Programs and practices that support pregnant people who use drugs' access to sexual and reproductive health care in Canada: a scoping review.

BACKGROUND: Pregnant people who use unregulated drugs (PPWUD) are at high risk of health complications yet experience a range of barriers to sexual and reproductive health care. Given that improving maternal health and access to reproductive health care are key targets underpinning the Sustainable Development Goals (SDG), there is an urgent need to improve access to appropriate supports and services for this population. Little is known about what programs and practices exist to support PPWUD's access to sexual and reproductive health care. This scoping review aimed to identify the available literature on these programs and practices in Canada. METHODS: A scoping review was conducted using JBI methodology and reported using PRISMA guidelines. Scholarly databases and grey literature sources were searched to identify literature published between 2016-2023 in English or French that discussed, defined, conceptualised, or evaluated programs and practices that support PPWUD's access to sexual and reproductive health care in Canada. Identified literature was screened using Covidence. Data were extracted from included texts, then analysed descriptively. Frequencies and key concepts were reported. RESULTS: A total of 71 articles were included, most of which were grey literature. Of the total, 46 unique programs were identified, as well as several useful practices. Most programs were in urban centres in Western Canada, and most programs offered holistic 'wrap-around services.' Several programs delivered these services on-site or as 'drop-in' programs with the support of staff with lived/living experience of substance use. Most frequent program outcomes included keeping parents and children together, improving connection to other services, and reducing substance use harms. Noted helpful practices included non-judgmental care and the use of harm-reduction strategies. CONCLUSIONS: Several programs and practices that support PPWUD exist in Canada, though few focus exclusively on sexual and reproductive health. There remain opportunities to improve access to programs, including expanding geographic availability and range of services. The review has clinical application by providing an overview of available programs that may support clinicians in identifying services for PPWUD. Future research should consider client perspectives and experiences of these programs. REVIEW REGISTRATION NUMBER: Open Science Framework https://osf.io/5y64j .

Acceptability and influence of a complex personalized intervention on changes in photoprotection behaviours among people with xeroderma pigmentosum.

OBJECTIVES: Rigorous photoprotection is the only means to prevent skin cancer in people with the rare condition of xeroderma pigmentosum (XP). We conducted a qualitative process evaluation of patient experiences and responses to a highly personalized, multi-component intervention, 'XPAND', designed to influence the psychosocial determinants of inadequate photoprotection among adults with XP. DESIGN: Qualitative study of 15 patients following participation in a RCT. METHODS: Semi-structured interviews explored acceptability, changes in photoprotection and attributions for behavioural changes. Analysis followed a framework approach. RESULTS: Participants were overwhelmingly positive in their views of the quality and range of components of XPAND and the relevance to their personal photoprotection barriers. All participants reported improved adherence to at least one photoprotection activity and nearly two-thirds of participants noted improvements across multiple activities. Participants believed improvements in their photoprotection behaviours were influenced by different change mechanisms. Sunscreen application, was mainly facilitated by habit formation, prompted by text messages, whereas the wearing of a photoprotective face buff was influenced by strategies, learnt during one-to-one sessions, to overcome worry about looking different. Enhancement of general self-confidence and perceived support from XPAND described by participants facilitated change more broadly. CONCLUSIONS: Exploration of responses to XPAND is required in the international XP population, followed by adaptation and evaluation to see if it could benefit other patient groups at higher risk of skin cancer. Implications for approaches to behaviour change include the acceptability of complex multidimensional interventions, the importance of dynamic personalization and the interactive nature of behaviour change mechanisms.

Identifying the psychosocial predictors of ultraviolet exposure to the face in patients with xeroderma pigmentosum: a study of the behavioural factors affecting clinical outcomes in this genetic disease.

BACKGROUND: For patients with xeroderma pigmentosum (XP), the main means of preventing skin and eye cancers is extreme protection against ultraviolet radiation (UVR), particularly for the face. We have recently developed a methodology for objectively measuring photoprotection behaviour ('UVR dose to facial skin') and have found that the degree of photoprotection varies greatly between patients with XP. We have previously identified factors affecting photoprotection behaviour in XP using a subjective measure of photoprotection. Here, we have used this objective methodology to identify the factors which determine photoprotection behaviour in XP. METHODS: We studied 29 psychological, social, demographic and clinical variables in 36 patients with XP. We have previously objectively measured UVR protection (by measuring the dose of UVR reaching the skin of the face over a 3-week period) in these patients. Here, we use linear mixed-effects model analysis to identify the factors which lead to the differences in degree of photoprotection observed in these patients. RESULTS: Psychosocial factors accounted for as much of the interindividual variation in photoprotection behaviour (29%) as demographic and clinical factors (24%). Psychosocial factors significantly associated with worse UVR protection included: automaticity of the behaviours, and a group of beliefs and perceptions about XP and photoprotection known to associate with poor treatment adherence in other diseases. CONCLUSIONS: We have identified factors contributing to poor photoprotection in XP. Identifying these potentially reversible psychosocial features has enabled us to design an intervention to improve photoprotection in patients with XP, aiming to prevent skin and eye cancers in these patients.

Why? What? How? Using an Intervention Mapping approach to develop a personalised intervention to improve adherence to photoprotection in patients with Xeroderma Pigmentosum.

Background: Intervention Mapping (IM) is a systematic approach for developing theory-based interventions across a variety of contexts and settings. This paper describes the development of a complex intervention designed to reduce the dose of ultraviolet radiation (UVR) reaching the face of adults with Xeroderma Pigmentosum (XP), by improving photoprotection. XP is a genetic condition that without extreme UVR photoprotection, leads to high risk of developing skin cancer. Methods: The IM protocol of 6 steps was applied, involving comprehensive mixed-methods formative research. Key stakeholders (XP clinical staff and Patient and Public Involvement Panel), were instrumental at every step. Behaviour change methods were informed by the IM taxonomy, therapeutic approaches (e.g. ACT, CBT) and coded according to the taxonomy of behaviour change techniques (version 1). Results: We designed a personalised modular intervention to target psychosocial determinants of photoprotective activities that influence the amount of UVR reaching the face. Content was developed to target determinants of motivation to protect and factors preventing the enactment of behaviours. Participants received personalised content addressing determinants/barriers most relevant to them, as well as core 'behaviour-change' material, considered important for all (e.g. SMART goals). Core and personalised content was delivered via 7 one-to-one sessions with a trained facilitator using a manual and purpose designed materials: Magazine; text messages; sunscreen application video; goal-setting tools (e.g. UVR dial and face protection guide); activity sheets. Novel features included use of ACT-based values to enhance intrinsic motivation, targeting of emotional barriers to photoprotection, addressing appearance concerns and facilitating habit formation. Conclusion: IM was an effective approach for complex intervention design. The structure (e.g. use of matrices) tethered the intervention tightly to theory and evidence-based approaches. The significant amount of time required needs to be considered and may hinder translation of IM into clinical and non-academic settings.

Improving photoprotection in adults with xeroderma pigmentosum: personalisation and tailoring in the 'XPAND' intervention.

BACKGROUND: Individualised behaviour change interventions can result in greater effects than one-size-fits-all approaches. Factors linked to success include dynamic (vs. static) tailoring, and tailoring on behaviour, multiple theoretical variables, and participant characteristics. XP is a very rare (∼100 UK patients) genetic disease, involving an inability to repair ultraviolet radiation (UVR)-induced damage, resulting in skin cancers and eye damage from an early age, and mean life expectancy of 32-years. Management involves rigorous UVR photoprotection, which is often inadequate, and no interventions have been published. UK-based care is personalised and delivered by a multidisciplinary team at the National XP Service in London. Following an intensive, mixed-methods formative phase with patients diagnosed with XP (n-of-1, qualitative interviews, objective UVR measurement, cross-sectional survey) and relevant stakeholder consultation (clinical and patient/public teams), the 'XPAND' intervention was developed. This paper describes the comprehensive and novel tailoring and personalisation processes used to deliver the intervention. METHODS: XPAND consists of core and personalised modules targeting cue-based (time of day, weather, symptoms), belief-based (motivation, priority), self-regulatory (effort, barriers, planning), and emotional (stress, self-consciousness, mental exhaustion) factors, social support, disclosure, habit, and willingness, using appropriately-matched BCTs. A-priori, phase I data and a baseline profiling questionnaire (data sources) were used to allocate modules to participants ('personalisation') and to adapt module content ('tailoring'). Iterative decisions about delivery were based on patient response to feedback, identification of additional barriers (e.g. reasons for varying protection across contexts), and emergence of new barriers as improvements in protection were attempted or achieved (e.g. appearance concerns). CONCLUSIONS: Dynamic multi-level personalisation and tailoring based on mixed-methods in XPAND allowed for insights and decision-making not possible with cross-sectional quantitative or qualitative methods alone. Data collection and allocation/adaptation methods may be of use in other rare conditions where small patient numbers mean that within-participant, individual-level delivery is well-suited and feasible.

Evaluation of a personalised adherence intervention to improve photoprotection in adults with Xeroderma Pigmentosum (XP): protocol for the trial of XPAND.

INTRODUCTION: Poor adherence to photoprotection for people with xeroderma pigmentosum (XP) can be life-threatening. A randomised controlled trial (RCT) is being conducted to test the efficacy of a personalised adherence intervention (XPAND) to reduce the level of ultraviolet radiation (UVR) reaching the face, by improving photoprotection activities in adults with XP. METHODS AND ANALYSIS: A two-armed parallel groups RCT, where we randomised 24 patients with suboptimal adherence to either an intervention group who received XPAND in 2018 or a delayed intervention group who will receive XPAND in 2019. XPAND involves seven sessions, one-to-one with a facilitator, using behaviour change techniques and specially designed materials to target barriers to photoprotection. Following baseline assessment in April 2018 (t0) and intervention, the primary outcome will be measured across 21 consecutive days in June and July 2018 (t1). The primary outcome is the average daily UVR dose to the face (D-to-F), calculated by combining objective UVR exposure at the wrist (measured by a dosimeter) with face photoprotection activities recorded on a daily UVR protection diary. Secondary outcomes include average daily UVR D-to-F across 21 days in August (t2); psychosocial process variables measured by daily questions (t0, t1, t2) and self-report questionnaires (t0, t1, t2, December 2018 (t3)). Intervention cost-utility is assessed by service use and personal cost questionnaires (t0, t3). The delayed intervention control arm participants will complete three further assessments in April 2019 (t4) and June-July 2019 (t5), and December 2019 (t6) with dosimetry and UVR protection diary completed for 21 days at t4 and t5. A process evaluation will be conducted using mixed methods. ETHICS AND DISSEMINATION: Ethical approval has been received from West London & GTAC REC 17/LO/2110. Results will be disseminated in peer-reviewed journals and at conferences. This study tests a novel intervention, which, if successful, will be integrated into routine care. TRIAL REGISTRATION NUMBER: NCT03445052; Pre-results.

Psychological correlates of adherence to photoprotection in a rare disease: International survey of people with Xeroderma Pigmentosum.

OBJECTIVES: Xeroderma pigmentosum (XP) is an extremely rare genetic disorder (approximately 100 known cases in the United Kingdom), where DNA damage caused by ultraviolet radiation in daylight cannot be repaired. Adherence to photoprotection is essential to prevent skin cancer. We investigated psychological correlates of photoprotection in the XP population of Western Europe and the United States. DESIGN: Cross-sectional survey of adults with XP and caregivers of patients <16 years and those with cognitive impairment in the United Kingdom, Germany, the United States, and France (n = 156). METHODS: Photoprotection activities to protect the face and body when outdoors; avoidance of going outside during daylight hours; intention; self-efficacy; and social support were assessed using measures developed for this study. Participants answered questions about their illness representations of XP (BIPQ); beliefs about photoprotection (BMQ); automaticity (i.e., without conscious effort) (SRBAI); clinical and demographic characteristics. Ordinal logistic regressions determined factors associated with photoprotection. RESULTS: One third did not achieve optimal face photoprotection. After controlling for demographic and clinical factors, modifiable correlates of higher photoprotection included greater perceived control of XP, stronger beliefs in necessity and effectiveness of photoprotection, and higher intention. Avoidance of going outside was associated with greater photoprotection concerns, more serious illness consequences, and higher XP-related distress. Greater automaticity and higher self-efficacy were associated with better protection across all outcomes. CONCLUSIONS: Approximately half of all known cases across three European countries participated. Identified modifiable predictors of photoprotection may be targeted by interventions to reduce the incidence of skin cancers in the immediate future, when a treatment breakthrough is unlikely. Statement of contribution What is already known on this subject? Adherence to photoprotection in other populations at elevated risk from skin cancer is poor; however, the level in XP is unknown. Research across chronic conditions shows that adherence to treatment and lifestyle recommendations are influenced by illness perceptions, self-efficacy, and treatment beliefs. Studies on photoprotection conducted with the general population have found that perceived risk, perceptions of ultraviolet radiation (UVR) protection, self-efficacy for the behaviour, and automaticity (behaviours that are enacted with little conscious awareness) are related to better photoprotection. What does this study add? This is the first international survey to examine adherence and its correlates in people with XP (an under-researched group at very high risk of fatal skin cancer). Adherence varies and at least one third have potential for improvement. Perceptions about XP, photoprotection beliefs, self-efficacy, intention, and automaticity were associated with photoprotection of the face and body when outdoors. Negative emotional representations of XP were associated with avoidance of going outside during daylight hours.

An investigation of the predictors of photoprotection and UVR dose to the face in patients with XP: a protocol using observational mixed methods.

INTRODUCTION: Xeroderma pigmentosum (XP) is a rare genetic condition caused by defective nucleotide excision repair and characterised by skin cancer, ocular and neurological involvement. Stringent ultraviolet protection is the only way to prevent skin cancer. Despite the risks, some patients' photoprotection is poor, with a potentially devastating impact on their prognosis. The aim of this research is to identify disease-specific and psychosocial predictors of photoprotection behaviour and ultraviolet radiation (UVR) dose to the face. METHODS AND ANALYSIS: Mixed methods research based on 45 UK patients will involve qualitative interviews to identify individuals' experience of XP and the influences on their photoprotection behaviours and a cross-sectional quantitative survey to assess biopsychosocial correlates of these behaviours at baseline. This will be followed by objective measurement of UVR exposure for 21 days by wrist-worn dosimeter and daily recording of photoprotection behaviours and psychological variables for up to 50 days in the summer months. This novel methodology will enable UVR dose reaching the face to be calculated and analysed as a clinically relevant endpoint. A range of qualitative and quantitative analytical approaches will be used, reflecting the mixed methods (eg, cross-sectional qualitative interviews, n-of-1 studies). Framework analysis will be used to analyse the qualitative interviews; mixed-effects longitudinal models will be used to examine the association of clinical and psychosocial factors with the average daily UVR dose; dynamic logistic regression models will be used to investigate participant-specific psychosocial factors associated with photoprotection behaviours. ETHICS AND DISSEMINATION: This research has been approved by Camden and King's Cross Research Ethics Committee 15/LO/1395. The findings will be published in peer-reviewed journals and presented at national and international scientific conferences.

The "Refrige-a-RAT-or": an accurate, inexpensive, and clinically relevant small animal model of therapeutic hypothermia.

BACKGROUND: Physical and molecular mechanisms for the neuroprotective effect of therapeutic hypothermia are not completely understood, and new therapeutic applications incorporating hypothermia remain to be developed and tested. Clinically relevant animal models of therapeutic hypothermia are not well established or consistent. OBJECTIVES: The objective was to develop and test an inexpensive small animal therapeutic hypothermia system that models those in widespread clinical use and verify that such a system confers neuroprotection in a rat model of global brain ischemia. METHODS: A water-cooled extracorporeal system and attendant anesthesia/sedation protocol were developed and tested. In Stage 1, animals were instrumented for brain, temporalis, and rectal temperature monitoring, and the system was tested for its effect on temperature and hemodynamics. In Stage 2, animals were instrumented for rectal temperature only, subjected to global brain ischemia by two-vessel occlusion and hypotension for 8 minutes, and given either sham therapy (37°C) or hypothermia (32°C) for 4 hours. Viable CA1 neurons were counted at 7 days. RESULTS: The system was well tolerated, provided exquisite control of animal core and brain temperatures, and conferred robust neuroprotection at 7 days. The median and interquartile ranges (IQRs) of viable neurons per 300-µm field were 130 (IQR = 128 to 135) for sham control, 19 (IQR = 15 to 30) for untreated ischemic animals, and 101 (IQR = 94 to 113) for ischemic animals treated with hypothermia (p < 0.05 for comparison between all groups). CONCLUSIONS: Like human protocols, this model incorporates sedation and analgesia, results in robust neuroprotection, is well tolerated, and offers exquisite temperature control. The system is noninvasive and inexpensive and offers a model that is similar to methods used in clinical practice. This system will be of interest to investigators using small animal models to examine neuroprotective mechanisms of hypothermia and translational strategies that combine hypothermia with targeted pharmacotherapy.

Bioengineered three-dimensional physiological model of colonic longitudinal smooth muscle in vitro.

BACKGROUND: The objective of this study was to develop a physiological model of longitudinal smooth muscle tissue from isolated longitudinal smooth muscle cells arranged in the longitudinal axis. METHODS: Longitudinal smooth muscle cells from rabbit sigmoid colon were isolated and expanded in culture. Cells were seeded at high densities onto laminin-coated Sylgard surfaces with defined wavy microtopographies. A highly aligned cell sheet was formed, to which addition of fibrin resulted in delamination. RESULTS: (1) Acetylcholine (ACh) induced a dose-dependent, rapid, and sustained force generation. (2) Absence of extracellular calcium attenuated the magnitude and sustainability of ACh-induced force by 50% and 60%, respectively. (3) Vasoactive intestinal peptide also attenuated the magnitude and sustainability of ACh-induced force by 40% and 60%, respectively. These data were similar to force generated by longitudinal tissue. (4) Bioengineered constructs also maintained smooth muscle phenotype and calcium-dependence characteristics. SUMMARY: This is a novel physiologically relevant in vitro three-dimensional model of colonic longitudinal smooth muscle tissue. Bioengineered three-dimensional longitudinal smooth muscle presents the ability to generate force, and respond to contractile agonists and relaxant peptides similar to native longitudinal tissue. This model has potential applications to investigate the underlying pathophysiology of dysfunctional colonic motility. It also presents as a readily implantable band-aid colonic longitudinal muscle tissue.

Transition from paediatric to adult service in epidermolysis bullosa.

Children with chronic health needs are living longer than they have in the past (Department of Health, 2006) and are becoming adults with complex health needs. This has implications for the health service, which needs to address the arrangements for transfer of young adults from paediatric to adult centres. This article describes the transitional care arrangements established at Great Ormond Street Hospital to address the needs of children with severe epidermolysis bullosa as they move on to adult care. It emphasises the close liaison between paediatric and adult clinical nurse specialists, and recognizes the role of the wider family who also have long-standing links with staff in the paediatric environment and can find transfer to an adult unit traumatic. The article concludes by recognizing that the young adult and specialist teams need to work together to continue the transition process for future generations.

Impact of static and dynamic A-form heterogeneity on the determination of RNA global structural dynamics using NMR residual dipolar couplings.

We examined how static and dynamic deviations from the idealized A-form helix propagate into errors in the principal order tensor parameters determined using residual dipolar couplings (rdcs). A 20-ns molecular dynamics (MD) simulation of the HIV-1 transactivation response element (TAR) RNA together with a survey of spin relaxation studies of RNA dynamics reveals that pico-to-nanosecond local motions in non-terminal Watson-Crick base-pairs will uniformly attenuate base and sugar one bond rdcs by approximately 7%. Gaussian distributions were generated for base and sugar torsion angles through statistical comparison of 40 RNA X-ray structures solved to <3.0 A resolution. For a typical number (>or=11) of one bond C-H base and sugar rdcs, these structural deviations together with rdc uncertainty (1.5 Hz) lead to average errors in the magnitude and orientation of the principal axis of order that are <9% and <4 degrees, respectively. The errors decrease to <5% and <4 degrees for >or=17 rdcs. A protocol that allows for estimation of error in A-form order tensors due to both angular deviations and rdc uncertainty (Aform-RDC) is validated using theoretical simulations and used to analyze rdcs measured previously in TAR in the free state and bound to four distinct ligands. Results confirm earlier findings that the two TAR helices undergo large changes in both their mean relative orientation and dynamics upon binding to different targets.

Complete maternal isodisomy of chromosome 3 in a child with recessive dystrophic epidermolysis bullosa but no other phenotypic abnormalities.

The mechanobullous disease Hallopeau-Siemens recessive dystrophic epidermolysis bullosa (HS-RDEB) results from mutations in the type VII collagen gene (COL7A1) on chromosome 3p21.31. Typically, there are frameshift, splice site, or nonsense mutations on both alleles. In this report, we describe a patient with HS-RDEB, who was homozygous for a new frameshift mutation, 345insG, in exon 3 of COL7A1. However, sequencing of parental DNA showed that although the patient's mother was a heterozygous carrier of this mutation, the father's DNA contained only wild-type sequence. Microsatellite marker analysis confirmed paternity and genotyping of 28 microsatellites spanning chromosome 3 revealed that the affected child was homozygous for every marker tested with all alleles originating from a single maternal chromosome 3. Thus, the HS-RDEB phenotype in this patient is due to complete maternal isodisomy of chromosome 3 and reduction to homozygosity of the mutant COL7A1 gene locus. To our knowledge, there are no published reports of uniparental disomy (UPD) in HS-RDEB; moreover, this case represents only the third example of UPD of chromosome 3 to be reported. The severity of the HS-RDEB in this case was similar to other affected individuals and no additional phenotypic abnormalities were observed, suggesting an absence of maternally imprinted genes on chromosome 3.