Physical activity (PA) interventions help people with advanced incurable diseases to manage symptoms and improve their quality of life. However, little is known about the extent to which PA is currently delivered in hospice care in England.

To determine the extent of and intervention features of PA service provision in hospice care in England alongside barriers and facilitators to their delivery.

An embedded mixed-methods design using (1) a nationwide online survey of 70 adult hospices in England and (2) focus groups and individual interviews with health professionals from 18 hospices. Analysis of the data involved applying descriptive statistics to the numeric items and thematic analysis to the open-ended questions. Quantitative and qualitative data were collected and analyzed separately.

The majority of responding hospices (n = 47/70, 67%) promoted PA in routine care. Sessions were most often delivered by a physiotherapist (n = 40/47, 85%) using a personalized approach (n = 41/47, 87%) and included resistance/thera bands, Tai Chi/Chi Qong, circuit exercises, and yoga. The following qualitative findings were revealed: (1) variation among hospices in their capacity to deliver PA, (2) a desire to embed a hospice culture of PA, and (3) a need for an organizational commitment to PA service provision.

While many hospices in England deliver PA, there is considerable variation in its delivery across sites. Funding and policy action may be needed to support hospices to initiate or scale up services and address inequity in access to high-quality interventions.

To investigate the clinical features, therapeutic efficacy and symptom time course of post-coronavirus disease 2019 parosmia.

A 22-item online questionnaire was distributed to AbScent research group and Facebook coronavirus disease 2019 anosmia group adult members to assess clinical features, interventions and their subjective efficacy for parosmia.

A total of 209 participants (86 per cent females) reported: smell loss on average 3 days after coronavirus symptoms, recovery 4 weeks later, and first parosmia symptoms 12 weeks post infection. Respondents reported 10 per cent body weight loss, and listed onion and garlic as significant parosmia triggers. Regarding quality of life, depression was the most cited item (54 per cent). Smell training was trialled by 74 per cent of participants, followed by nasal corticosteroid spray (49 per cent). Stellate ganglion block, trialled by 16 per cent of respondents, had the highest reported improvement (45 per cent), with 21 per cent reporting a sustained benefit – the highest rate amongst registered treatment options.

Post-coronavirus parosmia has a significant impact and remains challenging to treat. Stellate ganglion block appears to be successful relative to other reported treatments. Further research into the pathophysiology, efficacy and mechanism of stellate ganglion block effect is warranted.

Preclinical evidence has identified the trace amine-associated receptor 1 (TAAR1) as a novel regulator of metabolic control. Ulotaront is a TAAR1 and 5-HT1A agonist currently in Phase 3 clinical trials for the treatment of schizophrenia. Here we summarize preclinical results assessing the effects of ulotaront on weight and metabolic parameters.

Effects of ulotaront administration were evaluated on oral glucose tolerance (oGTT), gastric emptying, and in rodent models of weight gain (high-fat diet [HFD]-, corticosterone-, and olanzapine-induced).

Following 15-day oral administration of ulotaront, rats on HFD showed dose-dependent reduction in body weight, food intake, and liver triglyceride content compared to controls. In addition, a more rapid reversal of olanzapine-induced weight gain and food intake was observed in rats switched to ulotaront (vs. vehicle). Consistent with weight-lowering effects in rats, chronic ulotaront treatment normalized corticosterone-induced weight gain in mice. Assessment of oGTT showed a dose-dependent reduction of glucose excursion in response to acute ulotaront administration in naive and diabetic db/db mice. Ulotaront administration also delayed gastric emptying in mice—a likely mechanism driving reductions in glucose excursions during the oGTT. Whole-brain c-fos imaging of ulotaront-treated mice revealed increased neuronal activity in several brain regions associated with regulation of food intake and metabolic signals.

The data indicate that ulotaront not only lacks metabolic liabilities typically associated with antipsychotics but can reduce body weight and improve glucose tolerance in rodent models. The underlying mechanisms may include TAAR1-mediated peripheral effects on glucose homeostasis and/or direct modulation of homeostatic and hedonic neurocircuits regulating energy balance. The beneficial metabolic effects of ulotaront may suggest a substantially improved risk-benefit profile compared to established antipsychotics.

Sunovion Pharmaceuticals Inc. and Otsuka Pharmaceutical Development & Commercialization, Inc.

Ulotaront is a trace amine-associated receptor 1 (TAAR1) agonist with serotonin 5-HT1A agonist activity that has received FDA Breakthrough Therapy Designation for the treatment of schizophrenia. Here we summarize ongoing clinical research characterizing the efficacy and safety of ulotaront as a member of the novel trace amine-associated receptor 1 (TAAR1) agonist class.

Summarized are results from a double-blind, placebo-controlled study to evaluate the efficacy and safety of ulotaront (50 mg or 75 mg) in an acute exacerbation of schizophrenia, and a 6-month, open-label follow-up study. Also summarized are post-hoc analyses evaluating negative symptom efficacy, and key safety and adverse event (AE) outcomes.

In the short-term study, treatment with ulotaront was associated with significant (p<0.001) endpoint improvement in the PANSS total score (effect size [ES]: 0.45), the CGI-Severity score (ES: 0.52) and the Brief Negative Symptom Scale total score (ES: 0.48). The incidence of any AE was lower on ulotaront versus placebo (45.8% vs. 50.4%), and the number needed to harm (NNH) for individual AEs on ulotaront were all >40. Ulotaront was associated with lower risk for antipsychotic class-related AEs (extrapyramidal symptoms, akathisia, somnolence, nausea/vomiting, increased weight/metabolic labs, prolactinemia). The 6-month study demonstrated further improvement, with a completion rate (67%) that was higher than reported for current dopamine D2 antipsychotics.

The emerging profile of ulotaront is characterized by significant improvement in positive and negative symptoms of schizophrenia. The safety and tolerability profile of ulotaront is markedly different with respect to antipsychotic class-related AEs. The benefit-risk profile of ulotaront, as a member of a novel TAAR1 agonist class, is distinguished from antipsychotics by lack of AEs related to D2 and serotonin 5-HT2A receptor blockade.

Sunovion Pharmaceuticals, Inc., and Otsuka Pharmaceutical Development & Commercialization, Inc.

Trace amine-associated receptors (TAARs) are a family of G-protein-coupled receptors (GPCRs) first identified in 2001. TAAR1 has emerged as a promising therapeutic target due to its ability to modulate monoaminergic and glutamatergic neurotransmission. Ulotaront is a trace amine-associated receptor 1 (TAAR1) agonist with serotonin 5-HT1A agonist activity that has received FDA Breakthrough Therapy Designation for the treatment of schizophrenia. Here we provide a brief review of the discovery of ulotaront and preclinical research suggesting efficacy in schizophrenia, leading to the first clinical trial of ulotaront resulting in FDA Breakthrough Therapy Designation.

Ulotaront was discovered through a target-agnostic approach optimized to identify drug candidates that demonstrate an antipsychotic-like profile in vivo but lack D2 and 5-HT2A receptor antagonism. Ulotaront was further characterized by in vitro pharmacology, electrophysiology, behavioral, and imaging studies.

Ulotaront demonstrated an antipsychotic-like profile in a high-throughput, phenotypic behavior screening platform, as well as efficacy in preclinical models of schizophrenia, including phencyclidine (PCP)-induced hyperactivity, prepulse inhibition of acoustic startle, and subchronic PCP-induced deficits in social interaction. Although not fully elucidated, ulotaront’s mechanism of action appears to be mediated by agonism at trace amine-associated 1 (TAAR1) and 5-HT1A receptors. This was further corroborated with whole cell patch clamp recordings, demonstrating inhibition of dorsal raphe nucleus (DRN) and ventral tegmental area (VTA) neuronal firing via 5-HT1A and TAAR1 receptors. Furthermore, ulotaront attenuated the ketamine-induced increase in striatal dopamine synthesis capacity, suggesting that it may modulate presynaptic dopamine dysfunction which is hypothesized to contribute to the pathophysiology of schizophrenia.

Preclinical studies have identified ulotaront as a TAAR1 agonist with antipsychotic-like activity. Ulotaront’s unique receptor profile led to its designation as a member of the new “-taront” class of TAAR1 agonists, distinct in pharmacology from the D2/5-HT2A class of antipsychotics. A companion poster will summarize the efficacy and safety of ulotaront based on initial clinical trials in schizophrenia.

Sunovion Pharmaceuticals, Inc., and Otsuka Pharmaceutical Development & Commercialization, Inc.

We aimed to examine the attitudes of Pennsylvania rural residents toward data sharing in the setting of the COVID-19 pandemic. Specifically, we were interested in better understanding their willingness to provide personal information for contact tracing to public health staff investigating COVID-19 cases, as well as their concerns. We used a validated scale to describe the influence of distrust of healthcare organizations on their attitudes.

We mailed 4000 surveys to rural residents identified from the electronic medical record of a healthcare system in central Pennsylvania. Data were entered into a REDCap database and analyzed using descriptive summaries, and both binomial and multivariable logistic regression.

Binomial logistic regression showed that both distrust in healthcare organizations and political values influence respondents’ willingness to share information with contact tracers as well as their concerns about sharing personal data. When our multivariable model was applied, political values remained and were consistently associated with willingness to share and concerns about sharing their data.

This study is a first step in eliciting rural residents’ willingness to share personal data for contact tracing by public health officials. Understanding and addressing rural residents’ willingness to share personal data and their concerns about sharing those data will help public health officials identify effective strategies for managing COVID-19 and future pandemics in rural communities. By involving community members at the ground level, public health staff can ensure residents’ buy-in for the need to collect their personal data, thereby helping to mitigate the public health crises.