Pastor, PharmD, PhD, Janssen: Employee of Janssen Pharmaceutica NV.

Introduction Spinal muscular atrophy (SMA) is a rare, genetic neuromuscular disorder caused by deletion/mutation of the survival motor neuron 1 gene, characterized by progressive loss of motor neurons, resulting in increasing muscular weakness, deteriorating motor function, and, in its most severe form, death before 2 years. Nusinersen, an antisense oligonucleotide that increases expression of the functional SMN protein, was approved for SMA by US and European regulatory agencies in 2016 and 2017, respectively. The indicated regimen requires intrathecal injections every 4 months, following the first four injections during the loading phase. Adherence is integral to treatment success. Adherence to nusinersen may pose particular challenges as most patients with SMA are young children who require complex multidisciplinary care (including ongoing intrathecal treatment administration and potential specialized anesthetic and surgical procedures) at specialized centers. However, real-world data on adherence to nusinersen are limited. Methods We conducted a retrospective claims database analysis from December 23, 2016, to November 20, 2019, to study nusinersen adherence and discontinuation/persistence in US patients with SMA types 1–3 who completed the loading phase, and to determine the impact of non-adherence or treatment discontinuation on SMA-related comorbidities, health care resource utilization (HCRU), and costs. Results We identified 23 patients with SMA type 1, 41 patients with SMA type 2, and 260 patients with SMA type 3 who had completed the loading phase. Deviations from the indicated nusinersen treatment schedule were frequent in real-world usage, with most patients receiving ≥1 dose outside the scheduled interval. Across SMA types, non-adherent patients were more likely to have had SMA-related comorbidities (e.g., feeding difficulties, dyspnea and respiratory anomalies, and muscle weakness) and greater HCRU. Persistence rates 12 months after treatment initiation for patients with SMA types 1, 2, and 3 were 55.2%, 42.4%, and 54.6%, respectively. Patients who discontinued nusinersen and those who did not had generally similar comorbidity profiles. Discontinuation was associated with greater health care costs across SMA types. Conclusion Our analysis of claims data indicated that discontinuation and non-adherence to nusinersen treatment were prevalent, and associated with greater frequency of comorbidities, greater HCRU, and increased costs for patients. Supplementary Information The online version contains supplementary material available at 10.1007/s12325-021-01938-w.

Describe symptoms associated with ADHD/treatment-related adverse side effects among adults with ADHD in the US and assess their impact on quality of life (QoL) and work productivity.An online survey among adults receiving ADHD medications in the US was conducted to collect information relating to symptoms associated with ADHD/treatment-related adverse side effects. Participants were recruited from the panel of a well-established market research firm, Dynata, from 26 July to 30 July 2021 and were included in the study if they met the eligibility criteria and were willing to participate in the survey. Correlations between symptoms and key outcomes (QoL/employment/work impairment) were estimated using linear regression analyses.Of 585 participants, 95.2% experienced ≥1 symptom associated with ADHD/treatment-related adverse side effects in the past month (average = 5.8 symptoms). The number of symptoms was significantly correlated with reduced QoL, reduced probability of being employed, and increased work/activity impairment. Among subgroups with insomnia/other sleep disturbances and emotional impulsivity/mood lability, 50.4% and 44.7% reported their symptoms had "a lot" or "extremely" negative impact on their overall well-being, respectively.Symptoms associated with ADHD/treatment-related adverse side effects are common and have a substantial negative impact on QoL and reduces patients' probability of employment. Improved management of ADHD/treatment-related adverse side effects and more tolerable treatment options have the potential to improve QoL and work productivity among adults with ADHD.

To assess treatment patterns in adults with attention-deficit/hyperactivity disorder (ADHD) and associated healthcare costs in a real-world US setting. Claims data from the IBM MarketScan Commercial Subset (Q1/2014-Q4/2018) was used to identify adults diagnosed with ADHD who newly initiated on ADHD treatment (index date). Treatment sequences were defined using an algorithm; for each sequence, the regimen comprised all ADHD-related agents observed within 30 d of the first agent during the 12-month study period. Treatment changes included discontinuation, switch, add-on, and drop. Treatment characteristics were described for the first treatment regimen observed. Total adjusted annual healthcare costs were compared between patients with no treatment change and patients with 1, 2, and ≥3 treatment changes. Among 122,881 adults with ADHD, the majority initiated a stimulant (95.1%) as their first treatment regimen observed; 9.3% of patients initiated combination therapy of ≥2 ADHD-related agents, and 34.9% of patients had psychotherapy. After an average first treatment regimen duration of 7.1 months, 50.2% of patients experienced a treatment change (22.5% discontinued, 17.5% switched, 5.3% had an add-on, and 4.6% had a treatment drop). Among those who discontinued, 44.8% did so within the first month of initiation. Mean annual healthcare costs were higher among patients with at least 1 treatment change compared to those with no treatment changes; excess costs increased with each additional treatment change. Treatment changes were commonly observed and were associated with excess healthcare cost, emphasizing the unmet treatment needs of adults with ADHD in the US.

Objectives To describe characteristics and compare clinical outcomes including falls, fractures, infections, and neuropsychiatric symptoms (NPS) among long-term care residents with dementia with and without agitation. Methods A cross-sectional secondary analysis of administrative healthcare data was conducted whereby residents with dementia residing in a long-term care facility for ≥12 months were identified from the AnalytiCare LLC database (10/2010-06/2014) and were classified into mutually exclusive cohorts (Agitation Cohort or No-Agitation Cohort) based on available agitation-related symptoms. Entropy balancing was used to balance demographic and clinical characteristics between the two cohorts. The impact of agitation on clinical outcomes was compared between balanced cohorts using weighted logistic regression models. Results The study included 6,265 long-term care residents with dementia among whom, 3,313 were included in the Agitation Cohort and 2,952 in the No-Agitation Cohort. Prior to balancing, residents in the Agitation Cohort had greater dementia-related cognitive impairment and clinical manifestations compared to the No-Agitation Cohort. After balancing, residents with and without agitation, respectively, received a median of five and four distinct types of medications (including antipsychotics). Further, compared to residents without agitation, those with agitation were significantly more likely to have a recorded fall (OR = 1.58), fracture (OR = 1.29), infection (OR = 1.18), and other NPS (OR = 2.11). Conclusions Agitation in long-term care residents with dementia was associated with numerically higher medication use and an increased likelihood of experiencing falls, fractures, infections, and additional NPS compared to residents without agitation, highlighting the unmet need for effective management of agitation symptoms in this population.

This article analyzes how a meta-organization (M-O) can shape a coherent collective identity over time. Previous foundational work on identity formation in M-Os has provided fragmented but insightful ideas on several activities that this process entails. However, we currently lack a dynamic, integrative, and empirically supported model that demonstrates how these activities interrelate to shape a coherent collective identity over time. Using an in-depth case study of an association of cider producers in Québec (Canada) over a 23-year period, we develop a model of collective identity dynamics, in which an M-O plays an orchestrator role that is both dual and continuous. On the one hand, an M-O balances the internal identity claims of its organizational members through alignment and differentiation. On the other hand, an M-O builds an externally coherent identity by assembling and positioning legitimacy among institutional actors. Our paper provides new insights into activities performed by an M-O during identity creation by analyzing whether this process includes both organizational and institutional actors, thereby reinforcing the intermediary nature of an M-O. Furthermore, it contributes to the collective identity dynamics literature by elaborating the stabilizing role of a bounded organization in collective identity dynamics at the interorganizational level.

Background: Few studies have examined patient characteristics and treatment patterns among patients with dementia and agitation in the United States (US). Objective: To examine real-world treatment patterns and characteristics of patients with agitation related to dementia who were treated with antipsychotics in US residential care and community-based settings. Methods: This retrospective chart review collected US physician-level data from patients 55 to 90 years old initiated on an antipsychotic medication for the treatment of agitation related to dementia from January 2018 to May 2018. Clinical characteristics and treatment patterns were assessed overall and stratified by residential care and community-based settings. Results: A total of 313 participating physicians, 59.5% of whom were primary care physicians, abstracted 801 patient charts (residential care: n = 312; community-based: n = 489). Of patients with agitation who were initiated on an antipsychotic, most patients (74.5%) were initiated within 3 months of the onset of their studied agitation episode, and 62.8% experienced multiple agitation episodes before initiation. While non-pharmacological therapies are recommended first-line approach for agitation in dementia, use of non-pharmacological therapy before initiation of antipsychotics was reported for only 37.8% of patients in residential care and 21.3% in community-based settings. Conclusion: Most patients were initiated on an antipsychotic treatment after multiple episodes of agitation and largely without initial non-pharmacological therapy, suggesting that current treatment guideline recommendations for first-line non-pharmacological intervention may not be adequately followed in clinical practice. Understanding the clinical burden and treatment patterns among dementia patients with agitation is imperative for effective disease management.

Les concepts de strategie collective et d’entrepreneuriat collectif sont mobilises dans l’etude de l’emergence et de la formation de deux routes touristiques a theme (RT). Basee sur une recherche multicas de deux RT, la Loire a velo (France) et la Route des cidres (Monteregie, Quebec, Canada), les resultats soulignent l’interet d’examiner : (1) les acteurs cles (parties prenantes) engages dans une demarche entrepreneuriale collective ainsi que leur role ; (2) les dynamiques a l’œuvre entre ces acteurs ; et (3) la nature et les caracteristiques du projet strategique collectif provenant de sa phase d’emergence et de formation.

Background Autosomal dominant polycystic kidney disease (ADPKD) is one of the most common inherited kidney diseases characterized by progressive development of renal cysts and numerous extra-renal manifestations, eventually leading to kidney failure. Given its chronic and progressive nature, ADPKD is expected to carry a substantial economic burden over the course of the disease. However, there is a paucity of evidence on the impact of ADPKD from a societal perspective. This study aimed to estimate the direct and indirect costs associated with ADPKD in the United States (US). Methods A prevalence-based approach using data from scientific literature, and governmental and non-governmental organizations was employed to estimate direct healthcare costs (i.e., medical services, prescription drugs), direct non-healthcare costs (i.e., research and advocacy, donors/recipients matching for kidney transplants, transportation to/from dialysis centers), and indirect costs (i.e., patient productivity loss from unemployment, reduced work productivity, and premature mortality, caregivers’ productivity loss and healthcare costs). The incremental costs associated with ADPKD were calculated as the difference between costs incurred over a one-year period by individuals with ADPKD and the US population. Sensitivity analyses using different sources and assumptions were performed to assess robustness of estimates and account for variability in published estimates. Results The estimated total annual costs attributed to ADPKD in 2018 ranged from $7.3 to $9.6 billion in sensitivity analyses, equivalent to $51,970 to $68,091 per individual with ADPKD. In the base scenario, direct healthcare costs accounted for $5.7 billion (78.6%) of the total $7.3 billion costs, mostly driven by patients requiring renal replacement therapy ($3.2 billion; 43.3%). Indirect costs accounted for $1.4 billion (19.7%), mostly driven by productivity loss due to unemployment ($784 million; 10.7%) and reduced productivity at work ($390 million; 5.3%). Total excess direct non-healthcare costs were estimated at $125 million (1.7%). Conclusions ADPKD carries a considerable economic burden, predominantly attributed to direct healthcare costs, the majority of which are incurred by public and private healthcare payers. Effective and timely interventions to slow down the progression of ADPKD could substantially reduce the economic burden of ADPKD.

Purpose Supported by a service ecosystem that is increasingly immersed into digital transformation, small- and medium-sized enterprises (SMEs) have access to turnkey information technology (IT) applications, which may come free of charge but not free of concerns. The purpose of this paper is to explore a group conceptualisation and associated perceptions of IT issues within an ecosystem that includes three subgroup profiles: entrepreneurs, IT professionals and socioeconomic support professionals. Design/methodology/approach Using group concept mapping, a bottom-up and participatory mixed methods-based approach, a concept map was estimated, based on a list of items, to define seven clusters pertaining to issues and challenges of adoption and use of turnkey IT applications in SMEs of less than 20 employees. Perceptions measures of relative importance and feasibility were obtained by subgroup profiles. Findings The relative importance and relative feasibility measures for the seven clusters indicate significant statistical differences in ratings among the subgroup profiles. A discussion on the importance of relational capital in addressing challenges of digital transformation in SMEs is developed. Originality/value Results highlight signifiant differences concerning key dimensions in the adoption and use of IT from the perspective of three subgroup profiles of actors within the ecosystem. First, the results stress the need to develop a shared understanding of IT challenges. Second, they suggest policymakers could use these conceptual representations to further develop and strengthen the IT-related support agenda for SMEs, especially the smaller ones (e.g. training programs, business support and coaching initiatives, etc.).

We outline a public license (open source) electron microscopy platform, referred to as NanoMi. NanoMi offers a modular, flexible electron microscope platform that can be utilized for a variety of applications, such as microscopy education and development of proof-of-principle experiments, and can be used to complement an existing experimental apparatus. All components are ultra-high vacuum compatible and the electron optics elements are independent from the vacuum envelope. The individual optical components are mounted on a 127 mm (5-inch) diameter half-pipe, allowing customizing of electron optics for a variety of purposes. The target capabilities include SEM, TEM, scanning TEM (STEM), and electron diffraction (ED) at up to 50 keV incident electron energy. The intended image resolution in SEM, TEM and STEM modes is ≈ 10 nm. We describe the existing components and the interfaces among components that ensure their compatibility and interchangeability. The paper provides a resource for those who consider building or utilizing their own NanoMi.

This study synthesized evidence regarding the prevalence of post-traumatic stress disorder (PTSD) in the United States (US).A systematic literature review (SLR) identified recently published (2015-2019) observational studies of PTSD prevalence in the USData from 38 identified articles were categorized by population, diagnostic criteria, and lookback period. Among civilians, point prevalence ranged from 8.0% to 56.7%, 1-year prevalence from 2.3% to 9.1%, and lifetime prevalence from 3.4% to 26.9%. In military populations, point prevalence ranged from 1.2% to 87.5%, 1-year prevalence from 6.7% to 50.2%, and lifetime prevalence from 7.7% to 17.0%. Within these ranges, several estimates were derived from relatively high quality data; these articles are highlighted in the review. Prevalence was elevated in subpopulations including emergency responders, refugees, American Indian/Alaska Natives, individuals with heavy substance use, individuals with a past suicide attempt, trans-masculine individuals, and women with prior military sexual trauma. Female sex, lower income, younger age, and behavioral health conditions were identified as risk factors for PTSD.PTSD prevalence estimates varied widely, partly due to different study designs, populations, and methodologies, and recent nationally representative estimates were lacking. Efforts to increase PTSD screening and improve disease awareness may allow for a better detection and management of PTSD.

International audience; Background: Ofatumumab, a subcutaneous anti-CD20 monoclonal antibody, selectively depletes B cells. Teriflunomide, an oral inhibitor of pyrimidine synthesis, reduces T-cell and B-cell activation. The relative effects of these two drugs in patients with multiple sclerosis are not known.Methods: In two double-blind, double-dummy, phase 3 trials, we randomly assigned patients with relapsing multiple sclerosis to receive subcutaneous ofatumumab (20 mg every 4 weeks after 20-mg loading doses at days 1, 7, and 14) or oral teriflunomide (14 mg daily) for up to 30 months. The primary end point was the annualized relapse rate. Secondary end points included disability worsening confirmed at 3 months or 6 months, disability improvement confirmed at 6 months, the number of gadolinium-enhancing lesions per T1-weighted magnetic resonance imaging (MRI) scan, the annualized rate of new or enlarging lesions on T2-weighted MRI, serum neurofilament light chain levels at month 3, and change in brain volume.Results: Overall, 946 patients were assigned to receive ofatumumab and 936 to receive teriflunomide; the median follow-up was 1.6 years. The annualized relapse rates in the ofatumumab and teriflunomide groups were 0.11 and 0.22, respectively, in trial 1 (difference, -0.11; 95% confidence interval [CI], -0.16 to -0.06; P

The coherence and systemic strength of the collaborative process among thematic route stakeholders are key factors to economic success for individual businesses and regional economic development. The objective of this article is to identify the economic action set to rejuvenate the Cider Route and the Wine Route of the Montérégie region (Quebec, Canada). Group concept mapping is used to estimate the conceptualization and perceptions of stakeholders (cideries, wineries, tourism professionals, visitors) regarding the articulation of the action set. The contribution is threefold. Methodologically, the approach taken supports both the estimation of the concept map and associated perception measures. Empirically, eight action clusters are identified to articulate stakeholders’ “organizational” and “selling” dimensions of the routes. Practically, action priorities identified and feasibility constraints are helpful to target the capability development support needed by route stakeholders to collaborate. (JEL Classifications: D02, L23, L26, L66, Q18)

La litterature en cognition entrepreneuriale de la croissance insiste sur le manque de connaissances permettant de comprendre ce phenomene. De plus, peu de travaux ont porte sur l’efficacite des dispositifs d’accompagnement dedies a la croissance de la jeune TPE (Tres Petite Entreprise). Pourtant, dans la pratique, des divergences de representations collectives entre acteurs entrepreneuriaux au sujet des actions de croissance a mettre en œuvre menacent l’efficacite de ces dispositifs d’accompagnement. Une comprehension plus affinee des convergences et des divergences de representations entre les entrepreneurs et les accompagnateurs, en ce qui concerne les actions a mettre en œuvre pour soutenir la croissance comme resultat d’un processus d’orchestration des ressources, serait pertinente pour guider les acteurs entrepreneuriaux faisant face a ce defi. Afin d’eclairer cette problematique, la cartographie des concepts en groupe (CCG) doublee d’une analyse de Procuste aleatoire ont ete employees. Ce cadre methodologique mixte et ascendant permet de determiner empiriquement les representations des entrepreneurs et des accompagnateurs en isolant leurs correspondances spatiales respectives. L’empirie permet ainsi de determiner et de mesurer les convergences et les divergences de representations des actions de croissance qu’entretiennent ces acteurs entrepreneuriaux. Un positionnement epistemologique en realisme critique (RC) rend possible une contribution theorique en articulant les mecanismes generateurs (MG) de la croissance extraits des representations des acteurs entrepreneuriaux. Concernant la contribution manageriale de la recherche, des divergences de representations ont ete etablies quant aux actions de croissance associees au soutien, au financement et a la gestion des risques.