Airway and Systemic Immunoglobulin Profiling and Immune Response in Adult Asthma.

INTRODUCTION: Immunoglobulins play a vital role in host immune response and in the pathogenesis of conditions like asthma. Therapeutic agents such as monoclonal antibodies target specific elements of the asthmatic inflammatory cascade. Decisions to utilize these medications are often based on systemic inflammatory profiling without direct insight into the airway inflammatory profile. We sought to investigate the relationship between immunoglobulin and cytokine profiles in the airway and systemic immune compartments of adult asthmatics. METHODS: Blood sampling and bronchoscopy with bronchoalveolar lavage (BAL) were performed in 76 well-defined adult asthmatics. Antibody and cytokine profiles were measured in both BAL and serum using ELISA and quantibody arrays. RESULTS: There was no relationship between BAL and serum levels of IgE. This is of significance in an asthma population. For some analytes, correlation analysis was significant (P < 0.05) indicating representativeness of our cohort and experimental setup in those cases. Nevertheless, the predictive power (r2) of the BAL-to-serum comparisons was mostly low except for TNF-α (r2 = 0.73) when assuming a simple (linear) relationship. CONCLUSION: This study highlights the importance of sample site when investigating the roles of immunoglobulins and cytokines in disease pathogenesis and suggests that both localized and systemic immune responses are at play. The prescription of asthma monoclonal therapy is generally based on systemic evaluation of cytokine and immunoglobulin levels. Our research suggests that this approach may not fully reflect the pathophysiology of the disease and may provide insight into why some patients respond to these targeted therapies while others do not.

Nurse-led approach to standardising the management of iron-deficiency anaemia, achieving the 2-week cancer pathway targets and reducing hospital admissions: practicalities and learnings from a success story.

The most significant and common cause of anaemia is iron deficiency, which occurs when iron absorption cannot meet the body's demands due to growth, pregnancy, poor nutrition, malabsorption or blood loss. It is estimated that in the UK 11% of the adult population have iron-deficiency anaemia (IDA) and investigation is essential to exclude significant pathology as the underlying cause. It has been shown that IDA is responsible for 57 000 hospital admissions in the UK, and at least 10% of gastroenterology referrals per annum. IDA is a major red flag symptom for gastrointestinal cancer. At the Royal Liverpool University Hospital, a dedicated nurse-led IDA service was developed in 2005 to help alleviate the clinical pressures created by the two week suspected cancer referral pathway. With the success of this service, investigation and management of IDA has been extended to referrals from accident and emergency, with the aim of reducing hospital admissions and to investigating and optimising iron replacement therapy in preoperative patients. Delivering this as a nurse consultant-led service was proposed by the gastroenterology medical team who felt that, as a clinical problem with well established, published investigative algorithms, IDA would be suitable for management in a dedicated nurse-led clinic. This article will focus on the strategies employed to achieve sufficient resources and clinic capacity to run this service effectively, develop strong nurse education and training, and the development of agreed investigation pathways. A robust results review process, with rapid management of abnormal results, was established with timely discharge for those patients with normal results. Optimisation of iron replacement therapy and verification of sustained haematological response was prioritised as this was identified as being poorly managed across all specialties. A process for ongoing audit of results was included to show the success of the service and highlight areas for redesign. Here, we demonstrate the effectiveness of our nurse-led IDA service and suggest it as the basis for other IDA services in the UK and beyond.

Regulatory and HTA Considerations for Development of Real-World Data Derived External Controls.

Regulators and Health Technology Assessment (HTA) bodies are increasingly familiar with, and publishing guidance on, external controls derived from real-world data (RWD) to generate real-world evidence (RWE). We recently conducted a systematic literature review (SLR) evaluating publicly available information on the use of RWD-derived external controls to contextualize outcomes from uncontrolled trials submitted to the European Medicines Agency (EMA), the US Food and Drug Administration (FDA), and/or select HTA bodies. The review identified several key operational and methodological aspects for which more detailed guidance and alignment within and between regulatory agencies and HTA bodies is necessary. This paper builds on the SLR findings by delineating a set of key takeaways for the responsible generation of fit-for-purpose RWE. Practical methodological and operational guidelines for designing, conducting, and reporting RWD-derived external control studies are explored and discussed. These considerations include: (i) early engagement with regulators and HTA bodies during the study planning phase; (ii) consideration of the appropriateness and comparability of external controls across multiple dimensions, including eligibility criteria, temporality, population representation, and clinical evaluation; (iii) ensuring adequate sample sizes, including hypothesis testing considerations; (iv) implementation of a clear and transparent strategy for assessing and addressing data quality, including data missingness across trials and RWD; (v) selection of comparable and meaningful endpoints that are operationalized and analyzed using appropriate analytic methods; and (vi) conduct of sensitivity analyses to assess the robustness of findings in the context of uncertainty and sources of potential bias.

Effectively Leveraging RWD for External Controls: A Systematic Literature Review of Regulatory and HTA Decisions.

Real-world data (RWD)-derived external controls can be used to contextualize efficacy findings for investigational therapies evaluated in uncontrolled trials. As the number of submissions to regulatory and health technology assessment (HTA) bodies using external controls rises, and in light of recent regulatory and HTA guidance on the appropriate use of RWD, there is a need to address the operational and methodological challenges impeding the quality of real-world evidence (RWE) generation and the consistency in evaluation of RWE across agencies. This systematic review summarizes publicly available information on the use of external controls to contextualize outcomes from uncontrolled trials for all indications from January 1, 2015, through August 20, 2021, that were submitted to the European Medicines Agency, the US Food and Drug Administration, and/or select major HTA bodies (National Institute for Health and Care Excellence (NICE), Haute Autorité de Santé (HAS), Institut für Qualität und Wirtschaftlichkeit im Gesundheitswesen (IQWiG), and Gemeinsamer Bundesausschuss (G-BA)). By systematically reviewing submissions to regulatory and HTA bodies in the context of recent guidance, this study provides quantitative and qualitative insights into how external control design and analytic choices may be viewed by different agencies in practice. The primary operational and methodological aspects identified for discussion include, but are not limited to, engagement of regulators and HTA bodies, approaches to handling missing data (a component of data quality), and selection of real-world endpoints. Continued collaboration and guidance to address these and other aspects will inform and assist stakeholders attempting to generate evidence using external controls.

Impact of Airway Virus in Severe Asthmatic Patients: A Pilot Study.

The lungs have their own microbiota which seems to be altered in disease processes such as asthma. Viral infection accounts for many asthma exacerbations. Little is known about the lung virome, and the role that viruses play in non-exacerbating asthmatics. We aimed to assess if detection of virus in bronchoscopy samples of asthmatic patients in a non-exacerbating state influences their asthma control and modulates airway cytokine composition. Patients were recruited from a specialist asthma clinic and underwent bronchoscopy with standardised bronchoalveolar lavage (BAL). Viral analysis was performed; cell differential and cytokine levels were measured. Forty-six samples were obtained of which 10.8% demonstrated evidence of airway virus, and 91.3% of patients in the cohort were classed as severe asthmatics. Oral steroid use was significantly higher in severe asthmatic patients with virus detected, and the forced expiratory volume in one second tended to be lower in the virus-detected group. It was also found that BAL interleukin-13 and tumor necrosis factor-α levels were significantly higher in severe asthmatic patients with virus detected. Our results suggest that in severe asthmatics in a non-exacerbating state, the presence of virus resulted in overall poorer asthma control. The pattern of cytokine elevation seen in asthmatic patients with virus detected may provide insight to the pathophysiology involved.

A new multiplex SARS-CoV-2 antigen microarray showed correlation of IgG, IgA, and IgM antibodies from patients with COVID-19 disease severity and maintenance of relative IgA and IgM antigen binding over time.

Zoonotic spillover of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) to humans in December 2019 caused the coronavirus disease 2019 (COVID-19) pandemic. Serological monitoring is critical for detailed understanding of individual immune responses to infection and protection to guide clinical therapeutic and vaccine strategies. We developed a high throughput multiplexed SARS-CoV-2 antigen microarray incorporating spike (S) and nucleocapsid protein (NP) and fragments expressed in various hosts which allowed simultaneous assessment of serum IgG, IgA, and IgM responses. Antigen glycosylation influenced antibody binding, with S glycosylation generally increasing and NP glycosylation decreasing binding. Purified antibody isotypes demonstrated a binding pattern and intensity different from the same isotype in whole serum, probably due to competition from the other isotypes present. Using purified antibody isotypes from naïve Irish COVID-19 patients, we correlated antibody isotype binding to different panels of antigens with disease severity, with binding to the S region S1 expressed in insect cells (S1 Sf21) significant for IgG, IgA, and IgM. Assessing longitudinal response for constant concentrations of purified antibody isotypes for a patient subset demonstrated that the relative proportion of antigen-specific IgGs decreased over time for severe disease, but the relative proportion of antigen-specific IgA binding remained at the same magnitude at 5 and 9 months post-first symptom onset. Further, the relative proportion of IgM binding decreased for S antigens but remained the same for NP antigens. This may support antigen-specific serum IgA and IgM playing a role in maintaining longer-term protection, important for developing and assessing vaccine strategies. Overall, these data demonstrate the multiplexed platform as a sensitive and useful platform for expanded humoral immunity studies, allowing detailed elucidation of antibody isotypes response against multiple antigens. This approach will be useful for monoclonal antibody therapeutic studies and screening of donor polyclonal antibodies for patient infusions.

Keloid treatments: an evidence-based systematic review of recent advances.

BACKGROUND: Keloids are pathologic scars that pose a significant functional and cosmetic burden. They are challenging to treat, despite the multitude of treatment modalities currently available. OBJECTIVE: The aim of this study was to conduct an evidence-based review of all prospective data regarding keloid treatments published between 2010 and 2020. METHODS: A systematic literature search of PubMed (National Library of Medicine), Embase (Elsevier), and Cochrane Library (Wiley) was performed in November of 2020. Search strategies with the keywords "keloid" and "treatment" were performed by a medical librarian. The search was limited to prospective studies that were peer-reviewed, reported on clinical outcomes of keloid therapies, and were published in the English language between January 1, 2010, and November 24, 2020. RESULTS: A total of 3462 unique citations were identified, of which 108 studies met inclusion criteria. Current literature supports silicone gel or sheeting with corticosteroid injections as first-line therapy for keloids. Adjuvant intralesional 5-fluorouracil (5-FU), bleomycin, or verapamil can be considered, although mixed results have been reported with each. Laser therapy can be used in combination with intralesional corticosteroids or topical steroids with occlusion to improve drug penetration. Excision of keloids with immediate post-excision radiation therapy is an effective option for recalcitrant lesions. Finally, silicone sheeting and pressure therapy have evidence for reducing keloid recurrence. CONCLUSIONS: This review was limited by heterogeneity of subject characteristics and study outcome measures, small sample sizes, and inconsistent study designs. Larger and more robust controlled studies are necessary to further understand the variety of existing and emerging keloid treatments, including corticosteroids, cryotherapy, intralesional injections, lasers, photodynamic therapy, excision and radiation, pressure dressings, and others.

Heterogeneous trajectories of suicidal ideation among homeless youth: predictors and suicide-related outcomes.

The current study examined heterogeneous trajectories of suicidal ideation among homeless youth experiencing suicidal ideation over 9 months in a randomized controlled intervention study. Suicidal homeless youth (N = 150) were randomly assigned to Cognitive Therapy for Suicide Prevention (CTSP) + Treatment as Usual (TAU) or TAU alone. Youth reported their suicidal ideation four times during a 9-month period. We also assessed pretreatment mental health, demographic information and session attendance as predictors of the subgroups, as well as suicide-related factors as outcomes at the 9-month follow-up. Growth mixture models suggested three distinct trajectory groups among youth: Fast Declining (74.7%), Chronic (19.3%), and Steadily Declining (6.0%). Youth in the Chronic group used more substances at baseline than the Steadily Declining group, were more likely to be White, non-Hispanic than the Fast Declining group, and attended more CTSP sessions than other groups. Contrastingly, youth in the Steadily Declining group all experienced childhood abuse. Finally, youth in the Chronic group showed significant higher risk for future suicide compared to those in the Fast Declining group at 9 months. Findings support the heterogeneity of treatment responses in suicide intervention among homeless youth, with implications to improve treatment efforts in this very high-risk population.

Housing and supportive services for substance use and self-efficacy among young mothers experiencing homelessness: A randomized controlled trial.

AIMS: Homeless mothers with young children in their care contend with high rates of substance use and low self-efficacy. However, a limited number of studies have examined these outcomes associated with housing and supportive services. DESIGN: Participants were randomly assigned to: (1) housing + support services (n = 80), (2) housing-only (n = 80), or (3) services as usual (SAU) (n = 80) and were re-assessed at 3-, 6-, 9- and 12-months postbaseline. SETTINGS: The study recruited a community-based sample from homeless service agencies and advertisements in a large Midwestern city. PARTICIPANTS: The study recruited two hundred forty (N = 240) women between the ages of 18 to 24 years, experiencing homelessness and with a substance use disorder (SUD) who also had a biological child under the age of 6 years in their care. MEASUREMENTS: We measured frequency of alcohol and drug use using the Form 90 semi-structured interview, and self-efficacy using Pearlin and Schooler's (1978) 7-item Mastery Scale. FINDINGS: Overall, mothers showed significant improvement in substance use and self-efficacy over time in each condition. However, as expected, patterns of change differentiated intervention groups with more mothers showing better substance use and self-efficacy outcomes in housing + supportive services than in SAU. Unexpectedly, more mothers in SAU showed better outcomes than those in housing-only. CONCLUSIONS: Substance use decreased and self-efficacy increased over time, but patterns of change characterized the intervention groups. In particular, findings suggest that when providing housing to this population, supportive services should also be offered.

Environmental influences on childhood asthma-The effect of diet and microbiome on asthma.

Early life dietary patterns and timely maturation of mucosa-associated microbial communities are important factors influencing immune development and for establishing robust immune tolerance networks. Microbial fermentation of dietary components in vivo generates a vast array of molecules, some of which are integral components of the molecular circuitry that regulates immune and metabolic functions. These in turn protect against aberrant inflammatory processes and promote effector immune responses that quickly eliminate pathogens. Multiple studies suggest that changes in dietary habits, altered microbiome composition, and microbial metabolism are associated with asthma risk and disease severity. While it remains unclear whether these microbiome alterations are a cause or consequence of dysregulated immune responses, there is significant potential for using diet in targeted manipulations of the gut microbiome and its metabolic functions in promoting immune health. In this article, we will summarize our knowledge to date on the role of dietary patterns and microbiome activities on immune responses within the airways. Given the malleability of the human microbiome, its integration into the immune system, and its responsiveness to diet, this makes it a highly attractive target for therapeutic and nutritional intervention in children with asthma.

Illicit Drug Use, Cognitive Distortions, and Suicidal Ideation Among Homeless Youth: Results From a Randomized Controlled Trial.

Illicit drug use and cognitive distortions confer significant risks to youth suicidal thoughts and behaviors. However, there has been limited evidence regarding the efficacy of suicide prevention interventions with homeless youth, especially studies testing whether such interventions can reduce the risk for suicidal ideation associated with illicit drug use. Suicidal homeless youth (N = 150) between the ages of 18 to 24 years were recruited from a drop-in center. Youth were randomly assigned to Cognitive Therapy for Suicide Prevention (CTSP) + Treatment as Usual (TAU) or TAU alone. Youth reported their illicit drug use, cognitive distortions, and suicidal ideation 4 times over 9 months. A multiple-group multilevel structural equation model showed that higher illicit drug use at baseline predicted a slower reduction in cognitive distortions and suicidal ideation in the TAU group. These associations were not found in the CTSP + TAU group, suggesting an interruption of such risk from illicit drug use. Findings suggest that CTSP can reduce the risk of illicit drug use as a treatment barrier towards cognitive distortions and suicidal ideation among homeless youth, with implications to improve treatment efforts and to reduce premature mortality in a vulnerable population.

Timing of cesarean delivery in women with ≥2 previous cesarean deliveries.

BACKGROUND: The rate of cesarean delivery is continuously increasing with the leading indication being a previous cesarean delivery. For women with 1 previous cesarean delivery, it is generally agreed that the optimal timing of delivery by elective cesarean delivery is during the 39th week of gestation, whereas for women with ≥2 previous cesarean deliveries, the optimal delivery time remains debatable. OBJECTIVE: To assess the maternal and neonatal risks associated with elective delivery at different gestational ages ranging from 37 0/7 to 39 6/7 weeks' gestation and to compare it with expectant management among women with at least 2 previous cesarean deliveries. STUDY DESIGN: This was a retrospective, population-based cohort study of all women with at least 2 previous cesarean deliveries who delivered after 36 6/7 weeks of gestation in Ontario, Canada, between April 2012 and March 2019. Women with multifetal pregnancies or major fetal anomalies were excluded. For each completed gestational week, outcomes of women who had an elective repeat cesarean delivery at that week solely because of 2 previous cesarean deliveries were compared with the outcomes of those who were managed expectantly and delivered at a later gestational age. The primary outcome was a composite of maternal outcomes including mortality and severe maternal morbidity. Secondary outcomes were adverse neonatal outcomes. RESULTS: A total of 26,522 women met the inclusion criteria. The maternal risk was similar for elective delivery at 37 0/7 to 38 6/7 weeks of gestation compared with expectant management. However, elective delivery at 39 0/7 to 39 6/7 weeks' gestation was associated with a decreased risk for adverse outcomes when compared with expectant management (adjusted risk ratio, 0.51; 95% confidence interval, 0.29-0.91). For the neonate, elective delivery during the 37th week of gestation significantly increased the incidence of the composite adverse outcome than in an ongoing pregnancy (adjusted risk ratio, 1.68; 95% confidence interval, 1.39-2.01), but was comparable for elective delivery at 38 0/7 to 39 6/7 weeks' gestation and expectant management. The risk for an unplanned cesarean delivery increased from 6.5% before 38 weeks' gestation to 21.7% before 39 weeks' gestation and to 32.6% before 40 weeks' gestation. CONCLUSION: For women with ≥2 cesarean deliveries, elective delivery at 38 0/7 to 38 6/7 weeks' gestation likely represents the optimal balance between neonatal and maternal risk while decreasing the likelihood of an unplanned cesarean delivery.

Real-World clinical outcomes of asthma patients switched from reslizumab to mepolizumab or benralizumab.

Introduction: Approximately 3%-10% of asthma patients will remain uncontrolled despite maximum, optimal conventional therapy. Treatment of severe refractory asthma often involves the use of targeted biological therapy. Randomised controlled trials have shown improvements in clinical parameters with these treatments but real-world data is lacking. Methods: The clinical parameters, frequency of exacerbations, number of hospital admissions, asthma control questionnaire score (ACQ), forced expiratory volume in one second (FEV1) and maintenance oral corticosteroid (OCS) dose of twenty asthma patients switched from reslizumab to benralizumab or mepolizumab at 1 year prior and 6 months after switching were compared, with adjustments for time. Results: The mean frequency of exacerbations (0.35 v 0.3) and the mean ACQ were essentially unchanged (1.6 v 1.5) following the switch. The number of hospital admissions was one in the 6 months post switch compared to one in 1-year pre switch. 25% of patients were on maintenance OCS before and after switching but one patient required an increased dose post switch resulting in an increase in the mean maintenance OCS dose (1.6 mg to 2.4 mg). The mean FEV1 was unchanged (80% v 77.9%) six months post switching. Regarding asthma control (n = 19), 47.4% were controlled pre and post switch (ACQ < 1.5), 36.8% remained uncontrolled despite switching, 10.5% improved control while 5.3% disimproved. Conclusion: We present real-world clinical outcomes of asthma patients switched from reslizumab to either benralizumab or mepolizumab without a loss of clinical effectiveness in the majority.

Use of non-invasive ventilation in motor neuron disease - a retrospective cohort analysis.

Motor neuron disease (MND) is a neurodegenerative disorder which leads to progressive muscle weakness including respiratory muscle decline. The introduction of non-invasive ventilation (NIV) has been shown to improve quality of life, survival and slow the rate of pulmonary function decline. A retrospective chart analysis of patients who attended the MND clinic from 2014 to 2019 at a tertiary-referral, academic, teaching hospital was carried out to evaluate if NIV and greater compliance with NIV was associated with improved survival. 111 patients were included. The mean age at diagnosis was 63.8 years and 61.3% were males. 66.7% of our cohort used NIV and of this 66.7%, 44.1% were compliant. There was a significantly longer survival in those who used NIV (p = 0.002) and in those who used NIV optimally (p = 0.02) when both groups were compared to those who did not use NIV. In the bulbar MND group those who were compliant with NIV survived longer than who those who did not use NIV (p = 0.001). We found a significantly longer survival with the use of NIV, the use of NIV optimally and with use of NIV in those with bulbar onset MND compared to those who did not use NIV.

Association of Maternal Influenza Vaccination During Pregnancy With Early Childhood Health Outcomes.

Importance: Seasonal influenza vaccination in pregnancy can reduce influenza illness among pregnant women and newborns. Evidence is limited on whether seasonal influenza vaccination in pregnancy is associated with adverse childhood health outcomes. Objective: To assess the association between maternal influenza vaccination during pregnancy and early childhood health outcomes. Design, Setting, and Participants: Retrospective cohort study, using a birth registry linked with health administrative data. All live births in Nova Scotia, Canada, between October 1, 2010, and March 31, 2014, were included, with follow-up until March 31, 2016. Adjusted hazard ratios (HRs) and incidence rate ratios (IRRs) with 95% confidence intervals were estimated while controlling for maternal medical history and other potential confounders using inverse probability of treatment weighting. Exposures: Seasonal influenza vaccination during pregnancy. Main Outcomes and Measures: Childhood outcomes studied were immune-related (eg, asthma, infections), non-immune-related (eg, neoplasms, sensory impairment), and nonspecific (eg, urgent or inpatient health care utilization), measured from emergency department and hospitalization databases. Results: Among 28 255 children (49% female, 92% born at ≥37 weeks' gestation), 10 227 (36.2%) were born to women who received seasonal influenza vaccination during pregnancy. During a mean follow-up of 3.6 years, there was no significant association between maternal influenza vaccination and childhood asthma (incidence rate, 3.0 vs 2.5 per 1000 person-years; difference, 0.53 per 1000 person-years [95% CI, -0.15 to 1.21]; adjusted HR, 1.22 [95% CI, 0.94 to 1.59]), neoplasms (0.32 vs 0.26 per 1000 person-years; difference, 0.06 per 1000 person-years [95% CI, -0.16 to 0.28]; adjusted HR, 1.26 [95% CI, 0.57 to 2.78]), or sensory impairment (0.80 vs 0.97 per 1000 person-years; difference, -0.17 per 1000 person-years [95% CI, -0.54 to 0.21]; adjusted HR, 0.82 [95% CI, 0.49 to 1.37]). Maternal influenza vaccination in pregnancy was not significantly associated with infections in early childhood (incidence rate, 184.6 vs 179.1 per 1000 person-years; difference, 5.44 per 1000 person-years [95% CI, 0.01 to 10.9]; adjusted IRR, 1.07 [95% CI, 0.99 to 1.15]) or with urgent and inpatient health services utilization (511.7 vs 477.8 per 1000 person-years; difference, 33.9 per 1000 person-years [95% CI, 24.9 to 42.9]; adjusted IRR, 1.05 [95% CI, 0.99 to 1.16]). Conclusions and Relevance: In this population-based cohort study with mean follow-up duration of 3.6 years, maternal influenza vaccination during pregnancy was not significantly associated with an increased risk of adverse early childhood health outcomes.

Housing First Combined with Suicide Treatment Education and Prevention (HOME + STEP): study protocol for a randomized controlled trial.

BACKGROUND: Youth experiencing homelessness are at high risk for suicide, yet few studies have evaluated risk reduction interventions targeting suicidal ideation in this vulnerable population. A comprehensive approach to risk-reduction is needed that addresses basic needs and provides targeted interventions for those at highest risk. The protocol described builds on the design of the first randomized trial of Housing First (HF) for homeless youth. The primary objective is to determine whether housing combined with supportive services that include suicide screening and targeted psychotherapy (Cognitive Therapy for Suicide Prevention) is effective for reducing suicidal ideation and other secondary outcomes (depression and suicide attempts). Additionally, we will explore mediators of the treatment effect (housing stability and substance use) and determinants of implementation. METHODS: Youth recruited to the HF trial will be randomized to HF + supportive services (n = 120), or supportive services alone (n = 120). The "Suicide Treatment Education and Prevention" (STEP) protocol will additionally screen youth in both arms at baseline and 3 months for suicidal ideation (SSI-W). Those who screen as moderate risk for suicide (SSI-W ≥ 10) will be offered CTSP, which includes up to 9 sessions over the first 6 months following enrollment. CTSP will be delivered in one-on-one sessions by a trained advocate. Research assessments will be collected to assess outcomes (including suicidal ideation) at baseline, 3, 6, 9 and 12 months. Qualitative interviews with subjects receiving CTSP and other stakeholders will explore implementation determinants. DISCUSSION: The study will fill an important gap in the literature about the added benefit of HF combined with supportive services including suicide screening and treatment for reducing suicidal ideation in homeless youth. With the urgent need to address both homelessness and suicide risk, evidence is needed about services that can be integrated into delivery settings for youth experiencing homelessness. TRIAL REGISTRATION: NCT04135703 . Date of registration: October 23, 2019.

Predictors of Treatment Engagement Among Suicidal Youth Experiencing Homelessness.

Homeless youth experience high rates of suicidal ideation and attempts, yet limited research has examined predictors of treatment engagement among this population. Suicidal homeless youth (N = 150) between the ages of 18 and 24 years were recruited from a drop-in center in Columbus, Ohio. Participants were randomly assigned to Cognitive Therapy for Suicide Prevention + treatment as usual through a local drop-in center (CTSP + TAU) (N = 75) or TAU alone (N = 75), and treatment attendance among those assigned to CTSP + TAU was examined in this study. As expected, among youth engaged in CTSP + TAU, those with a history of intimate partner violence (IPV) showed decreased odds of treatment attendance. Additionally, youth randomized into CTSP + TAU with higher acquired capability for suicide (ACS) scores and those identifying as Black were more likely to attend treatment sessions. Findings suggest that effective treatment implementation must consider youth's trauma history, demographics and severity of suicidal ideation and behaviors.

Housing, opportunities, motivation and engagement (HOME) for homeless youth at-risk for opioid use disorder: study protocol for a randomized controlled trial.

BACKGROUND: Homeless youth experience high rates of substance use disorders, exposures to violence, mental and physical health conditions, and mortality. They have been particularly affected by the opioid crisis. However, no study to date has used a randomized controlled design to test preventive interventions of opioid and other drug use among this vulnerable population. Resolution of youth homelessness through housing and supportive services including prevention services, often referred to as "Housing First," has great potential to reduce the likelihood for the development of an opioid use disorder as well as other problem behaviors associated with living on the streets. Housing First has been tested through randomized trials among homeless adults with mental health and substance use disorders, but has not been empirically tested for opioid prevention among homeless youth. METHODS: Homeless youth will be recruited from a drop-in shelter site frequented by disconnected youth; they will be screened for eligibility, including current homelessness, age 18-24 years, and not currently meeting criteria for opioid use disorder (OUD). In a controlled trial, 240 youth will then be randomized to one of two conditions, (1) housing + opioid and related risk prevention services, or (2) opioid and related risk prevention services alone. This project utilizes existing efficacious models of prevention to address opioid-related risks, including motivational interviewing, strengths-based outreach and advocacy, and an HIV risk preventive intervention. Follow-up will be conducted at 3, 6, 9 and 12-months post-baseline. The economic cost of each intervention will be determined to support implementation decisions with other providers and their funders. DISCUSSION: This study will provide essential information for researchers and providers on the efficacy of housing + opioid and related risk prevention services in an RCT for effects on opioid use and mechanisms underlying change. Because youth experiencing homelessness are at increased risk for a variety of adverse outcomes, the proposed intervention may produce substantial health care benefits to the youths and society at large. Trial registration ClinicalTrials.gov, NCT04135703, Registered October 13, 2019, https://clinicaltrials.gov/ct2/show/NCT04135703?term=NCT04135703&draw=2&rank=1#contacts.