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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).

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.)

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.

Objective: This paper reports on the rationalization of a substantial pool of in vivo dosimetry (IVD) data from patients treated with total skin electron beam therapy (TSEBT) and the application of this to verify the accurate delivery of TSEBT when changing linac manufacturer., Methods: Thermoluminescent dosimeter IVD data from 149 patients were analyzed comparing the population mean and standard deviation for each site. The number of sites required to confirm the prescribed dose were reviewed considering both dosimetric and clinical relevance. The reduced sites were then used to assess the continued dosimetric accuracy on new equipment and the results were compared statistically using the Mann-Witney test., Results: The trunk dose measurement points were reduced from nine to six and five extra trunk sites were identified and reviewed clinically prior to removal.Following change in manufacturer the trunk dose points showed no statistically significant change and confirmed that patients had received within 1.3% of the intended mean trunk dose using both delivery methods.A statistically significant change in 4 out of the 13 extra trunk sites was seen following the move to the new centre. However, all but one site showed a change of less than 1 standard deviation., Conclusion: The total number of measurement points per patient were reduced from 27 to 19 which constituted a 25% saving in preparation and read out.Accurate delivery of prescribed dose was confirmed following measurement point reduction for treatments delivered on linacs from two different manufacturers., Advances in Knowledge: Proven methodology for rationalization of IVD measurements for TSEBT., (© 2019 The Authors. Published by the British Institute of Radiology.)

When a solution of polyanionic chains is placed in contact with a polycationic brush, the polyanions adsorb into the brush. We investigate the influence of the charge sequences of the free and bound species on the thermodynamics of polyelectrolyte adsorption. As model systems, we consider free and brush polyelectrolytes with either block or alternating charge sequences, and study the adsorption process using coarse-grained Langevin dynamics with implicit solvent, explicit counterions, and excess salt. Free energy, internal energy, and entropy of adsorption are computed using umbrella sampling methods. When the number of polyanions exceed the number of polycations, the brush becomes overcharged. Free chains adsorb most strongly when both free and tethered chains have a block charge sequence, and most weakly when both species have an alternating sequence. Adsorption is stronger when the free polyanion has a block sequence and the tethered polycation is alternating than in the reverse case of an alternating free polymer and a tethered block copolymer. Sequence-dependent effects are shown to be largely energetic, rather than entropic, in origin.

In the title 1:2 co-crystal, C 10 H 9 N 2 + ·(C 6 H 7.75 O 6 ·C 6 H 7.25 O 6 ) - , l-ascorbic acid (LAA) and 4,4'-bi-pyridine (BPy) co-crystallize in the chiral space group P 2 1 with two mol-ecules of LAA, and one mol-ecule of bpy in the asymmetric unit. The structure was modeled in two parts due to possible proton transfer from LAA to the corresponding side of the bpy mol-ecule having an occupancy of approximately 0.25 and part 2 with an occupancy of approximately 0.75. In this structure, LAA forms hydrogen bonds with neighboring LAA mol-ecules, forming extended sheets of LAA mol-ecules which are bridged by bpy mol-ecules. A comparison to a related and previously published co-crystal of LAA and 3-bromo-4-pyridone is presented.

Aims Suspected sepsis remains a leading causes of Neonatal Intensive Care Unit admission, with infants often receiving 48-72 hours of empirical antibiotic therapy. Early in treatment it is difficult to predict infants who will require prolonged antibiotic therapy. Our aim was to assess if vital sign measurements in the initial period of treatment can predict those neonates requiring prolonged antibiotic therapy in term and late-preterm infants. Methods Data was retrospectively collected over 1 year on neonates admitted to our institute for antibiotics. Infants were classified as standard (<48hours duration) or prolonged (>48hours duration) antibiotic therapy. Results Respiratory rate on admission and 12 hours after initiation of therapy correlated significantly with duration of antibiotic therapy and infants requiring prolonged therapy were more likely to have one or more abnormal vital signs 12 hours after initiation of treatment (p<0.05). Conclusion Respiratory rate shows a weak positive correlation with antibiotic duration. Infants requiring prolonged therapy were more likely to have abnormal vital signs 12 hours after initiating antibiotic therapy. Changes in vital signs maybe useful in detecting infants who will require prolonged antibiotic therapy., Competing Interests: The authors declare that they have no conflict of interest.

Background: Acid sphingomyelinase deficiency (ASMD), a rare lysosomal storage disease, results from mutations in SMPD1, the gene encoding acid sphingomyelinase (ASM). As a result, sphingomyelin accumulates in multiple organs including spleen, liver, lung, bone marrow, lymph nodes, and in the most severe form, in the CNS and peripheral nerves. Clinical manifestations range from rapidly progressive and fatal infantile neurovisceral disease, to less rapidly progressing chronic neurovisceral and visceral forms that are associated with significant morbidity and shorter life span due to respiratory or liver disease., Objectives: To provide a contemporary guide of clinical assessments for disease monitoring and symptom management across the spectrum of ASMD phenotypes., Methods: An international group of ASMD experts in various research and clinical fields used an evidence-informed consensus process to identify optimal assessments, interventions, and lifestyle modifications., Results: Clinical assessment strategies for major organ system involvement, including liver, spleen, cardiovascular, pulmonary, and neurological/developmental are described, as well as symptomatic treatments, interventions, and/or life style modifications that may lessen disease impact., Conclusions: There is currently no disease-specific treatment for ASMD, although enzyme replacement therapy with a recombinant human ASM (olipudase alfa) is in clinical development. Current monitoring addresses symptoms and multisystem involvement. Recommended interventions and lifestyle modifications are designed to address morbidity and disease complications and improve patient quality of life. While infantile neurovisceral ASMD is uniformly fatal in early childhood, patients with chronic visceral and chronic neurovisceral ASMD require appropriate management throughout childhood and adulthood by an interdisciplinary clinical team., (Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.)

Competing Interests: Competing interests: None declared.

We analysed socio-economic inequalities in stunting in South Asia and investigated disparities associated with factors at the individual, caregiver, and household levels (poor dietary diversity, low maternal education, and household poverty). We used time-series analysis of data from 55,459 children ages 6-23 months from Demographic and Health Surveys in Bangladesh, India, Nepal, and Pakistan (1991-2014). Logistic regression models, adjusted for age, sex, birth order, and place of residency, examined associations between stunting and multiple types of socio-economic disadvantage. All countries had high stunting rates. Bangladesh and Nepal recorded the largest reductions-2.9 and 4.1 percentage points per year, respectively-compared to 1.3 and 0.6 percentage points in India and Pakistan, respectively. Socio-economic adversity was associated with increased risk of stunting, regardless of disadvantage type. Poor children with inadequate diets and with poorly educated mothers experienced greater risk of stunting. Although stunting rates declined in the most deprived groups, socio-economic differences were largely preserved over time and in some cases worsened, namely, between wealth quintiles. The disproportionate burden of stunting experienced by the most disadvantaged children and the worsening inequalities between socio-economic groups are of concern in countries with substantial stunting burdens. Closing the gap between best and worst performing countries, and between most and least disadvantaged groups within countries, would yield substantial improvements in stunting rates in South Asia. To do so, greater attention needs to be paid to addressing the social, economic, and political drivers of stunting with targeted efforts towards the populations experiencing the greatest disadvantage and child growth faltering., (© 2017 The Authors. Maternal and Child Nutrition Published by John Wiley & Sons, Ltd.)

Background: Epidemiologic studies have shown that low levels of high-density lipoprotein-cholesterol (HDL-C) and elevated triglycerides are independent predictors of cardiovascular (CV) events, though randomized trials of HDL-C-raising therapies to reduce clinical events have been largely disappointing. The Atherothrombosis Intervention in Metabolic Syndrome with Low HDL/High Triglycerides and Impact on Global Health Outcomes (AIM-HIGH) trial failed to show that extended release niacin (ERN) reduced CV events in patients with atherogenic dyslipidemia who were on statin-based therapy., Objective: We sought to determine whether extended follow-up of AIM-HIGH participants changed these null results., Methods: AIM-HIGH was a placebo-controlled trial of 3414 patients with established CV disease, low baseline HDL-C, and elevated triglycerides levels randomized to ERN 1500-2000 mg/d vs placebo. Participants also received simvastatin with or without ezetimibe to attain on-treatment low-density lipoprotein cholesterol levels of 40-80 mg/dL. The trial was halted after a mean 3-year follow-up because of futility., Results: Among 3236 participants alive at the end of blinded study, 2613 (81%; ERN = 1,312, placebo = 1301) were followed a mean 1.1 additional years. Ninety-five percent of subjects remained on statin, but only 4% on ERN. At a mean total follow-up of 4.1 years, there were 343 primary CV endpoints in the ERN arm and 305 CV endpoints in placebo participants (HR 1.11, 95% CI 0.96, 1.30). Ischemic stroke was also not significantly different after extended follow-up in the two groups (2.2% vs 1.5%, P = .13)., Conclusions: In patients with CV disease and atherogenic dyslipidemia on statin-based therapy, 3 years of ERN treatment did not lower CV event rates. An additional year of follow-up off assigned treatment did not alter these findings., (Copyright © 2018 National Lipid Association. All rights reserved.)

Aim: From birth to old age, males generally have poorer disease outcomes compared to females. Preterm infants display a marked gender disparity in disease outcomes, and the underlying mechanisms are not well delineated. Our aim was to review the literature on clinical outcomes between preterm infants of different genders and discuss the potential mechanisms underlying the differences observed., Methods: A literature review was undertaken for experimental and clinical research related to gender differences in preterm outcomes., Results: Preterm male infants appear to have consistently worse outcomes compared to females, and the aetiology of these differences, while mostly undetermined, is likely multifactorial., Conclusion: The male disadvantage in preterm outcomes is likely multifactorial with hormonal, genetic and immunological differences likely playing key roles. Gender is an important variable in preterm outcome and should be considered when designing clinical and experimental research., (©2018 Foundation Acta Pædiatrica. Published by John Wiley & Sons Ltd.)

Background: There are limited treatments for progressive multiple sclerosis. Ibudilast inhibits several cyclic nucleotide phosphodiesterases, macrophage migration inhibitory factor, and toll-like receptor 4 and can cross the blood-brain barrier, with potential salutary effects in progressive multiple sclerosis., Methods: We enrolled patients with primary or secondary progressive multiple sclerosis in a phase 2 randomized trial of oral ibudilast (≤100 mg daily) or placebo for 96 weeks. The primary efficacy end point was the rate of brain atrophy, as measured by the brain parenchymal fraction (brain size relative to the volume of the outer surface contour of the brain). Major secondary end points included the change in the pyramidal tracts on diffusion tensor imaging, the magnetization transfer ratio in normal-appearing brain tissue, the thickness of the retinal nerve-fiber layer, and cortical atrophy, all measures of tissue damage in multiple sclerosis., Results: Of 255 patients who underwent randomization, 129 were assigned to ibudilast and 126 to placebo. A total of 53% of the patients in the ibudilast group and 52% of those in the placebo group had primary progressive disease; the others had secondary progressive disease. The rate of change in the brain parenchymal fraction was -0.0010 per year with ibudilast and -0.0019 per year with placebo (difference, 0.0009; 95% confidence interval, 0.00004 to 0.0017; P=0.04), which represents approximately 2.5 ml less brain-tissue loss with ibudilast over a period of 96 weeks. Adverse events with ibudilast included gastrointestinal symptoms, headache, and depression., Conclusions: In a phase 2 trial involving patients with progressive multiple sclerosis, ibudilast was associated with slower progression of brain atrophy than placebo but was associated with higher rates of gastrointestinal side effects, headache, and depression. (Funded by the National Institute of Neurological Disorders and Stroke and others; NN102/SPRINT-MS ClinicalTrials.gov number, NCT01982942 .).

Objectives: The new immunochemistry cobas e 801 module (Roche Diagnostics) was developed to meet increasing demands on routine laboratories to further improve testing efficiency, while maintaining high quality and reliable data., Design and Methods: During a non-interventional multicenter evaluation study, the overall performance, functionality and reliability of the new module was investigated under routine-like conditions. It was tested as a dedicated immunochemistry system at four sites and as a consolidator combined with clinical chemistry at three sites., Results: We report on testing efficiency and analytical performance of the new module. Evaluation of sample workloads with site-specific routine request patterns demonstrated increased speed and almost doubled throughput (maximal 300 tests per h), thus revealing that one cobas e 801 module can replace two cobas e 602 modules while saving up to 44% floor space. Result stability was demonstrated by QC analysis per assay throughout the study. Precision testing over 21 days yielded excellent results within and between labs, and, method comparison performed versus the cobas e 602 module routine results showed high consistency of results for all assays under study. In a practicability assessment related to performance and handling, 99% of graded features met (44%) or even exceeded (55%) laboratory expectations, with enhanced reagent management and loading during operation being highlighted., Conclusion: By nearly doubling immunochemistry testing efficiency on the same footprint as a cobas e 602 module, the new module has a great potential to further consolidate and enhance laboratory testing while maintaining high quality analytical performance with Roche platforms., (Copyright © 2018 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.)

Background: Electronic referrals or e-referrals can be defined as the electronic transmission of patient data and clinical requests between health service providers. National electronic referral systems have proved challenging to implement due to problems of fit between the technical systems proposed and the existing sociotechnical systems. In seeming contradiction to a sociotechnical approach, the Irish Health Service Executive initiated an incremental implementation of a National Electronic Referral Programme (NERP), with step 1 including only the technical capability for general practitioners to submit electronic referral requests to hospital outpatient departments. The technology component of the program was specified, but any changes required to embed that technology in the existing sociotechnical system were not specified., Objective: This study aimed to theoretically frame the lessons learned from the NERP step 1 on the design and implementation of a national health information technology program., Methods: A case study design was employed, using qualitative interviews with key stakeholders of the NERP step 1 (N=41). A theory-driven thematic analysis of the interview data was conducted, using Barker et al's Framework for Going to Full Scale., Results: The NERP step 1 was broadly welcomed by key stakeholders as the first step in the implementation of electronic referrals-delivering improvements in the speed, completeness of demographic information, and legibility and traceability of referral requests. National leadership and digitalized health records in general practice were critical enabling factors. Inhibiting factors included policy uncertainty about the future organizational structures within which electronic referrals would be implemented; the need to establish a central referral office consistent with these organizational structures; outstanding interoperability issues between the electronic referral solution and hospital patient administration systems; and an anticipated need to develop specialist referral templates for some specialties. A lack of specification of the sociotechnical elements of the NERP step 1 inhibited the necessary testing and refinement of the change package used to implement the program., Conclusions: The key strengths of the NERP step 1 are patient safety benefits. The NERP was progressed beyond the pilot stage despite limited resources and outstanding interoperability issues. In addition, a new electronic health unit in Ireland (eHealth Ireland) gained credibility in delivering national health information technology programs. Limitations of the program are its poor integration in the wider policy and quality improvement agenda of the Health Service Executive. The lack of specification of the sociotechnical elements of the program created challenges in communicating the program scope to key stakeholders and restricted the ability of program managers and implementers to test and refine the change package. This study concludes that while the sociotechnical elements of a national health information technology program do not need to be specified in tandem with technical elements, they do need to be specified early in the implementation process so that the change package used to implement the program can be tested and refined., (©Marcella McGovern, Maria Quinlan, Gerardine Doyle, Gemma Moore, Susi Geiger. Originally published in JMIR Medical Informatics (http://medinform.jmir.org), 18.07.2018.)

Objectives: Clinical mentoring is important for novice clinicians as they are developing advanced critical-thinking skills. Research exploring innovative mentoring strategies to reduce barriers and enhance learning is needed. The purpose of this study was to examine the effects of providing online clinical mentoring to small international groups of novice clinicians treating patients with spinal dysfunction in the outpatient setting., Methods: Eleven novice and four expert clinicians were allocated into small international groups. Four one-hour group video-conference mentoring sessions were held in which each novice clinician presented a case study. Data were collected from pre- and post-participation surveys and post-participation focus groups. Data were evaluated with a mixed-methods phenomenological analysis., Results: Four themes emerged from the novice qualitative data: improved confidence, enhanced critical thinking, appreciation of the structured design and accessibility to peers and mentors. The quantitative data revealed significant improvement in three confidence measures, improvement of 1.48 points on self-selected clinical goals, and 82.0% reported improved clinical decision-making. Two themes emerged from the expert data: value of the model to fill a need within the profession and viability of the model to stand alone or as part of an educational program. All participants rated their experience on average at 8.76/10 and expressed interest in future mentoring programs., Discussion: Online small group international clinical mentoring appears to be an effective strategy to provide clinical mentoring to promote confidence and critical-thinking skills. This research could provide a viable model to increase accessibility to clinical mentors and fill a need within the profession.

Maintaining optimal circulatory status is a key component of preterm neonatal care. Low-cardiac output (CO) in the preterm neonate leads to inadequate perfusion of vital organs and has been linked to a variety of adverse outcomes with heightened acute morbidity and mortality and adverse neurodevelopmental outcomes. Having technology available to monitor CO allows us to detect low-output states and potentially intervene to mitigate the unwanted effects of reduced organ perfusion. There are many technologies available for the monitoring of CO in the preterm neonatal population and while many act as useful adjuncts to aid clinical decision-making no technique is perfect. In this review, we discuss the relative merits and limitations of various common methodologies available for monitoring CO in the preterm neonatal population. We will discuss the ongoing challenges in monitoring CO in the preterm neonate along with current gaps in our knowledge. We conclude by discussing emerging technologies and areas that warrant further study.

DSL ligands activate the Notch receptor in many cellular contexts across metazoa to specify cell fate. In addition, Notch receptor activity is implicated in post-mitotic morphogenesis and neuronal function. In C. elegans, the DSL family ligand APX-1 is expressed in a subset of cells of the proximal gonad lineage, where it can act as a latent proliferation-promoting signal to maintain proximal germline tumors. Here we examine apx-1 in the proximal gonad and uncover a role in the maintenance of normal ovulation. Depletion of apx-1 causes an endomitotic oocyte (Emo) phenotype and ovulation defects. We find that lag-2 can substitute for apx-1 in this role, that the ovulation defect is partially suppressed by loss of ipp-5, and that lin-12 depletion causes a similar phenotype. In addition, we find that the ovulation defects are often accompanied by a delay of spermathecal distal neck closure after oocyte entry. Although calcium oscillations occur in the spermatheca, calcium signals are abnormal when the distal neck does not close completely. Moreover, oocytes sometimes cannot properly transit through the spermatheca, leading to fragmentation of oocytes once the neck closes. Finally, abnormal oocytes and neck closure defects are seen occasionally when apx-1 or lin-12 activity is reduced in adult animals, suggesting a possible post-developmental role for APX-1 and LIN-12 signaling in ovulation., (Copyright © 2018 Elsevier Inc. All rights reserved.)