Identifying Drug-Drug Interactions in Spontaneous Reports Utilizing Signal Detection and Biological Plausibility Aspects.

Translational approaches can benefit post-marketing drug safety surveillance through the growing availability of systems pharmacology data. Here, we propose a novel Bayesian framework for identifying drug-drug interaction (DDI) signals and differentiating between individual drug and drug combination signals. This framework is coupled with a systems pharmacology approach for automated biological plausibility assessment. Integrating statistical and biological evidence, our method achieves a 16.5% improvement (AUC: from 0.620 to 0.722) with drug-target-adverse event associations, 16.0% (AUC: from 0.580 to 0.673) with drug enzyme, and 15.0% (AUC: from 0.568 to 0.653) with drug transporter information. Applying this approach to detect potential DDI signals of QT prolongation and rhabdomyolysis within the FDA Adverse Event Reporting System (FAERS), we emphasize the significance of systems pharmacology in enhancing statistical signal detection in pharmacovigilance. Our study showcases the promise of data-driven biological plausibility assessment in the context of challenging post-marketing DDI surveillance.

Exploring the engagement behaviours of Smile4life practitioners: lessons from an evaluation of the national oral health improvement programme for people experiencing homelessness in Scotland.

Introduction: Smile4life is Scotland's national oral health improvement programme for people experiencing homelessness, aimed at reducing oral health inequalities experienced by this population. This study forms part of an evaluation of how the Smile4life intervention was being implemented within Scottish NHS Boards. The aim was to investigate the influence of the Smile4life intervention upon the engagement behaviours of Smile4life practitioners. Methods: Focus groups were conducted with Smile4life practitioners, to provide an insight into how the Smile4life intervention affected their skills, attitudes and experiences while interacting with people experiencing homelessness and their services providers. A purposive sample of oral health practitioners, including dental health support workers, oral health promoters/educators, and oral health improvement coordinators working in three NHS Boards were invited to take part. One focus group was conducted in each of the three NHS Boards. The focus groups were audio-recorded and transcribed. The COM-B model of behaviour was used as a framework for analysis. Results: Eleven Smile4life practitioners took part in the focus groups. All had first-hand experience of working with the Smile4life intervention. The average focus group length was 67 min. Working on the Smile4life intervention provided the Smile4life practitioners with: (i) the capability (physical and psychological), (ii) the opportunity (to establish methods of communication and relationships with service providers and service users) and (iii) the motivation to engage with Third Sector homelessness services and service users, by reflecting upon their positive and negative experiences delivering the intervention. Enablers and barriers to this engagement were identified according to each of the COM-B categories. Enablers included: practitioners' sense of responsibility, reflecting on positive past experiences and success stories with service users. Barriers included: lack of resources, negative past experiences and poor relationships between Smile4life practitioners and Third Sector staff. Conclusion: The Smile4life programme promoted capability, provided opportunities and increased motivation in those practitioners who cross disciplinary boundaries to implement the Smile4life intervention, which can be conceptualised as "boundary spanning". Practitioners who were found to be boundary spanners often had a positive mindset and proactive attitude towards the creation of strategies to overcome the challenges of implementation by bridging the gaps between the NHS and the Third Sector, and between oral health and homelessness, operating across differing fields to achieve their aims.

Perinatal depression screening: a systematic review of recommendations from member countries of the Organisation for Economic Co-operation and Development (OECD).

Perinatal depression (PND) screening recommendations are made by national, state-based and professional organisations; however, there is disagreement regarding screening timing, provider responsible, screening setting, screening tool as well as the follow-up and referral pathways required post-screening. This systematic review aimed to identify, describe and compare PND screening recommendations from member countries of the Organisation for Economic Co-operation and Development (OECD). Publications were identified through systematically searching PubMed, Google and the Guidelines International Network (GIN). Recommendations regarding PND screening endorsement, timing, frequency, responsible provider, tools/assessments and follow-up and referral were extracted. Twenty-one publications, including guidelines, from five countries were included. Most made recommendations in support of PND screening using the Edinburgh Postnatal Depression Scale. Details differed regarding terminology used, as well as frequency of screening, follow-up mechanisms and referral pathways. A broad range of health providers were considered to be responsible for screening. This is the first review to identify and compare PND screening recommendations from OECD member countries; however, only online publications published in English, from five countries were included. Heterogeneity of publication types and inconsistency in definitions rendered quality assessment inappropriate. While most publications generally endorsed PND screening, there are exceptions and the associated details pertaining to the actual conduct of screening vary between and within countries. Developing clear, standardised recommendations based on current evidence is necessary to ensure clarity amongst healthcare providers and a comprehensive approach for the early detection of PND.

Intervening in the cycle of poverty, poor housing and poor health: the role of housing providers in enhancing tenants' mental wellbeing.

Poverty, poor housing and poor health are complexly interconnected in a cycle that has proven resistant to intervention by housing providers or policy makers. Research often focuses on the impacts of the physical housing defects, particularly upon rates of (physical) illness and disease. There has been comparatively little research into the ways in which housing services can underpin the generation of positive health and, especially, wellbeing. Drawing on qualitative data from 75 tenants in the social and private rented sectors, this paper describes the findings of a research project that tracked tenants' experiences across their first year in a new tenancy in Greater Glasgow, Scotland. The project collected data on tenants' perceptions of housing and housing service quality, financial coping and health and wellbeing, which was analysed using the principles of Realist Evaluation to elucidate impacts and causal pathways. Being able to establish a sense of home was key to tenants' wellbeing. The home provided many tenants with a recuperative space in which to shelter from daily stressors and was a source of autonomy and social status. A sense of home was underpinned by aspects of the housing service, property quality and affordability which are potentially amenable to intervention by housing providers. These findings raise questions about the extent to which social housing providers and the private rental market in the UK are able to meet the needs of vulnerable tenants. They suggest that approaches to housing provision that go beyond providing a basic dwelling are needed to successfully intervene in the cycle of poverty, poor housing and poor health.

Assessing the feasibility, acceptability and accessibility of a peer-delivered intervention to reduce harm and improve the well-being of people who experience homelessness with problem substance use: the SHARPS study.

BACKGROUND: For people experiencing homelessness and problem substance use, access to appropriate services can be challenging. There is evidence that the development of trusting relationships with non-judgemental staff can facilitate service engagement. Peer-delivered approaches show particular promise, but the evidence base is still developing. METHODS: The study used mixed methods to assess the feasibility, acceptability and accessibility of a peer-delivered, relational intervention to reduce harms and improve health/well-being, quality of life and social functioning, for people experiencing homelessness and problem substance use. Four Peer Navigators were employed to support individuals (n = 68 total, intervention participants). They were based in outreach services and hostels in Scotland and England. Qualitative interviews were conducted with intervention participants, Peer Navigators and staff in services, and observations were conducted in all settings. Quantitative outcomes relating to participants' substance use, physical and mental health, and quality of the Peer Navigator relationship, were measured via a 'holistic health check' with six questionnaires completed at two time-points. RESULTS: The intervention was found to be acceptable to, and feasible and accessible for, participants, Peer Navigators, and service staff. Participants reported improvements to service engagement, and feeling more equipped to access services independently. The lived experience of the Peer Navigators was highlighted as particularly helpful, enabling trusting, authentic, and meaningful relationships to be developed. Some challenges were experienced in relation to the 'fit' of the intervention within some settings. Among participants there were reductions in drug use and risky injecting practices. There were increases in the number of participants receiving opioid substitution therapy. Overall, the intervention was positively received, with collective recognition that the intervention was unique and highly valuable. While most of the measures chosen for the holistic health check were found to be suitable for this population, they should be streamlined to avoid duplication and participant burden. CONCLUSIONS: The study established that a peer-delivered, relational harm reduction intervention is acceptable to, and feasible and accessible for, people experiencing homelessness and problem substance use. While the study was not outcomes-focused, participants did experience a range of positive outcomes. A full randomised controlled trial is now required to assess intervention effectiveness. TRIAL REGISTRATION: Study registered with ISRCTN: 15900054.

A peer-delivered intervention to reduce harm and improve the well-being of homeless people with problem substance use: the SHARPS feasibility mixed-methods study.

BACKGROUND: For people experiencing homelessness and problem substance use, access to appropriate services can be challenging. There is evidence that development of trusting relationships with non-judgemental staff can facilitate service engagement. Peer-delivered approaches show particular promise, but the evidence base is still developing. This study tested the feasibility and acceptability of a peer-delivered intervention, through 'Peer Navigators', to support people who are homeless with problem substance use to address a range of health and social issues. OBJECTIVES: The study objectives were to design and implement a peer-delivered, relational intervention to reduce harms and improve health/well-being, quality of life and social functioning for people experiencing homelessness and problem substance use, and to conduct a concurrent process evaluation to inform a future randomised controlled trial. DESIGN: A mixed-methods feasibility study with concurrent process evaluation was conducted, involving qualitative interviews [staff interviews (one time point), n = 12; Peer Navigator interviews (three or four time points), n = 15; intervention participant interviews: first time point, n = 24, and second time point, n = 10], observations and quantitative outcome measures. SETTING: The intervention was delivered in three outreach services for people who are homeless in Scotland, and three Salvation Army hostels in England; there were two standard care settings: an outreach service in Scotland and a hostel in England. PARTICIPANTS: Participants were people experiencing homelessness and problem substance use (n = 68) (intervention). INTERVENTION: This was a peer-delivered, relational intervention drawing on principles of psychologically informed environments, with Peer Navigators providing practical and emotional support. MAIN OUTCOME MEASURES: Outcomes relating to participants' substance use, participants' physical and mental health needs, and the quality of Peer Navigator relationships were measured via a 'holistic health check', with six questionnaires completed at two time points: a specially created sociodemographic, health and housing status questionnaire; the Patient Health Questionnaire-9 items plus the Generalised Anxiety Disorder-7; the Maudsley Addiction Profile; the Substance Use Recovery Evaluator; the RAND Corporation Short Form survey-36 items; and the Consultation and Relational Empathy Measure. RESULTS: The Supporting Harm Reduction through Peer Support (SHARPS) study was found to be acceptable to, and feasible for, intervention participants, staff and Peer Navigators. Among participants, there was reduced drug use and an increase in the number of prescriptions for opioid substitution therapy. There were reductions in risky injecting practice and risky sexual behaviour. Participants reported improvements to service engagement and felt more equipped to access services on their own. The lived experience of the Peer Navigators was highlighted as particularly helpful, enabling the development of trusting, authentic and meaningful relationships. The relationship with the Peer Navigator was measured as excellent at baseline and follow-up. Some challenges were experienced in relation to the 'fit' of the intervention within some settings and will inform future studies. LIMITATIONS: Some participants did not complete the outcome measures, or did not complete both sets, meaning that we do not have baseline and/or follow-up data for all. The standard care data sample sizes make comparison between settings limited. CONCLUSIONS: A randomised controlled trial is recommended to assess the effectiveness of the Peer Navigator intervention. FUTURE WORK: A definitive cluster randomised controlled trial should particularly consider setting selection, outcomes and quantitative data collection instruments. TRIAL REGISTRATION: This trial is registered as ISRCTN15900054. FUNDING: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 26, No. 14. See the NIHR Journals Library website for further project information.

People who are homeless have worse physical and mental health, and higher rates of drug/alcohol (substance) use, than the general population. For people experiencing these challenges, completely stopping the use of substances can be difficult. Harm reduction services can be useful in reducing risks. Approaches delivered by people who have had similar experiences (peers) are also promising. Some research has highlighted the importance of trusting relationships with service staff. More research is needed on how all of these should work with people who are homeless and who use substances. This study consisted of four 'Peer Navigators' providing practical and emotional support to a group of people who are homeless and use substances to help improve their quality of life and health. The Peer Navigators had similar past experiences. The Peer Navigators were hired, and worked with around 15 'participants' each, for 2­12 months. They were based in third-sector homelessness residential and outreach services in Scotland and England. The Peer Navigators developed relationships with participants. They worked with (and often accompanied) them to access services, such as substance use treatment, health care, housing and welfare/benefits. The Peer Navigators had access to a small budget to pay for essentials, including food and bus fares. The relationship between the Peer Navigators and participants was most important, so the Peer Navigators spent time getting to know and listening to them. The aim was to understand if this intervention could be delivered to individuals experiencing these challenges. This study was not designed to know if the intervention worked; a larger study is needed for that. Despite some challenges, the participants were able to make positive changes to their lives, and they valued working with their Peer Navigator. The Peer Navigators enjoyed their roles and staff generally supported the intervention. The next step is to conduct more research to assess if this intervention can make a difference.

Influence of Psychosocial Variables on the Health of People Living in Housing Exclusion.

The aim of this study was to analyze the influence of some personal characteristics, health variables, and social support on the self-rated health of people in housing exclusion in Spain. For that purpose, we used the FOESSA Survey of Social Integration and Needs database, with a final sample of 1574 households. Being more educated and reporting a good life satisfaction stood out as the main factors preventing worse health status. Furthermore, results showed that being female, experiencing poverty-related food insecurity, not having health insurance, experiencing widowhood or partner bereavement, and having caring responsibilities for others or having a disabled person in the household are associated with increased reporting of regular or poor health. On the other hand, being young, having a diagnosed/long-term illness, and a big household size are preventive factors for good health. These results allowed identifying risk and prevention factors to inform interventions to improve the health of those living in housing exclusion. Promoting better education levels, social support, and overall life satisfaction could be important to improve health in this population. Developing social support policies for caring responsibilities and food insecurity must be a priority to improve the health of people living in housing exclusion.

Are Laboratory Parameter (Biomarker) Values Similar to the Healthy Volunteer Reference Range in Individuals with Diabetes.

BACKGROUND: Identification of laboratory parameter clinical safety signals depends on the terminology and scoring criteria. Grade 1 scoring criteria in the Common Terminology Criteria for Adverse Events (CTCAE) is typically based on the healthy volunteer reference range (HVRR). The objectives of this study were to determine 1) what laboratory parameters in individuals with diabetes are potentially different from the HVRR and 2) what fold change from baseline should be expected in this population. MATERIALS AND METHODS: Baseline data from the individuals with diabetes clinical trial data (TransCelerate dataset) were compared to the HVRR using a 10% threshold above HVRR to classify laboratory parameters as potentially different from the HVRR. These parameters were then evaluated longitudinally to determine the expected x-baseline values for individuals with diabetes for potential use in identifying drug-induced changes. RESULTS: The baseline data determined that 28% of the laboratory parameters evaluated were potentially different from the HVRR. Longitudinal data analysis determined 1) thresholds for 13 of these laboratory parameters with the subjects above the threshold having greater variability than those below the threshold, and 2) the expected upper limits (x-baseline) were calculated for the laboratory parameters. For example, a 1.8-2.6 x-baseline value for alanine aminotransferase, depending on how the baseline is calculated, is expected in individuals with diabetes. CONCLUSION: It is not uncommon for laboratory parameters in individuals with diabetes clinical trials to be potentially different from the HVRR, and the x-baseline criteria for 13 of these laboratory biomarkers was determined for this population. This suggests consideration in modifying the current CTCAE grade 1 criteria of >1.5-3.0 x-baseline should be further investigated as to if the current criteria detects too many false-positive signals in this population.

Housing as a social determinant of health and wellbeing: developing an empirically-informed realist theoretical framework.

BACKGROUND: The role of housing as a social determinant of health is well-established, but the causal pathways are poorly understood beyond the direct effects of physical housing defects. For low-income, vulnerable households there are particular challenges in creating a sense of home in a new tenancy which may have substantial effects on health and wellbeing. This study examines the role of these less tangible aspects of the housing experience for tenants in the social and private rented sectors in west central Scotland. METHODS: The paper analyses quantitative data from a mixed methods, longitudinal study of tenants from three housing organisations, collected across the first year of their tenancy. The paper postulates causal hypotheses on the basis of staff interviews and then uses a Realist Research approach to test and refine these into a theoretical framework for the connections between tenants' broader experience of housing and their health and wellbeing. RESULTS: Housing service provision, tenants' experience of property quality and aspects of neighbourhood are all demonstrated to be significantly correlated with measures of of health and wellbeing. Analysis of contextual factors provides additional detail within the theoretical framework, offering a basis for further empirical work. CONCLUSIONS: The findings provide an empirically-informed realist theoretical framework for causal pathways connecting less tangible aspects of the housing experience to health and wellbeing. Applying this within housing policy and practice would facilitate a focus on housing as a public health intervention, with potential for significant impacts on the lives of low-income and vulnerable tenants. The framework also offers a basis for further research to refine our understanding of housing as a social determinant of health.

Hybridity in the housing sector: Examining impacts on social and private rented sector tenants in Scotland.

Housing Associations in many countries exhibit increasing levels of 'hybridity', as reductions in state financing for social housing, exacerbated by austerity policies since the 2008 crash, have instigated 'enterprising' approaches to maintaining income. Alongside this, hybrid organisations have emerged in the Private Rented Sector (PRS), responding to sectoral growth and consequent increases in vulnerable households entering private renting. These developing hybridities have been considered at a strategic level, but there has been little exploration of the impacts on tenants. This paper examines two organisations, operating across the social and private rented sectors, to elucidate potential implications for tenants. The research suggests that different forms of hybridity can affect tenant outcomes and, moreover, that examining such impacts is important in understanding hybridity itself. Furthermore, the study suggests that emerging forms of hybridity, particularly in the PRS, may be blurring the boundaries between housing sectors, with implications for policy and research.

Homelessness and self-rated health: evidence from a national survey of homeless people in Spain.

BACKGROUND: Internationally, acute homelessness is commonly associated with complex health and social care needs. While homelessness can be understood as an outcome of structural housing exclusion requiring housing led solutions, the health care issues faced by homeless people equally require attention. A substantive evidence base on the health needs of homeless people exists, but relatively little is known about what influences the self-rated health of homeless people. This article presents new evidence on whether drug use (alcohol consumption, ever having used drugs), health variables (visiting a hospital once in the last year, visiting the doctor in the last month, having a health card, sleeping difficulties, and having a disabling impairment) and sociodemographic characteristics are significantly associated with Self-Rated Health (SRH) among Spanish homeless people. METHOD: The approach applies secondary analysis to cross-sectional data from a sample of 2437 homeless adults in Spain (83.8% were male). Multinomial logistic regression modelling was used to analyse the relationships between drug use, other health variables and SRH. RESULTS: Being male, an abstainer, having a health card and being in the youngest age groups were significant factors associated with perceived good health. On the other hand, ever having used drugs, having been a night in hospital, having gone to the doctor in the last month, having sleeping difficulties, having a disabling impairment and being in the older age group were all significant risk factors associated with perceived poor health. CONCLUSIONS: These results help to improve understanding of the key factors that influence the SRH among homeless people. The findings can contribute to development and delivery of preventive policies, suggesting that interventions to reduce drug consumption and ensure access to a health card/health services, as well as enhancing services for older, female and disabled homeless people are all measures which could improve health and well-being for those who face homelessness. Effective housing interventions (e.g. Housing First or Permanent Supported Housing programmes) are equally important to underpin the effectiveness of measures to improve the self-rated health of homeless people.

Supporting Harm Reduction through Peer Support (SHARPS): testing the feasibility and acceptability of a peer-delivered, relational intervention for people with problem substance use who are homeless, to improve health outcomes, quality of life and social functioning and reduce harms: study protocol.

BACKGROUND: While people who are homeless often experience poor mental and physical health and problem substance use, getting access to appropriate services can be challenging. The development of trusting relationships with non-judgemental staff can facilitate initial and sustained engagement with health and wider support services. Peer-delivered approaches seem to have particular promise, but there is limited evidence regarding peer interventions that are both acceptable to, and effective for, people who are homeless and using drugs and/or alcohol. In the proposed study, we will develop and test the use of a peer-to-peer relational intervention with people experiencing homelessness. Drawing on the concept of psychologically informed environments, it will focus on building trusting and supportive relationships and providing practical elements of support such as access to primary care, treatment and housing options. METHODS: A mixed-method feasibility study with concurrent process evaluation will be conducted to explore the feasibility and acceptability of a peer-delivered, relational intervention for people with problem substance use who are homeless. Peer Navigators will be based in homelessness outreach and residential services in Scotland and England. Peer Navigators will work with a small number of participants for up to 12 months providing both practical and emotional support. The sample size for the intervention is 60. Those receiving the intervention must be currently homeless or at risk of homelessness, over the age of 18 years and self-report alcohol/drug problems. A holistic health check will be conducted in the first few months of the intervention and repeated towards the end. Health checks will be conducted by a researcher in the service where the Peer Navigator is based. Semi-structured qualitative interviews with intervention participants and staff in both intervention and standard care settings, and all Peer Navigators, will be conducted to explore their experiences with the intervention. Non-participant observation will be conducted in intervention and standard care sites to document similarities and differences between care pathways. DISCUSSION: The SHARPS study will provide evidence regarding whether a peer-delivered harm reduction intervention is feasible and acceptable to people experiencing homelessness and problem substance use in order to develop a definitive trial. TRIAL REGISTRATION: SRCTN registry ISRCTN15900054, protocol version 1.3, March 12, 2018.

Implementing an Oral Health Intervention for People Experiencing Homelessness in Scotland: A Participant Observation Study.

Smile4life is an intervention aimed at improving the oral health of people experiencing homelessness in Scotland. The purpose of this research was to determine how this intervention was being translated from guidance into action. Data concerning Smile4life working practices were collected in three NHS Boards using participant observation. Fieldnotes taken during these observations were analysed using content analysis. This analysis revealed that there were working alliances between the oral health practitioner, the Third Sector staff, and the homeless service users, and that these alliances were affected by various barriers and enablers. The observation sessions also highlighted variations in working practices.

Housing and self-neglect: the responses of health, social care and environmental health agencies.

Substantiated cases of elder self-neglect have been reported to be more common than either elder abuse or neglect. It is a problem that often requires the active involvement of a whole range of health, social, housing, police and voluntary agencies. The ways in which these various agencies respond to self-neglect and how they interact with one another is not known. This research explored the ways in which different health and social care organizations respond to the problems associated with self-neglect. Research methods involved qualitative in-depth interviews with housing, healthcare, environmental health and social workers and a sample of their clients who were described as living in self-neglecting circumstances. This study revealed a lack of joint working across the relevant professions in relation to self-neglect. Better co-ordinated intervention could improve effectiveness and help make available resources go further. The study also suggests a need for a preventative approach to self-neglect, although further work would be required to develop indicators for early intervention.

Self-neglect: the role of judgements and applied ethics.

Self-neglect is more common than currently recognised. This article highlights the issue of self-neglect and the accompanying ethical values and judgements associated with it. A multidisciplinary framework for managing self-neglect is also described.

Sociological and psychological theories of self-neglect.

BACKGROUND: Self-neglect can be defined as the failure to engage in those self-care actions necessary to maintain a socially acceptable standard of personal and household hygiene and/or a failure to adequately care for one's own health. It is generally acknowledged that research and practice in the area of self-neglect has been hampered by a lack of theoretical development. Socio-psychological theories, such as 'social constructivism' and 'negotiated interactionism' can contribute to a deeper understanding of the phenomenon and to the further development of self-neglect theory. AIMS: This paper seeks to apply social and psychological theories to understanding self-neglect. Self-neglect is an underconceptualized phenomenon, which requires to be studied within a broader theoretical context than is at present the case. IMPLICATIONS: Sociological and psychological theories offer radically different ways of looking at self-neglect, as opposed to the medical model, as they seek to explain and understand, rather than simply classify it as a medical disorder caused by some form of underlying psychopathology. These theories emphasize the dynamic and interpretative nature of self-neglect and illustrate the arbitrary way in which this label is applied.