Neuroticism is a significant predictor of adverse psychological outcomes in patients with cancer. Less is known about how this relationship manifests in those with noncancer illness at the end-of-life (EOL). The objective of this study was to examine the impact of neuroticism as a moderator of physical symptoms and development of depression in patients with amyotrophic lateral sclerosis (ALS), chronic obstructive pulmonary disease (COPD), end-stage renal disease (ESRD), and frailty in the last 6 months of life.

We met this objective using secondary data collected in the Dignity and Distress across End-of-Life Populations study. The data included N = 404 patients with ALS (N = 101), COPD (N = 100), ESRD (N = 101), and frailty (N = 102) in the estimated last 6 months of life, with a range of illness-related symptoms, assessed longitudinally at 2 time points. We examined neuroticism as a moderator of illness-related symptoms at Time 1 (∼6 months before death) and depression at Time 2 (∼3 months before death) using ordinary least squares regression.

Results revealed that neuroticism significantly moderated the relationship between the following symptoms and depression measured 3 months later: drowsiness, fatigue, shortness of breath, wellbeing (ALS); drowsiness, trouble sleeping, will to live, activity (COPD); constipation (ESRD); and weakness and will to live (frailty).

These findings suggest that neuroticism represents a vulnerability factor that either attenuates or amplifies the relationship of specific illness and depressive symptoms in these noncancer illness groups at the EOL. Identifying those high in neuroticism may provide insight into patient populations that require special care at the EOL.

Community health workers and promotoras (CHW/Ps) have a fundamental role in facilitating research with communities. However, no national standard training exists as part of the CHW/P job role. We developed and evaluated a culturally- and linguistically tailored online research best practices course for CHW/Ps to meet this gap.

After the research best practices course was developed, we advertised the opportunity to CHW/Ps nationwide to complete the training online in English or Spanish. Following course completion, CHW/Ps received an online survey to rate their skills in community-engaged research and their perceptions of the course using Likert scales of agreement. A qualitative content analysis was conducted on open-ended response data.

104 CHW/Ps completed the English or Spanish course (n = 52 for each language; mean age 42 years SD ± 12); 88% of individuals identified as female and 56% identified as Hispanic, Latino, or Spaniard. 96%–100% of respondents reported improvement in various skills. Nearly all CHW/Ps (97%) agreed the course was relevant to their work, and 96% felt the training was useful. Qualitative themes related to working more effectively as a result of training included enhanced skills, increased resources, and building bridges between communities and researchers.

The CHW/P research best practices course was rated as useful and relevant by CHW/Ps, particularly for communicating about research with community members. This course can be a professional development resource for CHW/Ps and could serve as the foundation for a national standardized training on their role related to research best practices.

Autism and epilepsy often occur together. Epilepsy and other associated conditions have a substantial impact on the well-being of autistic people and their families, reduce quality of life, and increase premature mortality. Despite this, there is a lack of studies investigating the care pathway of autistic children with co-occurring epilepsy in Europe.

We analyzed the care pathway for autistic children with associated epilepsy in Italy, Spain, and the United Kingdom from the perspective of caregivers (using a survey aimed at caregivers of autistic children 0–18 years old), the autistic community, and professionals, in order to identify major barriers preventing caregivers and autistic children from receiving timely screening and treatment of possible co-occurring epilepsy.

Across all three countries, an analysis of the current care pathway showed a lack of systematic screening of epilepsy in all autistic children, lack of treatment of co-occurring epilepsy, and inappropriate use of antiepileptic drugs. A major challenge is the lack of evidence-based harmonized guidelines for autism with co-occurring epilepsy in these countries.

Our findings show both heterogeneity and major gaps in the care pathway for autism with associated epilepsy and the great efforts that caregivers must make for timely screening, diagnosis, and adequate management of epilepsy in autistic children. We call for policy harmonization in Europe in order to improve the experiences and quality of life of autistic people and their families.

Evidence suggests inflammation may be a key mechanism by which psychosocial stress, including loneliness, predisposes to depression. Observational and clinical studies have suggested simvastatin, with its anti-inflammatory properties, may have a potential use in the treatment of depression. Previous experimental medicine trials investigating 7-day use of statins showed conflicting results, with simvastatin displaying a more positive effect on emotional processing compared with atorvastatin. It is possible that statins require longer administration in predisposed individuals before showing the expected positive effects on emotional processing.

Here, we aim to test the neuropsychological effects of 28-day simvastatin administration versus placebo, in healthy volunteers at risk for depression owing to loneliness.

This is a remote experimental medicine study. One hundred participants across the UK will be recruited and randomised to either 28-day 20 mg simvastatin or placebo in a double-blind fashion. Before and after administration, participants will complete an online testing session involving tasks of emotional processing and reward learning, processes related to vulnerability to depression. Working memory will also be assessed and waking salivary cortisol samples will be collected. The primary outcome will be accuracy in identifying emotions in a facial expression recognition task, comparing the two groups across time.

Obsessive–compulsive disorder (OCD) is a psychiatric condition leading to significant distress and poor quality of life. Successful treatment of OCD is restricted by the limited knowledge about its pathophysiology. This study aimed to investigate the pathophysiology of OCD using electroencephalographic (EEG) event-related potentials (ERPs), elicited from multiple tasks to characterise disorder-related differences in underlying brain activity across multiple neural processes.

ERP data were obtained from 25 OCD patients and 27 age- and sex-matched healthy controls (HCs) by recording EEG during flanker and go/nogo tasks. Error-related negativity (ERN) was elicited by the flanker task, while N200 and P300 were generated using the go/nogo task. Primary comparisons of the neural response amplitudes and the topographical distribution of neural activity were conducted using scalp field differences across all time points and electrodes.

Compared to HCs, the OCD group showed altered ERP distributions. Contrasting with the previous literature on ERN and N200 topographies in OCD where fronto-central negative voltages were reported, we detected positive voltages. Additionally, the P300 was found to be less negative in the frontal regions. None of these ERP findings were associated with OCD symptom severity.

These results indicate that individuals with OCD show altered frontal neural activity across multiple executive function-related processes, supporting the frontal dysfunction theory of OCD. Furthermore, due to the lack of association between altered ERPs and OCD symptom severity, they may be considered potential candidate endophenotypes for OCD.

reSET-O® is an FDA-authorized prescription digital therapeutic (PDT) for opioid use disorder (OUD) providing cognitive behavioral therapy as an adjunct to buprenorphine therapy. This analysis describes differences in inpatient hospitalization rates over a 2-year period between patients treated with the PDT and those who were not.

A real-world claims analysis using the HealthVerity Private Source 20 database compared inpatient hospitalization rates (including intensive care unit stays and rehospitalizations) in patients who filled a reSET-O prescription (“cases”) to patients not filling their prescription (“controls”). Index date was date of reSET-O initiation for cases, and prescription date for controls, from January 1, 2019 to June 30, 2020. Pre- and post-index incidence rates of HCRU were compared with the incidence rate ratio (IRR) using a repeated-measures negative binomial model, adjusted for age, sex, region, payer type, Charlson comorbidity index (CCI) score, and number of similar services in the 12 months pre-index with an offset for number of days in the 12-month post-index period. Adjusted differences in inpatient hospitalizations in cases vs. controls were evaluated at 3-month intervals beginning at 12 months pre-index through 12 months post-index, using a difference in differences (DID) approach.

In this analysis, 901 cases (median age 36 years, 62.4% female, 73.9% Medicaid recipients, 95% treated with buprenorphine in the post-index period) were compared with 978 controls (median age 38 years, 55.1% female, 65.4% Medicaid recipients, 95% treated with buprenorphine in the post-index period). Incidence rate ratios of inpatient stays trended lower in later pre-post comparison periods among cases (IRRs 0.80, 0.95, 0.87, and 0.75 at 3-, 6-, 9-, and 12 months pre-post, respectively), and trended higher in later pre-post periods in controls (IRRs 0.93, 0.83, 0.86, 0.88 at 3-, 6-, 9-, and 12-month intervals respectively). The DID for controls vs. cases during the 12-month post interval compared to the 12-month pre-index rates, represented a 44% lower incidence of inpatient hospitalizations vs. controls between the first and last quarters of observation.

This difference in difference analysis showed a lower 12-month pre-post incidence rate ratio of inpatient hospitalizations for patients using reSET-O vs. controls, and a 24-month change in quarterly inpatient hospitalizations in reSET-O patients that was almost half that of controls.

Pear Therapeutics (US), Inc.

Naloxone use has increased in recent years in response to the nation’s opioid crisis. Once only available to health care professionals, it is now obtainable by prescription for persons at risk for substance overdose and their families. Increasing its availability is seen by some as an “over-the-counter solution” to the opioid problem. However, while naloxone has been viewed as relatively safe, with a low side effect profile when appropriately dosed and monitored, it is not without safety concerns that may go unrecognized or misattributed to other causes.

Here we present a case study of a 41-year-old female who presented to our medication-assisted treatment (MAT) clinic complaining of sudden onset weight gain, shortness of breath, upper and lower extremity peripheral edema, tachycardia, insomnia, and nocturnal enuresis. These symptoms made it difficult for her to work at her housekeeping job, resulting in missed workdays. She had seen a primary care provider for her symptoms and been prescribed a rescue inhaler for her shortness of breath. This patient had previously been treated for opioid use disorder with buprenorphine/naloxone and experienced similar symptoms, which disappeared when she relapsed on opioids. However, symptoms reappeared upon resuming her prescribed treatment.

The patient was identified as experiencing side effects to naloxone, causing noncardiogenic edema. Her MAT medication was switched to buprenorphine. Within two weeks her heart rate had returned to normal, she had lost weight, and she no longer had nocturnal enuresis or needed the rescue inhaler. Her peripheral edema resolved so she was able to walk better and resume work. At the same time, buprenorphine continued to relieve her cravings.

There is a dearth of information related to naloxone-induced edema. Our patient had not received a formal evaluation of pulmonary edema, but her pulmonary and cardiac symptoms were consistent with that diagnosis. Although pulmonary edema is mentioned in the product literature, peripheral edema is not. A literature search indicates that the number of case studies on naloxone-induced pulmonary edema have increased since 2018, but only one other case of naloxone-induced peripheral edema was discovered.

Naloxone is used in a variety of settings by differing types of health care providers. As the number of persons treated with naloxone increases, there will likely be a corresponding increase in incidences of pulmonary and/or peripheral edema as side effects. Providers and patients who are not aware of these manifestations and their relationship to naloxone treatment may easily attribute presenting symptoms to cardiogenic or other causes, as this case illustrates. It is important for providers in all settings to consider new onset shortness of breath and edema within the context of the person’s whole health and to be aware of their implications for mental as well as physical health.

No Funding

Reward processing has been proposed to underpin the atypical social feature of autism spectrum disorder (ASD). However, previous neuroimaging studies have yielded inconsistent results regarding the specificity of atypicalities for social reward processing in ASD.

Utilising a large sample, we aimed to assess reward processing in response to reward type (social, monetary) and reward phase (anticipation, delivery) in ASD.

Functional magnetic resonance imaging during social and monetary reward anticipation and delivery was performed in 212 individuals with ASD (7.6–30.6 years of age) and 181 typically developing participants (7.6–30.8 years of age).

Across social and monetary reward anticipation, whole-brain analyses showed hypoactivation of the right ventral striatum in participants with ASD compared with typically developing participants. Further, region of interest analysis across both reward types yielded ASD-related hypoactivation in both the left and right ventral striatum. Across delivery of social and monetary reward, hyperactivation of the ventral striatum in individuals with ASD did not survive correction for multiple comparisons. Dimensional analyses of autism and attention-deficit hyperactivity disorder (ADHD) scores were not significant. In categorical analyses, post hoc comparisons showed that ASD effects were most pronounced in participants with ASD without co-occurring ADHD.

Our results do not support current theories linking atypical social interaction in ASD to specific alterations in social reward processing. Instead, they point towards a generalised hypoactivity of ventral striatum in ASD during anticipation of both social and monetary rewards. We suggest this indicates attenuated reward seeking in ASD independent of social content and that elevated ADHD symptoms may attenuate altered reward seeking in ASD.

Autism is a lifelong complex neurodevelopmental condition that affects brain development and behaviour with significant consequences for everyday life (WHO, 2018). Despite its personal, familial and societal impact, there is still a European-wide lack of harmonised guidelines about the support needed from early stages, the most sensitive time to gain positive future outcomes (Berajamo-Martin et al, 2019).

The objectives were: 1. To analyse autistic children care pathway and patient/carer journey in three European countries: Italy, Spain and U.K. 2. To propose policy recommendations on how to improve this pathway.

To identify major barriers and treatment gaps, we conducted a rapid literature review of the care pathway in Europe and a survey aimed at parents or carers of autistic children ages 0 to 18 living in the three countries. The survey gathered information on screening, diagnosis, accessibility and support received before, during and after diagnosis. Members of the working group met to discuss results and propose policy recommendations.

1. Current care pathway analysis showed the following treatment gaps: Long waiting time from first concerns until screening visit and confirmed diagnosis. Delayed or no access to intervention once diagnosis has been confirmed. Overall limited information about autism and how to access early detection services. Overall deficient support to families. 2. Please see Box 1 for our proposed policy recommendations.

Box 1. Policy recommendations

Our findings and recommendations will inform policy harmonisation in Europe to shorten long waiting times, diagnosis process and intervention, and therefore, improve autistic people and their families’ journey experience and quality of life.

No significant relationships.

Frailty is defined as a clinical syndrome that encompasses a combination of decreased physiological reserve and low resistance to stressors. There is an association between mental illness and frailty among elderly cohorts. Frailty is also associated with obesity and smoking. There are high rates of treatment resistant schizophrenia among patients in secure forensic services. Patients with schizophrenia have high rates of morbidity and early mortality.

The primary aim of this study was to examine the rates of frailty present in a complete cohort of forensic in-patients.

An assessment using Fried Frailty criteria was offered to all in-patients (n=95) in Ireland’s National Forensic Service, which included measures of walking speed, grip strength, low physical activity and exhaustion. Demographic details and details pertaining to diagnoses and medications were also gathered.

Of the 95 in-patients, 92 patients agreed to participate. The majority were male (89%). The most common diagnosis was schizophrenia (71.7%). Mean age was 44.7 years (SD 11.42), and 58.2% met criteria for obesity. Of the total group, 47 patients met criteria for ‘pre-frail’ and 10 met criteria for ‘frail’ using Fried criteria.

This is the first study examining frailty in a cohort of patients in secure forensic settings. We found high rates of patients meeting frailty criteria at very young ages. Rates of frailty in this group were comparable to those found amongst elders in community settings. We consider this demonstrates significant medical vulnerability in this patient group.

No significant relationships.