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Background: Acid Sphingomyelinase Deficiency (ASMD) is a rare autosomal recessive disorder caused by mutations in the SMPD1 gene. This rarity contributes to misdiagnosis, delayed diagnosis and barriers to good care. There are no published national or international consensus guidelines for the diagnosis and management of patients with ASMD. For these reasons, we have developed clinical guidelines that defines standard of care for ASMD patients., Methods: The information contained in these guidelines was obtained through a systematic literature review and the experiences of the authors in their care of patients with ASMD. We adopted the Appraisal of Guidelines for Research and Evaluation (AGREE II) system as method of choice for the guideline development process., Results: The clinical spectrum of ASMD, although a continuum, varies substantially with subtypes ranging from a fatal infantile neurovisceral disorder to an adult-onset chronic visceral disease. We produced 39 conclusive statements and scored them according to level of evidence, strengths of recommendations and expert opinions. In addition, these guidelines have identified knowledge gaps that must be filled by future research., Conclusion: These guidelines can inform care providers, care funders, patients and their carers about best clinical practice and leads to a step change in the quality of care for patients with ASMD with or without enzyme replacement therapy (ERT)., (© 2023. The Author(s).)

Tumor hypoxia drives resistance to many cancer therapies, including radiotherapy and chemotherapy. Methods that increase tumor oxygen pressures, such as hyperbaric oxygen therapy and microbubble infusion, are utilized to improve the responses to current standard-of-care therapies. However, key obstacles remain, in particular delivery of oxygen at the appropriate dose and with optimal pharmacokinetics. Toward overcoming these hurdles, gas-entrapping materials (GeMs) that are capable of tunable oxygen release are formulated. It is shown that injection or implantation of these materials into tumors can mitigate tumor hypoxia by delivering oxygen locally and that these GeMs enhance responsiveness to radiation and chemotherapy in multiple tumor types. This paper also demonstrates, by comparing an oxygen (O 2 )-GeM to a sham GeM, that the former generates an antitumorigenic and immunogenic tumor microenvironment in malignant peripheral nerve sheath tumors. Collectively the results indicate that the use of O 2 -GeMs is promising as an adjunctive strategy for the treatment of solid tumors., (© 2023 The Authors. Advanced Science published by Wiley-VCH GmbH.)

Improving access to grant funding is a critical aspect of strengthening research capacity outside of higher income settings, particularly in HIV/AIDS where randomized control trials (RCTs) that require substantial resources are common. In this article, we assessed recent RCTs to examine variation in how studies were funded, depending on study location and the countries where publication authors were based. We conducted a PubMed literature review to identify RCTs with HIV status or viral load endpoints published in 2019 and 2020, then analyzed cross-tabulations of funding sources by study characteristics. One hundred sixteen publications met the inclusion criteria. Research in higher income countries was most likely to be funded by biotech/pharmaceutical companies, whereas research in lower- and middle-income countries was most likely to be funded by U.S. government sources. Overall, we found the distribution of funding sources differed significantly by study and author location ( χ 2  = 23, p  < .001). Published RCTs with HIV status or viral load endpoints are financed differently based on where studies take place and where the authors are based. As part of future research, understanding why this variation exists is critical for assessing how funding contributes to global imbalances in scientific resources.

Objective: To conduct a systematic review of observational studies on methamphetamine-associated heart failure (MethHF) ., Methods: Six databases were searched for original publications on the topic. Title/abstract and included full-text publications were reviewed in duplicate. Data extraction and critical appraisal for risk of bias were performed in duplicate., Results: Twenty-one studies are included in the final analysis. Results could not be combined because of heterogeneity in study design, population, comparator, and outcome assessment. Overall risk of bias is moderate due to the presence of confounders, selection bias and poor matching; overall certainty in the evidence is very low. MethHF is increasing in prevalence, affects diverse racial/ethnic/sociodemographic groups with a male predominance; up to 44% have preserved left-ventricular ejection fraction. MethHF is associated with significant morbidity including worse heart failure symptoms compared with non-methamphetamine related heart failure. Female sex, methamphetamine abstinence and guideline-directed heart failure therapy are associated with improved outcomes. Chamber dimensions on echocardiography and fibrosis on biopsy predict the extent of recovery after abstinence., Conclusions: The increasing prevalence of MethHF with associated morbidity underscores the urgent need for well designed prospective studies of people who use methamphetamine to accurately assess the epidemiology, clinical features, disease trajectory and outcomes of MethHF. Methamphetamine abstinence is an integral part of MethHF treatment; increased availability of effective non-pharmacological interventions for treatment of methamphetamine addiction is an essential first step. Availability of effective pharmacological treatment for methamphetamine addiction will further support MethHF treatment. Using harm reduction principles in an integrated addiction/HF treatment programme will bolster efforts to stem the increasing tide of MethHF., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Objectives: This study aims to compare primary care providers and medical assistants in degrees of comfort, confidence, and consistency when addressing behavioral health concerns with patients before and after the implementation of a model of integrated behavioral health in primary care (IBHPC), and evaluate whether these perceptions differ based on increased access to behavioral health clinicians., Methods: This longitudinal study was conducted at 2 primary care clinics in Northern California while implementing an IBHPC model. The Integrated Behavioral Health Staff Perceptions Survey was administered to assess the comfort, confidence, and consistency of behavioral health practices. Confidential online surveys were distributed to primary care faculty and staff members before and post-implementation. Responses from providers and medical assistants were compared between pre- and post-implementation with linear regression analyses. The relationships between accessibility to behavioral health clinicians and a change in comfort, confidence, and consistency of behavioral health practices were explored using a linear mixed-effects model., Results: A total of 35 providers and medical assistants completed the survey both before and post-implementation of IBHPC. Over time, there were increasingly positive perceptions about the consistency of behavioral health screening ( P  = .03) and overall confidence in addressing behavioral health concerns ( P  = .005). Comfort in addressing behavioral health concerns did not significantly change for either providers or staff over time. Medical assistants were initially more confident and comfortable addressing behavioral health concerns than providers, but providers' attitudes increased post-IBHPC implementation. Improved access to behavioral health clinicians was associated with greater consistency of screening and referral to specialty mental health care ( P  < .001)., Conclusion: The present study is the first to explore differences in provider and medical assistant perceptions during the course of an IBHPC implementation. Findings underscore the importance of integrating medical assistants, along with providers, into all phases of the implementation process.

The treatment of central nervous system (CNS) tumors is complicated by high rates of recurrence and treatment resistance that contribute to high morbidity and mortality (Nat Rev Neurol. 2022;18:221-36. doi: 10.1038/s41582-022-00621-0). One of the challenges of treating these tumors is the limited permeability of the blood brain barrier (BBB). Early pharmacologic treatments worked to overcome the BBB by targeting vulnerabilities in the tumor cell replication process directly through alkylating agents like temozolomide. However, as advancements have been made options have expanded to include immunologic targets through the use of monoclonal antibodies. In the future, treatment will likely continue to focus on the use of immunotherapies, as well as emerging technology like the use of low-intensity focused ultrasound (LIFU). Ultimately, this paper serves as an introductory overview of current therapeutic options for post-resection primary brain tumors, as well as a look towards future work and emerging treatment options., Competing Interests: The views expressed in this article are those of the authors and do not necessarily reflect the official policy or position of the Uniformed Services University of the Health Sciences, the Department of Defense, or the U.S. Government., (© The Author(s) 2023.)

Introduction: The opioid epidemic has evolved into a combined stimulant epidemic, with escalating stimulant and fentanyl-related overdose deaths. Primary care providers are on the frontlines grappling with patients' methamphetamine use. Although effective models exist for treating opioid use disorder in primary care, little is known about current clinical practices for methamphetamine use., Methods: Six semistructured group interviews were conducted with 38 primary care providers. Interviews focused on provider perceptions of patients with methamphetamine use problems and their care. Data were analyzed using inductive and thematic analysis and summarized along the following dimensions: (1) problem identification, (2) clinical management, (3) barriers and facilitators to care, and (4) perceived needs to improve services., Results: Primary care providers varied in their approach to identifying and treating patient methamphetamine use. Unlike opioid use disorders, providers reported lacking standardized screening measures and evidence-based treatments, particularly medications, to address methamphetamine use. They seek more standardized screening tools, Food and Drug Administration-approved medications, reliable connections to addiction medicine specialists, and more training. Interest in novel behavioral health interventions suitable for primary care settings was also noteworthy., Conclusions: The findings from this qualitative analysis revealed that primary care providers are using a wide range of tools to screen and treat methamphetamine use, but with little perceived effectiveness. Primary care faces multiple challenges in effectively addressing methamphetamine use among patients singularly or comorbid with opioid use disorders, including the lack of Food and Drug Administration-approved medications, limited patient retention, referral opportunities, funding, and training for methamphetamine use. Focusing on patients' medical issues using a harm reduction, motivational interviewing approach, and linkage with addiction medicine specialists may be the most reasonable options to support primary care in compassionately and effectively managing patients who use methamphetamines., Competing Interests: The authors report no conflicts of interest., (Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Society of Addiction Medicine.)

Personalized polygenic risk information may be used to guide risk-based melanoma prevention and early detection at a population scale, but research on communicating this information is limited. This mixed-methods study aimed to assess the acceptability of a genetic counselor (GC) phone call in communicating polygenic risk information in the Melanoma Genomics Managing Your Risk randomized controlled trial. Participants ( n = 509) received personalized melanoma polygenic risk information, an educational booklet on melanoma prevention, and a GC phone call, which was audio-recorded. Participants completed the Genetic Counseling Satisfaction Survey 1-month after receiving their risk information ( n = 346). A subgroup took part in a qualitative interview post-study completion ( n = 20). Survey data were analyzed descriptively using SPSS, and thematic analysis of the qualitative data was conducted using NVivo 12.0 software. The survey showed a high level of acceptability for the GC phone call (mean satisfaction score overall: 4.3 out of 5, standard deviation (SD): 0.6) with differences according to gender (mean score for women: 4.4, SD: 0.6 vs. men: 4.2, SD: 0.7; p = 0.005), health literacy (lower literacy: 4.1, SD: 0.8; average: 4.3, SD: 0.6; higher: 4.4, SD: 0.6: p = 0.02) and polygenic risk group (low risk: 4.5, SD: 0.5, SD: average: 4.3, SD: 0.7, high: 4.3, SD: 0.7; p = 0.03). During the GC phone calls, the discussion predominately related to the impact of past sun exposure on personal melanoma risk. Together our findings point to the importance of further exploring educational and support needs and preferences for communicating personalized melanoma risk among population subgroups, including diverse literacy levels.

Neurosurgery has benefited from innovations as a result of military conflict. The volume and complexity of injuries sustained on the battlefield require medical teams to triage, innovate, and practice beyond their capabilities in order to treat wartime injuries. The neurosurgeons who practiced in the Pacific Command (PACOM) during World War II, the Korean War, and the War in Vietnam built upon field operating room knowledge and influenced the logistics of treating battle-injured patients in far-forward environments. Modern-day battles are held on new terrain, and the military neurosurgeon must adapt. War in the PACOM uniquely presented significant obstacles due to geographic isolation, ultimately accelerating the growth and adaptability of military neurosurgery and medical evacuation. The advancements in infrastructure and resource mobilization made during PACOM conflicts continue to inform modern-day practices and provide insight for future conflicts. In this historical article, the authors review the development and evolution of neurosurgical care, forward surgical teams, and mobile field hospitals with surgical capabilities through US conflicts in the PACOM.

Despite recent changes to mental health policy in Australia and overseas, physical restraint continues to be widely employed in mental health services. While mental health nurses have a critical role to play in supporting initiatives designed to reduce restraint, it is unclear how they feel about moves to restrict the use of prone restraint. In this qualitative study, focus group interviews were conducted with mental health nursing staff and lived experience workers (LEWs) to gain their perspectives on the use of physical restraint in general and the restrictions being placed on prone ('face down') restraint. Five themes emerged: justifying the need for restraint, reliance on the prone position, the position is not the issue, time limits, and the psychological impact. Although mental health nurses were concerned about the risks associated with physical restraint, they provided strong justification for continued use of the prone position. LEWs raised concerns about the psychological impact of prone restraint and noted the need for a greater emphasis on de-escalation and other restraint avoidance strategies. The findings highlight the complexities and challenges to be considered when developing initiatives to reduce reliance on the use of restraint in general, and prone in particular., (© 2022 John Wiley & Sons Australia, Ltd.)

Increasing terrestrial run-off from melting glaciers and thawing permafrost to Arctic coastal areas is expected to facilitate re-mobilization of stored legacy persistent organic pollutants (POPs) and mercury (Hg), potentially increasing exposure to these contaminants for coastal benthic organisms. We quantified chlorinated POPs and Hg concentrations, lipid content and multiple dietary markers, in a littoral deposit-feeding amphipod Gammarus setosus and sediments during the melting period from April to August in Adventelva river estuary in Svalbard, a Norwegian Arctic Aarchipelago. There was an overall decrease in concentrations of ∑POPs from April to August (from 58 ± 23 to 13 ± 4 ng/g lipid weight; lw), Hg (from 5.6 ± 0.7 to 4.1 ± 0.5 ng/g dry weight; dw) and Methyl Hg (MeHg) (from 5 ± 1 to 0.8 ± 0.7 ng/g dw) in G. setosus. However, we observed a seasonal peak in penta- and hexachlorobenzene (PeCB and HCB) in May (2.44 ± 0.3 and 23.6 ± 1.7 ng/g lw). Sediment concentrations of POPs and Hg (dw) only partly correlated with the contaminant concentrations in G. setosus. Dietary markers, including fatty acids and carbon and nitrogen stable isotopes, indicated a diet of settled phytoplankton in May-July and a broader range of carbon sources after the spring bloom. Phytoplankton utilization and chlorobenzene concentrations in G. setosus exhibited similar seasonal patterns, suggesting a dietary uptake of chlorobenzenes that is delivered to the aquatic environment during spring snowmelt. The seasonal decrease in contaminant concentrations in G. setosus could be related to seasonal changes in dietary contaminant exposure and amphipod ecology. Furthermore, this decrease implies that terrestrial run-off is not a significant source of re-mobilized Hg and legacy POPs to littoral amphipods in the Adventelva river estuary during the melt season., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Classical galactosemia (CG) is a disorder of galactose metabolism which results from deficiency of the enzyme galactose-1-phosphate uridylyl transferase (GALT). Treatment consists of immediately eliminating galactose from the diet in the new-born and lifelong restriction of dietary galactose. The inclusion of a wider variety of foods for people with CG may provide many benefits, including improved nutritional adequacy and quality of life. Galactose plays an important role in glycosylation of glycoproteins and glycolipids. Moderate liberalization of galactose restriction has been shown to improve immunoglobulin G (IgG) glycosylation for some individuals with CG. Moreover, recent outcome research suggests that strict restriction of nondairy galactose may have more unfavorable outcomes than moderate liberalization in CG patients. In the current work, based on patient feedback, we have analyzed the lactose and galactose content of different foods available in Ireland. These include a range of cheeses, yogurts, pizzas, soups, biscuits, cakes, pastries, crackers, mayonnaises, salad creams, fat spreads, crisps, corn chips, salamis, and gravies. This work provides information to support the development of a practical food-based approach to facilitate analysis of dietary galactose intake and to possibly increase overall variety of food choices for people with CG., Competing Interests: All authors declare that they have no conflict of interest., (© 2022 The Authors. Food Science & Nutrition published by Wiley Periodicals LLC.)

Decades of atmospheric and oceanic long-range transport from lower latitudes have resulted in deposition and storage of persistent organic pollutants (POPs) in Arctic regions. With increased temperatures, melting glaciers and thawing permafrost may serve as a secondary source of these stored POPs to freshwater and marine ecosystems. Here, we present concentrations and composition of legacy POPs in glacier- and permafrost-influenced rivers and coastal waters in the high Arctic Svalbard fjord Kongsfjorden. Targeted contaminants include polychlorinated biphenyls (PCBs), hexachlorobenzene (HCB), dichlorodiphenyltrichloroethanes (DDTs), hexachlorocyclohexanes (HCHs) and chlordane pesticides. Dissolved (defined as fraction filtered through 0.7 μm GF/F filter) and particulate samples were collected from rivers and near-shore fjord stations along a gradient from the heavily glaciated inner fjord to the tundra-dominated catchments at the outer fjord. There were no differences in contaminant concentration or pattern between glacier and tundra-dominated catchments, and the general contaminant pattern reflected snow melt with some evidence of pesticides released with glacial meltwater. Rivers were a small source of chlordane pesticides, DDTs and particulate HCB to the marine system and the particle-rich glacial meltwater contained higher concentrations of particle associated contaminants compared to the fjord. This study provides rare insight into the role of small Arctic rivers in transporting legacy contaminants from thawing catchments to coastal areas. Results indicate that the spring thaw is a source of contaminants to Kongsfjorden, and that expected increases in runoff on Svalbard and elsewhere in the Arctic could have implications for the contamination of Arctic coastal food-webs., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Climate change-driven increases in air and sea temperatures are rapidly thawing the Arctic cryosphere with potential for remobilization and accumulation of legacy persistent organic pollutants (POPs) in adjacent coastal food webs. Here, we present concentrations of selected POPs in zooplankton (spatially and seasonally), as well as zoobenthos and sculpin (spatially) from Isfjorden, Svalbard. Herbivorous zooplankton contaminant concentrations were highest in May [e.g., ∑polychlorinated biphenyls ( 8 PCB); 4.43, 95% CI: 2.72-6.3 ng/g lipid weight], coinciding with the final stages of the spring phytoplankton bloom, and lowest in August (∑ 8 PCB; 1.6, 95% CI: 1.29-1.92 ng/g lipid weight) when zooplankton lipid content was highest, and the fjord was heavily impacted by sediment-laden terrestrial inputs. Slightly increasing concentrations of α-hexachlorocyclohexane (α-HCH) in zooplankton from June (1.18, 95% CI: 1.06-1.29 ng/g lipid weight) to August (1.57, 95% CI: 1.44-1.71 ng/g lipid weight), alongside a higher percentage of α-HCH enantiomeric fractions closer to racemic ranges, indicate that glacial meltwater is a secondary source of α-HCH to fjord zooplankton in late summer. Except for α-HCH, terrestrial inputs were generally associated with reduced POP concentrations in zooplankton, suggesting that increased glacial melt is not likely to significantly increase exposure of legacy POPs in coastal fauna.

Introduction: Opioid use disorder (OUD) and related comorbid conditions are highly prevalent among patients presenting to emergency department (ED) settings. Research has developed few comprehensive disease management strategies for at-risk patients presenting to the ED that both decrease illicit opioid use and improve initiation and retention in medication treatment for OUD (MOUD)., Methods: The research team conducted a pilot pragmatic clinical trial that randomized 40 patients presenting to a single ED to a collaborative care intervention (n = 20) versus usual care control (n = 20) conditions. Interviewers blinded to patient intervention and control group status followed-up with participants at 1, 3, and 6 months after presentation to the ED. The 3-month Emergency Department Longitudinal Integrated Care (ED-LINC) collaborative care intervention for patients at risk for OUD included: 1) a Brief Negotiated Interview at bedside, 2) overdose education and facilitation of MOUD, 3) longitudinal proactive care management, 4) utilization of the statewide health information exchange platform for 24/7 tracking of recurrent ED utilization, and 5) weekly caseload supervision that incorporated measurement-based care treatment assessment with stepped-up care for patients with recalcitrant symptoms., Results: Overall, the ED-LINC intervention was feasibly delivered and acceptable to patients. The pilot study achieved >80% follow-up rates at 1, 3, and 6 months. In adjusted longitudinal mixed model regression analyses, no statistically significant differences existed in days of opioid use over the past 30 days for ED-LINC intervention patients when compared to patients receiving usual care (incidence-rate ratio (IRR) 1.50, 95% CI 0.54-4.16). The unadjusted mean number of days of illicit opioid use decreased at the 1-month and 3-month follow-up time points for both groups. ED-LINC intervention patients had increased rates of MOUD initiation compared to control patients (50% versus 30%); intervention versus control comparisons did not achieve statistical significance, although power to detect significant differences in the pilot was limited., Conclusions: The ED-LINC intervention for patients with OUD can be feasibly implemented and warrants testing in larger scale, adequately powered randomized pragmatic clinical trial investigations., Clinicaltrials: gov NCT03699085., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: Adaptation is an accepted part of implementing evidence-based practices. COVID-19 presented a unique opportunity to examine adaptation in evolving contexts. Delivering service to people with opioid use disorder during the pandemic required significant adaptation due to revised regulations and limited service access. This report evaluated changes to addiction medication services caused by the pandemic, challenges encountered in rapidly adapting service delivery, and initial impressions of which changes might be sustainable over time., Methods: Qualitatively-evaluated structured interviews (N  =  20) were conducted in late 2020 with key informants in Pinellas County (FL) to assess the pandemic's impact. Interviewees represented a cross-section of the professional groups including direct SUD/HIV service providers, and sheriff's office, Department of Health, and regional clinical program administrative staff. The interview questions examined significant changes necessitated by the pandemic, challenges encountered in adapting to this evolving context, and considerations for sustained change., Results: The most significant changes to service delivery identified were rapid adaptation to a telehealth format, and modifying service consistent with SAMHSA guidance, to allow for 'take-home' doses of methadone. Limitations imposed by access to technology, and the retraining of staff and patients to give and receive service differently were the most common themes identified as challenging adaptation efforts. Respondents saw shifts towards telehealth as most likely to being sustained., Conclusions: COVID-19 provided an unprecedented opportunity to examine adaptation in a fast-paced, dynamic, and evolving context. Adaptations identified will only be sustained through multisystem collaboration and validation. Results suggest that additional components could be added to implementation frameworks to assess rapid adaptation during unplanned events, such as access to additional resources or local decision-making that impacts service delivery. Findings will also be integrated with quantitative data to help inform local policy decisions., Plain Language Summary: Adaptation is an accepted part of implementing evidencebased practices. COVID-19 presented a unique opportunity to examine rapid adaptation necessitated within evolving contexts. Delivering services to people with opioid use disorder required significant adaptation due to changing regulations and limited access to lifesaving services. This study examined changes in service delivery due to the pandemic, challenges encountered in rapid adaptation, and initial impressions of which changes might be sustainable over time. Qualitatively-evaluated structured interviews were conducted with a cross-section of professional groups (direct substance use disorder (SUD) and human immunodeficiency virus (HIV) service providers, and sheriff's office, Department of Health, and clinical program administrative staff) in Pinellas County (FL). The most significant changes to service delivery were rapid adaptation to a telehealth format and increased allowance for 'takehome' doses of methadone medication. Limitations imposed by access to technology, as well as the education of and staff and patients were the most common themes identified as challenges. Respondents saw shifts towards telehealth as most likely to be sustained. COVID-19 provided an unprecedented opportunity to examine adaptation in a fast-paced, dynamic, and evolving context. Adaptations will only be sustained through multisystem collaboration and validation. Findings suggest that additional components could be added to implementation frameworks to assess rapid adaptation during unplanned events, such as access to additional resources or local decision-making that impacts service delivery., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2022.)

Competing Interests: Competing interests: None declared.

Background: Conversations about end of life rarely take place beyond healthcare spaces and in advance of imminent death. As the Canadian ageing population increases and new policies and options emerge for end-of-life choices, there will be an increasing need for supports for decision-making on end of life. Time Moving was a participatory art exhibit created to engage participants in reflections on end-of-life experiences and the ways in which their perception of time fluctuated within these moments., Design: A participatory and constructivist approach informed decisions on exhibit design and analysis. The Time Moving exhibit was installed in a downtown university hall for 10 days during the 2019 annual DesignTO festival, open to all members of the public. The exhibit was used as the primary method of data collection. There were three prompts informed by concepts from prior work on time perception. Participants were invited to respond by drawing, writing or constructing., Outcome: There were over 120 contributions of participants over the duration of the Time Moving exhibit. These contributions revealed new insights related to temporal perception and end-of-life experiences. Participants shared their perception of time during end-of-life experiences in a variety of ways, revealing a diversity of perceptions of time beyond calendar and clock time, including time experienced as a spiral., Conclusions: The insights on time perception highlight opportunities for approaching dialogue on end of life and in grief support, and for exhibit as a mechanism for research and education., Patient or Public Contribution: As a public exhibit, over 120 people contributed ideas, personal stories, drawings and other creative outputs to the exhibit. An estimated 250 people visited the exhibit., (© 2022 The Authors. Health Expectations published by John Wiley & Sons Ltd.)

Context: Most patients in need of behavioral health (BH) care are seen in primary care, which often has difficulty responding. Some practices integrate behavioral health care (IBH), with medical and BH providers at the same location, working as a team. However, it is difficult to achieve high levels of integration. Objective: Test the effectiveness of a practice intervention designed to increase BH integration. Study Design: Pragmatic, cluster-randomized controlled trial. Setting: 43 primary care practices with on-site BH services in 13 states. Population: 2,460 adults with multiple chronic medical and behavioral conditions. Intervention: 24-month practice change process including an online curriculum, a practice redesign and implementation workbook, remote quality improvement coaching services, and an online learning community. Outcomes: Primary outcomes were changes in the 8 Patient-Reported Outcomes Measurement Information System (PROMIS-29) domain scores. Secondary outcomes were changes in medication adherence, self-reported healthcare utilization, time lost due to disability, cardiovascular capacity, patient centeredness, provider empathy, and several condition-specific measures. A sample of practice staff completed the Practice Integration Profile at each time point to estimate the degree of BH integration in that site. Practice-level case studies estimated the typical costs of implementing the intervention. Results: The intervention had no significant effect on any of the primary or secondary outcomes. Subgroup analyses showed no convincing patterns of effect in any populations. COVID-19 was apparently not a moderating influence of the effect of the intervention on outcomes. The intervention had a modest effect on the degree of practice integration, reaching statistical significance in the Workflow domain. The median cost of the intervention was $18,204 per practice. In post-hoc analysis, level of BH integration was associated with improved patient outcomes independent of the intervention, both at baseline and longitudinally. Conclusions: The specific intervention tested in this study was inexpensive, but had only a small impact on the degree of BH integration, and none on patient outcomes. However, practices that had more integration at baseline had better patient outcomes, independent of the intervention. Although this particular intervention was ineffective, IBH remains an attractive strategy for improving patient outcomes., Competing Interests: Authors report none., (© 2021 Annals of Family Medicine, Inc.)

Case: A patient presented with acute paralysis in the setting of undiagnosed Lemierre's syndrome. Streptococcus pyogenes was the causative organism leading to internal jugular vein thrombosis, sternocleidomastoid abscess, vertebral osteomyelitis, and epidural phlegmon. The patient was treated both surgically, with abscess evacuation, hemicorpectomy, and fusion, and medically, with antibiotics and anticoagulation. Postoperatively, the patient regained upper extremity strength and lower extremity sensation, but the paraplegia remained., Conclusion: Lemierre's syndrome is a rare complication of oropharyngeal infection with a constellation of findings including jugular thrombophlebitis, metastatic abscesses, and frequent involvement of anaerobic pathogens that may present acutely with paralysis., Competing Interests: Disclosure: The Disclosure of Potential Conflicts of Interest forms are provided with the online version of the article (http://links.lww.com/JBJSCC/B794)., (Copyright © 2022 by The Journal of Bone and Joint Surgery, Incorporated.)

Introduction: Perinatal depression affects 13% of childbearing individuals in the U.S. and has been linked to an increased risk of household economic insecurity in the short term. This study aims to assess the relationship between perinatal depression and long-term economic outcomes., Methods: This was a longitudinal analysis of a cohort of mothers from the Fragile Families and Child Wellbeing Study starting at delivery in 1998-2000 and followed until 2014-2017. Analysis was conducted in 2021. Maternal depression was assessed using the Composite International Diagnostic Interview-Short Form 1 year after childbirth, and the outcomes included measures of material hardship, household poverty, and employment. Associations between maternal depression and outcomes were analyzed using logistic regression and group-based trajectory modeling., Results: In total, 12.2% of the sample met the criteria for a major depressive episode 1 year after delivery. Maternal depression had a strong and sustained positive association with material hardship and not working for pay in Years 3, 5, 9, and 15 after delivery. Maternal depression also had a significant positive association with household poverty across Years 3-9 and with unemployment in Year 3. Trajectory modeling established that maternal depression was associated with an increased probability of being in a persistently high-risk trajectory for material hardship, a high-risk trajectory for household poverty, and a high-declining risk trajectory for unemployment., Conclusions: Supporting perinatal mental health is crucial for strengthening the economic well-being of childbearing individuals and reducing the impact of maternal depression on intergenerational transmission of adversity., (Copyright © 2021 American Journal of Preventive Medicine. Published by Elsevier Inc. All rights reserved.)

In October of 2017 and 2019, Sonoma County California endured historic wildfires and subsequent community trauma. The Sonoma Wildfire Mental Health Collaborative was created to (a) democratize access to evidence-based mental health resources and services for personal recovery and long-term community resilience building, and to (b) measure the reach and efficacy of the strategies employed in order to create a knowledge base to inform disaster response in other communities. Offerings included a mind-body yoga program and training in Skills for Psychological Recovery (SPR) for counselors who wished to provide services to individuals impacted by the wildfires. An evaluation of the mental health strategies employed revealed that (a) the mind-body program was well-received, with a high degree of satisfaction and self-reported benefit among individuals who attended trauma-informed yoga classes and (b) counselors found SPR to be a practical, flexible short-term intervention for individuals in the aftermath of the wildfires and expressed moderate to high levels of intent to use it in practice. Importantly, the evaluation of the 2017 wildfire mental health response was compromised by the Kincade Fire in 2019, in which prolonged mandatory evacuations and power outages impacted response rates. The origin story is shared for how a community collaborative was built. Lessons learned are discussed and recommendations summarized so as to contribute to the science and practice of disaster mental health outreach. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Objectives: To examine if the COVID-19 pandemic is associated with a differential effect over time in relation to its psychological and social impact on patients with established anxiety disorders., Methods: Semi-structured interviews were conducted with 24 individuals attending the Galway-Roscommon Mental Health Services with an International Classification of Diseases (ICD)-10 diagnosis of an anxiety disorder at two time points (six months apart) to determine the impact of the COVID-19 restrictions on anxiety and depressive symptoms, social and occupational functioning and quality of life., Results: No statistical difference in symptomatology was noted between the two time points in relation to anxiety symptoms as measured by utilising psychometric rating scales (BAI and HARS) or utilising a Likert scale. The greatest impact of COVID-19 at both time points is related to social functioning and quality of life. Significant variability was noted for individual participants. Qualitative analysis noted social isolation, concern for the participants' future and increased difficulty managing anxiety with ongoing restrictions., Conclusions: No significant overall change in symptomatology or functioning over time was noted for individuals with pre-existing anxiety disorders. Variability was, however, demonstrated between individuals, with some individuals describing ongoing anxiety, social isolation and concern for their future. Identifying those with ongoing symptoms or distress and providing multidisciplinary support to this cohort is suggested.

In October 2017, Northern California experienced devastating and historic wildfires leaving the community in need of support to foster emotional resilience during the recovery process. Adolescents represent a particularly vulnerable population in the wake of disaster, and digital mental health interventions may hold promise for reaching teens at scale. The present study examined the feasibility and efficacy of a mobile mental health app for disaster, Sonoma Rises. A multiple-baseline single-case experimental design (SCED) utilizing a research-enabled version of the app was employed with seven adolescents who experienced significant damage to their homes and schools in the wildfires. Participants completed daily mood ratings, weekly measures of posttraumatic stress symptoms, internalizing and externalizing symptoms, psychosocial functioning, and then pre-post-measures of anxiety, depression, wellbeing, sleep, academic engagement, and perceived social support as well as quantitative and qualitative measures of intervention satisfaction and feasibility. Sonoma Rises was found to be feasible in terms of engagement, satisfaction, and likelihood of recommending to a friend. During the study, another wildfire occurred and all participants underwent a prolonged mandated evacuation and were subject to a series of extended power outages. Uptake of the publicly available version of the Sonoma Rises app among the general population was modest but engagement among users was sustained. Lessons learned are offered to contribute to the science and practice of building, disseminating, and implementing digital tools to conduct more equitable disaster mental health outreach and research. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Objectives: To define the mean angle of a series of diaphyseal nonunions based on radiographic analysis., Design: A retrospective cohort study., Setting: Two level-1 trauma centers., Patients: One hundred twenty patients presenting with nonunion., Intervention: A mean nonunion angle was calculated from a series of AP and lateral X-rays using a standardized technique. The nonunion angle was then estimated in a single plane by considering the greater of the 2 measured angles. Additional data collected included patient age, sex, nonunion site, initial fracture angle, and original fracture pattern., Main Outcome Measurement: Single plane nonunion angle., Results: The mean angles of all nonunion in coronal plane was 42 degrees (SD 17 degrees) and 42 degrees in sagittal plane (SD 18 degrees) and 48 degrees (SD 15 degrees) in single plane. The single plane nonunion angle in fractures which were originally multiplanar was steeper to those occurring in originally single plane fractures (P 0.002) although both were close to 45 degrees. There was no significant difference in the nonunion angles on subgroup analysis of cohort location, sex, or anatomic location., Conclusions: This study demonstrates the mean angle of diaphyseal nonunions from long bones of the lower limb approaches 45 degrees. This is noted in all types of fractures and is irrespective of anatomic location or sex. This confirms the hypothesis that shear is likely to play a role in the development of a nonunion. This study provides further evidence that nonunions occur primarily because of mechanical instability., Level of Evidence: Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence., Competing Interests: R. M. Smith provides consultancy for KCI and Globus. R. M. Smith is on the speaker's bureau for Depuy and AO International. A. J. Trompeter provides consultancy for R&D to Stryker. A. J. Trompeter is on the speaker's bureau for Stryker, Smith, and Nephew and Orthofix. The remaining authors report no conflict of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Objectives: To examine the psychological and social impact of the COVID-19 pandemic on patients with established anxiety disorders during a period of stringent mandated social restrictions., Methods: Semi-structured interviews were conducted with 30 individuals attending the Galway-Roscommon Mental Health Services with an International Classification of Diseases diagnosis of an anxiety disorder to determine the impact of the COVID-19 restrictions on anxiety and mood symptoms, social and occupational functioning and quality of life., Results: Twelve (40.0%) participants described COVID-19 restrictions as having a deleterious impact on their anxiety symptoms. Likert scale measurements noted that the greatest impact of COVID-19 related to social functioning (mean = 4.5, SD = 2.9), with a modest deleterious effect on anxiety symptoms noted (mean = 3.8, SD = 2.9). Clinician rated data noted that 8 (26.7%) participants had disimproved and 14 (46.7%) participants had improved since their previous clinical review, prior to commencement of COVID-19 restrictions. Conditions associated with no 'trigger', such as generalised anxiety disorder, demonstrated a non-significant increase in anxiety symptoms compared to conditions with a 'trigger', such as obsessive compulsive disorder. Psychiatric or physical comorbidity did not substantially impact on symptomatology secondary to COVID-19 mandated restrictions., Conclusions: The psychological and social impact of COVID-19 restrictions on individuals with pre-existing anxiety disorders has been modest with only minimal increases in symptomatology or social impairment noted.

Background: Chronic diseases that drive morbidity, mortality, and health care costs are largely influenced by human behavior. Behavioral health conditions such as anxiety, depression, and substance use disorders can often be effectively managed. The majority of patients in need of behavioral health care are seen in primary care, which often has difficulty responding. Some primary care practices are providing integrated behavioral health care (IBH), where primary care and behavioral health providers work together, in one location, using a team-based approach. Research suggests there may be an association between IBH and improved patient outcomes. However, it is often difficult for practices to achieve high levels of integration. The Integrating Behavioral Health and Primary Care study responds to this need by testing the effectiveness of a comprehensive practice-level intervention designed to improve outcomes in patients with multiple chronic medical and behavioral health conditions by increasing the practice's degree of behavioral health integration., Methods: Forty-five primary care practices, with existing onsite behavioral health care, will be recruited for this study. Forty-three practices will be randomized to the intervention or usual care arm, while 2 practices will be considered "Vanguard" (pilot) practices for developing the intervention. The intervention is a 24-month supported practice change process including an online curriculum, a practice redesign and implementation workbook, remote quality improvement coaching services, and an online learning community. Each practice's degree of behavioral health integration will be measured using the Practice Integration Profile. Approximately 75 patients with both chronic medical and behavioral health conditions from each practice will be asked to complete a series of surveys to measure patient-centered outcomes. Change in practice degree of behavioral health integration and patient-centered outcomes will be compared between the two groups. Practice-level case studies will be conducted to better understand the contextual factors influencing integration., Discussion: As primary care practices are encouraged to provide IBH services, evidence-based interventions to increase practice integration will be needed. This study will demonstrate the effectiveness of one such intervention in a pragmatic, real-world setting., Trial Registration: ClinicalTrials.gov NCT02868983 . Registered on August 16, 2016.

Background : A cascade of care (CoC) model may improve understanding of gaps in addiction treatment availability and quality over current single measure methods. Despite increased funding, opioid overdose rates remain high. Therefore, it is critical to understand where the health-care system is failing to provide appropriate care for people with opioid use disorder (OUD) diagnoses, and to assess disparities in receipt of medication for OUD (MOUD). Objective : Using a CoC framework, assess treatment quality and outcomes for OUD in the Florida Medicaid population in 2017/2018 by demographics and primary vs. secondary diagnosis. Methods : Data from Florida Medicaid claims for 2017 and 2018 were used to calculate the number of enrollees who were diagnosed, began MOUD, were retained on medication for a minimum of 180 days, and who died. Results : Only 28% of those diagnosed with OUD began treatment with an FDA approved MOUD (buprenorphine, methadone, or injectable naltrexone). Once on medication, 38% of newly diagnosed enrollees were retained in treatment for180 days. Those who remained on MOUD for 180 days had a hazard ratio of death of 0.226 (95% CI = 0.174 to 0.294) compared to those that did not initiate MOUD, a reduction in mortality from 10% without MOUD to 2% with MOUD. Conclusions : Initiating medication after OUD diagnosis offers the greatest opportunity for intervention to reduce overdose deaths, though efforts to increase retention are also warranted. Analyzing claims data with CoC identifies system functioning for specific populations, and suggests policies and clinical pathways to target for improvement.

Suicide is a serious problem globally, especially in Europe, with suicide rates varying between different countries. Self-harm is a known risk factor for dying by suicide and represents an opportunity to intervene in order to treat any associated mental illness and reduce risk. This study aimed to compare the characteristics of people presenting to hospital with self-harm at two clinical sites: Galway, Ireland and Kaunas, Lithuania. Data were obtained from the services' database and anonymised for analysis. Over a 5-month period, 89 patients presented with self-harm at the Lithuanian site and 224 patients presented with self-harm at the Irish site. This study found significant differences in presentation, diagnosis and treatment between the two sites. All patients at the Lithuanian site were admitted to psychiatry, compared to 22% of patients at the Irish site ( p < 0.001). In Lithuania, the main clinical diagnoses were adjustment disorder (37.1%) and major depression (20.2%), compared to substance misuse being the main clinical diagnosis (33.8%) in Ireland ( p < 0.001). There were significant differences in the prescription of psychotropic medications (which were three times more commonly prescribed at the Lithuanian site) after controlling for age, gender and psychiatric history ( p < 0.001). Further research is required to understand the cultural context behind and further association between hospitalisation and future death by suicide.

The Arctic is experiencing dramatic changes including increases in precipitation, glacial melt, and permafrost thaw, resulting in increasing freshwater runoff to coastal waters. During the melt season, terrestrial runoff delivers carbon- and nutrient-rich freshwater to Arctic coastal waters, with unknown consequences for the microbial communities that play a key role in determining the cycling and fate of terrestrial matter at the land-ocean interface. To determine the impacts of runoff on coastal microbial (bacteria and archaea) communities, we investigated changes in pelagic microbial community structure between the early (June) and late (August) melt season in 2018 in the Isfjorden system (Svalbard). Amplicon sequences of the 16S rRNA gene were generated from water column, river and sediment samples collected in Isfjorden along fjord transects from shallow river estuaries and glacier fronts to the outer fjord. Community shifts were investigated in relation to environmental gradients, and compared to river and marine sediment microbial communities. We identified strong temporal and spatial reorganizations in the structure and composition of microbial communities during the summer months in relation to environmental conditions. Microbial diversity patterns highlighted a reorganization from rich communities in June toward more even and less rich communities in August. In June, waters enriched in dissolved organic carbon (DOC) provided a niche for copiotrophic taxa including Sulfitobacter and Octadecabacter . In August, lower DOC concentrations and Atlantic water inflow coincided with a shift toward more cosmopolitan taxa usually associated with summer stratified periods (e.g., SAR11 Clade Ia), and prevalent oligotrophic marine clades (OM60, SAR92). Higher riverine inputs of dissolved inorganic nutrients and suspended particulate matter also contributed to spatial reorganizations of communities in August. Sentinel taxa of this late summer fjord environment included taxa from the class Verrucomicrobiae ( Roseibacillus , Luteolibacter ), potentially indicative of a higher fraction of particle-attached bacteria. This study highlights the ecological relevance of terrestrial runoff for Arctic coastal microbial communities and how its impacts on biogeochemical conditions may make these communities susceptible to climate change., Competing Interests: 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., (Copyright © 2021 Delpech, Vonnahme, McGovern, Gradinger, Præbel and Poste.)

Between January 2016 and June 2020, the Substance Abuse and Mental Health Services Administration rapidly distributed $7.5 billion in response to the U.S. opioid crisis. These funds are designed to increase access to medications for addiction treatment, reduce unmet treatment need, reduce overdose death rates, and provide and sustain effective prevention, treatment and recovery activities. It is unclear whether or not the services developed using these funds will be sustained beyond the start-up period. Based on 34 (64%) State Opioid Response (SOR) applications, we assessed the states' sustainability plans focusing on potential funding sources, policies, and quality monitoring. We found variable commitment to sustainability across response plans with less than half the states adequately describing sustainability plans. States with higher proportions of opioid prescribing, opioid misuse, and poverty had somewhat higher scores on sustainment. A text mining/machine learning approach automatically rated sustainability in SOR applications with an 82% accuracy compared to human ratings. Because life saving evidence-based programs and services may be lost, intentional commitment to sustainment beyond the bolus of start-up funding is essential., Competing Interests: The authors have declared that no competing interests exist.

An orally administered, fixed-dose coformulation of sodium phenylbutyrate-taurursodiol (PB-TURSO) significantly slowed functional decline in a randomized, placebo-controlled, phase 2 trial in ALS (CENTAUR). Herein we report results of a long-term survival analysis of participants in CENTAUR. In CENTAUR, adults with ALS were randomized 2:1 to PB-TURSO or placebo. Participants completing the 6-month (24-week) randomized phase were eligible to receive PB-TURSO in the open-label extension. An all-cause mortality analysis (35-month maximum follow-up post-randomization) incorporated all randomized participants. Participants and site investigators were blinded to treatment assignments through the duration of follow-up of this analysis. Vital status was obtained for 135 of 137 participants originally randomized in CENTAUR. Median overall survival was 25.0 months among participants originally randomized to PB-TURSO and 18.5 months among those originally randomized to placebo (hazard ratio, 0.56; 95% confidence interval, 0.34-0.92; P = .023). Initiation of PB-TURSO treatment at baseline resulted in a 6.5-month longer median survival as compared with placebo. Combined with results from CENTAUR, these results suggest that PB-TURSO has both functional and survival benefits in ALS., (© 2020 The Authors. Muscle & Nerve published by Wiley Periodicals LLC.)

Background: Behavioral health services, integrated into primary care practices, have become increasingly implemented. Although patient satisfaction has been studied, limited information exists about patient preferences for integrated behavioral health in primary care and how perceptions may vary. Objective: To determine patient preferences for integrated behavioral health within primary care and explore differences across patient groups. Methods: A self-report survey was distributed within a quality improvement initiative in an academic health system. A brief 8-item self-report questionnaire of perceptions and preferences for integrated behavioral health was administered to 752 primary care patients presenting before their visits at two primary care clinics. Participation was voluntary, responses were anonymous, and all patients presenting during a three-week timeframe were eligible. Results: In general, patients preferred to have behavioral health concerns addressed within primary care (n = 301; 41%) rather than referral to a specialist (7.5%; n = 55). There was no evidence of variation in preferences by demographic characteristics. Comfort levels to receive behavioral health services ( P  < .001) and perceived needs being met were significantly associated with preferences for receiving IBHPC ( P  < .001). Conclusion: This project provided valuable data to support the implementation of integrated behavioral health services in primary care clinics. In general, patients prefer to have behavioral health issues addressed within their primary care experience rather than being referred to specialty mental health care. This study adds to an expanding pool of studies exploring patient preferences for integrated behavioral health in primary care.

To design PARTNER-MH, a peer-led, patient navigation program for implementation in Veterans Health Administration (VHA) mental health care settings, we conducted a pre-implementation evaluation during intervention development to assess stakeholders' views of the intervention and to explore implementation factors critical to its future adoption. This is a convergent mixed-methods study that involved qualitative semi-structured interviews and survey data. Data collection was guided by the Consolidated Framework for Implementation Research (CFIR). We interviewed and administered the surveys to 23 peers and 10 supervisors from 12 midwestern VHA facilities. We used deductive and inductive approaches to analyze the qualitative data. We also conducted descriptive analysis and Fisher Exact Test to compare peers and supervisors' survey responses. We triangulated findings to refine the intervention. Overall, participants viewed PARTNER-MH favorably. However, they saw the intervention's focus on minority Veterans and social determinants of health framework as potential barriers, believing this could negatively affect the packaging of the intervention, complicate its delivery process, and impact its adoption. They also viewed clinic structures, available resources, and learning climate as potential barriers. Peers and supervisors' selections and discussions of CFIR items were similar. Our findings informed PARTNER-MH development and helped identify factors that could impact its implementation. This project is responsive to the increasing recognition of the need to incorporate implementation science in healthcare disparities research. Understanding the resistance to the intervention's focus on minority Veterans and the potential barriers presented by contextual factors positions us to adjust the intervention prior to testing, in an effort to maximize implementation success.

Background: The US 21st Century Cures Act provided $7.5 billion in grant funding to states and territories for evidence-based responses to the opioid epidemic. Currently, little is known about optimal strategies for sustaining these programs beyond this start-up funding., Methods: Using an inductive, conventional content analysis, we conducted key informant interviews with former and current state leaders (n = 16) about barriers/facilitators to sustainment and strategies for sustaining time-limited grants., Results: Financing and reimbursement, service integration, and workforce capacity were the most cited barriers to sustainment. Status in state government structure, public support, and spending flexibility were noted as key facilitators. Effective levers to increase chances for sustainment included strong partnerships with other state agencies, workforce and credentialing changes, and marshalling advocacy through public awareness campaigns., Conclusions: Understanding the strategies that leaders have successfully used to sustain programs in the past can inform how to continue future time-limited, grant-funded initiatives.

BACKGROUND Resettled refugees are at increased risk of poor health outcomes due to acculturation challenges, logistical barriers, experiences of trauma, and other barriers to care that are poorly understood. Refugee children may be particularly vulnerable due to disruptions in health, well-being, education, and nutrition during the resettlement process. METHOD To describe the health care barriers facing refugees in the North Carolina Triangle area (comprised of Durham, Chapel Hill, Raleigh, and their surrounding areas), we conducted three focus group interviews (in Arabic, French, and Swahili) with 25 refugee parents from Syria, Iraq, Central African Republic, the Democratic Republic of the Congo, and Chad. We also administered a survey to nine organizations that provide services for refugees. RESULTS Focus group responses highlighted the multidimensional nature of health care barriers for refugee families and children, encompassing challenges with acculturation, communication, transportation, finances, and health literacy. Organizations emphasized similar challenges and described their efforts to improve access to services through increased communication, coordination, and seeking new financial support for programs. LIMITATIONS Given the geographic focus of the study, results may not be generalizable to other populations and settings. Men spoke more than women in some focus groups, and participants may have been influenced by more vocal contributors. Furthermore, this study is limited by a lack of health outcomes data. CONCLUSIONS This study suggests that the health care needs of refugees living in the North Carolina Triangle area can be better met by providing comprehensive, coordinated, and culturally relevant care. This could include minimizing the number of visits by integrating multiple services under one roof, providing trauma-informed interpreters, and offering accessible transportation services., (©2020 by the North Carolina Institute of Medicine and The Duke Endowment. All rights reserved.)

Background: Sodium phenylbutyrate and taurursodiol have been found to reduce neuronal death in experimental models. The efficacy and safety of a combination of the two compounds in persons with amyotrophic lateral sclerosis (ALS) are not known., Methods: In this multicenter, randomized, double-blind trial, we enrolled participants with definite ALS who had had an onset of symptoms within the previous 18 months. Participants were randomly assigned in a 2:1 ratio to receive sodium phenylbutyrate-taurursodiol (3 g of sodium phenylbutyrate and 1 g of taurursodiol, administered once a day for 3 weeks and then twice a day) or placebo. The primary outcome was the rate of decline in the total score on the Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R; range, 0 to 48, with higher scores indicating better function) through 24 weeks. Secondary outcomes were the rates of decline in isometric muscle strength, plasma phosphorylated axonal neurofilament H subunit levels, and the slow vital capacity; the time to death, tracheostomy, or permanent ventilation; and the time to death, tracheostomy, permanent ventilation, or hospitalization., Results: A total of 177 persons with ALS were screened for eligibility, and 137 were randomly assigned to receive sodium phenylbutyrate-taurursodiol (89 participants) or placebo (48 participants). In a modified intention-to-treat analysis, the mean rate of change in the ALSFRS-R score was -1.24 points per month with the active drug and -1.66 points per month with placebo (difference, 0.42 points per month; 95% confidence interval, 0.03 to 0.81; P = 0.03). Secondary outcomes did not differ significantly between the two groups. Adverse events with the active drug were mainly gastrointestinal., Conclusions: Sodium phenylbutyrate-taurursodiol resulted in slower functional decline than placebo as measured by the ALSFRS-R score over a period of 24 weeks. Secondary outcomes were not significantly different between the two groups. Longer and larger trials are necessary to evaluate the efficacy and safety of sodium phenylbutyrate-taurursodiol in persons with ALS. (Funded by Amylyx Pharmaceuticals and others; CENTAUR ClinicalTrials.gov number, NCT03127514.)., (Copyright © 2020 Massachusetts Medical Society.)

Background: Acid sphingomyelinase deficiency (ASMD) also known as Niemann-Pick disease, is a rare lysosomal storage disorder with a diverse disease spectrum that includes slowly progressive, chronic visceral (type B) and neurovisceral forms (intermediate type A/B), in addition to infantile, rapidly progressive fatal neurovisceral disease (type A)., Purpose and Methods: We review the published evidence on the relevance of splenomegaly and reduced lung diffusion capacity to the clinical burden of chronic forms of ASMD. Targeted literature searches were conducted to identify relevant ASMD and non-ASMD studies for associations between diffusing capacity of the lungs for carbon monoxide (DL CO ) and splenomegaly, with clinical parameters and outcome measures., Results: Respiratory disease and organomegaly are primary and independent contributors to mortality, disease burden, and morbidity for patients with chronic ASMD. The degree of splenomegaly correlates with short stature, atherogenic lipid profile, and degree of abnormality of hematologic parameters, and thus may be considered a surrogate marker for bleeding risk, abnormal lipid profiles and possibly, liver fibrosis. Progressive lung disease is a prevalent clinical feature of chronic ASMD, contributing to a decreased quality of life (QoL) and an increased disease burden. In addition, respiratory-related complications are a major cause of mortality in ASMD., Conclusions: The reviewed evidence from ASMD natural history and observational studies supports the use of lung function and spleen volume as clinically meaningful endpoints in ASMD trials that translate into important measures of disease burden for patients., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: Evidence to date, while sparse, suggests that patients taking long-term opioids require special considerations and protections to prevent potential iatrogenic harms from opioid de-prescribing, such as increased pain or suffering. Following this study protocol, the EMPOWER study seeks to address multiple unmet needs of patients with chronic pain who desire to reduce long-term opioid therapy, and provide the clinical evidence on effective methodology., Methods: EMPOWER applies patient-centered methods for voluntary prescription opioid reduction conducted within a comprehensive, multi-state, 3-arm randomized controlled comparative effectiveness study of three study arms (1) group cognitive behavioral therapy for chronic pain; (2) group chronic pain self-management; and (3) usual care (taper only). Specialized electronic data capture systems collect patient reported symptoms and satisfaction data weekly and monthly during the taper, with real-time clinical alerts and electronic feedback loops informing, documenting, and steering needed care actions., Conclusion: The EMPOWER study seeks to provide granular evidence on patient response to voluntary opioid tapering, and will provide evidence to inform clinical systems changes, clinical care, patient satisfaction, and patient outcomes for opioid reduction., (© 2019 American Academy of Pain Medicine.)

Sepsis remains a leading cause of morbidity and mortality in the neonatal population, and at present, there is no unified definition of neonatal sepsis. Existing consensus sepsis definitions within paediatrics are not suited for use in the NICU and do not address sepsis in the premature population. Many neonatal research and surveillance networks have criteria for the definition of sepsis within their publications though these vary greatly and there is typically a heavy emphasis on microbiological culture. The concept of organ dysfunction as a diagnostic criterion for sepsis is rarely considered in neonatal literature, and it remains unclear how to most accurately screen neonates for organ dysfunction. Accurately defining and screening for sepsis is important for clinical management, health service design and future research. The progress made by the Sepsis-3 group provides a roadmap of how definitions and screening criteria may be developed. Similar initiatives in neonatology are likely to be more challenging and would need to account for the unique presentation of sepsis in term and premature neonates. The outputs of similar consensus work within neonatology should be twofold: a validated definition of neonatal sepsis and screening criteria to identify at-risk patients earlier in their clinical course. IMPACT: There is currently no consensus definition of neonatal sepsis and the definitions that are currently in use are varied.A consensus definition of neonatal sepsis would benefit clinicians, patients and researchers.Recent progress in adults with publication of Sepsis-3 provides guidance on how a consensus definition and screening criteria for sepsis could be produced in neonatology.We discuss common themes and potential shortcomings in sepsis definitions within neonatology.We highlight the need for a consensus definition of neonatal sepsis and the challenges that this task poses.

Background: In order to close the gap between discoveries that could improve health, and widespread impact on routine health care practice, there is a need for greater attention to the factors that influence dissemination and implementation of evidence-based practices. Evidence synthesis projects (e.g., systematic reviews) could contribute to this effort by collecting and synthesizing data relevant to dissemination and implementation. Such an advance would facilitate the spread of high-value, effective, and sustainable interventions., Objective: The objective of this paper is to evaluate the feasibility of extracting factors related to implementation during evidence synthesis in order to enhance the replicability of successes of studies of interventions in health care settings., Design: Drawing on the implementation science literature, we suggest 10 established implementation measures that should be considered when conducting evidence synthesis projects. We describe opportunities to assess these constructs in current literature and illustrate these methods through an example of a systematic review., Subjects: Twenty-nine studies of interventions aimed at improving clinician-patient communication in clinical settings., Key Results: We identified acceptability, adoption, appropriateness, feasibility, fidelity, implementation cost, intervention complexity, penetration, reach, and sustainability as factors that are feasible and appropriate to extract during an evidence synthesis project., Conclusions: To fully understand the potential value of a health care innovation, it is important to consider not only its effectiveness, but also the process, demands, and resource requirements involved in downstream implementation. While there is variation in the degree to which intervention studies currently report implementation factors, there is a growing demand for this information. Abstracting information about these factors may enhance the value of systematic reviews and other evidence synthesis efforts, improving the dissemination and adoption of interventions that are effective, feasible, and sustainable across different contexts.

As part of the State Targeted Response to the opioid epidemic, California has adopted the Hub and Spoke model to expand access to medications for opioid use disorder, particularly buprenorphine, throughout the state. By aligning opioid treatment programs as hubs with primary care, office-based practitioners, and other health care settings as spokes, a broader treatment model can reach more people with opioid use disorder, improve access to medications for opioid use disorders, and decrease overdose deaths. Expanding access requires expanding knowledge and intensive implementation support of new practices. This paper describes the rationale, specific activities and anticipated impact of the implementation plan in California's Hub and Spoke system. Training and technical assistance are designed to: increase the number and capacity of waivered prescribers; enhance skills of prescribers and multidisciplinary teams; and create systems change. Activities include buprenorphine waiver trainings and provider support, a practice facilitator program, Project ECHO sessions, webinars, clinical skills trainings, and regional learning collaboratives. This overview highlights the steps California is taking to build treatment capacity to address the opioid epidemic., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Objectives: The Vasarhelyi Method of Child Art Psychotherapy (CAP) is a largely understudied psychotherapeutic modality. This study aims to describe the Vasarhelyi Method of CAP and to describe a stakeholder survey of the views and attitudes of CAP placement supervisors towards CAP among various Child and Adolescent Mental Health Services (CAMHS) teams nationwide., Methods: A phone- and letter-based survey of 17 CAP placement supervisors who oversee CAP masters students attached to CAMHS teams was performed. A questionnaire was designed enquiring about their experiences with CAP in their clinic and their thoughts on the validity of CAP in various conditions/patient demographics. Participants received written correspondence and were asked to return the survey by post; this was followed up by a telephone call to complete missing surveys., Results: In all, 12 (70.6%) complete surveys were returned. Of the 12 respondents, all considered the CAP student to be a valuable member of the team. In total, 10 respondents (83.33%) stated they would make regular use of the service if it were made available to them. With regard to the therapy itself, nine respondents (75%) believed it was better for internalising symptoms than externalising symptoms. Depression, anxiety, attachment difficulties, trauma, deliberate self-harm and possible psychosomatic illnesses are the conditions viewed as receiving the most benefit from CAP. No gender difference was reported., Conclusion: CAP is considered an effective modality and valuable addition to a psychotherapeutic repertoire. Further, more extensive studies are needed in this field.