Treating Obsessive Compulsive Disorder in Adolescents and Adults with Down Syndrome: Results from a Scoping Rapid Review.

PURPOSE: Adolescents and adults with Down syndrome are noted to display symptoms and behaviors consistent with a diagnosis of Obsessive Compulsive Disorder. While evidenced-based interventions, including psychopharmacology and therapeutic interventions including exposure and response prevention, exist and effectively treat obsessive-compulsive symptoms in neurotypical populations, less is known about effective treatments for similar presentations in persons with Down syndrome. METHODS: A scoping rapid review was conducted in April 2023 to determine what treatments are being used to target obsessive-compulsive symptoms and related behaviors in adolescents and adults with Down syndrome, the quality of those treatments, and their alignment with current evidenced-based interventions. RESULTS: A total of eleven articles, all single case or case series, published between 1992 and 2017 were identified describing the treatment of 32 adolescents and adults with Down syndrome and obsessive-compulsive traits and behaviors including: hoarding, cleaning, gross motor compulsions, and food, hygiene, dressing, and checking rituals. Interventions used most often aligned with evidenced-based guidelines for treating obsessive compulsive disorder and included psychopharmacology, psychotherapy, and complementary and alternative medicine. CONCLUSIONS: While the outcomes of most interventions yielded partial or significant reduction in symptoms, poor research quality and limited generalizability noted across all studies make it difficult to inform guidelines for caring for this high-needs population. In the future, we believe it is necessary to perform more rigorous research focused on treating obsessive compulsive symptoms in individuals with Down syndrome with sufficient follow-up to fully assess treatment effectiveness.

Bathing Adaptations in the Homes of Older Adults (BATH-OUT-2): study protocol for a randomised controlled trial, economic evaluation and process evaluation.

BACKGROUND: The onset of disability in bathing is particularly important for older adults as it can be rapidly followed by disability in other daily activities; this may represent a judicious time point for intervention in order to improve health, well-being and associated quality of life. An important environmental and preventative intervention is housing adaptation, but there are often lengthy waiting times for statutory provision. In this randomised controlled trial (RCT), we aim to evaluate the effectiveness and cost-effectiveness of bathing adaptations compared to no adaptations and to explore the factors associated with routine and expedited implementation of bathing adaptations. METHODS: BATH-OUT-2 is a multicentre, two-arm, parallel-group RCT. Adults aged 60 and over who are referred to their local authority for an accessible level access shower will be randomised, using pairwise randomisation, 1:1, to receive either an expedited provision of an accessible shower via the local authority or a usual care control waiting list. Participants will be followed up for a maximum of 12 months and will receive up to four follow-ups in this duration. The primary outcome will be the participant's physical well-being, assessed by the Physical Component Summary score of the Short Form-36 (SF-36), 4 weeks after the intervention group receives the accessible shower. The secondary outcomes include the Mental Component Summary score of the SF-36, self-reported falls, health and social care resource use, health-related quality of life (EQ-5D-5L), social care-related quality of life (Adult Social Care Outcomes Toolkit (ASCOT)), fear of falling (Short Falls Efficacy Scale), independence in bathing (Barthel Index bathing question), independence in daily activities (Barthel Index) and perceived difficulty in bathing (0-100 scale). A mixed-methods process evaluation will comprise interviews with stakeholders and a survey of local authorities with social care responsibilities in England. DISCUSSION: The BATH-OUT-2 trial is designed so that the findings will inform future decisions regarding the provision of bathing adaptations for older adults. This trial has the potential to highlight, and then reduce, health inequalities associated with waiting times for bathing adaptations and to influence policies for older adults. TRIAL REGISTRATION: ISRCTN Registry ISRCTN48563324. Prospectively registered on 09/04/2021.

The Hidden Economic Consequences of Migraine to the UK Government: Burden-of-Disease Analysis Using a Fiscal Framework.

Background: Migraine is a highly prevalent and incapacitating neurological disorder associated with the highest global disability burden in people aged 15 to 49 years. Europe has the fourth-highest prevalence of migraine, after North America, South America, and Central America, and above Asia and Africa. Migraine leads to relatively modest direct healthcare expenditure but has substantial indirect costs due to reduced productivity. Methods: The economic burden of migraine was estimated in comparison with the general population of the United Kingdom (UK) using an analytical fiscal modeling framework applying the government cost perspective. Published measures of migraine's impact on labor participation were applied to rates of economic activity/inactivity of the general population. The model estimates lifetime changes to earnings from employment, direct and indirect taxes paid, and financial support requirements over the life course. Incremental differences between those affected and unaffected by migraine are reported as net fiscal consequences to public accounts. Fiscal costs are reported as the discounted average per capita over a 20-year time horizon and for the entire annual UK cohort with prevalent migraine. Results: People affected by migraine are more likely to be absent from work, unemployed, and disabled, and to retire early. A 44-year-old individual affected by migraine was associated with £19 823 in excess fiscal costs to the UK government, £1379 per year living with the condition, compared with someone not affected by the disease. Annually, migraine was estimated to represent £12.20 billion to the public economy, approximately £130.63 per migraine episode. The model predicted annual productivity losses in the health and social care workforce to be £2.05 billion and total annual productivity losses to be over £5.81 billion. Conclusions: This fiscal analysis monetizes the occupational consequences of migraine to the UK government, both in terms of lost tax revenue and transfer payments. The findings are substantial and useful to characterize disease severity and to inform the body of evidence considered by decision makers appraising the cost-effectiveness of health technologies.

Quantifying The Burden of Persistent Musculoskeletal Pain in Employees at Rolls-Royce in The United Kingdom: A Real-World Cross-Sectional Survey.

OBJECTIVE: We aimed to investigate the burden of persistent musculoskeletal (MSK) pain in Rolls-Royce UK employees. METHODS: Employees with ( n = 298) and without ( n = 329) persistent MSK pain completed a cross-sectional survey. Weighted regression analyses were conducted to compare sickness absence, work ability, workplace accommodations/adaptations, and emotional well-being between these cohorts, controlling for confounders. RESULTS: Persistent MSK pain (particularly back pain) had a significant impact on physical work ability and was associated with increased sickness absence due to pain. Many employees (56%) had not disclosed their condition to their managers. Of these, 30% felt uncomfortable doing so, and 19% of employees reported insufficient support at work for their pain. CONCLUSIONS: These findings highlight the importance of creating a workplace culture that encourages the disclosure of work-relevant pain, enabling organizations to consider improved, tailored support for employees.

The Utility of Monitoring Potassium in Transgender, Gender Diverse, and Nonbinary Individuals on Spironolactone.

Context: Current Endocrine Society guidelines recommend that transgender women taking spironolactone have their potassium levels checked every 3 months for the first year after initiating therapy and annually thereafter to monitor for hyperkalemia. Objective: The goal of this study was to assess the need for such frequent potassium monitoring and to investigate whether age plays a role in potassium abnormalities in transgender, gender diverse, and nonbinary (TGDNB) individuals taking spironolactone. Methods: Using EPIC-Clarity, a retrospective study of healthy, adult individuals with gender-identity disorder listed in their problem list and taking spironolactone was performed. We analyzed the incidence of hyperkalemia in this population. Data from June 2006 through November 2021 were obtained. Exclusion criteria included hypertension, renal failure, diabetes mellitus, heart failure, and medications that affect the renin-angiotensin-aldosterone system. Results: 318 healthy TGDNB individuals met our inclusion criteria. We identified 8/318 (2.5%) individuals with hyperkalemia on spironolactone. There was a significant difference in incidence of hyperkalemia events in those >45 years old and those ≤45 years old (8.9% vs 1.5%, P = .016). Conclusion: Our data suggest the incidence of hyperkalemia in our TGDNB population is low, particularly in those ≤45 years old; however, this risk increases with age. These findings suggest practice guidelines may need to be adjusted to minimize unnecessary testing in the population ≤45 years old who are not plagued by comorbidities that affect potassium handling.

Acute Worsening of Atypical Parkinson's Syndrome After Receiving Second Dose of Moderna COVID-19 Vaccine.

INTRODUCTION: Atypical Parkinson's syndromes are a rare set of neurodegenerative conditions in which a patient experiences the typical symptoms of Parkinson's disease, in addition to various other unrelated issues. CASE PRESENTATION: We present the case of a 71-year-old White man with a 1-year history of weakness and upper extremity tremors that, per patient report, rapidly worsened after receiving the second dose of the Moderna COVID-19 vaccine. His symptoms were consistent with an asymmetric atypical Parkinson's disease, with electromyogram results indicating chronic motor neuron involvement. DISCUSSION: There have been multiple reports of deterioration in patients with Parkinson's disease and atypical Parkinson's syndromes in response to contracting COVID-19. However, there are few, if any, case reports that describe an acute change in Parkinson-related symptoms in association with the COVID-19 vaccines. CONCLUSIONS: As the pandemic continues, we must continue to remain vigilant as we learn more about the long-lasting effects of the virus and vaccines.

Risk of unplanned healthcare utilization in postpartum period for patients with hypertensive disorders of pregnancy.

OBJECTIVE: To determine which factors are associated with unplanned postpartum healthcare utilization, including hospital readmission and unplanned outpatient and emergency room visits, in patients with hypertensive disorders of pregnancy (HDP). STUDY DESIGN: This was a case control study of patients with HDP delivering at a single academic institution from 2014 through 2018. The diagnosis of HDP included chronic hypertension, gestational hypertension, preeclampsia and superimposed preeclampsia. Using bivariate and multivariate analysis, demographic and clinical characteristics were compared between patients who had unplanned healthcare utilization, defined as readmission to the hospital, emergency room visit or unplanned outpatient encounter in the first 6-weeks postpartum, and those patients who did not. RESULTS: Of the 1427 patients with HDP included in this analysis, 174 (12.2%) had unplanned postpartum healthcare utilization. Maternal non-Hispanic Black race and ethnicity and presence of mild blood pressures on the day of discharge after delivery were associated with higher odds of unplanned healthcare utilization (aOR 1.67, 95% CI 1.08 - 2.56 and aOR 1.59, 95% CI 1.12 - 2.27, respectively). In contrast, presence of chronic hypertension was associated with lower odds of unplanned postpartum healthcare utilization (aOR 0.47, 95% CI 0.28 - 0.79) CONCLUSION: Among postpartum patients with HDP, non-Hispanic Black race and ethnicity and discharge home with mild range blood pressures were associated with higher odds of unplanned healthcare utilization in the first 6 weeks postpartum, while chronic hypertension was associated with lower odds.

Quantifying the Employer Burden of Persistent Musculoskeletal Pain at a Large Employer in the United Kingdom: A Non-interventional, Retrospective Study of Rolls-Royce Employee Data.

OBJECTIVE: To quantify the burden of work-relevant persistent musculoskeletal (MSK) pain to a large UK employer. METHODS: A retrospective, longitudinal, analytical cohort study using linked Rolls-Royce data systems. Cases were employees with a MSK-related referral to occupational health; controls were age-, sex-, and job role-matched employees without such a referral. Outcomes were compared during 12 months' follow-up. RESULTS: Overall, 2382 matched case-control pairs were identified (mean age: 46 y; 82% male). Cases took 39,200 MSK-related sickness absence days in total (equating to £50 million in sickness absence costs). Cases took significantly more all-cause sickness absence days than controls (82,341 [£106 million] versus 19,628 [£26 million]; P < 0.0001). CONCLUSIONS: Despite access to extensive occupational health services, the burden of work-relevant persistent MSK pain remains high in Rolls-Royce. There is a clear need to better understand how to effectively reduce this burden.

Optogenetic Inhibition of Nav1.8 Expressing Corneal Afferents Reduces Persistent Dry Eye Pain.

Purpose: The aim of the present study was to investigate the contribution of Nav1.8 expressing corneal afferent neurons to the presence of ongoing pain in lacrimal gland excision (LGE)-induced dry eye. Methods: The proton pump archaerhodopsin-3/eGFP (ArchT/eGFP) was conditionally expressed in corneal afferents using Nav1.8-cre mice. Dry eye was produced by unilateral LGE. Real time place preference was assessed using a three-chamber apparatus. A neutral, unlit center chamber was flanked by one illuminated with a control light and one illuminated with an ArchT activating light. For real-time preference, animals were placed in the neutral chamber and tracked over five 10-minute sessions, with the lights turned on during the second and fourth sessions. In other studies, movement was tracked over three 10-minute sessions (the lights turned on only during the second session), with animals tested once per day over the course of 4 days. A local anesthetic was used to examine the role of ongoing corneal afferent activity in producing place preference. Results: The corneal afferent nerves and trigeminal ganglion cell bodies showed a robust eGFP signal in Nav1.8-cre;ArchT/eGFP mice. After LGE, Nav1.8-cre;ArchT/eGFP mice demonstrated a preference for the ArchT activating light paired chamber. Preference was prevented with pre-application to the cornea of a local anesthetic. Nav1.8-cre;ArchT/eGFP mice with sham surgery and LGE wild-type control mice did not develop preference. Conclusions: Results indicate LGE-induced persistent, ongoing pain, driven by Nav1.8 expressing corneal afferents. Inhibition of these neurons represents a potential strategy for treating ongoing dry eye-induced pain.

Prevalence of home parenteral nutrition in children.

BACKGROUND: Use of HPN in paediatrics in the UK has increased rapidly over the last 20 years but the prevalence of HPN has been challenging to define. Clinicians in the UK have noted an evolving complexity of cases and perceive improved outcomes and increased acceptability of long-term PN. These factors combined have the potential to increase the burden on existing paediatric gastroenterology services in the UK. METHODS: A national database was interrogated to define the prevalence of HPN in children in the UK and to explore outcomes for patients receiving HPN. RESULTS: Since 2015, 525 children were notified to the database; of these patients, mortality was <5% and intestinal transplant occurred in 1%. In 2019, 389 children received HPN in the UK; this is nearly double the number last reported in 2012 and is a prevalence of 30 per million children. Short bowel syndrome is the largest category of these patients. However, a poorly defined group including those with multisystem disease has increased 10 fold since 2012 and is now the second largest category. CONCLUSIONS: Long term HPN in childhood is safe and associated with good survival and low risk of the need for intestinal transplantation.

Maternal Outcomes of Ongoing Pregnancies Complicated by Fetal Life-Limiting Conditions.

OBJECTIVE: This study aimed to examine maternal outcomes of ongoing pregnancies complicated by fetal life-limiting conditions. STUDY DESIGN: This was a retrospective matched cohort study of women with a diagnosis of fetal life-limiting condition between 2010 and 2018 in a single academic center. Cases were matched to controls (women who had normal fetal anatomic survey) according to year of delivery, body mass index, and parity in a 1:4 ratio. Bivariable and multivariable analyses were performed to compare the prevalence of the primary composite outcome, which included any one of the following: preeclampsia, gestational diabetes, cesarean delivery, third and fourth degree laceration, postpartum hemorrhage, blood transfusion, endometritis or wound infection, maternal intensive care unit admission, hysterectomy and maternal death, between cases and controls. RESULTS: During the study period, we found 101 cases that met inclusion criteria, matched to 404 controls. The rate of the composite maternal outcome did not differ between the two groups (39.6 vs. 38.9%, p = 0.948). For individual outcomes, women with diagnosis of fetal life-limiting condition had higher rates of blood transfusion (2.0 vs. 0%, p = 0.005) and longer length of the first stage of labor (median of 12 [6.8-22.0] hours vs. 6.6 [3.9-11.0] hours; p < 0.001). In a multivariable analysis, first stage of labor continued to be longer by an average of 6.48 hours among women with a diagnosis of fetal life-limiting condition compared with controls. CONCLUSION: After controlling for confounding factors, except a longer first stage of labor, women diagnosed with fetal life-limiting conditions who continued the pregnancy did not have a higher rate of adverse maternal outcomes. KEY POINTS: · The rates of ongoing pregnancies with fetal life-limiting conditions are increasing.. · Women with ongoing pregnancies with fetal life-limiting conditions had longer first stage of labor.. · The rest of the adverse maternal outcomes were not increased in this obstetric population..

An investigation of the effects of walking frame height and width on walking stability.

BACKGROUND: Walking aids are designed for structural support during walking, however, surprisingly self-reported use of a walking aid ("Yes, I use one.") has been identified as a risk factor for falling. Adjustment and design of walking aids may affect their usefulness in facilitating a stable walking pattern. We previously identified that increased body weight transfer onto a walking frame ('device loading') is associated with increased user stability. RESEARCH QUESTION: We asked: "Could adjustment of walking frame height to a lower height than clinically recommended serve as a mechanism to facilitate device loading and thereby increase stability? And: "Do ultra-narrow frames have an adverse effect on stability as compared to standard-width frames? METHODS: Ten older adults that were users of front-wheeled walking frames walked with walking frames of 1) 'standard width, standard height', 2)'standard width, low height', 3)'narrow width, standard height'. Smart Walker technology was used to record forces acting on the walking frame and inside the user's shoes, and cameras recorded relative position of the user's feet in relation to the frame's feet. Stability of the user-frame system and device loading (percent body weight transferred onto the frame) were calculated. A general linear mixed effects model was used for statistical analysis. RESULTS: A lower height setting did not increase device loading and stability, therefore adjusting the height to a lower setting proved to be an unsuccessful mechanism to increase stability. However, device loading was positively correlated with stability for all frame conditions (p < 0.05). Finally, stability was reduced when walking with the ultra-narrow, as compared to standard-width, frame (p = 0.002). SIGNIFICANCE: To increase stability in fall-prone users, active encouragement to transfer body weight onto the walking frame is needed. Considering the adverse effects of ultra-narrow frames on stability, such frames should be prescribed and used with caution.

Emotional Wellbeing in Parents of Children on Home Parenteral Nutrition.

OBJECTIVES: Caring for a child on home parenteral nutrition (HPN) is stressful, and its emotional impact not fully appreciated. This study explored the emotional wellbeing and coping styles of parents and children on HPN. METHODS: Questionnaire data were collected for parents of children (0-18 years) on HPN. Children 8 years and older completed the revised children's anxiety and depression scale. Parents completed the Hospital Anxiety and Depression Scale, Paediatric Inventory for Parents (PIP) and brief COPE. RESULTS: A total of 14 children were included, 20 parents (13 females) and 4 children completed the survey. Parents had mean PIP difficulty and frequency score of 117.9 and 124, respectively, higher compared to parents of children with other chronic illness. PIP scores were significantly higher where children were also enterally tube fed (P < 0.05). Thirty-five per cent parents scored above clinical threshold on anxiety subscale of Hospital Anxiety and Depression Scale and 30% in borderline range. On depression subscale 15% scored above clinical threshold range and 15% in borderline range. Mean anxiety and depression scores in parents of children with short bowel syndrome (11.8, 7.8) were significantly higher than those with neuromuscular disease (5.8, 1.6) P < 0.05. Coping styles differed according to health condition and whether child was enterally fed. CONCLUSIONS: There is a significant emotional impact of caring for a child on HPN, assessment and treatment of anxiety, depression, and stress should be a routine part of care. Individual needs of the child and parent need to be taken into account in providing the most appropriate psychological support.

Pelvic Organ Prolapse: A Review of In Vitro Testing of Pelvic Support Mechanisms.

Background: Pelvic organ prolapse (POP) affects a significant portion of the female population, impacting quality of life and often requiring intervention. The exact cause of prolapse is unknown. Methods: We review some of the current research that focuses on defining the elements involved in POP, with a focus on in vitro testing. Results: Treatment for POP, ranging from physical therapy or pessary use to more invasive surgery, has varying success rates. This variation is, in part, because the pathophysiology of pelvic floor support-and thus dysfunction-is incompletely understood, particularly regarding the structural components and biomechanical properties of tissue. However, researchers are working to identify and quantify the structural and functional dysfunction that may lead to the development of this condition. Conclusion: Given the limited understanding of prolapse development, more research is needed to quantify the microstructure of the pelvic organs and pelvic support structures, with and without prolapse. Identifying biomechanical properties in multiaxial configurations will improve our understanding of pelvic tissue support, as well as our ability to establish predictive models and improve clinical treatment strategies.

Causal Pathways Between Severe Mental Illness and Behaviors Related to HIV: Patient Perspectives.

The purpose of this study was to identify causal pathways between HIV infection and severe mental illness. Data were collected through open-ended, semi-structured interviews. An integrated approach to the analysis, using inductive and deductive coding, was used to identify patterns among respondents. Standardized instruments were used to characterize the sample in terms of risk behaviors, physical and mental functioning and depression. Twenty-six men and women with a diagnosis of HIV and unipolar depression (n = 11) or schizophrenia/schizoaffective versus bipolar disorder (n = 15) participated. For persons with unipolar depression, the HIV diagnosis often preceded depressive symptoms. For persons with schizophrenia/schizoaffective versus bipolar disorder, mania and psychosis symptoms often preceded HIV. Substance use, incarceration and adverse childhood experiences were common across diagnoses. Attention to the directionality of effects between mental illness and HIV has important implications for anticipatory guidance for infectious disease specialists, primary care providers and public health practitioners as well as policymakers.

Progesterone Application to the Rat Forehead Produces Corneal Antinociception.

Purpose: Ocular pain and discomfort are the most defining symptoms of dry eye disease. We determined the ability of topical progesterone to affect corneal sensitivity and brainstem processing of nociceptive inputs. Methods: Progesterone or vehicle gel was applied to the shaved forehead in male Sprague Dawley rats. As a site control, gel also was applied to the cheek on the side contralateral to corneal stimulation. Corneal mechanical thresholds were determined using the Cochet-Bonnet esthesiometer in intact and lacrimal gland excision-induced dry eye animals. Eye wipe behaviors in response to hypertonic saline and capsaicin were examined, and corneal mustard oil-induced c-Fos immunohistochemistry was quantified in the brainstem spinal trigeminal nucleus. Results: Progesterone gel application to the forehead, but not the contralateral cheek, increased corneal mechanical thresholds in intact and lacrimal gland excision animals beginning <30 minutes after treatment. Subcutaneous injection of the local anesthetic bupivacaine into the forehead region before application of progesterone prevented the increase in corneal mechanical thresholds. Furthermore, progesterone decreased capsaicin-evoked eye wipe behavior in intact animals and hypertonic saline evoked eye wipe behavior in dry eye animals. The number of Fos-positive neurons located in the caudal region of the spinal trigeminal nucleus after corneal mustard oil application was reduced in progesterone-treated animals. Conclusions: Results from this study indicate that progesterone, when applied to the forehead, produces analgesia as indicated by increased corneal mechanical thresholds and decreased nociceptive responses to hypertonic saline and capsaicin.

Learning from the transfer of a fellowship programme to support primary care workforce needs in the UK: a qualitative study.

OBJECTIVES: Service redesign, including workforce development, is being championed by UK health service policy. It is allowing new opportunities to enhance the roles of staff and encourage multiprofessional portfolio working. New models of working are emerging, but there has been little research into how innovative programmes are transferred to and taken up by different areas. This study investigates the transferability of a 1-year post-Certification of Completion of Training fellowship in urgent and acute care from a pilot in the West Midlands region of England to London and the South East. DESIGN: A qualitative study using semistructured interviews supplemented by observational data of fellows' clinical and academic activities. Data were analysed using a thematic framework approach. SETTING AND PARTICIPANTS: Two cohorts of fellows (15 in total) along with key stakeholders, mentors, tutors and host organisations in London and the South East (LaSE). Fellows had placements in primary and secondary care settings (general practice, emergency department, ambulatory care, urgent care and rapid response teams), together with academic training. RESULTS: Seventy-six interviews were completed with 50 participants, with observations in eight clinical placements and two academic sessions. The overall structure of the West Midlands programme was retained and the core learning outcomes adopted in LaSE. Three fundamental adaptations were evident: broadening the programme to include multiprofessional fellows, changes to the funding model and the impact that had on clinical placements. These were felt to be key to its adoption and longer-term sustainability. CONCLUSION: The evaluation demonstrates a model of training that is adaptable and transferable between National Health Service regions, taking account of changing national and regional circumstances, and has the potential to be rolled out widely.

Cligosiban, A Novel Brain-Penetrant, Selective Oxytocin Receptor Antagonist, Inhibits Ejaculatory Physiology in Rodents.

INTRODUCTION: Few treatments are available for men with premature ejaculation (PE); oxytocin (OT) receptor antagonism in the central nervous system (CNS) is a potential new approach. AIM: To determine if cligosiban selectively inhibits human OT receptors, penetrates the CNS, shows pharmacology in the CNS, and effects ejaculatory physiology in pre-clinical systems. METHODS: Experiments complied with United Kingdom legislation and were subject to local ethical review. In vitro potency and selectivity of cligosiban was assessed using recombinant and native OT receptor systems including both neuronal and non-neuronal cell types. Selectivity was determined over neighboring V1A, V1B, and V2 vasopressin receptors using a combination of recombinant and native vasopressin receptor assay systems. To determine an effect on central OT receptors and on ejaculation, cligosiban was evaluated in 2 anesthetized rat models-the electromyography model of ejaculatory physiology and a model of OT-mediated CNS neuronal firing. The CNS penetration of cligosiban was also determined by measuring cerebrospinal fluid and plasma drug concentrations following an intravenous (IV) infusion in rats. MAIN OUTCOME MEASURE: These were functional measures of pharmacology in vitro, in cell lines and tissues, and in vivo in rats. RESULTS: Cligosiban is a potent OT receptor antagonist, with a base dissociation constant of 5.7 nmol/L against native human uterine smooth muscle cell OT receptors. Cligosiban displays similar antagonistic potency against human recombinant and rat native OT receptors, including neuronal OT receptors. Cligosiban demonstrates >100-fold selectivity over human V1A, V1B, and V2 vasopressin receptors. In the electromyography model, cligosiban (0.9 mg/kg, IV bolus) reduced the bulbospongiosum burst pattern and contraction amplitude associated with ejaculation. In the anesthetized CNS neuronal firing model, the same dosing regimen of cligosiban (0.9 mg/kg IV bolus) modulated the OT-mediated response in the nucleus tractus solitarius. After systemic dosing to rats, cligosiban showed good CNS penetration. CLINICAL IMPLICATIONS: As the first highly selective and centrally penetrant OT receptor antagonist, cligosiban represents a promising compound to test the clinical hypothesis that antagonism of central OT receptors may be of therapeutic benefit in the treatment of PE. STRENGTH & LIMITATIONS: The pharmacology and selectivity of cligosiban is determined using functional assays in recombinant cell lines, native cell lines, and tissue. Functional outcomes in in vivo systems are linked to CNS measures of pharmacology. The translation of the animal models of ejaculation to PE in man is unproven. CONCLUSION: Cligosiban, a potent, selective OT receptor antagonist, demonstrated CNS penetration and pharmacology and, using the same dosing regimen, inhibited apomorphine-induced ejaculation in rats. Cligosiban is a promising compound to test the clinical hypothesis that antagonism of central OT receptors may be of therapeutic benefit in the treatment of PE. Wayman C, Russell R, Tang K, et al. Cligosiban, A Novel Brain Penetrant Selective Oxytocin Receptor Antagonist, Inhibits Ejaculatory Physiology in Rodents. J Sex Med 2018;15:1698-1706.

Influence of Community-Level Cultural Beliefs about Autism on Families' and Professionals' Care for Children.

This qualitative study aimed to understand how community-level cultural beliefs affect families' and professionals' care for children with autism and developmental delays in immigrant communities, as a first step towards promoting early identification and access to early intervention services. The study was part of the larger New York City (NYC) Korean Community Autism Project, which was designed to identify strategies to increase awareness of autism and reduce delays in treatment seeking within the NYC Korean-American community. Our study elicited early childcare workers' and church leaders' beliefs about autism and developmental disorders and, in particular, early intervention. We also elicited responses to newly developed outreach materials targeting this community. An inductive approach was used to identify concepts and categories associated with autism. Our study confirmed that discomfort, stigma and discrimination are the prevailing community attitudes toward autism and developmental disorders in the Korean-American community. Families' and professionals' understanding of autism and their care for children are affected by these community beliefs. Approaching immigrant communities with general information about child development and education rather than directly talking about autism and developmental disorders is likely to engage more families and professionals in need for diagnostic evaluation and early intervention for autism.

The Development of a Design and Construction Process Protocol to Support the Home Modification Process Delivered by Occupational Therapists.

Modifying the home environments of older people as they age in place is a well-established health and social care intervention. Using design and construction methods to redress any imbalance caused by the ageing process or disability within the home environment, occupational therapists are seen as the experts in this field of practice. However, the process used by occupational therapists when modifying home environments has been criticised for being disorganised and not founded on theoretical principles and concepts underpinning the profession. To address this issue, research was conducted to develop a design and construction process protocol specifically for home modifications. A three-stage approach was taken for the analysis of qualitative data generated from an online survey, completed by 135 occupational therapists in the UK. Using both the existing occupational therapy intervention process model and the design and construction process protocol as the theoretical frameworks, a 4-phase, 9-subphase design and construction process protocol for home modifications was developed. Overall, the study is innovative in developing the first process protocol for home modifications, potentially providing occupational therapists with a systematic and effective approach to the design and delivery of home modification services for older and disabled people.