Impact of the iWHELD digital person-centered care program on quality of life, agitation and psychotropic medications in people with dementia living in nursing homes during the COVID-19 pandemic: A randomized controlled trial.

INTRODUCTION: iWHELD is a digital person-centered care program for people with dementia in nursing homes adapted for remote delivery during the COVID-19 pandemic. METHODS: A 16-week two-arm cluster-randomized controlled trial in 149 UK nursing homes compared iWHELD with treatment as usual (TAU). Primary outcome was the overall quality of life with secondary outcomes of agitation and psychotropic use. RESULTS: iWHELD conferred benefit to quality of life on the primary (F = 4.3, p = 0.04) and secondary measures of quality of life (F = 6.45, p = 0.01) and reduced psychotropic medication use (χ2  = 4.08, p = 0.04) with no worsening of agitation. Benefit was seen in participants who contracted COVID-19, those with agitation at baseline, and those taking psychotropic medications. DISCUSSION: iWHELD confers benefits to quality of life and key measures of well-being, can be delivered during the challenging conditions of a pandemic, and should be considered for use alongside any emerging pharmacological treatment for neuropsychiatric symptoms. HIGHLIGHTS: iWHELD is the only remote, digital delivery nursing home training programme for dementia care iWHELD improved quality of life in people with dementia and reduced antipsychotic use without worsening of agitation Residents who contracted Covid-19 during the study also experienced benefits from iWHELD iWHELD offers a valuable, pandemic-safe tool for improving dementia care.

Evaluating atezolizumab in patients with urinary tract squamous cell carcinoma (AURORA): study protocol for a single arm, open-label, multicentre, phase II clinical trial.

BACKGROUND: Bladder and urinary tract cancers account for approximately 21,000 new diagnoses and 5,000 deaths annually in the UK. Approximately 90% are transitional cell carcinomas where advanced disease is treated with platinum based chemotherapy and PD-1/PD-L1 directed immunotherapy. Urinary tract squamous cell carcinoma (UTSCC) accounts for about 5% of urinary tract cancers overall making this a rare disease. We have yet to establish definitive systemic treatment options for advanced UTSCC. Preliminary translational data, from UTSCC patient tumour samples, indicate high PD-L1 expression and tumour infiltrating lymphocytes in a proportion of cases. Both of these features are associated with differential gene expression consistent with a tumour/immune microenvironment predicted to be susceptible to immune checkpoint directed immunotherapy which we will evaluate in the AURORA trial. METHODS: AURORA is a single arm, open-label, multicentre,UK phase II clinical trial. 33 patients will be recruited from UK secondary care sites. Patients with UTSCC, suitable for treatment with palliative intent, will receive atezolizumab PD-L1 directed immunotherapy (IV infusion, 1680 mg, every 28 days) for one year if tolerated. Response assessment, by cross sectional imaging will occur every 12 weeks. AURORA uses a Simon's 2-stage optimal design with best overall objective response rate (ORR, by RECIST v1.1) at a minimum of 12 weeks from commencing treatment as the primary endpoint. Secondary endpoints will include overall survival, progression-free survival, duration of response, magnitude of response using waterfall plots of target lesion measurements, quality of life using the EORTC QLQ-C30 tool, safety and tolerability (CTCAE v5) and evaluation of potential biomarkers of treatment response including PD-L1 expression. Archival tumour samples and blood samples will be collected for translational analyses. DISCUSSION: If this trial shows atezolizumab to be safe and effective it may lead to a future late phase randomised controlled trial in UTSCC. Ultimately, we hope to provide a new option for treatment for such patients. TRIAL REGISTRATIONS: EudraCT Number: 2021-001995-32 (issued 8th September 2021); ISRCTN83474167 (registered 11 May 2022); NCT05038657 (issued 9th September 2021).

Counterintuitive race effects in legal and nonlegal contexts.

OBJECTIVE: Despite documented racial disparities in all facets of the criminal justice system, recent laboratory attempts to investigate racial bias in legal settings have produced null effects or racial-bias reversals. These counterintuitive findings may be an artifact of laboratory participants' attempts to appear unprejudiced in response to social norms that proscribe expressions of racial bias against Black individuals. Furthermore, given pervasive stereotypes linking Black people with crime and heightened attention to issues of racial injustice in the legal system, laboratory participants may be especially likely to attempt to appear unprejudiced in studies examining judgments of Black individuals in legal as opposed to nonlegal contexts. HYPOTHESES: We predicted that counterintuitive race effects (null and pro-Black effects) are more likely to occur in laboratory research examining race in legal than in nonlegal contexts. METHOD: We conducted a quantitative review of race effects in three leading social psychology and legal psychology journals over the last four decades (Personality and Social Psychology Bulletin [PSPB]; Law and Human Behavior [LHB]; Psychology, Public Policy, and Law [PPPL]). We then conducted two experiments in which students (N = 314; Experiment 1) and Mechanical Turk workers (N = 695; Experiment 2) read descriptions of White and Black targets in either legal or nonlegal contexts and rated each target along various characteristics (e.g., dangerous, trustworthy). RESULTS: Our analysis of the literature indicated that counterintuitive race effects were more frequent in studies examining race in legal compared with nonlegal contexts. Our experiments likewise revealed that pro-Black race effects were stronger in legal than in nonlegal contexts. CONCLUSIONS: Laboratory research on racial bias against Black people-especially in legal settings-may produce misleading conclusions about the effects of race on important real-world outcomes. Methodological innovations for studying racial bias are needed. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

The role of social desirability and establishing nonracist credentials on mock juror decisions about Black defendants.

OBJECTIVE: Recently, experimental work on racial bias in legal settings has diverged from real-world field data demonstrating racial disparities, instead often producing null or potential overcorrection effects favoring Black individuals over White individuals. We explored the role of social desirability in these counterintuitive effects and tested whether allowing participants to establish nonracist moral credentials increased their willingness to convict a Black defendant. HYPOTHESES: We predicted that establishing nonracist moral credentials would increase convictions of Black defendants-especially for participants likely to harbor racial bias and external motivation to control it. METHOD: In two experiments, we randomly assigned White mock jurors (Study 1: N = 1,018; Study 2: N = 1,253) to establish nonracist moral credentials by acquitting a Black defendant in an initial case, acquit a White defendant in the same case, or see no prior case. Next, they judged an ambiguous case against a Black (Studies 1 and 2) or White (Study 2) defendant. After choosing verdicts, they provided open-ended guesses of what the study was about. Participants completed measures of explicit prejudice, motivations to control prejudice, and political orientation. RESULTS: Most participants who were asked to judge at least one Black defendant guessed that the study was about racial bias and convicted Black defendants less often than did those who guessed the study was about something else. White participants who established nonracist credentials were significantly more likely to convict Black defendants compared with White participants who did not establish nonracist credentials. Subsequent analyses revealed that conservatives showed this predicted credentialing pattern, whereas liberals did not. Credentialed liberals' convictions of Black defendants remained low; instead, they convicted White defendants more than did noncredentialed liberals. CONCLUSIONS: Social desirability plays a clear role in whether White people acquit Black defendants in experiments, which does not align with persistent racial bias in the legal system. Research participants' concern about looking prejudiced might undermine the validity of experiments investigating racial bias in legal settings by artificially inflating pro-Black judgments. The opportunity to credential oneself as nonracist, however, might make conservatives more comfortable making anti-Black legal judgments-whereas credentialed liberals continue to judge Black individuals more favorably than White individuals in legal settings. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Extracting the truth through chemical analyses: Early life histories of Victorian-era dental patients in Aotearoa New Zealand.

OBJECTIVES: There are few bioarcheological analyses of life experiences in colonial period Aotearoa New Zealand, despite this being a time of major adaptation and social change. In our study, early life histories are constructed from multi-isotope and enamel peptide analysis of permanent first molars associated with Victorian era dental practices operating between AD 1881 and 1905 in Invercargill. Chemical analyses of the teeth provide insight into the childhood feeding practices, diet, and mobility of the people who had their teeth extracted. MATERIALS AND METHODS: Four permanent left mandibular first molars were analyzed from a cache of teeth discovered at the Leviathan Gift Depot site during excavations in 2019. The methods used were: (1) enamel peptide analysis to assess chromosomal sex; (2) bulk (δ13 Ccarbonate ) and incremental (δ13 Ccollagen and δ15 N) isotope analysis of dentin to assess childhood diet; and (3) strontium (87 Sr/86 Sr) and oxygen (δ18 O) isotope analysis of enamel to assess childhood residency. Two modern permanent first molars from known individuals were analyzed as controls. RESULTS: The archaeological teeth were from three chromosomal males and one female. The protein and whole diets were predominately based on C3 -plants and domestic animal products (meat and milk). A breastfeeding signal was only identified in one historic male. All individuals likely had childhood residences in Aotearoa. DISCUSSION: Unlike most bioarcheological studies that rely on the remains of the dead, the teeth analysed in this study were extracted from living people. We suggest that the dental patients were likely second or third generation colonists to Aotearoa, with fairly similar childhood diets. They were potentially lower-class individuals either living in, or passing through, the growing colonial center of Invercargill.

Evaluating the mechanisms of social cognition intervention in schizophrenia: A proof-of-concept trial.

BACKGROUND: Social cognition interventions have shown promise for improving social functioning in people with schizophrenia. However, it is unclear how changes in social cognition affect social functioning. This study evaluates the impact of a social cognition intervention (GRASP - GRoup trAining for Social skills in Psychosis) on social cognition and social functioning outcomes and explores how two mechanisms, affect and physiological arousal, may drive changes. METHOD: A two-arm single blind (assessor) randomized pilot trial comparing GRASP plus treatment-as-usual (TAU) with TAU alone in people with a diagnosis of schizophrenia. Participants were assessed with measures of social cognition, social functioning, and symptoms. All participants undertook a week-long mobile health assessment (experience sampling method) measuring social behavior and affect and used a wearable device recording autonomic activity. Assessments were performed at baseline and at week 10. RESULTS: Forty-eight participants were randomly allocated to the treatment or control condition. Individuals randomized to GRASP did not show improvements on experience sampled social behavior and social cognition measures compared to controls. However, participants in the GRASP group enjoyed social contact more and had lower levels of negative affect and higher levels of positive affect compared to controls. There was no evidence of autonomic changes (i.e., electrodermal activity) associated with social behavior resulting from the therapy. CONCLUSION: Social cognition interventions may be helpful in improving the quality of social contacts in people with schizophrenia by decreasing negative affect. Increase in social behavior may require longer periods to be evident. Future studies should consider how social cognition interventions may alter qualitative aspects associated with social behavior.

Effectiveness of spironolactone for women with acne vulgaris (SAFA) in England and Wales: pragmatic, multicentre, phase 3, double blind, randomised controlled trial.

OBJECTIVE: To assess the effectiveness of oral spironolactone for acne vulgaris in adult women. DESIGN: Pragmatic, multicentre, phase 3, double blind, randomised controlled trial. SETTING: Primary and secondary healthcare, and advertising in the community and on social media in England and Wales. PARTICIPANTS: Women (≥18 years) with facial acne for at least six months, judged to warrant oral antibiotics. INTERVENTIONS: Participants were randomly assigned (1:1) to either 50 mg/day spironolactone or matched placebo until week six, increasing to 100 mg/day spironolactone or placebo until week 24. Participants could continue using topical treatment. MAIN OUTCOME MEASURES: Primary outcome was Acne-Specific Quality of Life (Acne-QoL) symptom subscale score at week 12 (range 0-30, where higher scores reflect improved QoL). Secondary outcomes were Acne-QoL at week 24, participant self-assessed improvement; investigator's global assessment (IGA) for treatment success; and adverse reactions. RESULTS: From 5 June 2019 to 31 August 2021, 1267 women were assessed for eligibility, 410 were randomly assigned to the intervention (n=201) or control group (n=209) and 342 were included in the primary analysis (n=176 in the intervention group and n=166 in the control group). Baseline mean age was 29.2 years (standard deviation 7.2), 28 (7%) of 389 were from ethnicities other than white, with 46% mild, 40% moderate, and 13% severe acne. Mean Acne-QoL symptom scores at baseline were 13.2 (standard deviation 4.9) and at week 12 were 19.2 (6.1) for spironolactone and 12.9 (4.5) and 17.8 (5.6) for placebo (difference favouring spironolactone 1.27 (95% confidence interval 0.07 to 2.46), adjusted for baseline variables). Scores at week 24 were 21.2 (5.9) for spironolactone and 17.4 (5.8) for placebo (difference 3.45 (95% confidence interval 2.16 to 4.75), adjusted). More participants in the spironolactone group reported acne improvement than in the placebo group: no significant difference was reported at week 12 (72% v 68%, odds ratio 1.16 (95% confidence interval 0.70 to 1.91)) but significant difference was noted at week 24 (82% v 63%, 2.72 (1.50 to 4.93)). Treatment success (IGA classified) at week 12 was 31 (19%) of 168 given spironolactone and nine (6%) of 160 given placebo (5.18 (2.18 to 12.28)). Adverse reactions were slightly more common in the spironolactone group with more headaches reported (20% v 12%; p=0.02). No serious adverse reactions were reported. CONCLUSIONS: Spironolactone improved outcomes compared with placebo, with greater differences at week 24 than week 12. Spironolactone is a useful alternative to oral antibiotics for women with acne. TRIAL REGISTRATION: ISRCTN12892056.

Cost-effectiveness of Spironolactone for Adult Female Acne (SAFA): economic evaluation alongside a randomised controlled trial.

OBJECTIVE: This study aims to estimate the cost-effectiveness of oral spironolactone plus routine topical treatment compared with routine topical treatment alone for persistent acne in adult women from a British NHS perspective over 24 weeks. DESIGN: Economic evaluation undertaken alongside a pragmatic, parallel, double-blind, randomised trial. SETTING: Primary and secondary healthcare, community and social media advertising. PARTICIPANTS: Women ≥18 years with persistent facial acne judged to warrant oral antibiotic treatment. INTERVENTIONS: Participants were randomised 1:1 to 50 mg/day spironolactone (increasing to 100 mg/day after 6 weeks) or matched placebo until week 24. Participants in both groups could continue topical treatment. MAIN OUTCOME MEASURES: Cost-utility analysis assessed incremental cost per quality-adjusted life year (QALY) using the EQ-5D-5L. Cost-effectiveness analysis estimated incremental cost per unit change on the Acne-QoL symptom subscale. Adjusted analysis included randomisation stratification variables (centre, baseline severity (investigator's global assessment, IGA <3 vs ≥3)) and baseline variables (Acne-QoL symptom subscale score, resource use costs, EQ-5D score and use of topical treatments). RESULTS: Spironolactone did not appear cost-effective in the complete case analysis (n=126 spironolactone, n=109 control), compared with no active systemic treatment (adjusted incremental cost per QALY £67 191; unadjusted £34 770). Incremental cost per QALY was £27 879 (adjusted), just below the upper National Institute for Health and Care Excellence's threshold value of £30 000, where multiple imputation took account of missing data. Incremental cost per QALY for other sensitivity analyses varied around the base-case, highlighting the degree of uncertainty. The adjusted incremental cost per point change on the Acne-QoL symptom subscale for spironolactone compared with no active systemic treatment was £38.21 (complete case analysis). CONCLUSIONS: The results demonstrate a high level of uncertainty, particularly with respect to estimates of incremental QALYs. Compared with no active systemic treatment, spironolactone was estimated to be marginally cost-effective where multiple imputation was performed but was not cost-effective in complete case analysis. TRIAL REGISTRATION NUMBER: ISRCTN registry (ISRCTN12892056).

A randomised controlled trial of a digital intervention (Renewed) to support symptom management, wellbeing and quality of life in cancer survivors.

BACKGROUND: Many cancer survivors following primary treatment have prolonged poor quality of life. AIM: To determine the effectiveness of a bespoke digital intervention to support cancer survivors. DESIGN: Pragmatic parallel open randomised trial. SETTING: UK general practices. METHODS: People having finished primary treatment (<= 10 years previously) for colo-rectal, breast or prostate cancers, with European-Organization-for-Research-and-Treatment-of-Cancer QLQ-C30 score <85, were randomised by online software to: 1)detailed 'generic' digital NHS support ('LiveWell';n=906), 2) a bespoke complex digital intervention ('Renewed';n=903) addressing symptom management, physical activity, diet, weight loss, distress, or 3) 'Renewed-with-support' (n=903): 'Renewed' with additional brief email and telephone support. RESULTS: Mixed linear regression provided estimates of the differences between each intervention group and generic advice: at 6 months (primary time point: n's respectively 806;749;705) all groups improved, with no significant between-group differences for EORTC QLQ-C30, but global health improved more in both intervention groups. By 12 months there were: small improvements in EORTC QLQ-C30 for Renewed-with-support (versus generic advice: 1.42, 95% CIs 0.33-2.51); both groups improved global health (12 months: renewed: 3.06, 1.39-4.74; renewed-with-support: 2.78, 1.08-4.48), dyspnoea, constipation, and enablement, and lower NHS costs (generic advice £265: in comparison respectively £141 (153-128) and £77 (90-65) lower); and for Renewed-with-support improvement in several other symptom subscales. No harms were identified. CONCLUSION: Cancer survivors quality of life improved with detailed generic online support. Robustly developed bespoke digital support provides limited additional short term benefit, but additional longer term improvement in global health enablement and symptom management, with substantially lower NHS costs.

An Open Label, Adaptive, Phase 1 Trial of High-Dose Oral Nitazoxanide in Healthy Volunteers: An Antiviral Candidate for SARS-CoV-2.

Repurposing approved drugs may rapidly establish effective interventions during a public health crisis. This has yielded immunomodulatory treatments for severe coronavirus disease 2019 (COVID-19), but repurposed antivirals have not been successful to date because of redundancy of the target in vivo or suboptimal exposures at studied doses. Nitazoxanide is a US Food and Drug Administration (FDA) approved antiparasitic medicine, that physiologically-based pharmacokinetic (PBPK) modeling has indicated may provide antiviral concentrations across the dosing interval, when repurposed at higher than approved doses. Within the AGILE trial platform (NCT04746183) an open label, adaptive, phase I trial in healthy adult participants was undertaken with high-dose nitazoxanide. Participants received 1,500 mg nitazoxanide orally twice-daily with food for 7 days. Primary outcomes were safety, tolerability, optimum dose, and schedule. Intensive pharmacokinetic (PK) sampling was undertaken day 1 and 5 with minimum concentration (Cmin ) sampling on days 3 and 7. Fourteen healthy participants were enrolled between February 18 and May 11, 2021. All 14 doses were completed by 10 of 14 participants. Nitazoxanide was safe and with no significant adverse events. Moderate gastrointestinal disturbance (loose stools or diarrhea) occurred in 8 participants (57.1%), with urine and sclera discoloration in 12 (85.7%) and 9 (64.3%) participants, respectively, without clinically significant bilirubin elevation. This was self-limiting and resolved upon drug discontinuation. PBPK predictions were confirmed on day 1 but with underprediction at day 5. Median Cmin was above the in vitro target concentration on the first dose and maintained throughout. Nitazoxanide administered at 1,500 mg b.i.d. with food was safe with acceptable tolerability a phase Ib/IIa study is now being initiated in patients with COVID-19.

Using wearable technology to detect the autonomic signature of illness severity in schizophrenia.

INTRODUCTION: Research suggests that people with schizophrenia have autonomic dysfunctions. These have been linked to functioning problems, symptoms and considered a risk factor for illness chronicity. The aim of this study is to introduce a new Mobile Health (mHealth) method using wearable technology to assessing autonomic activity in people's everyday life. We aim to evaluate the new method acceptability and characterise the association between schizophrenia illness features and autonomic abnormalities. METHOD: Thirty participants with schizophrenia and 25 controls were asked to wear a mHealth device measuring autonomic activity and movements during their normal everyday life. Measures of device use acceptability were collected from all participants. Participants with schizophrenia were also assessed for symptoms and functioning levels. Measures of heart rate variability (HRV), electrodermal activity (EDA) and movement were collected by the device and groups were compared. Correlation between physiological measures, functioning, symptoms and medication levels were assessed in people with schizophrenia. RESULTS: The mHealth device method proved to be acceptable and produced reliable measures of autonomic activity and behaviour. Compared to controls, people with schizophrenia showed lower levels of HRV, movement and functioning. In people with schizophrenia illness severity, particularly positive symptoms, was associated with parasympathetic deregulation. CONCLUSIONS: Autonomic abnormalities can be detected using wearable technology from people's everyday life. These are in line with previous research and support the notion that autonomic deregulation are relevant illness features for mental and physical health in schizophrenia. This method may be developed as a monitoring system for well-being and relapse prevention.

The beat of social cognition: Exploring the role of heart rate variability as marker of mentalizing abilities.

There is a long-standing debate on the influence of physiological signals on social behavior. Recent studies suggested that heart rate variability (HRV) may be a marker of social cognitive processes. However, this evidence is preliminary and limited to laboratory studies. In this study, 25 participants were assessed with a social cognition battery and asked to wear a wearable device measuring HRV for 6 consecutive days. The results showed that reduced HRV correlated with higher hostility attribution bias. However, no relationship was found between HRV and other social cognitive measures including facial emotion recognition, theory of mind or emotional intelligence. These results suggest that HRV may be linked to specific social cognitive processes requiring online emotional processing, in particular those related to social threat. These findings are discussed in the context of the neurovisceral integration model.

Social cognition interventions for people with schizophrenia: a systematic review focussing on methodological quality and intervention modality.

BACKGROUND: People with a diagnosis of schizophrenia have significant social and functional difficulties. Social cognition was found to influences these outcomes and in recent years interventions targeting this domain were developed. This paper reviews the existing literature on social cognition interventions for people with a diagnosis of schizophrenia focussing on: i) comparing focussed (i.e. targeting only one social cognitive domain) and global interventions and ii) studies methodological quality. METHOD: Systematic search was conducted on PubMed and PsycInfo. Studies were included if they were randomised control trials, participants had a diagnosis of schizophrenia or schizoaffective disorder, and the intervention targeted at least one out of four social cognition domains (i.e. theory of mind, affect recognition, social perception and attribution bias). All papers were assessed for methodological quality. Information on the intervention, control condition, study methodology and the main findings from each study were extracted and critically summarised. RESULTS: Data from 32 studies fulfilled the inclusion criteria, considering a total of 1440 participants. Taking part in social cognition interventions produced significant improvements in theory of mind and affect recognition compared to both passive and active control conditions. Results were less clear for social perception and attributional bias. Focussed and global interventions had similar results on outcomes. Overall study methodological quality was modest. There was very limited evidence showing that social cognitive intervention result in functional outcome improvement. CONCLUSIONS: The evidence considered suggests that social cognition interventions may be a valuable approach for people with a diagnosis of schizophrenia. However, evidence quality is limited by measure heterogeneity, modest study methodology and short follow-up periods. The findings point to a number of recommendations for future research, including measurement standardisation, appropriately powered studies and investigation of the impact of social cognition improvements on functioning problems.