The Oxford Agoraphobic Avoidance Scale.

BACKGROUND: Agoraphobic avoidance of everyday situations is a common feature in many mental health disorders. Avoidance can be due to a variety of fears, including concerns about negative social evaluation, panicking, and harm from others. The result is inactivity and isolation. Behavioural avoidance tasks (BATs) provide an objective assessment of avoidance and in situ anxiety but are challenging to administer and lack standardisation. Our aim was to draw on the principles of BATs to develop a self-report measure of agoraphobia symptoms. METHOD: The scale was developed with 194 patients with agoraphobia in the context of psychosis, 427 individuals in the general population with high levels of agoraphobia, and 1094 individuals with low levels of agoraphobia. Factor analysis, item response theory, and receiver operating characteristic analyses were used. Validity was assessed against a BAT, actigraphy data, and an existing agoraphobia measure. Test-retest reliability was assessed with 264 participants. RESULTS: An eight-item questionnaire with avoidance and distress response scales was developed. The avoidance and distress scales each had an excellent model fit and reliably assessed agoraphobic symptoms across the severity spectrum. All items were highly discriminative (avoidance: a = 1.24-5.43; distress: a = 1.60-5.48), indicating that small increases in agoraphobic symptoms led to a high probability of item endorsement. The scale demonstrated good internal reliability, test-retest reliability, and validity. CONCLUSIONS: The Oxford Agoraphobic Avoidance Scale has excellent psychometric properties. Clinical cut-offs and score ranges are provided. This precise assessment tool may help focus attention on the clinically important problem of agoraphobic avoidance.

Coronavirus conspiracy beliefs, mistrust, and compliance with government guidelines in England.

BACKGROUND: An invisible threat has visibly altered the world. Governments and key institutions have had to implement decisive responses to the danger posed by the coronavirus pandemic. Imposed change will increase the likelihood that alternative explanations take hold. In a proportion of the general population there may be strong scepticism, fear of being misled, and false conspiracy theories. Our objectives were to estimate the prevalence of conspiracy thinking about the pandemic and test associations with reduced adherence to government guidelines. METHODS: A non-probability online survey with 2501 adults in England, quota sampled to match the population for age, gender, income, and region. RESULTS: Approximately 50% of this population showed little evidence of conspiracy thinking, 25% showed a degree of endorsement, 15% showed a consistent pattern of endorsement, and 10% had very high levels of endorsement. Higher levels of coronavirus conspiracy thinking were associated with less adherence to all government guidelines and less willingness to take diagnostic or antibody tests or to be vaccinated. Such ideas were also associated with paranoia, general vaccination conspiracy beliefs, climate change conspiracy belief, a conspiracy mentality, and distrust in institutions and professions. Holding coronavirus conspiracy beliefs was also associated with being more likely to share opinions. CONCLUSIONS: In England there is appreciable endorsement of conspiracy beliefs about coronavirus. Such ideas do not appear confined to the fringes. The conspiracy beliefs connect to other forms of mistrust and are associated with less compliance with government guidelines and greater unwillingness to take up future tests and treatment.

COVID-19 vaccine hesitancy in the UK: the Oxford coronavirus explanations, attitudes, and narratives survey (Oceans) II.

BACKGROUND: Our aim was to estimate provisional willingness to receive a coronavirus 2019 (COVID-19) vaccine, identify predictive socio-demographic factors, and, principally, determine potential causes in order to guide information provision. METHODS: A non-probability online survey was conducted (24th September-17th October 2020) with 5,114 UK adults, quota sampled to match the population for age, gender, ethnicity, income, and region. The Oxford COVID-19 vaccine hesitancy scale assessed intent to take an approved vaccine. Structural equation modelling estimated explanatory factor relationships. RESULTS: 71.7% (n=3,667) were willing to be vaccinated, 16.6% (n=849) were very unsure, and 11.7% (n=598) were strongly hesitant. An excellent model fit (RMSEA=0.05/CFI=0.97/TLI=0.97), explaining 86% of variance in hesitancy, was provided by beliefs about the collective importance, efficacy, side-effects, and speed of development of a COVID-19 vaccine. A second model, with reasonable fit (RMSEA=0.03/CFI=0.93/TLI=0.92), explaining 32% of variance, highlighted two higher-order explanatory factors: 'excessive mistrust' (r=0.51), including conspiracy beliefs, negative views of doctors, and need for chaos, and 'positive healthcare experiences' (r=-0.48), including supportive doctor interactions and good NHS care. Hesitancy was associated with younger age, female gender, lower income, and ethnicity, but socio-demographic information explained little variance (9.8%). Hesitancy was associated with lower adherence to social distancing guidelines. CONCLUSIONS: COVID-19 vaccine hesitancy is relatively evenly spread across the population. Willingness to take a vaccine is closely bound to recognition of the collective importance. Vaccine public information that highlights prosocial benefits may be especially effective. Factors such as conspiracy beliefs that foster mistrust and erode social cohesion will lower vaccine up-take.

Acute abdominal surgical presentations in children.

Surgical conditions affecting the abdomen in children can be associated with significant morbidity and mortality if they are not recognised and managed appropriately. It is therefore important that the correct diagnosis is made quickly, and the appropriate intervention is initiated in a timely manner and, if necessary, rapid transfer is made to a specialist paediatric surgical facility. This article provides an overview of the different surgical presentations encountered in children, and outlines the most important points in the history, examination and management of such cases, whether encountered in the emergency setting or in the community. Two illustrative case studies have been included to demonstrate how these emergencies may present in clinical practice.

Recognition and management of leukaemia in children.

Leukaemia is the most common cancer in children. The presenting manifestations can be wide-ranging, from a relatively well child to life-threatening complications. Symptoms can be manifested in any of the bodily systems. Undertaking a thorough clinical assessment of the child, in addition to recognising and addressing parental concerns, is vital. Furthermore, recognising that children can commonly present with musculoskeletal or abdominal symptoms increases the diagnostic yield, thereby preventing missed or late diagnoses. Childhood cancer has a huge impact on the child and their family, both at diagnosis and in the long term; providing advice and signposting families to appropriate support groups is an important aspect of their management. Nurses play a vital role in managing children with cancers, starting from raising suspicion and identifying the child with leukaemia, ensuring that high-quality care is delivered throughout their treatment, managing complications, and providing support and information to children and their families. An illustrative case study is included to highlight some of the challenges that health professionals may encounter in their clinical practice.

Time-lapse imaging algorithms rank human preimplantation embryos according to the probability of live birth.

RESEARCH QUESTION: Can blastocysts leading to live births be ranked according to morphokinetic-based algorithms? DESIGN: Retrospective analysis of 781 single blastocyst embryo transfers, including all patient clinical factors that might be potential confounders for the primary outcome measure of live birth, was weighed using separate multi-variable logistic regression models. RESULTS: There was strong evidence of effect of embryo rank on odds of live birth. Embryos were classified A, B, C or D according to calculated variables; time to start (tSB) and duration (dB{tB - tSB}) of blastulation. Embryos of rank D were less likely to result in live birth than embryos of rank A (odds ratio [OR] 0.3046; 95% confidence interval [CI] 0.129, 0.660; P < 0.005). Embryos ranked B were less likely to result in live birth than those ranked A (OR 0.7114; 95% Cl 0.505, 1.001; P < 0.01), and embryos ranked C were less likely to result in live birth than those ranked A (OR 0.6501, 95% Cl 0.373, 1.118; P < 0.01). Overall, the LRT (Likelihood Ratio Test) p-value for embryo rank shows that there is strong evidence that embryo rank is informative as a whole in discriminating between live birth and no live birth outcomes (p = 0.0101). The incidence of live birth was 52.5% from rank A, 39.2% from rank B, 31.4% from rank C and 13.2% from rank D. CONCLUSIONS: Time-lapse imaging morphokinetic-based algorithms for blastocysts can provide objective hierarchical ranking of embryos for predicting live birth and may have greater discriminating power than conventional blastocyst morphology assessment.

Live births after embryo selection using morphokinetics versus conventional morphology: a retrospective analysis.

The increasing corpus of clinical studies using time-lapse imaging for embryo selection demonstrates considerable variation in study protocols and only limited-sized study cohorts. Outcome measures are based on implantation or clinical pregnancy; some predict blastulation from early cleavage-stage data, and few have evaluated live birth. Erroneously, most studies treat the embryos as independent variables and do not include patient or treatment variables in the statistical analyses. In this study, cohort size was 14,793 patients and 23,762 cycles. The incidence of live birth (n = 973 deliveries) after embryo selection by objective morphokinetic algorithms was compared with conventional embryology selection parameters (n = 6948 deliveries). A 19% increase in the incidence of live birth was observed when morphokinetic data were used to select embryos for the patient cohort aged younger than 38 years (OR 1.19 with 95% CI 1.06 to 1.34) using their own eggs, and an increase of 37% for oocyte recipients aged over 37 years (OR 1.370; 95% Cl 0.763 to 2.450). This is the largest study of the prospective use of time-lapse imaging algorithms in IVF reporting on live birth outcome, although the nature of purely a closed system versus standard incubation could not be assessed.

Recognition and nursing management of abusive head trauma in children.

Abusive head trauma (AHT) describes an injury to the head caused by a deliberate impact or shaking by a parent or carer. It can cause significant morbidity and mortality in infants, and is most commonly seen in those aged under 2 years. The initial presentation of AHT can include vague symptoms and the correct diagnosis may be missed by health professionals. Subdural haematoma, brain oedema and retinal haemorrhages are well-known features associated with AHT. However, other conditions such as birth trauma, accidental falls in infants and bleeding disorders can all mimic AHT, thus making its recognition difficult. Suspicion of AHT should lead to initiation of safeguarding procedures alongside organising neurological imaging to identify skull fracture and/or intracranial lesions. This article highlights different aspects of the clinical presentation of AHT and its management. Safeguarding and recognising child abuse is vital and requires every member of the multidisciplinary team to remain vigilant. An illustrative case study is included to highlight some of the challenges that health professionals working in different clinical set-ups are likely to come across while managing an infant with AHT.

Automated virtual reality cognitive therapy versus virtual reality mental relaxation therapy for the treatment of persistent persecutory delusions in patients with psychosis (THRIVE): a parallel-group, single-blind, randomised controlled trial in England with mediation analyses.

BACKGROUND: Persecutory delusions are a major psychiatric problem that often do not respond sufficiently to standard pharmacological or psychological treatments. We developed a new brief automated virtual reality (VR) cognitive treatment that has the potential to be used easily in clinical services. We aimed to compare VR cognitive therapy with an alternative VR therapy (mental relaxation), with an emphasis on understanding potential mechanisms of action. METHODS: THRIVE was a parallel-group, single-blind, randomised controlled trial across four UK National Health Service trusts in England. Participants were included if they were aged 16 years or older, had a persistent (at least 3 months) persecutory delusion held with at least 50% conviction, reported feeling threatened when outside with other people, and had a primary diagnosis from the referring clinical team of a non-affective psychotic disorder. We randomly assigned (1:1) patients to either THRIVE VR cognitive therapy or VR mental relaxation, using a permuted blocks algorithm with randomly varying block size, stratified by severity of delusion. Usual care continued for all participants. Each VR therapy was provided in four sessions over approximately 4 weeks, supported by an assistant psychologist or clinical psychologist. Trial assessors were masked to group allocation. Outcomes were assessed at 0, 2 (therapy mid-point), 4 (primary endpoint, end of treatment), 8, 16, and 24 weeks. The primary outcome was persecutory delusion conviction, assessed by the Psychotic Symptoms Rating Scale (PSYRATS; rated 0-100%). Outcome analyses were done in the intention-to-treat population. We assessed the treatment credibility and expectancy of the interventions and the two mechanisms (defence behaviours and safety beliefs) that the cognitive intervention was designed to target. This trial is prospectively registered with the ISRCTN registry, ISRCTN12497310. FINDINGS: From Sept 21, 2018, to May 13, 2021 (with a pause due to COVID-19 pandemic restrictions from March 16, 2020, to Sept 14, 2020), we recruited 80 participants with persistent persecutory delusions (49 [61%] men, 31 [39%] women, with a mean age of 40 years [SD 13, range 18-73], 64 [80%] White, six [8%] Black, one [1%] Indian, three [4%] Pakistani, and six [8%] other race or ethnicity). We randomly assigned 39 (49%) participants assigned to VR cognitive therapy and 41 (51%) participants to VR mental relaxation. 33 (85%) participants who were assigned to VR cognitive therapy attended all four sessions, and 35 (85%) participants assigned to VR mental relaxation attended all four sessions. We found no significant differences between the two VR interventions in participant ratings of treatment credibility (adjusted mean difference -1·55 [95% CI -3·68 to 0·58]; p=0·15) and outcome expectancy (-0·91 [-3·42 to 1·61]; p=0·47). 77 (96%) participants provided follow-up data at the primary timepoint. Compared with VR mental relaxation, VR cognitive therapy did not lead to a greater improvement in persecutory delusions (adjusted mean difference -2·16 [-12·77 to 8·44]; p=0·69). Compared with VR mental relaxation, VR cognitive therapy did not lead to a greater reduction in use of defence behaviours (adjusted mean difference -0·71 [-4·21 to 2·79]; p=0·69) or a greater increase in belief in safety (-5·89 [-16·83 to 5·05]; p=0·29). There were 17 serious adverse events unrelated to the trial (ten events in seven participants in the VR cognitive therapy group and seven events in five participants in the VR mental relaxation group). INTERPRETATION: The two VR interventions performed similarly, despite the fact that they had been designed to affect different mechanisms. Both interventions had high uptake rates and were associated with large improvements in persecutory delusions but it cannot be determined that the treatments accounted for the change. Immersive technologies hold promise for the treatment of severe mental health problems. However, their use will likely benefit from experimental research on the application of different therapeutic techniques and the effects on a range of potential mechanisms of action. FUNDING: Medical Research Council Developmental Pathway Funding Scheme and National Institute for Health and Care Research Oxford Health Biomedical Research Centre.

Automated Virtual Reality Cognitive Therapy (gameChange) in Inpatient Psychiatric Wards: Qualitative Study of Staff and Patient Views Using an Implementation Framework.

BACKGROUND: Automated virtual reality (VR) therapy could allow a greater number of patients to receive evidence-based psychological therapy. The aim of the gameChange VR therapy is to help patients overcome anxious avoidance of everyday social situations. gameChange has been evaluated with outpatients, but it may also help inpatients prepare for discharge from psychiatric hospital. OBJECTIVE: The aim of this study is to explore the views of patients and staff on the provision of VR therapy on psychiatric wards. METHODS: Focus groups or individual interviews were conducted with patients (n=19) and National Health Service staff (n=22) in acute psychiatric wards. Questions were derived from the nonadoption, abandonment, and challenges to the scale-up, spread, and sustainability framework. Expectations of VR therapy were discussed, and participants were then given the opportunity to try out the gameChange VR therapy before they were asked questions that focused on opinions about the therapy and feasibility of adoption. RESULTS: There was great enthusiasm for the use of gameChange VR therapy on psychiatric wards. It was considered that gameChange could help build confidence, reduce anxiety, and "bridge that gap" between the differences of being in hospital and being discharged to the community. However, it was reflected that the VR therapy may not suit everyone, especially if they are acutely unwell. VR on hospital wards for entertainment and relaxation was also viewed positively. Participants were particularly impressed by the immersive quality of gameChange and the virtual coach. It was considered that a range of staff groups could support VR therapy delivery. The staff thought that implementation would be facilitated by having a lead staff member, having ongoing training accessible, and involving the multidisciplinary team in decision-making for VR therapy use. The most significant barrier to implementation identified by patients and staff was a practical one: access to sufficient, private space to provide the therapy. CONCLUSIONS: Patients and staff were keen for VR to be used on psychiatric wards. In general, patients and staff viewed automated VR therapy as possible to implement within current care provision, with few significant barriers other than constraints of space. Patients and staff thought of many further uses of VR on psychiatric wards. The value of VR therapy on psychiatric wards now requires systematic evaluation. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR2-10.2196/20300.

Perseveration in a spatial-discrimination serial reversal learning task is differentially affected by MAO-A and MAO-B inhibition and associated with reduced anxiety and peripheral serotonin levels.

RATIONALE: Impairments in behavioral flexibility lie at the core of anxiety and obsessive-compulsive disorders. Few studies, however, have investigated the neural substrates of natural variation in behavioral flexibility and whether inflexible behavior is linked to anxiety and peripheral markers of stress and monoamine function. OBJECTIVE: The objective of the study was to investigate peripheral and central markers associated with perseverative behavior on a spatial-discrimination serial reversal learning task. METHODS: Rats were trained on a reversal learning task prior to blood sampling, anxiety assessment, and the behavioral evaluation of selective monoamine oxidase-A (MAO-A) and MAO-B inhibitors, which block the degradation of serotonin (5-HT), dopamine (DA), and noradrenaline (NA). RESULTS: Perseveration correlated positively with 5-HT levels in blood plasma and inversely with trait anxiety, as measured on the elevated plus maze. No significant relationships were found between perseveration and the stress hormone corticosterone or the 5-HT precursor tryptophan. Reversal learning was significantly improved by systemic administration of the MAO-A inhibitor moclobemide but not by the MAO-B inhibitor lazabemide. Moclobemide also increased latencies to initiate a new trial following an incorrect response suggesting a possible role in modulating behavioral inhibition to negative feedback. MAO-A but not MAO-B inhibition resulted in pronounced increases in 5-HT and NA content in the orbitofrontal cortex and dorsal raphé nuclei and increased 5-HT and DA content in the basolateral amygdala and dorsomedial striatum. CONCLUSIONS: These findings indicate that central and peripheral monoaminergic mechanisms underlie inter-individual variation in behavioral flexibility, which overlaps with trait anxiety and depends on functional MAO-A activity.

Live birth after polar body array comparative genomic hybridization prediction of embryo ploidy-the future of IVF?

OBJECTIVE: To ascertain meiotic aneuploidy of the human egg using array comparative genomic hybridization to evaluate the 23-paired chromosome copy number of first polar body as an objective prognosticator of embryo viability for embryo transfer in the same cycle. DESIGN: Case report. SETTING: Independent-sector IVF program. PATIENT(S): A 41-year-old woman with a history of 13 failed cycles of IVF. INTERVENTION(S): Polar body biopsy of metaphase II eggs. MAIN OUTCOME MEASURE(S): Birth. RESULT(S): Two of the nine eggs were euploid, and the resulting embryos, although morphologically inferior to sibling embryos, were selected for transfer to the uterus, resulting in the birth of a normal healthy baby. CONCLUSION(S): Selection of euploid eggs, as an objective parameter of subsequent embryo viability and with the opportunity to transfer embryos in the same cycle could maximise the opportunity for live birth after IVF even in cases with poor prognosis.