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Importance: The Medicare Part D Low Income Subsidy (LIS) program provides millions of beneficiaries with drug plan premium and cost-sharing assistance. The extent to which LIS recipients experience subsidy losses with annual redetermination cycles and the resulting associations with prescription drug affordability and use are unknown., Objective: To examine how frequently annual LIS benefits are lost among Medicare Part D beneficiaries and how this is associated with prescription drug use and out-of-pocket costs., Design, Setting, and Participants: In this cohort study of Medicare Part D beneficiaries from 2007 to 2018, annual changes in LIS recipients among those automatically deemed eligible (eg, due to dual eligibility for Medicare and Medicaid) and nondeemed beneficiaries who must apply for LIS benefits were analyzed using Medicare enrollment and Part D event data. Subsidy losses were classified in 4 groups: temporary losses (<1 year); extended losses (≥1 year); subsidy reductions (change to partial LIS); and disenrollment from Medicare Part D after subsidy loss. Temporary losses could more likely represent subsidy losses among eligible beneficiaries. Multinomial logit models were used to examine associations between beneficiary characteristics and subsidy loss; linear regression models were used to compare changes in prescription drug cost and use in the months after subsidy losses vs before. Analyses were conducted between November 2022 and November 2023., Exposure: Subsidy loss at the beginning of each year among subsidy recipients in December of the prior year., Main Outcomes and Measures: The main outcomes were out-of-pocket costs and prescription drug fills overall and for 4 classes: antidiabetes, antilipid, antidepressant, and antipsychotic drugs., Results: In 2008, 731 070 full LIS beneficiaries (17%) were not deemed automatically eligible (39% were aged <65 years; 59% were female). Nearly all beneficiaries deemed automatically eligible (≥99%) retained the subsidy annually from 2007 to 2018, compared with 78% to 84% of nondeemed beneficiaries. Among nondeemed beneficiaries, disabled individuals younger than 65 years and racial and ethnic minority groups were more likely to have temporary subsidy losses vs none. Temporary losses were associated with an average 700% increase in out-of-pocket drug costs (+$52.72/mo [95% CI, 52.52-52.92]) and 15% reductions in prescription fills (-0.58 fills/mo [95% CI, -0.59 to -0.57]) overall. Similar changes were found for antidiabetes, antilipid, antidepressant, and antipsychotic prescription drug classes. Beneficiaries who retained their subsidy had few changes., Conclusions and Relevance: The conclusions of this cohort study suggest that efforts to help eligible beneficiaries retain Medicare Part D subsidies could improve drug affordability, treatment adherence, and reduce disparities in medication access.

Background: Cervical dystonia (CD) is the most common form of focal dystonia encountered in the clinic. Approximately one-third of CD patients have co-existing tremor in the head and hands. Assessment of tremor as regular or irregular in context of its oscillation trajectory, frequency, and amplitude is a major clinical challenge and can confound the diagnosis of CD. The misdiagnosis may lead to therapeutic failures, poor quality of life, and poor utilization of medical and financial resources., Methods: We analyzed the largest cohort of CD patients ( n = 3117) available to date, collected from 37 movement disorder centers in North America, Europe, and Asia. We used machine learning to determine what clinical features from clinician reports predicted the presence of tremor as well as its regular or irregular appearance., Results: Out of 3,117 CD patients, 1,367 had neck tremor. The neck tremor was interpreted as irregular in 1,022, regular in 345, and mixed (both irregular and regular) in 442. A feature importance analysis determined that greater severity of CD, longer disease duration, and older age, in descending order, predicted the presence of neck tremor. The probability of neck tremor was reduced if the dystonia affected other body parts in addition to the neck. We also found a significantly heightened risk for developing neck tremor in women. An additional feature importance analysis indicated that increased severity of dystonia affecting other body parts, severity of CD, and prolonged disease duration was associated with a lower likelihood of regular neck tremor while increased age predicted a higher likelihood., Conclusion: Machine learning recognized the most relevant clinical features that can predict concurrent neck tremor and its irregularity in a large multi-center dystonia cohort. These results may facilitate a more accurate description of neck tremor and improved care path in CD., Competing Interests: Conflict of interest The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

This study examined COVID-19 infection and hospitalizations among people with serious mental illness who resided in residential care group homes in Massachusetts during the first year of the COVID-19 pandemic. The authors analyzed data on 2261 group home residents and COVID-19 data from the Massachusetts Department of Public Health. Outcomes included positive COVID-19 tests and COVID-19 hospitalizations March 1, 2020-June 30, 2020 (wave 1) and July 1, 2020-March 31, 2021 (wave 2). Associations between hazard of outcomes and resident and group home characteristics were estimated using multi-level Cox frailty models including home- and city-level frailties. Between March 2020 and March 2021, 182 (8%) residents tested positive for COVID-19, and 51 (2%) had a COVID-19 hospitalization. Compared with the Massachusetts population, group home residents had age-adjusted rate ratios of 3.0 (4.86 vs. 1.60 per 100) for COVID infection and 13.5 (1.99 vs. 0.15 per 100) for COVID hospitalizations during wave 1; during wave 2, the rate ratios were 0.5 (4.55 vs. 8.48 per 100) and 1.7 (0.69 vs. 0.40 per 100). In Cox models, residents in homes with more beds, higher staff-to-resident ratios, recent infections among staff and other residents, and in cities with high community transmission risk had greater hazard of COVID-19 infection. Policies and interventions that target group home-specific risks are needed to mitigate adverse communicable disease outcomes in this population.Clinical Trial Registration Number This study provides baseline (i.e., pre-randomization) data from a clinical trial study NCT04726371., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Purpose: Following major lower extremity amputation (LEA), patients experience significant emotional distress and are at risk for anxiety and depression. There is a lack of mental health supports for this population, and internet-based cognitive behavioural therapy (iCBT) may be a useful resource to meet this need. The purpose of this study was to use a qualitative approach to explore the mental health needs of LEA patients and to gauge their attitudes of the use of iCBT to help them cope with their amputation., Methods: Semi-structured qualitative interviews were conducted with inpatients and outpatients with LEA recruited from a major urban rehabilitation hospital. Data were analysed using inductive codebook thematic analysis (TA)., Results: Ten interviews were completed with individuals with LEA. The main themes identified were: (1) Fixating on the past; (2) Worry about the future; (3) Unmet mental health needs; (4) Barriers to Mental Health Support; (5) Importance of peer support; and (6) Tailoring iCBT., Conclusions: Our findings highlight that patients with LEA are open to learning more about iCBT to meet their mental health needs. Key iCBT implementation considerations include taking into account issues of stigma associated with mental health, timing of delivery, levels of digital literacy, online security, and interactive content.IMPLICATIONS FOR REHABILITATIONFollowing lower extremity amputation (LEA), people experience significant emotional distress and are at risk for the development of anxiety and/or depression.Patients with LEA are receptive to an online mental health resource (i.e., internet-based cognitive behavioural therapy [iCBT]) but it needs to be tailored to meet the various mental health needs and digital literacy of the LEA population.The use of an implementation science approach can help identify factors related to the development and potential uptake of an iCBT for patients with LEA.

Objective: To provide a research agenda and recommendations to address inequities in access to health care., Data Sources and Study Setting: The Agency for Healthcare Research and Quality (AHRQ) organized a Health Equity Summit in July 2022 to evaluate what equity in access to health care means in the context of AHRQ's mission and health care delivery implementation portfolio. The findings are a result of this Summit, and subsequent convenings of experts on access and equity from academia, industry, and the government., Study Design: Multi-stakeholder input from AHRQ's Health Equity Summit, author consensus on a framework and key knowledge gaps, and summary of evidence from the supporting literature in the context of the framework ensure comprehensive recommendations., Data Collection/extraction Methods: Through a stakeholder-engaged process, themes were developed to conceptualize access with a lens toward health equity. A working group researched the most appropriate framework for access to care to classify limitations identified during the Summit and develop recommendations supported by research in the context of the framework. This strategy was intentional, as the literature on inequities in access to care may itself be biased., Principal Findings: The Levesque et al. framework, which incorporates multiple dimensions of access (approachability, acceptability, availability, accommodation, affordability, and appropriateness), is the backdrop for framing research priorities for AHRQ. However, addressing inequities in access cannot be done without considering the roles of racism and intersectionality. Recommendations include funding research that not only measures racism within health care but also tests burgeoning anti-racist practices (e.g., co-production, provider training, holistic review, discrimination reporting, etc.), acting as a convener and thought leader in synthesizing best practices to mitigate racism, and forging the path forward for research on equity and access., Conclusions: AHRQ is well-positioned to develop an action plan, strategically fund it, and convene stakeholders across the health care spectrum to employ these recommendations., (© 2023 The Authors. Health Services Research published by Wiley Periodicals LLC on behalf of Health Research and Educational Trust.)

We report ATP1A3-associated rapid-onset dystonia-parkinsonism with an atypical presentation including myoclonus and exaggerated startle in four patients. Their prominence over parkinsonism prompted consideration of a syndromic diagnosis of myoclonus dystonia. ATP1α3 dysfunction in GABAergic neurons could explain these examination findings. The spectrum of ATP1A3-associated movement disorders includes myoclonus-dystonia., Competing Interests: Declaration of competing interest No COI., (Copyright © 2023. Published by Elsevier Ltd.)

Polar surfaces undergo polarity compensation, which can lead to significantly different surface chemistry from their nonpolar counterparts. This process in turn can substantially alter the binding of adsorbates on the surface. Here, we find that hydrogen binds much more strongly to the polar (110) surface than the nonpolar (100) surface for a wide range of ABO3 perovskites, forming a hydroxyl layer on the O24- termination and a hydride layer on the ABO4+ termination of the (110) surface. The stronger adsorption on the polar surfaces can be explained by polarity compensation: hydrogen atoms can act as electron donors or acceptors to compensate for the polarity of perovskite surfaces. The relative stability of the surface terminations is further compared under different gas environments and several perovskites have been found to form stable surface hydride layers under oxygen-poor conditions. These results demonstrate the feasibility of creating stable surface hydrides on perovskites by polarity compensation which might lead to new hydrogenation catalysts based on ABO3 perovskites., (© 2023 Author(s). Published under an exclusive license by AIP Publishing.)

Background: Adults with mental illnesses are more likely to have low income and diet-related chronic diseases., Objective: This study examined associations of mental illness diagnosis status with food insecurity and diet quality and whether the relationship between food security status and diet quality differed by mental illness diagnosis status in adult Medicaid beneficiaries., Design: This was a secondary cross-sectional analysis of baseline (2019-2020) data collected as part of the LiveWell study, a longitudinal study evaluating a Medicaid food and housing program., Participants/setting: Participants were 846 adult Medicaid beneficiaries from an eastern Massachusetts health system., Main Outcome Measures: Food security was measured with the 10-item US Adult Food Security survey module (0 = high food security, 1-2 = marginal food security, 3-10 = low/very low food security). Mental illness diagnoses included health record-documented anxiety, depression, or serious mental illness (eg, schizophrenia, bipolar disorder). Healthy Eating Index (HEI-2015) scores were calculated from 24-hour dietary recalls., Statistical Analyses: Multivariable regression analyses adjusted for demographics, income, and survey date., Results: Participants' mean (standard deviation) age was 43.1 (11.3) years, and 75% were female, 54% Hispanic, 33% non-Hispanic White, and 9% non-Hispanic Black. Fewer than half (43%) of participants reported high food security, with almost one third (32%) reporting low or very low food security. The 341 (40%) participants with one or more mental illness diagnosis had greater odds of low/very low food security (adjusted odds ratio [OR], 1.94; 95% confidence interval [CI], 1.38-2.70) and had similar mean HEI-2015 scores (53.1 vs 56.0; P = 0.12) compared with participants with no mental illness diagnosis. Mean adjusted HEI-2015 scores did not significantly differ by high vs low/very low food security for those without a mental illness diagnosis (57.9 vs 54.9; P = 0.052) or those with a mental illness diagnosis (53.0 vs 52.9; P = 0.99)., Conclusion: In a cohort of adults with Medicaid, those with mental illness diagnoses had higher odds of experiencing food insecurity. Overall, diet quality among adults in this sample was low but did not differ by mental illness diagnosis or food security status. These results highlight the importance of augmenting efforts to improve both food security and diet quality among all Medicaid participants., (Copyright © 2023 Academy of Nutrition and Dietetics. Published by Elsevier Inc. All rights reserved.)

Platinum nanoparticles (Pt-NPs) supported on titania surfaces are costly but indispensable heterogeneous catalysts because of their highly effective and selective catalytic properties. Therefore, it is vital to understand their physicochemical processes during catalysis to optimize their use and to further develop better catalysts. However, simulating these dynamic processes is challenging due to the need for a reliable quantum chemical method to describe chemical bond breaking and bond formation during the processes but, at the same time, fast enough to sample a large number of configurations required to compute the corresponding free energy surfaces. Density functional theory (DFT) is often used to explore Pt-NPs; nonetheless, it is usually limited to some minimum-energy reaction pathways on static potential energy surfaces because of its high computational cost. We report here a combination of the density functional tight binding (DFTB) method as a fast but reliable approximation to DFT, the steered molecular dynamics (SMD) technique, and the Jarzynski equality to construct free energy surfaces of the temperature-dependent diffusion and growth of platinum particles on a titania surface. In particular, we present the parametrization for Pt-X (X = Pt, Ti, or O) interactions in the framework of the second-order DFTB method, using a previous parametrization for titania as a basis. The optimized parameter set was used to simulate the surface diffusion of a single platinum atom (Pt 1 ) and the growth of Pt 6 from Pt 5 and Pt 1 on the rutile (110) surface at three different temperatures ( T = 400, 600, 800 K). The free energy profile was constructed by using over a hundred SMD trajectories for each process. We found that increasing the temperature has a minimal effect on the formation free energy; nevertheless, it significantly reduces the free energy barrier of Pt atom migration on the TiO 2 surface and the transition state (TS) of its deposition. In a concluding remark, the methodology opens the pathway to quantum chemical free energy simulations of Pt-NPs' temperature-dependent growth and other transformation processes on the titania support.

Adoptive immunotherapy with Tregs is a promising approach for preventing or treating type 1 diabetes. Islet antigen-specific Tregs have more potent therapeutic effects than polyclonal cells, but their low frequency is a barrier for clinical application. To generate Tregs that recognize islet antigens, we engineered a chimeric antigen receptor (CAR) derived from a monoclonal antibody with specificity for the insulin B chain 10-23 peptide presented in the context of the IAg7 MHC class II allele present in NOD mice. Peptide specificity of the resulting InsB-g7 CAR was confirmed by tetramer staining and T cell proliferation in response to recombinant or islet-derived peptide. The InsB-g7 CAR redirected NOD Treg specificity such that insulin B 10-23-peptide stimulation enhanced suppressive function, measured via reduction of proliferation and IL-2 production by BDC2.5 T cells and CD80 and CD86 expression on dendritic cells. Cotransfer of InsB-g7 CAR Tregs prevented adoptive transfer diabetes by BDC2.5 T cells in immunodeficient NOD mice. In WT NOD mice, InsB-g7 CAR Tregs prevented spontaneous diabetes. These results show that engineering Treg specificity for islet antigens using a T cell receptor-like CAR is a promising therapeutic approach for the prevention of autoimmune diabetes.

Sequencing plays a critical role in protein engineering, where the genetic information encoding for a desired mutation can be identified. We evaluated the performance of two commercially available NGS technologies (Illumina NGS and nanopore sequencing) on the available mutant libraries that were either previously constructed for other protein engineering projects or constructed in-house for this study. The sequencing results from Illumina sequencing indicated that a substantial proportion of the reads exhibited strand exchange, which mixed information of different mutants. When nanopore sequencing was used, the occurrence of strand exchange was substantially reduced compared with that of Illumina sequencing. We then developed a new library preparation workflow for nanopore sequencing and were successful in further reducing the incidence of strand exchange. The optimized workflow was successfully used to aid selection of improved alcohol dehydrogenase mutants in cells where their activities were coupled with the cell growth rate. The workflow quantified the enrichment fold change of most mutants in the library (size = 1728) in the growth-based selection passaging. A mutant that was >500% more active than its parent variant was identified based on the fold change data but not with the absolute abundance data (random sampling of the passaged cells), highlighting the usefulness of this rapid and affordable sequencing workflow in protein engineering.

In 2021 the American Rescue Plan Act increased premium subsidies for people purchasing insurance from the Affordable Care Act Marketplaces and provided zero-premium Marketplace plans that covered 94 percent of medical care costs (silver 94 plans) to recipients of unemployment compensation. Using data on adult enrollees in on- and off-Marketplace individual plans in California in 2021, we found that 41 percent reported incomes at or below 400 percent of the federal poverty level and that 39 percent reported living in households receiving unemployment compensation. Overall, 72 percent of enrollees reported having no difficulty paying premiums, and 76 percent reported that out-of-pocket expenses did not affect their seeking of medical care. The majority of enrollees eligible for plans with cost-sharing subsidies were enrolled in Marketplace silver plans (56-58 percent). Many of these enrollees, however, may have missed opportunities for premium or cost-sharing subsidies: 6-8 percent enrolled in off-Marketplace plans and were more likely to have difficulty paying premiums than those in Marketplace silver plans, and more than one-quarter enrolled in Marketplace bronze plans and were more likely to delay care because of cost than those in Marketplace silver plans. In the coming era of expanded Marketplace subsidies under the Inflation Reduction Act of 2022, helping consumers identify high-value and subsidy-eligible plans could mitigate remaining affordability problems.

Objective: The authors examined associations between criminal legal involvement (CLI) and serious psychological distress and how these associations differed by racial-ethnic group., Methods: The authors conducted a retrospective analysis of multiple cross-sections of data from the National Survey on Drug Use and Health (2015-2019) and used multivariable linear probability regression models to assess lifetime CLI and past-year probation, parole, supervised release, or other conditional release in a nationally representative sample of noninstitutionalized U.S. adults, ages ≥18 years (N=214,505), with and without serious psychological distress., Results: Adults with serious psychological distress had higher rates of CLI than adults without such distress (difference of 4.1 percentage points, 95% CI=3.3-4.8, p<0.001). The rate of CLI increased as distress severity increased, from mild (3.2 percentage-point difference, 95% CI=2.6-3.8, p<0.001) to high (7.2 percentage-point difference, 95% CI=6.4-8.0, p<0.001). The risk for CLI among those with serious psychological distress was even greater for Black and Latinx adults than for White adults (1.8 percentage-point difference, 95% CI=0.1-3.5, p<0.05, and 3.2 percentage-point difference, 95% CI=1.3-5.2, p<0.01, respectively)., Conclusions: Rates of CLI were higher for adults with serious psychological distress. Efforts are needed to equitably triage individuals with acute mental health needs to timely psychiatric care instead of carceral settings. Collaborative models of care that commingle resources from mental health and law enforcement organizations are needed to prevent unnecessary incarceration of individuals experiencing mental health crises and to increase access to community-based treatment., Competing Interests: Dr. Fung serves as a consultant for Headspace and owns equity in and receives financial support from Vertex Pharmaceuticals. The other authors report no financial relationships with commercial interests.

Importance: Health systems are increasingly addressing health-related social needs. The Massachusetts Flexible Services program (Flex) is a 3-year pilot program to address food insecurity and housing insecurity by connecting Medicaid accountable care organization (ACO) enrollees to community resources., Objective: To understand barriers and facilitators of Flex implementation in 1 Medicaid ACO during the first 17 months of the program., Design, Setting, and Participants: This mixed-methods qualitative evaluation study from March 2020 to July 2021 used the Reach, Efficacy, Adoption, Implementation, Maintenance/Practical, Robust Implementation, and Sustainability Model (RE-AIM/PRISM) framework. Two Mass General Brigham (MGB) hospitals and affiliated community health centers were included in the analysis. Quantitative data included all MGB Medicaid ACO enrollees. Qualitative interviews were conducted with 15 members of ACO staff and 17 Flex enrollees., Main Outcomes and Measures: Reach was assessed by the proportion of ACO enrollees who completed annual social needs screening (eg, food insecurity and housing insecurity) and the proportion and demographics of Flex enrollees. Qualitative interviews examined other RE-AIM/PRISM constructs (eg, implementation challenges, facilitators, and perceived effectiveness)., Results: Of 67 098 Medicaid ACO enrollees from March 2020 to July 2021 (mean [SD] age, 28.8 [18.7] years), 38 442 (57.3%) completed at least 1 social needs screening; 10 730 (16.0%) screened positive for food insecurity, and 7401 (11.0%) screened positive for housing insecurity. There were 658 (1.6%) adults (mean [SD] age, 46.6 [11.8] years) and 173 (0.7%) children (<21 years; mean [SD] age, 10.1 [5.5]) enrolled in Flex; of these 831 people, 613 (73.8%) were female, 444 (53.4%) were Hispanic/Latinx, and 172 (20.7%) were Black. Most Flex enrollees (584 [88.8%] adults; 143 [82.7%] children) received the intended nutrition or housing services. Implementation challenges identified by staff interviewed included administrative burden, coordination with community organizations, data-sharing and information-sharing, and COVID-19 factors (eg, reduced clinical visits). Implementation facilitators included administrative funding for enrollment staff, bidirectional communication with community partners, adaptive strategies to identify eligible patients, and raising clinician awareness of Flex. In Flex enrollee interviews, those receiving nutrition services reported increased healthy eating and food security; they also reported higher program satisfaction than Flex enrollees receiving housing services. Enrollees who received nutrition services that allowed for selecting food based on preferences reported higher satisfaction than those not able to select food., Conclusions and Relevance: This mixed-methods qualitative evaluation study found that to improve implementation, Medicaid and health system programs that address social needs may benefit from providing funding for administrative costs, developing bidirectional data-sharing platforms, and tailoring support to patient preferences.

Background: Collaborative care models (CoCM) that integrate mental health and primary care improve outcomes and could help address racial and ethnic mental health disparities. We examined whether use of these programs differs by race/ethnicity., Methods: This retrospective study examined two CoCM interventions implemented across primary care clinics in a large health system in Massachusetts: 1) a primary care-based behavioral health program for depression or anxiety (IMPACT model) and 2) referral to community-based specialty care services (Resource-finding). Outcomes included enrollment, non-completion, and symptom screening rates, and discharge status for Black, Hispanic and White patients referred for CoCM, 2017-2019., Results: Black and Hispanic vs. White patients referred to CoCM (n = 17,280) were more likely to live in high poverty ZIP codes (34% and 40% vs. 9%). Rates of program enrollment, non-completion, and symptom screening were similar across groups (e.g., 76%, 77%, and 75% of Black, Hispanic, and White patients enrolled). Hispanic vs. White patients were more likely to be enrolled in IMPACT (56%) vs. Resource-finding (43%). Among those completing IMPACT, Hispanic vs. White patients were more likely to be stepped to psychiatry vs. discharged to their primary care provider (51% vs. 20%, aOR = 1.55, 95% CI: 1.02-2.35)., Conclusions: Black and Hispanic patients referred to CoCM were similarly likely to use the program as White patients. Hispanic patients completing IMPACT were more frequently referred to psychiatry., Implications: These results highlight the promise of CoCMs for engaging minority populations in mental healthcare. Hispanic patients may benefit from additional intervention or earlier linkage to specialty care., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Dr. Kovachy: None. Dr. Chang: None. Dr. Vogeli: Grant support from the National Institute of Aging, and National Institute of Diabetes and Digestive and Kidney Diseases Suzanne Tolland: None Susan Garrels: None Dr. Forester: Grant support from National Institute of Aging, Rogers Family Foundation Spier Family Foundation, Biogen, and Lilly. Dr. Fung: Grant support from the National Institutes of Health, Agency for Healthcare Research and Quality; Holds equity in Vertex pharmaceuticals, (Copyright © 2023 Elsevier Inc. All rights reserved.)

Microsurgical breast reconstruction accounts for 22% of breast reconstructions in the UK. Despite thromboprophylaxis, venous thromboembolism (VTE) occurs in up to 4% of cases. Using a Delphi process, this study established a UK consensus on VTE prophylaxis strategy, for patients undergoing autologous breast reconstruction using free-tissue transfer. It captured geographically divergent views, producing a guide that reflected the peer opinion and current evidence base., Methods: Consensus was ascertained using a structured Delphi process. A specialist from each of the UK's 12 regions was invited to the expert panel. Commitment to three to four rounds of questions was sought at enrollment. Surveys were distributed electronically. An initial qualitative free-text survey was distributed to identify likely lines of consensus and dissensus. Each panelist was provided with full-text versions of key papers on the topic. Initial free-text responses were analyzed to develop a set of structured quantitative statements, which were refined via a second survey as a consensus was approached., Results: The panel comprised 18 specialists: plastic surgeons and thrombosis experts from across the UK. Each specialist completed three rounds of surveys. Together, these plastic surgeons reported having performed more than 570 microsurgical breast reconstructions in the UK in 2019. A consensus was reached on 27 statements, detailing the assessment and delivery of VTE prophylaxis., Conclusion: To our knowledge, this is the first study to collate current practice, expert opinion from across the UK, and a literature review. The output was a practical guide for VTE prophylaxis for microsurgical breast reconstruction in any UK microsurgical breast reconstruction unit., Competing Interests: Conflicts of interest None of the authors hold any conflicts of interest., (Copyright © 2023 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.)

Objective: Individuals with serious mental illness have a high prevalence of tobacco use disorder and related early mortality but underutilize smoking cessation medication. The authors determined whether clinician-delivered education to primary care providers regarding safety, efficacy, and importance of cessation medication (provider education [PE]) alone or combined with community health worker (CHW) support would increase tobacco abstinence in this population, compared with usual care., Methods: All adult current tobacco smokers receiving psychiatric rehabilitation for serious mental illness through two community agencies in Greater Boston were eligible, regardless of readiness to quit smoking. Primary care clinics were cluster randomized to PE or usual care, with a nested, participant-level randomization to CHW or no CHW in PE-assigned clinics. The primary outcome was blindly assessed, biochemically verified tobacco abstinence at year 2., Results: Overall, 1,010 eligible participants were enrolled. PE was delivered to providers in 53 of 55 assigned clinics; 220 of 336 CHW-assigned participants consented to CHW support. Year 2 abstinence rates were significantly higher among participants assigned to PE+CHW versus usual care (12% vs. 5%; adjusted odds ratio [AOR]=2.40, 95% confidence interval [CI]=1.20-4.79) or PE alone (12% vs. 7%; AOR=1.84, 95% CI=1.04-3.24). No effect of PE alone on abstinence was detected. Compared with participants assigned to usual care, those assigned to PE+CHW had greater odds of varenicline use (OR=2.77, 95% CI=1.61-4.75), which was associated with higher year 2 abstinence (OR=1.97, 95% CI=1.16-3.33)., Conclusions: Combined PE and CHW tobacco cessation support increased tobacco abstinence rates among adults with serious mental illness.

Introduction: Smoke-free policies (SFP) in multi-unit housing are a promising tool for reducing exposure to tobacco smoke among residents. Concerns about increased housing instability due to voluntary or involuntary transitions induced by SFPs have been a primary barrier to greater widespread adoption. The impact of SFP implementation on transitions out of public housing in federally funded public housing authorities in Massachusetts was evaluated., Methods: Tenancy data from the Department of Housing and Urban Development were used to determine the time from admission to transitioning out of public housing based on a cohort study design. Periods of exposure to SFPs were defined based on dates of SFP implementation at each PHA. Multi-level Cox regression models were fit to estimate the effects of SFPs on the hazard of transitioning, adjusting for household- and PHA-level characteristics. Analyses were conducted in 2021‒2022., Results: There were 44,705 households with a record of residence in Massachusetts PHAs over 2009‒2018. Over this period, despite increasing adoption of SFPs among the PHAs, rates of transition remained steady at around 5‒8 transitions per 1,000 household-months. There was no overall association between exposure to SFPs and transitions among the full sample (adjusted HR=0.99, 95% CI=0.95, 1.04, p=0.794). However, the association varied significantly by age group, race/ethnicity, timing of SFP adoption, and era of admission., Conclusions: Adoption of SFPs in public housing had a minimal overall impact on turnover for households in Massachusetts, though disparities in the impact were observed between different demographic and PHA-level subgroups., (Copyright © 2022 American Journal of Preventive Medicine. Published by Elsevier Inc. All rights reserved.)

Human epidermal growth factor receptor 2 (HER2) is a receptor tyrosine kinase that plays an oncogenic role in breast, gastric and other solid tumors. However, anti-HER2 therapies are only currently approved for the treatment of breast and gastric/gastric esophageal junction cancers and treatment resistance remains a problem. Here, we engineer an anti-HER2 IgG1 bispecific, biparatopic antibody (Ab), zanidatamab, with unique and enhanced functionalities compared to both trastuzumab and the combination of trastuzumab plus pertuzumab (tras + pert). Zanidatamab binds adjacent HER2 molecules in trans and initiates distinct HER2 reorganization, as shown by polarized cell surface HER2 caps and large HER2 clusters, not observed with trastuzumab or tras + pert. Moreover, zanidatamab, but not trastuzumab nor tras + pert, elicit potent complement-dependent cytotoxicity (CDC) against high HER2-expressing tumor cells in vitro. Zanidatamab also mediates HER2 internalization and downregulation, inhibition of both cell signaling and tumor growth, antibody-dependent cellular cytotoxicity (ADCC) and phagocytosis (ADCP), and also shows superior in vivo antitumor activity compared to tras + pert in a HER2-expressing xenograft model. Collectively, we show that zanidatamab has multiple and distinct mechanisms of action derived from the structural effects of biparatopic HER2 engagement., (© 2023. The Author(s).)

Background: The aim of this study is to review long-term outcome and identify risk factors for patients with peripheral arterial disease (PAD) with percutaneous transluminal angioplasty/stent as a primary treatment strategy for intermittent claudication (IC) or chronic limb-threatening ischemia (CLTI)., Methods: A retrospective cohort study with data collected prospectively from Clinical Data Analysis and Reporting System, departmental database, and Clinical Management System. All patients who underwent endovascular procedures for PAD between January 2011 and December 2020 were identified. The primary outcomes are overall survival and amputation-free survival. Predictive factors for OS and AFS were determined using Cox Model., Results: A total number of 640 patients with PAD (IC, n = 243; CLTI, n = 377) underwent endovascular percutaneous transluminal angioplasty/stenting for PAD from January 2011 to December 2020. Patients with CLTI had a significantly higher 30 days readmission rate (18.8% vs. 6.5%, P < 0.001), emergency reoperation within 30 days (3.4% vs. 0%, P = 0.002), and death within same admission (2.7% vs. 0%, P = 0.008) compared to IC patients. The overall survival and amputation-free survival rates were significantly lower in CLTI patients (P < 0.0001 and P < 0.0001, respectively). On Cox multivariate analysis, CLTI was strongly predictive of all-cause mortality and amputation (hazard ratio [HR] 2.33 and HR 14.92, respectively). In patients with CLTI, chronic kidney disease was an independent predictor of mortality and amputation (HR 1.66 and HR 2.36, respectively). Smoking and ischemic heart disease were also independent predictors of mortality in this subgroup (HR 2.06 and HR 2.43, respectively)., Conclusions: Although patients with IC and CLTI both manifest from atherosclerotic occlusive disease of the lower limb arteries, these patients may have different clinical outcomes with significant mortality occurred in both IC and CLTI groups. In patients with IC, the risk of amputation was less than 1% at 5 years following revascularization., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Objective: Patients with bipolar disorder treated with lithium often require additional antipsychotics or anticonvulsants. However, the comparative effectiveness and safety of these agents as add-on to lithium has not been studied., Methods: This secondary analysis combined two similar 24-week trials on outpatients with bipolar disorder randomized to lithium (target serum level 0.4-0.6 mEq/L). Guideline-based adjunctive antipsychotics (Li+AP) and anticonvulsants (Li+AC) could be used if clinically indicated and was assessed at every study visit. Response was measured on the Clinical Global Impression scale and we performed adjusted mixed effects linear regression analyses. Analysis of variance tests compared metabolic measures including a binary diagnosis of metabolic syndrome before and after 24 weeks of treatment., Results: Among 379 outpatients (57% female, mean age 38 years, mean Clinical Global Impression 4.4), users of Li+AP ( N  = 50, primarily quetiapine and aripiprazole) improved to a similar degree (mean Clinical Global Impression improvement = 1.6, standard deviation = 1.5) as those using lithium-only (i.e. without adjunctive antipsychotics or anticonvulsants, N  = 149, mean Clinical Global Impression improvement = 1.7, standard deviation = 1.4) ( p  = 0.59). Users of Li+AC ( N  = 107, primarily lamotrigine and valproate, mean Clinical Global Impression improvement = 1.2, standard deviation = 1.3) and users of Li+AP+AC ( N  = 73, mean Clinical Global Impression improvement = 1.1, standard deviation = 1.3) showed worse response compared to lithium-only users (all p  < 0.01). When comparing Li+AP to Li+AC, users of Li+AP improved slightly better on general ( p  = 0.05) and manic symptoms ( p  = 0.01), but showed a worse development of glucose, triglycerides, and metabolic syndrome., Conclusion: Despite treatment-by-indication confounding, these findings are relevant for real-world treatment settings and emphasize the need for randomized trials on this clinically important topic.

Many older Americans do not receive needed care for mental health and substance use disorders (MHSUD), and there are substantial racial and ethnic disparities in receipt of this care across the lifespan. Medicare introduced cost-sharing parity for outpatient MHSUD care during the period 2010-14, reducing beneficiaries' out-of-pocket share of MHSUD spending from 50 percent to 20 percent. Among traditional Medicare beneficiaries ages sixty-five and older, we examined changes in MHSUD use and spending during the period 2008-18 for low-income beneficiaries with the cost-sharing reduction versus a control group of beneficiaries with free care throughout the study period among Black, Hispanic, Asian, and American Indian/Alaska Native versus White beneficiaries. Among older Medicare beneficiaries, overall use of MHSUD services increased during this period. For White beneficiaries, MHSUD cost-sharing parity was associated with an increased likelihood of having specialty MHSUD visits and medication use and a reduced likelihood of having unmonitored MHSUD medication use and MHSUD emergency department visits and hospitalizations. However, cost-sharing parity was associated with smaller or no gains in MHSUD services use for racial and ethnic minority beneficiaries compared with White beneficiaries, thus widening racial and ethnic disparities in MHSUD care.

A 2018 rule requiring federally-subsidized public housing authorities (PHAs) in the United States to adopt smoke-free policies (SFPs) has sparked interest in how housing agencies can best implement SFPs. However, to date, there is little quantitative data on the implementation of SFPs in public housing. Massachusetts PHAs were among the pioneers of SFPs in public housing, and many had instituted SFPs voluntarily prior to the federal rule. The aim of this study was to examine the adoption, implementation, and outcomes of SFPs instituted in Massachusetts PHAs prior to 2018 using a survey conducted that year. The survey asked if PHAs had SFPs and, if so, what activities were used to implement them: providing information sessions, offering treatment or referral for smoking cessation, soliciting resident input, training staff, partnering with outside groups, using a toolkit, and/or providing outdoor smoking areas. We used multivariable regression to investigate associations between implementation activities and respondent-reported policy outcomes (resident support, complaints about neighbors' smoking, and the number of violations reported per year). Of 238 Massachusetts PHAs, 218 (91%) completed the survey and 161 had an SFP prior to 2018. Common implementation activities were offering smoking cessation treatment/referral (89%) and information sessions for residents (85%). Information sessions for residents were associated with higher resident support (adjusted odds ratio [AOR] 4.3; 95%CI 1.2-15.3). Training staff (AOR 6.3, 95%CI 1.2-31.8) and engaging in ≥5 implementation activities (AOR 4.1, 95%CI 1.2-14.1) were associated with fewer smoking-related complaints. Utilization of multiple implementation activities, especially ones that informed residents and trained PHA staff, was associated with more favorable policy outcomes. We identified five groups of PHAs that shared distinct patterns of SFP implementation activities. Our findings, documenting implementation activities and their associations with SFP outcomes among the early adopters of SPFs in Massachusetts public housing, can help inform best practices for the future implementation of SFPs in multiunit housing.

Colloidally prepared core@shell nanoparticles (NPs) were converted to monodisperse high entropy alloy (HEA) NPs by annealing, including quinary, senary, and septenary phases comprised of PdCuPtNi with Co, Ir, Rh, Fe, and/or Ru. Intraparticle heterogeneity, i.e., subdomains within individual NPs with different metal distributions, was observed for NPs containing Ir and Ru, with the phase stabilities of the HEAs studied by atomistic simulations. The quinary HEA NPs were found to be durable catalysts for the oxygen reduction reaction, with all but the PdCuPtNiIr NPs presenting better activities than commercial Pt. Density functional theory (DFT) calculations for PdCuPtNiCo and PdCuPtNiIr surfaces (the two extremes in performance) found agreement with experiment by weighting the adsorption energy contributions by the probabilities of each active site based on their DFT energies. This finding highlights how intraparticle heterogeneity, which we show is likely overlooked in many systems due to analytical limitations, can be leveraged toward efficient catalysis.

Objective: The authors used a large clinical data set to determine which index diagnoses of schizophrenia spectrum disorder were new diagnoses., Methods: Using the Massachusetts All-Payer Claims Database (2012–2016), the authors identified patients with a schizophrenia spectrum disorder diagnosis in 2016 (index diagnosis) and then reviewed patients’ care histories for the previous 12, 24, 36, and 48 months to identify previous diagnoses. Logistic regression was used to examine patient characteristics associated with the index diagnosis being a new diagnosis., Results: Overall, 7,217 individuals ages 15–35 years had a 2016 diagnosis of schizophrenia spectrum disorder; 67.7% had at least 48 months of historical data. Among those with at least 48 months of care history, 23% had no previous diagnoses. Diagnoses from inpatient psychiatric admissions or among female or younger patients were more likely to represent new diagnoses, compared with diagnoses from most other diagnosis locations or among males or older age groups, and outpatient diagnoses were less likely to represent new diagnoses than were most other diagnosis settings. Reviewing 48 instead of 12 months of data reduced estimated rates of new diagnoses from 112 to 66 per 100,000 persons; historical diagnoses were detected for 61% and 77% of patients with 12 or 48 months of care history, respectively., Conclusions: Examining multiple years of patient history spanning all payers and providers is critical to identifying new schizophrenia spectrum disorder diagnoses in large data sets. Review of 48 months of care history resulted in lower rates of new schizophrenia spectrum disorder diagnoses than previously reported.

Hydrogen spillover, involving the transfer of H atoms from metal sites onto the catalyst support, is ubiquitous in chemical processes such as catalytic hydrogenation and hydrogen storage. Atomic level information concerning the kinetics of this process, the structural evolution of catalysts during hydrogen spillover, as well as the nature of participation of the spilled over H in catalysis, remain vastly lacking. Here, we provide insights to those questions with a solubilized polyoxometalate-supported single-atom catalyst which allows for the use of characterization techniques generally inaccessible to the study of heterogeneous catalysts. Hydrogenation kinetics together with poisoning studies further reveal that hydrogen spillover can be either detrimental or beneficial for catalysis, the direction and magnitude of which depends mostly on the nature of the reducible functional group. Similar trends were observed on one of the most prototypical hydrogen spillover catalysts-Pt/WO 3 ., (© 2022 Wiley-VCH GmbH.)

Fungal entomopathogens can greatly reduce the fitness of their hosts, and it is therefore expected that susceptible insects will be selected to avoid exposure to pathogens. Metarhizium brunneum is a fungal pathogen that can infect Agriotes obscurus, which in its larval form is a destructive agricultural pest and is repelled by the presence of M. brunneum conidia. Due to the subterranean nature of larval A. obscurus, recent research has focused on targeting adult A. obscurus with M. brunneum. No-choice and choice behavioural assays were conducted to determine if male adult A. obscurus avoid M. brunneum mycosed cadavers, or conidia applied to either food or soil. To further investigate the response of A. obscurus beetles to conspecific cadavers, the movement and behaviour of beetles placed at the centre of a semi-circular arrangement of mycosed or control cadavers was examined using motion tracking software. We found little evidence to suggest that A. obscurus male beetles avoid M. brunneum conidia or mycosed conspecific cadavers or alter their behaviour in their presence., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022. Published by Elsevier Inc.)

Background: There is currently very limited data related to transition services for movement disorders., Objectives: Movement Disorders Society (MDS) Task Force on Pediatrics conducted a survey of current provision of transition for young adults with movement disorders., Methods: The survey questionnaire was based on review of available evidence, with questions designed to capture service location, transition clinic structure, and core issues discussed. The questionnaire was digitalized as an online survey and sent to all members of the MDS., Results: Responses were received from a total of 252 MDS members representing 67 countries. Of the responders, 59% confirmed that they provided transition clinics for adolescents with movement disorders. Overall, there was some consensus regarding transition services in terms of patient age at transition, movement disorder etiologies, staffing the service, and medical/social issues discussed., Conclusion: This survey provides first-hand data of existing movement disorder transition services and provides useful insights on transition clinics., Competing Interests: The authors declare that there are no funding sources or conflicts of interest relevant to this work., (© 2022 The Authors. Movement Disorders Clinical Practice published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.)

Objectives: The 2021 American Rescue Plan Act (ARPA) increased the availability and magnitude of premium tax credits (PTCs) for consumers purchasing individual marketplace plans in 2021-2022. Millions currently purchase PTC-ineligible plans off of the marketplace. We estimate the proportion of off-marketplace enrollees who would be eligible for the expanded PTCs under ARPA, calculate PTC amounts for eligible enrollees, and examine factors influencing plan choice that could inform outreach efforts., Study Design: We analyzed data from a survey of a random sample of off-marketplace enrollees in California in 2017 (n = 829)., Methods: Using survey data including self-reported income, household size, and employment status combined with 2021 benchmark premium data from Covered California, we estimate eligibility for PTCs and potential PTC amounts under ARPA among off-marketplace enrollees. We adjust for both survey design weights and poststratification weights., Results: Among off-marketplace enrollees, we estimate that approximately 12% are potentially ineligible for PTCs because they reported incomes less than 100% of the poverty level or because they had access to employer-sponsored coverage for their family through themselves or their partner. The median annual PTC in 2021 for eligible off-marketplace enrollees was $311 but varied greatly by age, family or individual plan, and household income (5%-95% range, $0-$14,836). In 2017, 69% of off-marketplace enrollees were unaware that they had to enroll in marketplace plans to receive PTCs, and 51% received enrollment assistance from insurance brokers., Conclusions: These findings suggest the need for targeted outreach to encourage off-marketplace enrollees to switch to marketplace plans.

Agricultural biomass remains as one of the commonly found waste on Earth. Although valorisation of these wastes has been studied in detail, the fermentation-based processes still need improvement due to the high cost of hydrolysing enzymes, and the presence of growth inhibitors which constrains the fermentation to produce high-value products. To address these challenges, we developed an integrated process in this study combining abiotic- and bio-catalysis to produce l-tyrosine from corn husk. The first step involved a one-pot hydrolytic hydrogenation tandem reaction without the use of the expensive enzymes, which yielded a mixture of polyols and sugars. Without any purification, these crude hydrolysates can be almost completely utilized by an engineered Escherichia coli strain, which did not exhibit any growth inhibition. The strain produced 0.44 g/L l-tyrosine from 10 g/L crude corn husk hydrolysates, demonstrating the feasibility of converting agricultural biomass into a valuable aromatic amino acid via an integrated process., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Importance: Young adults historically have had the highest uninsured rates among all age groups. In 2014, in addition to Medicaid expansion for adults with low income (≤133% of the federal poverty level [FPL]) through the Patient Protection and Affordable Care Act, Massachusetts also extended eligibility for children (≤150% FPL) to beneficiaries aged 19 to 20 years., Objective: To examine changes in insurance coverage continuity for Medicaid enrollees who turned age 19 years before and after eligibility policy changes., Design Setting and Participants: This cohort study used data from the Massachusetts All-Payer Claims Database (2012 to 2016) to compare coverage for Medicaid beneficiaries turning age 19 years before and after Medicaid expansion. Monthly coverage was examined for each cohort for 3 years as beneficiaries aged from 18 and 19 years to 19 and 20 years to 20 and 21 years. Analyses were performed between November 1, 2020, and May 12, 2022., Main Outcomes and Measures: In each year, the likelihood of being uninsured or having Medicaid, employer-sponsored insurance, or individual commercial coverage for 3 or more months was examined along with the likelihood of having continuous Medicaid enrollment for 12 or more and 24 or more months. Multivariable linear probability models were used to compare the likelihood of these outcomes for those in the postexpansion vs preexpansion cohorts, adjusting for sex, comorbidity levels, neighborhood socioeconomic status, and neighborhood race and ethnicity., Results: A total of 41 247 young adults turning age 18 to 19 years in the baseline year (20 876 [50.6%] men) were included in the study, with 20 777 in the preexpansion cohort and 20 470 in the postexpansion cohort. Enrollees who turned age 19 years after vs before the Medicaid eligibility expansion were less likely to have 3 or more uninsured months at ages 18 to 19 years (4.4% [n = 891] vs 22.9% [n = 4750]; adjusted difference, -18.4 [95% CI, -19.0 to -17.7] percentage points) and 19 to 20 years (13.2% [n = 2702] vs 35.8% [n = 7447]; adjusted difference, -22.4 [95% CI, -23.2 to -21.6] percentage points) and more likely to have continuous insurance coverage for 12 or more months (94.1% [n = 19 272] vs 63.7% [n = 13 234]; adjusted difference, 30.5 [95% CI, 29.7-31.2] percentage points) or 24 or more months (77.5% [n = 15 868] vs 44.4% [n = 9221]; adjusted difference, 33.0 [95% CI, 32.1-33.9] percentage points). Differences in the likelihood of having 3 or more uninsured months diminished at ages 20 to 21 years, when both groups had access to Medicaid (ie, in calendar years 2014 for the preexpansion cohort and 2016 for the postexpansion cohort)., Conclusions and Relevance: In this cohort study of young adults in Massachusetts, the combination of expanding Medicaid to lower-income adults and increasing the age threshold for child Medicaid eligibility was associated with reduced likelihood of becoming uninsured among Medicaid enrollees entering adulthood., Competing Interests: Conflict of Interest Disclosures: Dr Fung reported receiving grants from the National Institutes of Health (NIH) and Agency for Healthcare Research and Quality (AHRQ) and personal fees from Ginger outside the submitted work. Dr Yang reported receiving grants from AHRQ during the conduct of the study. Dr Hsu reported receiving grants from the NIH and AHRQ during the conduct of the study and personal fees for consulting from Cambridge Health Alliance, AltaMed, Columbia University, University of Southern California, Delta Health Alliance, and Community Servings outside the submitted work. Dr Newhouse reported receiving grants from the National Institute of Aging and AHRQ during the conduct of the study. No other disclosures were reported., (Copyright 2022 Fung V et al. JAMA Health Forum.)

Precise control of charge transfer between catalyst nanoparticles and supports presents a unique opportunity to enhance the stability, activity, and selectivity of heterogeneous catalysts. While charge transfer is tunable using the atomic structure and chemistry of the catalyst-support interface, direct experimental evidence is missing for three-dimensional catalyst nanoparticles, primarily due to the lack of a high-resolution method that can probe and correlate both the charge distribution and atomic structure of catalyst/support interfaces in these structures. We demonstrate a robust scanning transmission electron microscopy (STEM) method that simultaneously visualizes the atomic-scale structure and sub-nanometer-scale charge distribution in heterogeneous catalysts using a model Au-catalyst/SrTiO 3 -support system. Using this method, we further reveal the atomic-scale mechanisms responsible for the highly active perimeter sites and demonstrate that the charge transfer behavior can be readily controlled using post-synthesis treatments. This methodology provides a blueprint for better understanding the role of charge transfer in catalyst stability and performance and facilitates the future development of highly active advanced catalysts., (© 2022. The Author(s).)

Introduction: Sexual orientation and gender identity data collection is necessary to address health inequities. This study examines sexual orientation and gender identity data reporting among community health centers., Methods: Using the 2016-2019 Uniform Data System for 1,381 community health centers, trends in reporting of sexual orientation and gender identity data were examined. Multivariable logistic regression was used to assess associations between community health center characteristics and whether sexual orientation and gender identity data were available for ≥75% of a community health center's patients in 2019. Data were analyzed in 2021., Results: In 2016-2019, the percentage of community health centers with sexual orientation and gender identity data for ≥75% of patients increased from 14.9% to 53.0%. In 2019, community health centers were more likely to have this data for ≥75% of patients if they were in nonmetro counties (OR=1.48, 95% CI=1.04, 2.10 versus metro), were in the South (OR=2.27, 95% CI=1.57, 3.31) or West (OR=1.91, 95% CI=1.27, 2.88 versus the Northeast), and had more patients aged between 18 and 39 years (OR=1.04, 95% CI=1.02, 1.07), between 40 and 64 years (OR=1.04, 95% CI=1.02, 1.06 vs <18 years), or veterans (OR=1.10, 95% CI=1.01, 1.20). This was less likely among community health centers serving 10,000-20,000 patients (OR=0.70, 95% CI=0.52, 0.95) and >20,000 patients (OR=0.44, 95% CI=0.32, 0.61 vs <10,000) and community health centers with more patients of American Indian/Alaskan Native (OR=0.98, 95% CI=0.97, 0.99) or unknown race (OR=0.92, 95% CI=0.86, 0.97 versus White)., Conclusions: Collection of sexual orientation and gender identity data by community health centers has increased substantially since 2016, although gaps remain., (Copyright © 2022 American Journal of Preventive Medicine. Published by Elsevier Inc. All rights reserved.)

Emerging data suggest that adults with low income are at highest risk for COVID-19-related stressors and mental health disorders. This study aimed to determine if COVID-19-related stressors were associated with worsening depression and anxiety in a cohort of low-income adults one year after the start of the pandemic. Participants included 253 Medicaid and commercial accountable care organization recipients from 5 community health centers around Boston, MA who enrolled December 2019-March 2020 in a larger longitudinal study of a Medicaid program. Participants completed surveys at baseline and one-year follow-up that measured depression (Patient Health Questionnaire-8 [PHQ-8]) and anxiety (Generalized Anxiety Disorder-7 [GAD-7]) symptoms. Follow-up surveys assessed COVID-19-related stressors experienced over the prior 12 months. A stressor score included COVID-19-related infectious, social, and economic stressors categorized into tertiles (low, 0-3; medium, 4-6; high, 7-19). Mean age (SD) was 45.2 (11.5) years; 71.2% were female, 42.3% Hispanic and 14.6% Black. At baseline, 126 (49.8%) had moderate or severe depression (PHQ-8 ≥ 10), and 109 (43.1%) had moderate or severe anxiety (GAD-7 ≥ 10). The mean (SD) number of COVID-19 stressors was 4.9 (3.1); the most frequent were food insecurity (52.2%) and job or income loss (43.9%). Compared to the low tertile, those in high and medium tertiles had significantly greater one-year increases in depression and anxiety symptoms. Low-income adults facing multiple COVID-19-related stressors, particularly health-related social needs, had worsening mental health symptoms over one year. Interventions are urgently needed to address the dual burden of health-related social needs and poor mental health exacerbated by COVID-19., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2022 The Author(s).)

Background: The Affordable Care Act (ACA) increased funding for Federally Qualified Health Centers (FQHCs). We defined FQHC service areas based on patient use and examined the characteristics of areas that gained FQHC access post-ACA., Methods: We defined FQHC service areas using total patient counts by ZIP code from the Uniform Data System (UDS) and compared this approach with existing methods. We then compared the characteristics of ZIP codes included in Medically Underserved Areas/Populations (MUA/Ps) that gained access vs. MUA/P ZIP codes that did not gain access to FQHCs between 2011-15., Results: FQHC service areas based on UDS data vs. Primary Care Service Areas or counties included a higher percentage of each FQHC's patients (86% vs. 49% and 71%) and ZIP codes with greater use of FQHCs among low-income residents (29% vs. 22% and 22%), on average. MUA/Ps that gained FQHC access 2011-2015 included more poor, uninsured, publicly insured, and foreign-born residents than underserved areas that did not gain access, but were less likely to be rural (p < .05)., Conclusions: Measures of actual patient use provide a promising method of assessing FQHC service areas and access. Post-ACA funding, the FQHC program expanded access into areas that were more likely to have higher rates of poverty and uninsurance, which could help address disparities in access to care. Rural areas were less likely to gain access to FQHCs, underscoring the persistent challenges of providing care in these areas., (© 2022. The Author(s).)

More than 50 neurological and neuromuscular diseases are caused by short tandem repeat (STR) expansions, with 37 different genes implicated to date. We describe the use of programmable targeted long-read sequencing with Oxford Nanopore's ReadUntil function for parallel genotyping of all known neuropathogenic STRs in a single assay. Our approach enables accurate, haplotype-resolved assembly and DNA methylation profiling of STR sites, from a list of predetermined candidates. This correctly diagnoses all individuals in a small cohort ( n = 37) including patients with various neurogenetic diseases ( n = 25). Targeted long-read sequencing solves large and complex STR expansions that confound established molecular tests and short-read sequencing and identifies noncanonical STR motif conformations and internal sequence interruptions. We observe a diversity of STR alleles of known and unknown pathogenicity, suggesting that long-read sequencing will redefine the genetic landscape of repeat disorders. Last, we show how the inclusion of pharmacogenomic genes as secondary ReadUntil targets can further inform patient care.

Background: Social determinants of health (SDOH) are associated with cardiovascular disease, but little is known about mechanisms underlying those relationships. We hypothesized that SDOH would be associated with uncontrolled hypertension (HTN) in adults with Medicaid., Methods: This was a retrospective analysis of adults in a Medicaid accountable care organization who had HTN diagnoses, received regular care at community health centers, and enrolled in a cohort study between December 2019 and December 2020. Baseline surveys collected demographics and SDOH, including food insecurity, unstable housing, cost-related medication underuse, and financial stress. Blood pressure (BP) measurements over 12 months after survey completion were obtained from the electronic health record. Participants were categorized as: uncontrolled HTN (mean systolic BP ≥ 140 mm Hg and/or mean diastolic BP ≥ 90 mm Hg), controlled HTN, or unknown HTN control (no BP documented). We examined the association of individual and cumulative (count, 0-4) SDOH with uncontrolled HTN and unknown HTN control using multivariable logistic regression adjusting for demographics, smoking, diabetes, and HTN medication., Results: Participants (n = 245) were mean (SD) age 51.3 (8.6) years, 66.1% female, 43.7% Hispanic, 34.3% White, and 18.0% Black. Overall, 58.0% had food insecurity, 38.0% had unstable housing, 29.4% had financial stress, and 20.0% reported cost-related medication underuse. BP was documented for 180 participants; 44 (24.4%) had uncontrolled HTN. In multivariable models, neither individual nor cumulative SDOH were associated with uncontrolled HTN or unknown HTN control., Conclusions: In a Medicaid-insured population receiving care at community health centers, adverse SDOH were prevalent but were not associated with HTN control.

The COVID-19 pandemic has exacerbated the pressing need for mental health services. Digital mental health interventions could increase access to care and be an effective approach to reducing anxiety and depression at scale; however, research on their impact on healthcare expenditure is in the nascent stage and requires further investigation. The current study used claims data to examine the associations between use of an on-demand digital mental health platform and healthcare utilization costs compared to a matched control cohort. The study found that there were no significant differences between cohorts in total healthcare costs and pharmacy costs. There was a 16.8% reduction in outpatient costs (p=.08). On-demand digital mental health interventions can serve as a scalable approach to addressing the current mental health demands and potentially lower outpatient costs., (© 2022 Published by Elsevier B.V.)

Background: Food insecurity and poor nutrition are prevalent in the United States and associated with chronic diseases. Understanding relationships among food insecurity, diet, and health care utilization can inform strategies to reduce health disparities., Objective: Our aim was to determine associations between food security status and inpatient and outpatient health care utilization and whether they differed by dietary quality in lower-income adults., Design: This was a cross-sectional study of data from the 2009-2016 National Health and Nutrition Examination Survey., Participants/setting: Participants were 13,956 lower-income (<300% federal poverty level) adults 18 years and older in the United States., Main Outcome Measures: Self-reported health care utilization in the past 12 months included no usual source of care, any outpatient visit, any mental health service use, and any hospitalization., Statistical Analyses: Multiple logistic regression was used to study the association between food insecurity and health care utilization. Analyses were stratified by diet-related comorbidities to account for potential confounding and mediation of health care utilization, and by dietary quality., Results: In a sample of lower-income adults <300% federal poverty level, 4,319 participants (27.4%) were food insecure, 2,208 (15.0%) were marginally food secure, and 7,429 (57.6%) were food secure. Food insecurity was associated with having no usual source of care (adjusted odds ratio [aOR] 1.30; 95% CI 1.11 to 1.52), any mental health service use (aOR 2.02; 95% CI 1.61 to 2.52), and any hospitalization (aOR 1.19; 95% CI 1.01 to 1.41). Food-insecure adults were more likely to report no outpatient visits if they had diet-related comorbidities (aOR 1.45; 95% CI 1.10 to 1.92) or the lowest dietary quality (aOR 1.53; 95% CI 1.06 to 2.23). Marginal food security was associated with having no usual source of care (aOR 1.22; 95% CI 1.04 to 1.44)., Conclusions: Adults with food insecurity were more likely to be hospitalized, use mental health services, and have no usual source of care. Food-insecure participants with diet-related comorbidities or poor diet were less likely to have outpatient visits. Hospitalizations and mental health visits represent underused opportunities to identify and address food insecurity and dietary intake in lower-income patients., (Copyright © 2021 Academy of Nutrition and Dietetics. Published by Elsevier Inc. All rights reserved.)

Cervical dystonia (CD) is a neurological movement disorder causing the neck to move involuntarily away from the neutral position. CD is a network disorder, involving multiple brain areas and, therefore, may impair movement in parts of the body other than the neck. This study used clinical assessments to investigate walking, balance and upper limb function (UL) in people with CD; the reliability of scoring these assessments and examined for relationship between CD severity, usual exercise and clinical assessments. We conducted a prospective observational cohort study of participants with isolated, focal, idiopathic CD. Participants were assessed by experienced physiotherapists and completed three questionnaires and eight clinical assessments of fear of falling, balance confidence, walking, balance, UL function and usual exercise. Results were compared to published data from healthy adults and other neurological populations. Twenty-two people with mild to moderate CD participated. Fear of falling, gross UL function and usual exercise were worse in people with CD compared with healthy adults, while walking, balance and distal UL function were similar to healthy populations. All assessments were reliably performed by physiotherapists, and we found no correlations between the severity of dystonia or usual exercise and performance on the physical assessments. Routine performance of clinical assessment of walking and balance are likely not required in people with mild to moderate CD; however, fear of falling and gross upper limb function should be assessed to determine any problems which may be amenable to therapy., (© 2021. Crown.)

Single-atom catalysts are a relatively new type of catalyst active for numerous reactions but mainly for chemical transformations performed at low or intermediate temperatures. Here we report that singly dispersed Rh 1 O 5 clusters on TiO 2 can catalyze the partial oxidation of methane (POM) at high temperatures with a selectivity of 97% for producing syngas (CO + H 2 ) and high activity with a long catalytic durability at 650 °C. The long durability results from the substitution of a Ti atom of the TiO 2 surface lattice by Rh 1 , which forms a singly dispersed Rh 1 atom coordinating with five oxygen atoms (Rh 1 O 5 ) and an undercoordinated environment but with nearly saturated bonding with oxygen atoms. Computational studies show the back-donation of electrons from the d z 2 orbital of the singly dispersed Rh 1 atom to the unoccupied orbital of adsorbed CH n ( n > 1) results in the charge depletion of the Rh 1 atom and a strong binding of CH n to Rh 1 . This strong binding decreases the barrier for activating C-H, thus leading to high activity of Rh 1 /TiO 2 . A cationic Rh 1 single atom anchored on TiO 2 exhibits a weak binding to atomic carbon, in contrast to the strong binding of the metallic Rh surface to atomic carbon. The weak binding of atomic carbon to Rh 1 atoms and the spatial isolation of Rh 1 on TiO 2 prevent atomic carbon from coupling on Rh 1 /TiO 2 to form carbon layers, making Rh 1 /TiO 2 resistant to carbon deposition than supported metal catalysts for POM. The highly active, selective, and durable high-temperature single-atom catalysis performed at 650 °C demonstrates an avenue of application of single-atom catalysis to chemical transformations at high temperatures.

Purpose: We aimed to provide a perspective review of the available quantitative imaging modalities of the spine for prognostic evaluation of the adolescent idiopathic scoliosis (AIS)., Methods: A technical description of the current imaging technologies for quantitative assessment of the pediatric spine with scoliosis was provided, and the pros and cons of each method were discussed. Imaging modalities that quantify the overall 3D alignment of the spine as well as the structural specification of the spinal bone, intervertebral disc, endplates, and ligaments as it pertains to development and progression of the idiopathic spinal deformities in adolescents were discussed., Results: Low-dose and microdose stereoradiography, ultrasound, and rasterstereography provide quantitative imaging of the 3D spinal alignment with low or no radiation in standing posture which allows repetitive imaging for early detection of the curve development. Quantitative magnetic resonance imaging, including ultrashort dual-echo time and T1-rho can provide quantitative assessment of the spinal tissues relevant to development of idiopathic spinal deformity in pediatric population. New computed tomography scans that uses dual-energy can provides high-resolution measure of the current-state of the bone quality and morphology as well as the osteogenic properties of the bone by quantitative evaluation of the bone marrow., Conclusion: The presented imaging modalities can provide a wide spectrum of quantifiable information relevant to development and progression of the spinal deformity. Clinical application of these technologies can change the paradigm in clinical assessment of the pediatric scoliosis by improving our understanding of the pathogenesis of the idiopathic scoliosis., (© 2021. The Author(s), under exclusive licence to Springer-Verlag France SAS part of Springer Nature.)

Background: Avulsion fractures of the humeral lesser tuberosity are rare injuries in skeletally immature patients and can pose a diagnostic challenge that often leads to delayed identification., Objective: To describe the demographics, mechanism of injury and magnetic resonance imaging (MRI) findings of lesser tuberosity avulsion fractures in children., Materials and Methods: A retrospective search of children with lesser tuberosity avulsion fractures on MRI was done. Available radiographs were evaluated. Demographics, mechanism of injury, MRI characteristics and treatment were recorded., Results: Thirteen children, all male, were included (median age: 13.8 years, range: 12.5-16.8 years). The most common mechanism was blunt, overhead or hyperextension traumatic injury related to sports. All patients were skeletally immature and 10/13 demonstrated isolated avulsion fractures at the footprint. Only one patient had associated osteochondral injury to the humeral head and labral tear. Two children demonstrated medial dislocation/subluxation of the biceps tendon. The median size of the avulsed fragment was 15 mm (range: 5-29 mm), median anteroposterior displacement was 3 mm (range: 0-6 mm) and medial displacement was 1 mm (range: 0-20 mm). There was no correlation between age and the size of the avulsed fragment (P=0.29). Common injury patterns were complete avulsion of the subscapularis footprint (6/13) and partial avulsion of inferior footprint (6/13). Two-thirds of the radiographs were initially reported as normal, but retrospectively showed two missed fractures. One of the initial radiographs raised concern for bone tumor. The best view for identifying an avulsion fragment was the axillary view. Seven patients of the 13 patients underwent internal fixation., Conclusion: Avulsion fractures of the lesser tuberosity are rare, challenging to diagnose and often radiographically occult. MRI can identify the injury at the subscapularis tendon footprint with variable size and displacement. The long head of the biceps tendon is usually normal in location. Although this entity is rare, radiologists should be aware of it to allow for correct and prompt diagnosis and prevent unnecessary biopsy or contrast administration.

Background: Physicians often receive lower payments for dual-eligible Medicare-Medicaid beneficiaries versus nondual Medicare beneficiaries because of state reimbursement caps. The Affordable Care Act (ACA) primary care fee bump temporarily eliminated this differential in 2013-2014., Objective: To examine how dual payment policy impacts primary care physicians' (PCP) acceptance of duals., Research Design: We assessed differences in the likelihood that PCPs had dual caseloads of ≥10% or 20% in states with lower versus full dual reimbursement using linear probability models adjusted for physician and area-level traits. Using a triple-difference approach, we examined changes in dual caseloads for PCPs versus a control group of specialists in states with fee bumps versus no change during years postbump versus prebump., Subjects: PCPs and specialists (cardiologists, orthopedic surgeons, general surgeons) that billed fee-for-service Medicare., Measures: State dual payment policies and physicians' dual caseloads as a percentage of their Medicare patients., Results: In 2012, 81% of PCPs had dual caseloads of ≥10% and this was less likely among PCPs in states with lower versus full dual reimbursement (eg, difference=-4.52 percentage points; 95% confidence interval, -6.80 to -2.25). The proportion of PCPs with dual caseloads of ≥10% or 20% decreased significantly between 2012 and 2017 and the fee bump was not consistently associated with increases in dual caseloads., Conclusions: Pre-ACA, PCPs' participation in the dual program appeared to be lower in states with lower reimbursement for duals. Despite the ACA fee bump, dual caseloads declined over time, raising concerns of worsening access to care., Competing Interests: J.P.N. discloses that he was a director of Aetna until May 2018, held Aetna stock until November 2018, and currently owns stock in Novartis and Medtronic. There are no other relevant disclosures. The remaining authors declare no conflict of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Growing evidence suggests that non-motor symptoms (NMS) in Parkinson's disease (PD) have differential progression patterns that have a different natural history from motor progression and may be geographically influenced. We conducted a cross-sectional analysis of 1607 PD patients of whom 1327 were from Europe, 208 from the Americas, and 72 from Asia. The primary objective was to assess baseline non-motor burden, defined by Non-Motor Symptoms Scale (NMSS) total scores. Other aims included identifying the factors predicting quality of life, differences in non-motor burden between drug-naïve and non-drug-naïve treated patients, and non-motor phenotypes across different geographical locations. Mean age was 65.9 ± 10.8 years, mean disease duration 6.3 ± 5.6 years, median Hoehn and Yahr stage was 2 (2-3), and 64.2% were male. In this cohort, mean NMSS scores were 46.7 ± 37.2. Differences in non-motor burden and patterns differed significantly between drug-naïve participants, those with a disease duration of less than five years, and those with a duration of five years or over (p ≤ 0.018). Significant differences were observed in geographical distribution (NMSS Europe: 46.4 ± 36.3; Americas: 55.3 ± 42.8; Asia: 26.6 ± 25.1; p < 0.001), with differences in sleep/fatigue, urinary, sexual, and miscellaneous domains (p ≤ 0.020). The best predictor of quality of life was the mood/apathy domain (β = 0.308, p < 0.001). This global study reveals that while non-motor symptoms are globally present with severe NMS burden impacting quality of life in PD, there appear to be differences depending on disease duration and geographical distribution.

2D materials have attracted tremendous interest as functional materials because of their diverse and tunable properties, especially at their edges. A material's work function is a critical parameter in many electronic devices; however, a fundamental understanding and a path toward large alterations of the work function in 2D materials still remain elusive. Here, we report the first evidence for anisotropy of the work function in 2D MoS 2 from first-principles calculations. We also demonstrate large work-function tunability (in the range of 3.45-6.29 eV) choosing the 2H phase of MoS 2 as a model system by sampling various edge configurations. We furthermore reveal the origin of this work function anisotropy and tunability by extending the existing work function relation to the local dipole moment at surfaces of 3D materials to those at edges in 2D materials. We then use machine-learning approaches to correlate work function with edge structures. These results pave the way for intrinsic edge engineering for electronic and catalytic applications.