Workshop report: A study roadmap to evaluate the safety of recombinant human lactoferrin expressed in Komagataella phaffii intended as an ingredient in conventional foods - Recommendations of a scientific expert panel.

Human milk lactoferrin (hmLF) is a glycoprotein with well-known effects on immune function. Helaina Inc. has used a glycoengineered yeast, Komatagaella phaffii, to produce recombinant human lactoferrin (Helaina rhLF, Effera™) that is structurally similar to hmLF with intended uses as a food ingredient. However, earlier FDA reviews of rhLF were withdrawn due to insufficient safety data and unanswered safety questions the experts and FDA raised about the immunogenicity/immunotoxicity risks of orally ingested rhLF. Helaina organized a panel of leading scientists to build and vet a safety study roadmap containing the studies and safety endpoints needed to address these questions. Panelists participated in a one-day virtual workshop in June 2023 and ensuing discussions through July 2023. Relevant workshop topics included physicochemical properties of LF, regulatory history of bovine LF and rhLF as food ingredients in the FDA's generally recognized as safe (GRAS) program, and synopses of publicly available studies on the immunogenicity/alloimmunization, immunotoxicology, iron homeostasis, and absorption, distribution, metabolism, and excretion of rhLF. Panelists concluded that the safety study roadmap addresses the unanswered safety questions and the intended safe use of rhLF as a food ingredient for adults and agreed on broad applications of the roadmap to assess the safety and support GRAS of other recombinant milk proteins with immunomodulatory functions.

A review of the safety evidence on recombinant human lactoferrin for use as a food ingredient.

Published studies on the glycosylation, absorption, distribution, metabolism, excretion, and safety outcomes of orally ingested recombinant human lactoferrin (rhLF) were reviewed in the context of unanswered safety questions, including alloimmunization, allergenicity, and immunotoxicity potential of rhLF during repeated exposure. The primary objective was to summarize current safety data of rhLF produced in transgenic host expression systems. Overall, results from animal and human studies showed that rhLF was well tolerated and safe. Animal data showed no significant toxicity-related outcomes among any safety or tolerability endpoints. The no observed adverse effect levels (NOAEL) were at the highest level tested in both iron-desaturated and -saturated forms of rhLF. Although one study reported outcomes of rhLF on immune parameters, no animal studies directly assessed immunogenicity or immunotoxicity from a safety perspective. Data from human studies were primarily reported as adverse events (AE). They showed no or fewer rhLF-related AE compared to control and no evidence of toxicity, dose-limiting toxicities, or changes in iron status in various subpopulations. However, no human studies evaluated the immunomodulatory potential of rhLF as a measure of safety. Following this review, a roadmap outlining preclinical and clinical studies with relevant safety endpoints was developed to address the unanswered safety questions.

"It's like your days are empty and yet there's life all around": A mixed methods, multi-site study exploring boredom during and following homelessness.

PURPOSE: To identify experiences of boredom and associations with psychosocial well-being during and following homelessness. METHODS: Using a convergent, mixed-methods explanatory design, we conducted quantitative interviews with 164 participants) (n = 102 unhoused; n = 62 housed following homelessness) using a 92-item protocol involving demographic components and seven standardized measures of psychosocial well-being. A sub-sample (n = 32) was approached to participate in qualitative interviews. Data were analyzed by group (unhoused; housed). Quantitative data were analyzed using descriptive statistics designed to generate insights into boredom, meaningful activity engagement, and their associations with psychosocial well-being during and following homelessness. Qualitative data were analyzed using thematic analysis. Quantitative and qualitative findings were integrated at the stage of discussion. RESULTS: Quantitative analyses revealed small to moderate correlations between boredom and increased hopelessness (rs = .376, p < .01), increased drug use (rs = .194, p < .05), and lowered mental well-being (rs = -.366, p < .01). There were no statistically significant differences between unhoused and housed participants on any standardized measures. Hierarchical regression analyses revealed that housing status was not a significant predictor of boredom or meaningful activity engagement (p>.05). Qualitative interviews revealed profound boredom during and following homelessness imposing negative influences on mental well-being and driving substance use. CONCLUSIONS: Boredom and meaningful activity are important outcomes that require focused attention in services designed to support individuals during and following homelessness. Attention to this construct in future research, practice, and policy has the potential to support the well-being of individuals who experience homelessness, and to contribute to efforts aimed at homelessness prevention.

Dose Range-Finding Toxicity Study in Rats With Recombinant Human Lactoferrin Produced in Komagataella phaffii.

The oral toxicity of recombinant human lactoferrin (rhLF, Helaina rhLF, Effera™) produced in Komagataella phaffii was investigated in adult Sprague Dawley rats by once daily oral gavage for 14 consecutive days. The study used groups of 3-6 rats/sex/dose. The vehicle control group received sodium citrate buffer, and the test groups received daily doses of 200, 1000, and 2000 mg of rhLF in sodium citrate buffer per kg body weight. Bovine LF at 2000 mg/kg body weight per day was used as a comparative control. Clinical observations, body weight, hematology, clinical chemistry, iron parameters, immunophenotyping, and gross examination at necropsy were used as criteria for detecting the effects of treatment in all groups and to help select dose levels for future toxicology studies. Quantitative LF levels were also analyzed as an indication of bioavailability. Overall, administration of Helaina rhLF by once daily oral gavage for 14 days was well tolerated in rats at levels up to 2000 mg/kg/day, or 57 × Helaina's intended commercial use in adults, and indicating that a high dose of 2000 mg/kg/day is appropriate for future definitive toxicology studies.

Service restrictions from emergency shelters among people experiencing homelessness: Uncovering pathways into unsheltered homelessness and institutional circuitry.

Service restrictions refer to temporary or permanent bans of individuals from a program or an organization's services, and are widely used in emergency shelter systems. Limited research exists on how service restrictions unfold and their impacts on people experiencing homelessness. This qualitative study used in-depth interviews with timeline mapping to examine the antecedents and consequences of service restrictions from emergency shelters among people experiencing homelessness in two cities in Ontario, Canada. A total of 49 people experiencing homelessness who had been restricted from an emergency shelter program in the past year were recruited and included in the study analysis. A pragmatic and integrative approach was used for data analysis that involved the development of meta-matrices to identify prominent and divergent perspectives and experiences with regard to service restriction antecedents and consequences. Study findings underscored that service restrictions were often the result of violence and aggression, primarily between service users. There were regional differences in other service restriction reasons, including substance use and possession. Service restrictions affected the shelter status of almost all participants, with many subsequently experiencing unsheltered homelessness, and cycling through institutional health, social, and criminal justice services (i.e., institutional circuitry). Other health and social consequences included substance use relapses and hospitalizations; cold-related injuries due to post-restriction unsheltered homelessness; suicidality; food insecurity; diminished contact with support network and connections; and intense feelings of anger, fear, and hopelessness. Overall, the study findings advance our understanding of the role of homeless services in pathways into unsheltered homelessness and institutional circuitry, which raise critical questions about how to mitigate the harms associated with service restrictions, while concurrently facilitating safety and upholding the rights of people experiencing homelessness and emergency shelter staff.

Prevalence and nature of workplace bullying and harassment and associations with mental health conditions in England: a cross-sectional probability sample survey.

BACKGROUND: Evidence on workplace bullying and harassment (WBH) in the UK has not used probability-sample surveys with robust mental health assessments. This study aimed to profile the prevalence and nature of WBH in England, identify inequalities in exposure, and quantify adjusted associations with mental health. METHODS: Data were from the 2014 Adult Psychiatric Morbidity Survey, a cross-sectional probability-sample survey of the household population in England. Criteria for inclusion in the secondary analysis were being aged 16-70 years and in paid work in the past month (n = 3838). Common mental disorders (CMDs) were assessed using the Clinical Interview Schedule-Revised and mental wellbeing using the Warwick-Edinburgh Mental Wellbeing Scale. Analyses were weighted. We examined associations between past-year WBH and current CMD using multivariable regression modelling, adjusting for sociodemographic factors. Interaction terms tested for gender differences in associations. The study received ethical approval (ETH21220-299). RESULTS: One in ten employees (10.6%, n = 444/3838) reported past-year experience of WBH, with rates higher in women (12.2%, n = 284/2189), those of mixed, multiple, and other ethnicity (21.0%, n = 15/92), and people in debt (15.2%, n = 50/281) or living in cold homes (14.6%, n = 42/234). Most commonly identified perpetrators of WBH were line managers (53.6%, n = 244/444) or colleagues (42.8%, n = 194/444). Excessive criticism (49.3%, n = 212/444), verbal abuse (42.6%, n = 187/444), and humiliation (31.4%, n = 142/444) were the most common types. WBH was associated with all indicators of poor mental health, including CMD (adjusted odds ratio [aOR] 2.65, 95% CI 2.02-3.49), and 11 of 14 mental wellbeing indicators, including lower levels of confidence (aOR 0.57, 0.46-0.72) and closeness to others (aOR 0.57, 0.46-0.72). Patterns of association between WBH and mental health were similar in men and women. CONCLUSIONS: These findings reinforce a need for more cohesive UK legislation against WBH; guidance on recognition of bullying behaviours for employees, managers, and human resources, focusing on prevention and early intervention, and increased awareness of the impact of WBH on mental health among health service practitioners. Limitations include reliance on cross-sectional data collected before pandemic-related and other changes in workplace practices. Longitudinal data are needed to improve evidence on causality and the longevity of mental health impacts.

The experiences of familial mental illness stigma among individuals living with mental illnesses.

Persons with mental illnesses may experience stigma from their immediate family members in addition to other forms of stigma. Using semi-structured interviews, we investigated experiences of familial mental illness stigma among 15 people diagnosed with mental illnesses in a mid-sized city in Canada. We identified five themes that speak to participants' experiences of familial mental illness stigma and ways to reduce it. The themes include the following: diagnosis as a 'double-edged sword,' potential familial isolation, familial stigma as societal stigma localized, stories of acceptance, and confronting potential familial mental illness stigma. Participants' narratives indicate that familial mental illness stigma is rooted in the broader social or public stigma, which sees its way into familial relations as well. This stigma takes various forms, including relationship bias or unfair treatment, breakdown in romantic relationships, loss of status, verbal and emotional abuse, exclusion from decision-making, and alienation within their immediate and extended families. Familial mental illness stigma experiences negatively impact participant's psychological well-being and personal empowerment. However, participants also shared ways that family members create supportive environments or actively confront or prevent stigma. Overall, this study has contributed to knowledge on mental illness stigma, particularly familial mental illness stigma from the perspective of participants living with a mental illness in a high-income country. Suggestions for future research include a focus on strategies to prevent ongoing familial mental illness stigma and large-scale studies to explore familial mental illness stigma to understand why families might perpetrate stigma.

Effectiveness of Interventions for Meaningful Activity Participation in Homelessness: A Systematic Review.

Background. Meaningful activity participation has been identified as a key outcome of services designed to support individuals during and following homelessness. Little is known about the effectiveness of interventions for promoting this outcome. Purpose. To identify the range and effectiveness of interventions on promoting meaningful activity participation among persons with experiences of homelessness. Method. We conducted a systematic review using the Joanna Briggs Institute methodology following PRISMA guidelines including a critical appraisal and narrative synthesis. Findings. Of 12,343 titles and abstracts screened, we included 12 studies. The authors of the included studies primarily used standardized measures of meaningful activity engagement. Critical appraisal scores ranged from 50.0 to 77.8. The most common interventions evaluated in the included studies were psychosocial interventions (n = 6; 50.0%), followed by case management and housing support interventions (n = 4; 33.3%) and Housing First (n = 2; 16.7%). While several interventions demonstrated effectiveness in promoting meaningful activity participation including psychosocial and case management interventions, Housing First, Critical Time Intervention, and a peer support intervention were found to be ineffective for promoting engagement in meaningful activity. Conclusion. Few intervention studies have been conducted that demonstrate effectiveness for promoting participation in meaningful activity for individuals during and following homelessness. Occupational therapy researchers and practitioners can build on existing evidence by developing and evaluating novel approaches by co-designing interventions in collaboration with persons with experiences of homelessness and service providers.

What matters most to people with metastatic uveal melanoma? A qualitative study to inform future measurement of health-related quality of life.

Metastatic uveal melanoma (mUM) is a rare cancer with poor prognosis, but novel treatments are emerging. Currently, there are no mUM-specific health-related quality of life (HRQL) questionnaires available for clinical research. We aimed to explore how mUM and its treatment affect HRQL and assess the content validity of existing questionnaires. Participants were patients with mUM and healthcare professionals involved in their care. Qualitative data were collected using semi-structured interviews and focus groups. Data collection and analysis used an integrative approach involving inductive questions/coding to elicit new concepts and deductive questions/coding based on domains of existing HRQL questionnaires. Initial interviews/focus groups focussed on HRQL questionnaires designed for patients with uveal melanoma or liver metastases. As new concepts were elicited, domains and items from other questionnaires were subsequently added. Seventeen patients and 16 clinicians participated. HRQL concerns assessed by uveal melanoma-specific questionnaires were largely resolved by the time of metastasis. The Functional Assessment of Cancer Therapy - Immunotherapy Module (FACT-ICM) adequately captured most immunotherapy-related side effects during initial treatment cycles. However, most patients emphasised emotional impacts over physical ones, focussing on the existential threat posed by disease amidst uncertainty about treatment accessibility and effectiveness. Patients were also concerned with treatment burden, including time commitment, travel, need for hospitalisation, and expenses. The relative importance of HRQL issues varied over time and across treatment modalities, with no single questionnaire being sufficient. Pending further development and psychometric testing, clinical researchers may need to take a modular approach to measuring the HRQL impacts of mUM.

Early-life pulmonary viral infection leads to long-term functional and lower airway structural changes in the lungs.

Early-life respiratory virus infections have been correlated with enhanced development of childhood asthma. In particular, significant numbers of respiratory syncytial virus (RSV)-hospitalized infants go on to develop lung disease. It has been suggested that early-life viral infections may lead to altered lung development or repair that negatively impacts lung function later in life. Our data demonstrate that early-life RSV infection modifies lung structure, leading to decreased lung function. At 5 wk postneonatal RSV infection, significant defects are observed in baseline pulmonary function test (PFT) parameters consistent with decreased lung function as well as enlarged alveolar spaces. Lung function changes in the early-life RSV-infected group continue at 3 mo of age. The altered PFT and structural changes induced by early-life RSV were mitigated in TSLPR-/- mice that have previously been shown to have reduced immune cell accumulation associated with a persistent Th2 environment. Importantly, long-term effects were demonstrated using a secondary RSV infection 3 mo following the initial early-life RSV infection and led to significant additional defects in lung function, with severe mucus deposition within the airways, and consolidation of the alveolar spaces. These studies suggest that early-life respiratory viral infection leads to alterations in lung structure/repair that predispose to diminished lung function later in life.NEW & NOTEWORTHY These studies outline a novel finding that early-life respiratory virus infection can alter lung structure and function long-term. Importantly, the data also indicate that there are critical links between inflammatory responses and subsequent events that produce a more severe pathogenic response later in life. The findings provide additional data to support that early-life infections during lung development can alter the trajectory of airway function.

Participatory Research with Persons who Experience Mental Illness in Occupational Therapy: A Scoping Review.

Background. Persons who experience mental illness also face stigma and discrimination that frequently lead to a loss of ability to exercise autonomy and agency in their lives. Purpose. The range and breadth of literature exploring participatory research with persons living with mental illness are unknown in occupational therapy and occupation science. We initiated this study to fill this gap in the existing occupational therapy and occupational science literature. Method. Using the method of Arksey and O'Malley, we have conducted a scoping review to identify the range and breadth of literature. A qualitative content analysis was performed. Findings. A total of 34 articles were included in the narrative synthesis. The content analysis led to three related themes from the included studies: (1) coming together; (2) unique potential of participatory research; and (3) challenges in conducting participatory research. Conclusions. This review highlights that participatory research is well suited to research conducted with persons living with mental illness to support meaningful engagement and minimize stigma throughout the research process. This review can guide future participatory research and practice in occupational therapy and occupational science with persons living with mental illness.

A covalent fragment-based strategy targeting a novel cysteine to inhibit activity of mutant EGFR kinase.

Several generations of ATP-competitive anti-cancer drugs that inhibit the activity of the intracellular kinase domain of the epidermal growth factor receptor (EGFR) have been developed over the past twenty years. The first-generation of drugs such as gefitinib bind reversibly and were followed by a second-generation such as dacomitinib that harbor an acrylamide moiety that forms a covalent bond with C797 in the ATP binding pocket. Resistance emerges through mutation of the T790 gatekeeper residue to methionine, which introduces steric hindrance to drug binding and increases the Km for ATP. A third generation of drugs, such as osimertinib were developed which were effective against T790M EGFR in which an acrylamide moiety forms a covalent bond with C797, although resistance has emerged by mutation to S797. A fragment-based screen to identify new starting points for an EGFR inhibitor serendipitously identified a fragment that reacted with C775, a previously unexploited residue in the ATP binding pocket for a covalent inhibitor to target. A number of acrylamide containing fragments were identified that selectively reacted with C775. One of these acrylamides was optimized to a highly selective inhibitor with sub-1 µM activity, that is active against T790M, C797S mutant EGFR independent of ATP concentration, providing a potential new strategy for pan-EGFR mutant inhibition.

How Resources Combining Expertise and Social Support Help Breastfeeding Women Address Self-Doubt and Increase Breastfeeding Self-Efficacy: A Mixed-Methods Study.

Existing research on parental information literacy focuses on parents' ability to evaluate information. This approach does not account for conflicting or unwanted information and obscures the emotional impact of unsought information. We aimed to (1) document the sources women use most frequently for accessing breastfeeding information, (2) explore the reasons women choose some sources over others, (3) test the relationship between source characteristics and breastfeeding self-efficacy, and (4) determine the extent to which four source characteristics - competence, trustworthiness, goodwill, and social support - predict breastfeeding self-efficacy. This study was conducted in two phases. The first phase consisted of interviews and focus groups, which we analyzed inductively using a grounded theory approach. In phase two, we conducted a cross-sectional survey of women who were currently breastfeeding, collecting data on the source credibility and social support associated with the source they use most frequently and the participants' breastfeeding self-efficacy. We used multiple regression to analyze our survey data. The frequency with which our participants encountered conflicting and unsought prompted them to view sources that combine expertise and social support as ideal. However, these sources are often difficult to access, leading to a reliance on online sources. This compromise has implications for breastfeeding tenure, as both competence and social support predicted breastfeeding self-efficacy. This study demonstrates how emotional aspects of information seeking shape women's preferred sources, how accessibility limits the use of preferred sources, and how source competence and social support influence breastfeeding self-efficacy.

Prevalence and nature of workplace bullying and harassment and associations with mental health conditions in England: a cross-sectional probability sample survey.

BACKGROUND: Evidence on workplace bullying and harassment (WBH) in the UK has not used probability-sample surveys with robust mental health assessments. This study aimed to profile the prevalence and nature of WBH in England, identify inequalities in WBH exposure, and quantify adjusted associations with mental health. METHODS: Data were from the 2014 Adult Psychiatric Morbidity Survey, a cross-sectional probability-sample survey of the household population in England, interviewed with verbal informed consent. Criteria for inclusion in the secondary analysis were being aged 16-70 years and in paid work in the past month (n=3838). Common mental disorders were assessed using the Clinical Interview Schedule-Revised and mental wellbeing using the Warwick-Edinburgh Mental Wellbeing Scale. Analyses were weighted. We examined associations between past-year WBH and current common mental disorders using multivariable regression modelling, adjusting for demographic and socioeconomic factors. Interaction terms tested for gender differences in associations. The study received ethics approval (ETH21220-299). FINDINGS: One in ten employees (10·6% (weighted), n=444/3838) reported past-year experience of WBH, with rates higher in women (12·2%, n=284/2189); those of mixed, multiple, and other ethnicity (21·0%, n=15/92); and people in debt (15·2%, n=50/281) or living in cold homes (14·6%, n=42/234). Most commonly identified perpetrators of WBH were line managers (53·6%, n=244/444) or colleagues (42·8%, n=194/444). Excessive criticism (49·3%, n=212/444), verbal abuse (42·6%, n=187/444), and humiliation (31·4%, n=142/444) were the most common types. WBH was associated with all adverse mental health indicators, including common mental disorders (adjusted odds ratio [aOR] 2·65, 95% CI 2·02-3·49), and 11 of 14 mental wellbeing indicators, including lower levels of confidence (aOR 0·57, 0·46-0·72) and of closeness to others (aOR 0·57, 0·46-0·72). Patterns of association between WBH and mental health were similar in men and women. INTERPRETATION: These findings reinforce a need for more cohesive UK legislation at the national level; guidance on recognition of bullying behaviours for employees, managers, and human resources at the organisational level, focusing on prevention and early intervention, and increased awareness of the impact of WBH on mental health among health-service practitioners. Study limitations include reliance on cross-sectional data collected before pandemic-related and other major changes in workplace practices. Longitudinal data are needed to improve evidence on causality and the longevity of mental health impacts. FUNDING: UK Prevention Research Partnership.

Initiation and Duration of Breastfeeding in the Maternal Outcomes and Neurodevelopmental Effects of Antiepileptic Drugs Study.

BACKGROUND AND OBJECTIVES: Breastfeeding has important health benefits for both mother and child. We characterize breastfeeding initiation and duration in mothers with epilepsy relative to control mothers in a large prospective cohort. METHODS: The Maternal Outcomes and Neurodevelopmental Effects of Antiepileptic Drugs study is a prospective, multicenter observational, US cohort study. Pregnant individuals with and without epilepsy, aged 14-45 years, were enrolled between December 19, 2012, and February 11, 2016. Exclusion criteria included intelligence quotient (IQ) <70, and gestational age >20 weeks at enrollment. Breastfeeding was assessed through electronic diary and at study visits until 2 years postpartum. Odds of initiating breastfeeding was compared between cohorts using unadjusted and adjusted logistic regression models. Duration of breastfeeding was compared between cohorts using the log-rank test. RESULTS: Three hundred fifty-one pregnant individuals with epilepsy and 105 pregnant controls were enrolled. Breastfeeding data were available for 325 mothers with epilepsy and 98 controls. Study cohorts were similar demographically except race (p = 0.008); 84.9% of mothers with epilepsy and 71.4% of controls were White. The mean IQ was lower in mothers with epilepsy compared with that in controls (97.7 vs 104.2, p < 0.001). Breastfeeding was initiated by 74.8% mothers with epilepsy and 88.8% controls; this difference was significant in unadjusted logistic regression (odds ratio [OR] 0.4 [95% CI 0.2, 0.7], p = 0.004), but not in adjusted model (OR 0.5 [95% CI 0.2, 1.0], p = 0.051). Factors associated with breastfeeding were higher maternal education and IQ. There was no difference in duration of breastfeeding between mothers with and without epilepsy (median duration 8.5 months vs 9.9 months, p = 0.793). Among mothers with epilepsy, both convulsive seizures and all seizures that impair awareness during pregnancy were associated with lower breastfeeding initiation (OR 0.4 [95% CI 0.2, 0.8], p = 0.013) and (OR 0.4 [95% CI 0.2, 0.8], p = 0.003, respectively). Any peripartum seizures were associated with shorter breastfeeding duration (median 6 months vs 9.7 months, [p = 0.040]). DISCUSSION: Mothers with epilepsy were less likely to initiate breastfeeding compared with controls; however, this difference was not significant when controlling for maternal IQ and education level. Continuation of breastfeeding once initiated was not different between mothers with and without epilepsy. Seizure control was associated with breastfeeding initiation and duration in mothers with epilepsy. TRIAL REGISTRATION INFORMATION: ClinicalTrials.gov identifier NCT01730170.

Managing high-risk behaviours and challenges to prevent housing loss in permanent supportive housing: a rapid review.

Permanent supportive housing is an effective intervention for stably housing most people experiencing homelessness and mental illness who have complex support needs. However, high-risk behaviours and challenges are prevalent among this population and have the potential to seriously harm health and threaten housing tenures. Yet, the research on the relationship between high-risk issues and housing stability in permanent supportive housing has not been previously synthesized. This rapid review aimed to identify the housing-related outcomes of high-risk behaviours and challenges in permanent supportive housing settings, as well as the approaches used by agencies and residents to address them. A range of high-risk behaviours and challenges were examined, including risks to self (overdose, suicide/suicide attempts, non-suicidal self-injury, falls/fall-related injuries), and risks to multiple parties and/or building (fire-setting/arson, hoarding, apartment takeovers, physical/sexual violence, property damage, drug selling, sex trafficking). The search strategy included four components to identify relevant academic and grey literature: (1) searches of MEDLINE, APA PsycINFO, and CINAHL Plus; (2) hand searches of three journals with aims specific to housing and homelessness; (3) website browsing/searching of seven homelessness, supportive housing, and mental health agencies and networks; and (4) Advanced Google searches. A total of 32 articles were eligible and included in the review. Six studies examined the impacts of high-risk behaviours and challenges on housing tenancies, with overdose being identified as a notable cause of death. Twenty-six studies examined approaches and barriers to managing high-risk behaviours and challenges in PSH programs. These were categorized into eight types of approaches: (1) clinical, (2) relational/educational, (3) surveillant, (4) restrictive, (5) strategic, (6) design-based, (7) legal, and (8) self-defence. Consistent across all approaches was a lack of rigorous examination of their effectiveness. Further, some approaches that are legal, restrictive, surveillant, or strategic in nature may be used to promote safety, but may conflict with other program objectives, including housing stability, or resident empowerment and choice. Research priorities were identified to address the key evidence gaps and move toward best practices for preventing and managing high-risk behaviours and challenges in permanent supportive housing.

Dietitian-led micronutrient management in a public bariatric surgery outpatient clinic.

AIMS: This study aimed to explore the multidisciplinary team attitudes and knowledge of bariatric surgery micronutrient management (pre- and postoperative care) and to evaluate the implementation of an extended-scope of practice dietitian-led model of care for micronutrient monitoring and management. METHODS: A mixed method study design included quantitative evaluation of micronutrient testing practices and deficiency rates. Qualitative reflexive thematic analysis was used to interpret multidisciplinary experience with micronutrient monitoring in a traditional and dietitian-led model of care. In addition, deductive analysis used normalisation process theory mapping of multidisciplinary experience with the implementation of the dietitian-led model of care. RESULTS: In the traditional model, a lack of quality evidence to guide micronutrient management, and a tension in trust between surgeons and patients related to adherence to micronutrient prescriptions were described as challenges in current practice. The dietitian-led model was seen to overcome some of these challenges, increasing collaborative, and coordinated, consistent and personalised patient care that led to increased testing for and detection of micronutrient deficiencies. Barriers to sustainability of the dietitian-led model included a lack of workforce succession planning, and no clearly defined delegation for some aspects of care. CONCLUSION: An extended scope dietitian-led model of care for micronutrient management after bariatric surgery improves clinical care. Challenges such as succession planning must be considered in design of extended scope services.

Monitoring for micronutrient deficiency after bariatric surgery-what is the risk?

BACKGROUND: Bariatric surgery may increase the risk of micronutrient deficiencies; however, confounders including preoperative deficiency, supplementation and inflammation are rarely considered. OBJECTIVE: To examine the impact of bariatric surgeries, supplementation and inflammation on micronutrient deficiency. SETTING: Two public hospitals, Australia. METHODS: Participants were recruited to an observational study monitoring biochemical micronutrient outcomes, supplementation dose, inflammation and glycaemic control, pre-operatively and at 1-3, 6 and 12 months after gastric bypass (GB; Roux-en-Y Gastric Bypass and Single Anastomosis Gastric Bypass; N = 66) or sleeve gastrectomy (SG; N = 144). Participant retention at 12 months was 81%. RESULTS: Pre-operative micronutrient deficiency was common, for vitamin D (29-30%), iron (13-22%) and selenium (39% GB cohort). Supplement intake increased after surgery; however, dose was <50% of target for most nutrients. After SG, folate was vulnerable to deficiency at 6 months (OR 13 [95% CI 2, 84]; p = 0.007), with folic acid supplementation being independently associated with reduced risk. Within 1-3 months of GB, three nutrients had higher deficiency rates compared to pre-operative levels; vitamin B1 (21% vs. 6%, p < 0.01), vitamin A (21% vs. 3%, p < 0.01) and selenium (59% vs. 39%, p < 0.05). Vitamin B1 deficiency was independently associated with surgery and inflammation, selenium deficiency with improved glycaemic control after surgery and inflammation, whilst vitamin A deficiency was associated with inflammation only. CONCLUSION: In the setting of prophylactic post-surgical micronutrient prescription, few nutrients are at risk of de novo deficiency. Although micronutrient supplementation and monitoring remains important, rationalising high-frequency biochemical testing protocols in the first year after surgery may be warranted.

Effects of Moderate- to High-Impact Exercise Training on Bone Structure Across the Lifespan: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Moderate- to high-impact exercise improves bone mineral density (BMD) across the lifespan, but its effects on bone structure, which predicts fracture independent of areal BMD, are unclear. This systematic review and meta-analysis investigated effects of impact exercise on volumetric BMD (vBMD) and bone structure. Four databases (PubMed, Embase, SPORTDiscus, Web of Science) were searched up to March 2022 for randomized controlled trials (RCTs) investigating the effects of impact exercise, with ground reaction forces equal to or greater than running, compared with sham or habitual activity, on bone vBMD and structure. Bone variables were measured by quantitative computed tomography or magnetic resonance imaging at the tibia, radius, lumbar spine, and femur. Percentage changes in bone variables were compared among groups using mean differences (MD) and 95% confidence intervals (CI) calculated via random effects meta-analyses. Subgroup analyses were performed in children/adolescents (<18 years), adults (18-50 years), postmenopausal women, and older men. Twenty-eight RCTs (n = 2985) were included. Across all studies, impact exercise improved trabecular vBMD at the distal tibia (MD = 0.54% [95% CI 0.17, 0.90%]), total vBMD at the proximal femur (3.11% [1.07, 5.14%]), and cortical thickness at the mid/proximal radius (1.78% [0.21, 3.36%]). There was no effect on vBMD and bone structure at the distal radius, femoral shaft, or lumbar spine across all studies or in any subgroup. In adults, impact exercise decreased mid/proximal tibia cortical vBMD (-0.20% [-0.24, -0.15%]). In postmenopausal women, impact exercise improved distal tibia trabecular vBMD (0.79% [0.32, 1.25%]). There was no effect on bone parameters in children/adolescents in overall analyses, and there were insufficient studies in older men to perform meta-analyses. Impact exercise may have beneficial effects on bone structure and vBMD at various skeletal sites, but additional high-quality RCTs in different age and sex subgroups are needed to identify optimal exercise protocols for improving bone health across the lifespan. © 2023 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).

Victimization, safety, and overdose in homeless shelters: A systematic review and narrative synthesis.

The objective of this prospectively registered systematic review was to identify the factors that contribute to sense of safety, victimization, and overdose risk in homeless shelters, as well as groups that are at greater risk of shelter-based victimization. Fifty-five articles were included in the review. Findings demonstrated that fears of violence and other forms of harm were prominent concerns for people experiencing homelessness when accessing shelters. Service users' perceptions of shelter dangerousness were shaped by the service model and environment, interpersonal relationships and interactions in shelter, availability of drugs, and previous living arrangements. 2SLGBTQ+ individuals were identified as being at heightened risk of victimization in shelters. No studies examined rates of shelter-based victimization or tested interventions to improve safety, with the exception of overdose risk. These knowledge gaps hinder the establishment of evidence-based practices for promoting safety and preventing violence in shelter settings.