Addressing the workforce crisis in (rural) social care: A scoping review.

BACKGROUND: This scoping review identifies strategies potentially addressing the 'workforce crisis' in rural social care. The increasing global demand for social care has been coupled with widely recognised challenges in recruiting and retaining sufficient staff to provide this care. While the social care workforce crisis is a global phenomenon, it is particularly acute in rural areas. METHODS: The review identified 75 papers which (i) had been published since 2017, (ii) were peer reviewed, (iii) concerned social care, (iv) were relevant to rural settings, (v) referenced workforce shortages, and (vi) made recommendations for ways to address those shortages. Thematic synthesis was used to derive three analytical themes with a combined 17 sub-themes applying to recommended strategies and evidence supporting those strategies. RESULTS: The most common strategies for addressing social care workforce shortages were to improve recruitment and retention ('recruit and retain') processes without materially changing the workforce composition or service models. Further strategies involved 'revitalising' the social care workforce through redeploying existing staff or identifying new sources of labour. A small number of strategies involved 're-thinking' social care service models more fundamentally. Very few papers specifically considered how these strategies might apply to rural contexts, and evidence for the effectiveness of strategies was sparse. CONCLUSION: The review identifies a significant gap in the literature in relation to workforce innovation and placed-based studies in rural social care systems. It is unlikely that the social care workforce crisis can be addressed through continuing attempts to recruit and retain workers within existing service models.

Creating 'good' hospital to home transfers in the rural north of Sweden: informal workarounds and opportunities for improvement.

Hospital to home transfers for older people require effective communication, coordination and collaboration across multiple service settings. Rural Nursing Theory and the Beyond Periphery model explain why this is particularly difficult in rural areas, but there are few examples of how rural services respond. This paper presents a case study of the district of Tärnaby in the inland north of Sweden. Data are drawn from interviews with health and care staff in Tärnaby, observations, and experiences of the researchers. Data were analyzed thematically, with four main themes emerging - role clarity, communication, geography, and understanding of the rural context. Responses to challenges included increasing opportunities for communication between service providers and improving documentation. The paper concludes that informal "workarounds" run the risk of further disconnecting rural service settings from "the city". Rather, the aim needs to be to improve contextual understanding through formally incorporating "the rural" in service design.

Caregiver Burden and Its Relationship to Health-Related Quality of Life in Craniopharyngioma Survivors.

CONTEXT: Craniopharyngioma (CP) is a rare brain tumor associated with severe comorbidities that reduce survivor health-related quality of life (HRQOL). However, CP impact on caregivers is unknown. OBJECTIVE: To measure caregiver burden and examine its relationship to survivor HRQOL and other determinants in CP. METHODS: Eighty-two participants who self-identified as caregivers of CP survivors responded to an online survey including caregiver-reported Pediatric Quality of Life Inventory (PedsQL), and the Zarit Burden Interview (ZBI). RESULTS: Caregivers reported an average of 13 out of 29 health conditions in survivors following tumor treatment, including excess weight, hypopituitarism, fatigue, mood, cognition, social issues, temperature dysregulation, visual impairment, and sleep problems. Strikingly, 70% of survivors who experienced obesity also experienced hyperphagia. ZBI scores were moderate with a median of 37. PedsQL total scores were poor with a median of 46.2. ZBI scores were independent of caregiver level of education and care duration. Both scores were independent of income, survivor age, gender, age at diagnosis, or tumor recurrence. In contrast, both scores depended on the number (P < .001) and the type of survivor health problems, with significantly worse scores for caregivers or survivors with symptoms of hypothalamic dysfunction (P < .001) including hyperphagia but not obesity. PedsQL total scores significantly predicted ZBI scores (P < .001). CONCLUSION: Survivor poly-symptomatology predicted and incurred significant caregiver burden. Our study separated hyperphagia and obesity and identified hyperphagia and other hypothalamic dysfunction symptoms as understudied issues. Altogether, these findings draw particular attention to the unmet needs of CP survivors and their caregivers.

Innovation in Rural Health Services Requires Local Actors and Local Action.

Objectives: We examine the role of "local actors" and "local action" (LALA) in health service innovation in high-resource small rural settings and aim to inform debates about the extent to which communities can be empowered to drive change in service design and delivery. Methods: Using an adapted roles and activities framework we analyzed 32 studies of innovation projects in public health, clinical interventions, and service models. Results: Rural communities can investigate, lead, own and sustain innovation projects. However, there is a paucity of research reflecting limited reporting capacity and/or understanding of LALA. Highlighting this lack of evidence strengthens the need for study designs that enable an analysis of LALA. Conclusion: Innovation and community participation in health services are pressing issues in small rural settings where population size and distance from health infrastructure make service delivery challenging. Current reviews of community participation in rural health give little insight into the process of innovation nor understanding of how local actors produce improvements in innovation. This review outlines how communities and institutions can harness the essential role of LALA in supporting health innovations.

Postnatal oxytocin treatment improves survival and neurodevelopmental outcomes in an animal model of neonatal abstinence syndrome.

Prenatal exposure to drugs of abuse results in neonatal abstinence syndrome (NAS). NAS causes significant morbidity and is associated with costly and lengthy hospitalization. Current pharmacotherapy is suboptimal with no FDA approved treatments. We examined the effect of postnatal oxytocin treatment on survival and neurodevelopmental outcomes in rats prenatally exposed to opioids or benzodiazepines. Sprague-Dawley rat dams were injected with escalating doses of morphine (10-50 mg/kg/day) or diazepam (2-15 mg/kg/day) throughout gestation. In an initial experiment, exposed rat pups received subcutaneous injections of 2 mg/kg oxytocin or saline for the first 10 postnatal days and survival rates were assessed. In a second experiment, exposed rat pups received subcutaneous injections of 0.3, 1, or 2 mg/kg oxytocin or saline for the first 10 postnatal days and survival and body weight were assessed for 30 days. In animals surviving through adolescence, neurodevelopmental outcomes and biological parameters (blood glucose, corticosterone, aldosterone) were also measured. Postnatal oxytocin treatment improved survival in animals prenatally exposed to morphine or diazepam. Preliminary evidence showed that postnatal oxytocin treatment improves long-term learning and memory processes in animals prenatally exposed to morphine or diazepam. These findings highlight the potential of oxytocin as a novel treatment for NAS resulting from prenatal exposure to opioids or benzodiazepines.

Strengthening Community Health Systems Through Novel eHealth Initiatives? Commencing a Realist Study of the Virtual Health Rooms in Rural Northern Sweden.

BACKGROUND: Unlike the large body of research that has examined the 'success' or 'failure' of eHealth in terms of patient and provider perceptions or cost- and clinical effectiveness, the current study teases out ways through which a novel eHealth initiative in rural northern Sweden might result in more distal or systemic beneficial outcomes. More specifically, this paper aims to explore how and under what circumstances the so-called virtual health rooms (VHRs) are expected to improve access to person-centred care and strengthen community health systems, especially for elderly residents of rural areas. METHODS: The first phase of the realist evaluation methodology was conducted, involving qualitative interviews with 8 key stakeholders working with eHealth, business development, digitalisation, and process management. Using thematic analysis and following an abductive-retroductive analytical process, an intervention-context-actor-mechanism-outcome (ICAMO) configuration was developed and elicited into an initial programme theory. RESULTS: The findings indicate that a novel eHealth initiative, which provides reliable technologies in a customized facility that connects communities and providers, might improve access to person-centred care and strengthen community health systems for rural populations. This is theorized to occur if mechanisms acting at individual (such as knowledge, skills and trust) and collective (like a common vision and shared responsibilities) levels are triggered in contexts characterised by supportive societal transitions, sufficient organisational readiness and the harnessing of rural cohesiveness and creativity. CONCLUSION: The elicited initial programme theory describes and explains how a novel eHealth initiative in rural northern Sweden is presumed to operate and under what circumstances. Further testing, refinements and continued gradual building of theory following the realist evaluation methodology is now needed to ascertain if the 'VHRs' work as intended, for whom, in what conditions and why.

What a Pandemic Has Taught Us About the Potential for Innovation in Rural Health: Commencing an Ethnography in Canada, the United States, Sweden, and Australia.

The COVID-19 pandemic coincided with a multi-national federally funded research project examining the potential for health and care services in small rural areas to identify and implement innovations in service delivery. The project has a strong focus on electronic health (eHealth) but covers other areas of innovation as well. The project has been designed as an ethnography to prelude a realist evaluation, asking the question under what conditions can local health and care services take responsibility for designing and implementing new service models that meet local needs? The project had already engaged with several health care practitioners and research students based in Canada, Sweden, Australia, and the United States. Our attention is particularly on rural communities with fewer than 5,000 residents and which are relatively isolated from larger service centres. Between March and September 2020, the project team undertook ethnographic and auto-ethnographic research in their own communities to investigate what the service model responses to the pandemic were, and the extent to which local service managers were able to customize their responses to suit the needs of their communities. An initial program theory drawn from the extant literature suggested that "successful" response to the pandemic would depend on a level of local autonomy, "absorptive capacity,*" strong service-community connections, an "anti-fragile†" approach to implementing change, and a realistic recognition of the historical barriers to implementing eHealth and other innovations in these types of rural communities. The field research in 2020 has refined the theory by focusing even more attention on absorptive capacity and community connections, and by suggesting that some level of ignorance of the barriers to innovation may be beneficial. The research also emphasized the role and power of external actors to the community which had not been well-explored in the literature. This paper will summarize both what the field research revealed about the capacity to respond well to the COVID-19 challenge and highlight the gaps in innovative strategies at a managerial level required for rapid response to system stress. *Absorptive Capacity is defined as the ability of an organization (community, clinic, hospital) to adapt to change. Organizations with flexible capacity can incorporate change in a productive fashion, while those with rigid capacity take longer to adapt, and may do so inappropriately. †Antifragility is defined as an entities' ability to gain stability through stress. Biological examples include building muscle through consistent use, and bones becoming stronger through subtle stress. Antifragility has been used as a guiding principle in programme implementation in the past.

Nasal oxytocin for the treatment of psychiatric disorders and pain: achieving meaningful brain concentrations.

There is evidence of the therapeutic potential of intranasal oxytocin for the treatment of pain and various psychiatric disorders, however, there is scant evidence that oxytocin reaches the brain. We quantified the concentration and distribution pattern of [125I]-radiolabeled oxytocin in the brains and peripheral tissues of rats after intranasal delivery using gamma counting and autoradiography, respectively. Radiolabel was detected in high concentrations in the trigeminal and olfactory nerves as well as in brain regions along their trajectories. Considerable concentrations were observed in the blood, however, relatively low levels of radiolabel were measured in peripheral tissues. The addition of a mucoadhesive did not enhance brain concentrations. These results provide support for intranasal OT reaching the brain via the olfactory and trigeminal neural pathways. These findings will inform the design and interpretation of clinical studies with intranasal oxytocin.

Landscapes of care and despair for rural youth - a qualitative study in the northern Swedish 'periphery'.

BACKGROUND: This study emerges as a response to the lack of youth perspectives when it comes to discussions about access to and experiences of health and social services in rural areas. It subsequently contributes to the literature by positioning young people at the centre of this debate, and by taking a more holistic approach to the topic than is typically the case. Specifically, based on the idea that a good life in proper health for young people may be contingent on notions of care that are bounded up in multi-layered social and spatial environments, the aim of this study was to explore what characterises 'landscapes of care' for rural youth. METHODS: In this qualitative study, the participants included young people and professionals residing in five diverse areas across the northern Swedish 'peripheral' inland. Individual interviews (16 in total) and focus group discussions (26 in total) were conducted with 63 youth aged 14-27 years and with 44 professionals operating across sectors such as health centres, school health, integration units, youth clinics and youth clubs. Following an emergent design and using thematic analysis, we developed one main theme, 'landscapes of care and despair', comprising the two themes: '(dis)connectedness' and 'extended support or troubling gaps'. RESULTS: The findings illustrate how various health-promoting and potentially harmful aspects acting at structural, organisational and interpersonal levels contributed to dynamic landscapes characterised simultaneously by care and despair. In particular, our study shows how rural youths' feelings of belongingness to people and places coupled with opportunities to participate in society and access practical and emotional support appear to facilitate their care within rural settings. However, although the results indicate that some in the diverse group of rural youth were cared for and about, a negative picture was painted in parallel. These aspects of despair included youths' senses of exclusion and marginalisation, degrading attitudes towards them and their problems, as well as recurrent gaps in the provision and practices of care. CONCLUSIONS: To gain a more comprehensive understanding about the health of rural youth, this study highlights the benefits investigating 'care-ful' and 'uncaring' aspects bounded up in dynamic and multi-layered landscapes.

Patient and provider perspectives on eHealth interventions in Canada and Australia: a scoping review.

INTRODUCTION: Despite the promises of universal health care in most developed countries, health inequities remain prevalent within and between rural and remote communities. Remote health technologies are often promoted as solutions to increase health system efficiency, to enhance quality of care, and to decrease gaps in access to care for rural and remote communities. However, there is mixed evidence for these interventions, particularly related to how they are received and perceived by health providers and by patients. Health technologies do not always adequately meet the needs of patients or providers. To examine this, a broad-based scoping review was conducted to provide an overview of patient and provider perspectives of eHealth initiatives in rural communities. The unique objective of this review was to prioritize the voices of patients and providers in discussing the disparities between health interventions and needs of people in rural communities. eHealth initiatives were reviewed for rural communities of Australia and Canada, two countries that have similar geographies and comparable health systems at the local level. METHODS: Searches were performed in PubMed, Scopus, and Web of Science with results limited from 2000 to 2018. Keywords included combinations of 'eHealth', 'telehealth', 'telemedicine', 'electronic health', and 'rural/remote'. Individual patient and provider perspectives on health care were identified, followed by qualitative thematic coding based on the type of intervention, the feedback provided, the affected population, geographic location, and category of individual providing their perspective. Quotes from patients and providers are used to illustrate the identified benefits and disadvantages of eHealth technologies. RESULTS: Based on reviewed literature, 90.1% of articles reported that eHealth interventions were largely positive. Articles noted decreased travel time (18%), time/cost saving (15.1%), and increased access to services (13.9%) as primary benefits to eHealth. The most prevalent disadvantages of eHealth were technological issues (24.5%), lack of face-to-face contact (18.6%), limited training (10.8%), and resource disparities (10.8%). These results show where existing eHealth interventions could improve and can inform policymakers and providers in designing new interventions. Importantly, benefits to eHealth extend beyond geographic access. Patients reported ancillary benefits to eHealth that include reduced anxiety, disruption on family life, and improved recovery time. Providers reported closer connections to colleagues, improved support for complex care, and greater eLearning opportunity. Barriers to eHealth are recognized by patient and providers alike to be largely systemic, where lack of rural high-speed internet and unreliability of installed technologies were significant. CONCLUSION: Regional and national governments are seen as the key players in addressing these technical barriers. This scoping review diverges from many reviews of eHealth with the use of first-person perspectives. It is hoped that this focus will highlight the importance of patient voices in evaluating important healthcare interventions such as eHealth and associated technologies.

Umeå University's proposed "Rural Stream" - An effective alternative to the longitudinal integrated clerkship model for small rural communities?

Background: Umeå University Faculty of Medicine (UUFM), Sweden, has a regionalized medical program in which students spend the final 2½ years of their undergraduate degree in district hospitals. In late 2018, UUFM started a "rural stream" pilot exposing students to smaller rural locations. Methods: The objectives are to deliver the benefits for medical education and rural workforce development that have been observed in longitudinal integrated clerkships (LICs) while maintaining consistency between learning experiences in the main campus, regional campuses, and rural locations. This article compares the UUFM rural stream with those typical of the LICs described in the medical education literature. Comparisons are made in terms of the four key criteria for LIC success, and additional characteristics including peer and interprofessional learning, "'continuity," and curriculum development. Results: The rural stream has elements of length, immersion, position in the degree program, and community engagement that are both similar to, and different from, LICs. Key challenges are to ensure that participating students create close relationships with host medical facilities and communities. The rural stream also has some potential advantages, particularly in relation to team learning. Discussion: Alternatives to the LIC rural stream model as typically described in the literature may be required to allow for immersive medical education to occur in smaller rural communities and to be suitable for medical schools with more traditional approaches to education.

Blood oxytocin concentration positively predicts contagious yawning behavior in children with autism spectrum disorder.

Research suggests that children with autism spectrum disorder (ASD) may have reduced empathy, as measured by an impaired contagious yawn response, compared to typically developing (TD) children. Other research has failed to replicate this finding, instead attributing this phenomenon to group differences in attention paid to yawn stimuli. A third possibility is that only a subgroup of children with ASD exhibits the impaired contagious yawn response, and that it can be identified biologically. Here we quantified blood concentrations of the "social" neuropeptide oxytocin (OXT) and evaluated yawning behavior and attention rates during a laboratory task in children with ASD (N = 34) and TD children (N = 30) aged 6-12 years. No group difference in contagious yawning behavior was found. However, a blood OXT concentration × group (ASD vs. TD) interaction positively predicted contagious yawning behavior (F1,50 = 7.4987; P = 0.0085). Specifically, blood OXT concentration was positively related to contagious yawning behavior in children with ASD, but not in TD children. This finding was not due to delayed perception of yawn stimuli and was observed whether attention paid to test stimuli and clinical symptom severity were included in the analysis or not. These findings suggest that only a biologically defined subset of children with ASD exhibits reduced empathy, as measured by the impaired contagious yawn response, and that prior conflicting reports of this behavioral phenomenon may be attributable, at least in part, to variable mean OXT concentrations across different ASD study cohorts. Autism Res 2019, 12: 1156-1161. © 2019 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: People with autism may contagiously yawn (i.e., yawn in response to another's yawn) less often than people without autism. We find that people with autism who have lower levels of blood oxytocin (OXT), a hormone involved in social behavior and empathy, show decreased contagious yawning, but those who have higher blood OXT levels do not differ in contagious yawning from controls. This suggests that decreased contagious yawning may only occur in a biologically defined subset of people with autism.

A randomized placebo-controlled pilot trial shows that intranasal vasopressin improves social deficits in children with autism.

The social impairments of autism spectrum disorder (ASD) have a major impact on quality of life, yet there are no medications that effectively treat these core social behavior deficits. Preclinical research suggests that arginine vasopressin (AVP), a neuropeptide involved in promoting mammalian social behaviors, may be a possible treatment for ASD. Using a double-blind, randomized, placebo-controlled, parallel study design, we tested the efficacy and tolerability of a 4-week intranasal AVP daily treatment in 30 children with ASD. AVP-treated participants aged 6 to 9.5 years received the maximum daily target dose of 24 International Units (IU); participants aged 9.6 to 12.9 years received the maximum daily target dose of 32 IU. Intranasal AVP treatment compared to placebo enhanced social abilities as assessed by change from baseline in this phase 2 trial's primary outcome measure, the Social Responsiveness Scale, 2nd Edition total score (SRS-2 T score; F 1,20 = 9.853; P = 0.0052; ηp 2 = 33.0%; Cohen's d = 1.40). AVP treatment also diminished anxiety symptoms and some repetitive behaviors. Most of these findings were more pronounced when we accounted for pretreatment AVP concentrations in blood. AVP was well tolerated with minimal side effects. No AVP-treated participants dropped out of the trial, and there were no differences in the rate of adverse events reported between treatment conditions. Last, no changes from baseline were observed in vital signs, electrocardiogram tracings, height and body weight, or clinical chemistry measurements after 4 weeks of AVP treatment. These preliminary findings suggest that AVP has potential for treating social impairments in children with ASD.

"There is no reward penny for going out and picking up youths": issues in the design of accessible youth healthcare services in rural northern Sweden.

OBJECTIVE: There is a continuing challenge to ensure equitable access to youth healthcare services in small rural communities. Sweden's 'youth clinic' system is an attempt to provide comprehensive youth health services from a single centre, but many small rural communities have not adopted the youth clinic model. This study uses one case study to examine what the issues might be in establishing a youth clinic in a small rural community. The objective of this paper is to examine the issues around youth healthcare access in one municipality without a youth clinic, and to explore whether and how a youth clinic model might contribute to access in this municipality. RESULTS: Three categories emerged from the analysis; (i) rural closeness; both good and bad, (ii) youth are not in the centre of the healthcare organization, and (iii) adapting youth clinics to a rural setting. While limited to one case example, the study provides valuable insights into youth health service planning in particular types of rural communities. This paper identified structural barriers to developing youth-specific services, and some alternative approaches that might be more suitable to smaller communities.

Community engagement: A central feature of NOSM's socially accountable distributed medical education.

BACKGROUND: Northern Ontario School of Medicine (NOSM) serves as the Faculty of Medicine of Lakehead and Laurentian Universities, and views the entire geography of Northern Ontario as its campus. This paper explores how community engagement contributes to achieving social accountability in over 90 sites through NOSM's distinctive model, Distributed Community Engaged Learning (DCEL). METHODS: Studies involving qualitative and quantitative methods contribute to this paper, which draws on administrative data from NOSM and external sources, as well as surveys and interviews of students, graduates and other informants including the joint NOSM-CRaNHR (Centre for Rural and Northern Health Research) tracking and impact studies. RESULTS: Community engagement contributes throughout the lifecycle stages of preadmission, admission, and undergraduate medical education. High school students from 70 Northern Ontario communities participate in NOSM's week-long Health Sciences Summer Camps. The MD admissions process involves approximately 128 volunteers assessing written applications and over 100 volunteer interviewers. Thirty-six Indigenous communities host first year students and third-year students learn their core clinical medicine in 15 communities, throughout Northern Ontario. In general, learners and communities report net benefits from participation in NOSM programs. CONCLUSION: Community engagement makes a key contribution to the success of NOSM's socially accountable distributed medical education.

My Village Is Dying? Integrating Methods from the Inside Out.

The purpose of this paper is to confront the notion of "decline" at the village level by illustrating a more immersive approach to sociological and demographic research within rural and remote communities. The research uses case studies of three villages in Australia, Canada, and Sweden, all of which have been labeled as "declining villages," typified by population loss, an aging population, high rates of youth outmigration, and loss of businesses and services. This paper argues that focusing solely on quantitative indicators of demographic change provides a narrow view of rural village trajectories and ignores subtle processes of local adaptation that are hidden from quantitative data sets. Our research integrates quantitative data from the "outside" with qualitative data from the "inside," including visual ethnography, to develop a more balanced perspective on how villages have been changing and what change could mean locally. These objectives are accomplished by revisiting a Dirt Research methodology applicable to a broad range of research into rural and remote villages.

Le but de cet article est de confronter la notion de  "déclin" au niveau d'un village en illustrant une approche sociologique et démographique plus immersive dans le cadre de communautés rurales et éloignées. La recherche utilise les études de cas de trois villages en Australie, au Canada et en Suède, tout considérés comme des "villages en déclin," caractérisés par des pertes de population, une population vieillissante, et des taux élevés d'émigration des jeunes, ainsi que la perte d'entreprises et de services. Cet article prétend qu'une emphase sur des indicateurs seulement quantitatifs et des changements démographiques donne une vision réductrice des trajectoires des villages et ignore des processus subtils d'adaptation locale qui sont masqués par des données quantitatives. Notre recherche intègre des données quantitatives "externes" avec des données qualitatives "internes," incluant l'ethnographie visuelle, afin de développer une perspective plus équilibrée montrant comment ces villages ont changé et ce que le changement peut signifier localement. Ces objectifs sont réalisés en revisitant une méthodologie 'Dirt research' applicable à un éventail large de recherche sur les villages ruraux et éloignés.

Health care access for rural youth on equal terms? A mixed methods study protocol in northern Sweden.

BACKGROUND: The purpose of this paper is to propose a protocol for researching the impact of rural youth health service strategies on health care access. There has been no published comprehensive assessment of the effectiveness of youth health strategies in rural areas, and there is no clearly articulated model of how such assessments might be conducted. The protocol described here aims to gather information to; i) Assess rural youth access to health care according to their needs, ii) Identify and understand the strategies developed in rural areas to promote youth access to health care, and iii) Propose actions for further improvement. The protocol is described with particular reference to research being undertaken in the four northernmost counties of Sweden, which contain a widely dispersed and diverse youth population. METHODS: The protocol proposes qualitative and quantitative methodologies sequentially in four phases. First, to map youth access to health care according to their health care needs, including assessing horizontal equity (equal use of health care for equivalent health needs,) and vertical equity (people with greater health needs should receive more health care than those with lesser needs). Second, a multiple case study design investigates strategies developed across the region (youth clinics, internet applications, public health programs) to improve youth access to health care. Third, qualitative comparative analysis of the 24 rural municipalities in the region identifies the best combination of conditions leading to high youth access to health care. Fourth, a concept mapping study involving rural stakeholders, care providers and youth provides recommended actions to improve rural youth access to health care. DISCUSSION: The implementation of this research protocol will contribute to 1) generating knowledge that could contribute to strengthening rural youth access to health care, as well as to 2) advancing the application of mixed methods to explore access to health care.

Intranasal oxytocin treatment for social deficits and biomarkers of response in children with autism.

Autism spectrum disorder (ASD) is characterized by core social deficits. Prognosis is poor, in part, because existing medications target only associated ASD features. Emerging evidence suggests that the neuropeptide oxytocin (OXT) may be a blood-based biomarker of social functioning and a possible treatment for ASD. However, prior OXT treatment trials have produced equivocal results, perhaps because of variability in patients' underlying neuropeptide biology, but this hypothesis has not been tested. Using a double-blind, randomized, placebo-controlled, parallel design, we tested the efficacy and tolerability of 4-wk intranasal OXT treatment (24 International Units, twice daily) in 32 children with ASD, aged 6-12 y. When pretreatment neuropeptide measures were included in the statistical model, OXT compared with placebo treatment significantly enhanced social abilities in children with ASD [as measured by the trial's primary outcome measure, the Social Responsiveness Scale (SRS)]. Importantly, pretreatment blood OXT concentrations also predicted treatment response, such that individuals with the lowest pretreatment OXT concentrations showed the greatest social improvement. OXT was well tolerated, and its effects were specific to social functioning, with no observed decrease in repetitive behaviors or anxiety. Finally, as with many trials, some placebo-treated participants showed improvement on the SRS. This enhanced social functioning was mirrored by a posttreatment increase in their blood OXT concentrations, suggesting that increased endogenous OXT secretion may underlie this improvement. These findings indicate that OXT treatment enhances social abilities in children with ASD and that individuals with pretreatment OXT signaling deficits may stand to benefit the most from OXT treatment.

Oxytocin and Migraine Headache.

This article reviews material presented at the 2016 Scottsdale Headache Symposium. This presentation provided scientific results and rationale for the use of intranasal oxytocin for the treatment of migraine headache. Results from preclinical experiments are reviewed, including in vitro experiments demonstrating that trigeminal ganglia neurons possess oxytocin receptors and are inhibited by oxytocin. Furthermore, most of these same neurons contain CGRP, the release of which is inhibited by oxytocin. Results are also presented which demonstrate that nasal oxytocin inhibits responses of trigeminal nucleus caudalis neurons to noxious stimulation using either noxious facial shock or nitroglycerin infusion. These studies led to testing the analgesic effect of intranasal oxytocin in episodic migraineurs-studies which did not meet their primary endpoint of pain relief at 2 h, but which were highly informative and led to additional rat studies wherein inflammation was found to dramatically upregulate the number of oxytocin receptors available on trigeminal neurons. This importance of inflammation was supported by a series of in vivo rat behavioral studies, which demonstrated a clear craniofacial analgesic effect when a pre-existing inflammatory injury was present. The significance of inflammation was further solidified by a small single-dose clinical study, which showed analgesic efficacy that was substantially stronger in chronic migraine patients that had not taken an anti-inflammatory drug within 24 h of oxytocin dosing. A follow-on open label study examining effects of one month of intranasal oxytocin dosing did show a reduction in pain, but a more impressive decrease in the frequency of headaches in both chronic and high frequency episodic migraineurs. This study led to a multicountry double blind, placebo controlled study studying whether, over 2 months of dosing, "as needed" dosing of intranasal oxytocin by chronic and high frequency migraineurs would reduce the frequency of their headaches compared to a 1-month baseline period. This study failed to meet its primary endpoint, due to an extraordinarily high placebo rate in the country of most of the patients (Chile), but was also highly informative, showing strong results in other countries and strong post hoc indications of efficacy. The results provide a strong argument for further development of intranasal oxytocin for migraine prophylaxis.