Evaluation of a COVID-19 fundamental nursing care guideline versus usual care: The COVID-NURSE cluster randomized controlled trial.

AIM: To evaluate the impact of usual care plus a fundamental nursing care guideline compared to usual care only for patients in hospital with COVID-19 on patient experience, care quality, functional ability, treatment outcomes, nurses' moral distress, patient health-related quality of life and cost-effectiveness. DESIGN: Parallel two-arm, cluster-level randomized controlled trial. METHODS: Between 18th January and 20th December 2021, we recruited (i) adults aged 18 years and over with COVID-19, excluding those invasively ventilated, admitted for at least three days or nights in UK Hospital Trusts; (ii) nurses caring for them. We randomly assigned hospitals to use a fundamental nursing care guideline and usual care or usual care only. Our patient-reported co-primary outcomes were the Relational Aspects of Care Questionnaire and four scales from the Quality from the Patient Perspective Questionnaire. We undertook intention-to-treat analyses. RESULTS: We randomized 15 clusters and recruited 581 patient and 418 nurse participants. Primary outcome data were available for 570-572 (98.1%-98.5%) patient participants in 14 clusters. We found no evidence of between-group differences on any patient, nurse or economic outcomes. We found between-group differences over time, in favour of the intervention, for three of our five co-primary outcomes, and a significant interaction on one primary patient outcome for ethnicity (white British vs. other) and allocated group in favour of the intervention for the 'other' ethnicity subgroup. CONCLUSION: We did not detect an overall difference in patient experience for a fundamental nursing care guideline compared to usual care. We have indications the guideline may have aided sustaining good practice over time and had a more positive impact on non-white British patients' experience of care. IMPLICATIONS FOR THE PROFESSION AND/OR PATIENT CARE: We cannot recommend the wholescale implementation of our guideline into routine nursing practice. Further intervention development, feasibility, pilot and evaluation studies are required. IMPACT: Fundamental nursing care drives patient experience but is severely impacted in pandemics. Our guideline was not superior to usual care, albeit it may sustain good practice and have a positive impact on non-white British patients' experience of care. REPORTING METHOD: CONSORT and CONSERVE. PATIENT OR PUBLIC CONTRIBUTION: Patients with experience of hospitalization with COVID-19 were involved in guideline development and writing, trial management and interpretation of findings.

Identifying relapse predictors in individual participant data with decision trees.

BACKGROUND: Depression is a highly common and recurrent condition. Predicting who is at most risk of relapse or recurrence can inform clinical practice. Applying machine-learning methods to Individual Participant Data (IPD) can be promising to improve the accuracy of risk predictions. METHODS: Individual data of four Randomized Controlled Trials (RCTs) evaluating antidepressant treatment compared to psychological interventions with tapering ([Formula: see text]) were used to identify predictors of relapse and/or recurrence. Ten baseline predictors were assessed. Decision trees with and without gradient boosting were applied. To study the robustness of decision-tree classifications, we also performed a complementary logistic regression analysis. RESULTS: The combination of age, age of onset of depression, and depression severity significantly enhances the prediction of relapse risk when compared to classifiers solely based on depression severity. The studied decision trees can (i) identify relapse patients at intake with an accuracy, specificity, and sensitivity of about 55% (without gradient boosting) and 58% (with gradient boosting), and (ii) slightly outperform classifiers that are based on logistic regression. CONCLUSIONS: Decision tree classifiers based on multiple-rather than single-risk indicators may be useful for developing treatment stratification strategies. These classification models have the potential to contribute to the development of methods aimed at effectively prioritizing treatment for those individuals who require it the most. Our results also underline the existing gaps in understanding how to accurately predict depressive relapse.

Protocol for a pragmatic cluster randomised controlled trial assessing the clinical effectiveness and cost-effectiveness of Electronic RIsk-assessment for CAncer for patients in general practice (ERICA).

INTRODUCTION: The UK has worse cancer outcomes than most comparable countries, with a large contribution attributed to diagnostic delay. Electronic risk assessment tools (eRATs) have been developed to identify primary care patients with a ≥2% risk of cancer using features recorded in the electronic record. METHODS AND ANALYSIS: This is a pragmatic cluster randomised controlled trial in English primary care. Individual general practices will be randomised in a 1:1 ratio to intervention (provision of eRATs for six common cancer sites) or to usual care. The primary outcome is cancer stage at diagnosis, dichotomised to stage 1 or 2 (early) or stage 3 or 4 (advanced) for these six cancers, assessed from National Cancer Registry data. Secondary outcomes include stage at diagnosis for a further six cancers without eRATs, use of urgent referral cancer pathways, total practice cancer diagnoses, routes to cancer diagnosis and 30-day and 1-year cancer survival. Economic and process evaluations will be performed along with service delivery modelling. The primary analysis explores the proportion of patients with early-stage cancer at diagnosis. The sample size calculation used an OR of 0.8 for a cancer being diagnosed at an advanced stage in the intervention arm compared with the control arm, equating to an absolute reduction of 4.8% as an incidence-weighted figure across the six cancers. This requires 530 practices overall, with the intervention active from April 2022 for 2 years. ETHICS AND DISSEMINATION: The trial has approval from London City and East Research Ethics Committee, reference number 19/LO/0615; protocol version 5.0, 9 May 2022. It is sponsored by the University of Exeter. Dissemination will be by journal publication, conferences, use of appropriate social media and direct sharing with cancer policymakers. TRIAL REGISTRATION NUMBER: ISRCTN22560297.

A randomised controlled trial to investigate the clinical effectiveness and cost effectiveness of Mindfulness-Based Cognitive Therapy (MBCT) for depressed non-responders to Increasing Access to Psychological Therapies (IAPT) high-intensity therapies: study protocol.

BACKGROUND: Major depression represents a pressing challenge for health care. In England, Increasing Access to Psychological Therapies (IAPT) services provide evidence-based psychological therapies in a stepped-care approach to patients with depression. While introduction of these services has successfully increased access to therapy, estimates suggest that about 50% of depressed patients who have come to the end of the IAPT pathway still show significant levels of symptoms. This study will investigate whether Mindfulness-Based Cognitive Therapy (MBCT), a group intervention combining training in mindfulness meditation and elements from cognitive therapy, can have beneficial effects in depressed patients who have not responded to high-intensity therapy in IAPT. It will seek to establish the effectiveness and cost-effectiveness of MBCT as compared to the treatment these patients would usually receive. METHODS: In a 2-arm randomised controlled trial, patients who currently meet the criteria for major depressive disorder and who have not sufficiently responded to at least 12 sessions of IAPT high-intensity therapy will be allocated, at a ratio of 1:1, to receive either MBCT (in addition to treatment as usual [TAU]) or continue with TAU only. Assessments will take place at baseline, 10 weeks and 34 weeks post-randomisation. The primary outcome will be reduction in depression symptomatology 34 weeks post-randomisation as assessed using the Public Health Questionnaire-9 (PHQ-9). Secondary outcomes will include depressive symptomatology at 10 weeks post-randomisation and other clinical outcomes measured at 10-week and 34-week follow-up, along with a series of binarised outcomes to indicate clinically significant and reliable change. Evaluations of cost-effectiveness will be based on assessments of service use costs collected using the Adult Service Use Schedule and health utilities derived from the EQ-5D. DISCUSSION: This trial will add to the evidence base for the use of MBCT in depressed treatment non-responders. It will constitute the first trial to test MBCT following non-response to psychological therapy, with results providing a direct estimate of efficacy within the IAPT pathway. As such, its results will offer an important basis for decisions regarding the adoption of MBCT for non-responders within IAPT. TRIAL REGISTRATION: ClinicalTrials.gov NCT05236959. Registered on 11 February 2022. ISRCTN 17755571. Registered on 2 February 2021.

Patient stratification for determining optimal second-line and third-line therapy for type 2 diabetes: the TriMaster study.

Precision medicine aims to treat an individual based on their clinical characteristics. A differential drug response, critical to using these features for therapy selection, has never been examined directly in type 2 diabetes. In this study, we tested two hypotheses: (1) individuals with body mass index (BMI) > 30 kg/m2, compared to BMI ≤ 30 kg/m2, have greater glucose lowering with thiazolidinediones than with DPP4 inhibitors, and (2) individuals with estimated glomerular filtration rate (eGFR) 60-90 ml/min/1.73 m2, compared to eGFR >90 ml/min/1.73 m2, have greater glucose lowering with DPP4 inhibitors than with SGLT2 inhibitors. The primary endpoint for both hypotheses was the achieved HbA1c difference between strata for the two drugs. In total, 525 people with type 2 diabetes participated in this UK-based randomized, double-blind, three-way crossover trial of 16 weeks of treatment with each of sitagliptin 100 mg once daily, canagliflozin 100 mg once daily and pioglitazone 30 mg once daily added to metformin alone or metformin plus sulfonylurea. Overall, the achieved HbA1c was similar for the three drugs: pioglitazone 59.6 mmol/mol, sitagliptin 60.0 mmol/mol and canagliflozin 60.6 mmol/mol (P = 0.2). Participants with BMI > 30 kg/m2, compared to BMI ≤ 30 kg/m2, had a 2.88 mmol/mol (95% confidence interval (CI): 0.98, 4.79) lower HbA1c on pioglitazone than on sitagliptin (n = 356, P = 0.003). Participants with eGFR 60-90 ml/min/1.73 m2, compared to eGFR >90 ml/min/1.73 m2, had a 2.90 mmol/mol (95% CI: 1.19, 4.61) lower HbA1c on sitagliptin than on canagliflozin (n = 342, P = 0.001). There were 2,201 adverse events reported, and 447/525 (85%) randomized participants experienced an adverse event on at least one of the study drugs. In this precision medicine trial in type 2 diabetes, our findings support the use of simple, routinely available clinical measures to identify the drug class most likely to deliver the greatest glycemic reduction for a given patient. (ClinicalTrials.gov registration: NCT02653209 ; ISRCTN registration: 12039221 .).

Systematic Review to Identify Predictors of Treatment Response to Neuromodulation in Patients With Neuropathic Pain-Protocol.

OBJECTIVES: Patients who suffer from long-term, neuropathic pain that proves refractory to conventional medical management are high consumers of health care resources and experience poorer physical and mental health than people with other forms of pain. Pharmacologic treatments have adverse effects; nonpharmacologic interventions have limitations. Spinal cord stimulation (SCS) is an effective treatment for neuropathic pain, although 30% to 40% of patients fail to achieve acceptable levels of pain relief. There are currently no objective methods to predict the success of SCS to treat neuropathic pain, and therefore, it is important to understand which patient factors may be predictive of a lack of response to SCS, to inform future patient treatment options. This study proposes a protocol for a systematic review and meta-analysis of published studies to examine these predictive factors. MATERIALS AND METHODS: Several bibliographic databases will be searched to identify relevant studies published since 2012 that provide data on patient characteristics (eg, age, gender, pain severity) as predictors of SCS outcomes of pain, function, and health-related quality of life. Two independent reviewers will screen citations; data will be extracted after full-text screening. Risk of bias will be assessed using the Quality In Prognosis Studies tool. RESULTS: A formal quantitative synthesis is planned in which data from studies with the same predictive factors are available; this will be considered for pooling into separate meta-analyses. In cases of high heterogeneity or inconsistency in the data, subgroup analysis will be conducted. CONCLUSIONS: This study seeks to provide a contemporary review of patient predictors of success of neuromodulation for neuropathic pain. We anticipate that findings may guide the use of neuromodulation in patient subgroups and the design and reporting of future clinical studies in this field.

Evaluation of a complex intervention for prisoners with common mental health problems, near to and after release: the Engager randomised controlled trial.

BACKGROUND: Many male prisoners have significant mental health problems, including anxiety and depression. High proportions struggle with homelessness and substance misuse. AIMS: This study aims to evaluate whether the Engager intervention improves mental health outcomes following release. METHOD: The design is a parallel randomised superiority trial that was conducted in the North West and South West of England (ISRCTN11707331). Men serving a prison sentence of 2 years or less were individually allocated 1:1 to either the intervention (Engager plus usual care) or usual care alone. Engager included psychological and practical support in prison, on release and for 3-5 months in the community. The primary outcome was the Clinical Outcomes in Routine Evaluation Outcome Measure (CORE-OM), 6 months after release. Primary analysis compared groups based on intention-to-treat (ITT). RESULTS: In total, 280 men were randomised out of the 396 who were potentially eligible and agreed to participate; 105 did not meet the mental health inclusion criteria. There was no mean difference in the ITT complete case analysis between groups (92 in each arm) for change in the CORE-OM score (1.1, 95% CI -1.1 to 3.2, P = 0.325) or secondary analyses. There were no consistent clinically significant between-group differences for secondary outcomes. Full delivery was not achieved, with 77% (108/140) receiving community-based contact. CONCLUSIONS: Engager is the first trial of a collaborative care intervention adapted for prison leavers. The intervention was not shown to be effective using standard outcome measures. Further testing of different support strategies for prison with mental health problems is needed.

How well do Cognitive Behavioural Therapy and Behavioural Activation for depression repair anhedonia? A secondary analysis of the COBRA randomized controlled trial.

A secondary analysis of the COBRA randomized controlled trial was conducted to examine how well Cognitive Behavioural Therapy (CBT) and Behavioural Activation (BA) repair anhedonia. Patients with current major depressive disorder (N = 440) were randomized to receive BA or CBT, and anhedonia and depression outcomes were measured after acute treatment (six months) and at two further follow up intervals (12 and 18 months). Anhedonia was assessed using the Snaith Hamilton Pleasure Scale (SHAPS; a measure of consummatory pleasure). Both CBT and BA led to significant improvements in anhedonia during acute treatment, with no significant difference between treatments. Participants remained above healthy population averages of anhedonia at six months, and there was no further significant improvement in anhedonia at 12-month or 18-month follow up. Greater baseline anhedonia severity predicted reduced repair of depression symptoms and fewer depression-free days across the follow-up period in both the BA and CBT arms. The extent of anhedonia repair was less marked than the extent of depression repair across both treatment arms. These findings demonstrate that CBT and BA are similarly and only partially effective in treating anhedonia. Therefore, both therapies should be further refined or novel treatments should be developed in order better to treat anhedonia.

Performance of the imPulse device for the detection of atrial fibrillation in hospital settings.

Background: Atrial fibrillation (AF) increases thromboembolism and stroke risk; this can be reduced by oral anticoagulation, but only if AF is detected. A portable, point-of-care device, capable of accurately detecting and identifying AF, could reduce workload and diagnostic delay by minimizing need for follow-up 12-lead electrocardiogram (ECGs). Objective: To assess the diagnostic performance of the Plessey imPulse lead I ECG device compared with a 12-lead ECG in detecting AF. Methods: Cross-sectional diagnostic accuracy study. Participants underwent simultaneous 12-lead ECG and imPulse device recordings. The imPulse device reports AF to be "probable," "possible," "unlikely," or "uncontrolled AF unlikely." imPulse and ECG reference results were cross-tabulated; sensitivity, specificity, positive/negative predictive values, and positive/negative likelihood ratios with 95% confidence interval (CI) were estimated based on different imPulse device report categorizations and heart rate subgroups. Results: A total of 217 participants were recruited (mean age 70.2 [standard deviation 12.7]), 56% male, 57% outpatients, 43% inpatients) and 199 were included in analyses. AF was diagnosed on ECG for 41 of 199 (20.6%) participants and reported by imPulse as possible, probable, or uncontrolled AF unlikely present for 49 of 199 (24.6%). Sensitivity and specificity for imPulse detection of possible, probable, or uncontrolled AF unlikely vs unlikely, compared with ECG, were 80.5% (95% CI, 65.1%-91.2%) and 89.9% (84.1%-94.1%), respectively. When probable or uncontrolled AF unlikely were compared vs possible or unlikely AF, sensitivity and specificity were 63.4% (46.9%-77.9%) and 98.1% (94.6%-99.6%), respectively. Conclusion: The imPulse device has moderate sensitivity and good specificity compared with ECG AF detection in a hospital setting.

Higher Arm Versus Lower Arm Systolic Blood Pressure and Cardiovascular Outcomes: a Meta-Analysis of Individual Participant Data From the INTERPRESS-IPD Collaboration.

BACKGROUND: Guidelines recommend measuring blood pressure (BP) in both arms, adopting the higher arm readings for diagnosis and management. Data to support this recommendation are lacking. We evaluated associations of higher and lower arm systolic BPs with diagnostic and treatment thresholds, and prognosis in hypertension, using data from the Inter-arm Blood Pressure Difference-Individual Participant Data Collaboration. METHODS: One-stage multivariable Cox regression models, stratified by study, were used to examine associations of higher or lower reading arm BPs with cardiovascular mortality, all-cause mortality, and cardiovascular events, in individual participant data meta-analyses pooled from 23 cohorts. Cardiovascular events were modelled for Framingham and atherosclerotic cardiovascular disease risk scores. Model fit was compared throughout using Akaike information criteria. Proportions reclassified across guideline recommended intervention thresholds were also compared. RESULTS: We analyzed 53 172 participants: mean age 60 years; 48% female. Higher arm BP, compared with lower arm, reclassified 12% of participants at either 130 or 140 mm Hg systolic BP thresholds (both P<0.001). Higher arm BP models fitted better for all-cause mortality, cardiovascular mortality, and cardiovascular events (all P<0.001). Higher arm BP models better predicted cardiovascular events with Framingham and atherosclerotic cardiovascular disease risk scores (both P<0.001) and reclassified 4.6% and 3.5% of participants respectively to higher risk categories compared with lower arm BPs). CONCLUSIONS: Using BP from higher instead of lower reading arms reclassified 12% of people over thresholds used to diagnose hypertension. All prediction models performed better when using the higher arm BP. Both arms should be measured for accurate diagnosis and management of hypertension. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: CRD42015031227.

Adjunctive Ketamine With Relapse Prevention-Based Psychological Therapy in the Treatment of Alcohol Use Disorder.

OBJECTIVE: Early evidence suggests that ketamine may be an effective treatment to sustain abstinence from alcohol. The authors investigated the safety and efficacy of ketamine compared with placebo in increasing abstinence in patients with alcohol use disorder. An additional aim was to pilot ketamine combined with mindfulness-based relapse prevention therapy compared with ketamine and alcohol education as a therapy control. METHODS: In a double-blind placebo-controlled phase 2 clinical trial, 96 patients with severe alcohol use disorder were randomly assigned to one of four conditions: 1) three weekly ketamine infusions (0.8 mg/kg i.v. over 40 minutes) plus psychological therapy, 2) three saline infusions plus psychological therapy, 3) three ketamine infusions plus alcohol education, or 4) three saline infusions plus alcohol education. The primary outcomes were self-reported percentage of days abstinent and confirmed alcohol relapse at 6-month follow-up. RESULTS: Ninety-six participants (35 women; mean age, 44.07 years [SD=10.59]) were included in the intention-to-treat analysis. The treatment was well tolerated, and no serious adverse events were associated with the study drug. Although confidence intervals were wide, consistent with a proof-of-concept study, there were a significantly greater number of days abstinent from alcohol in the ketamine group compared with the placebo group at 6-month follow-up (mean difference=10.1%, 95% CI=1.1, 19.0), with the greatest reduction in the ketamine plus therapy group compared with the saline plus education group (15.9%, 95% CI=3.8, 28.1). There was no significant difference in relapse rate between the ketamine and placebo groups. CONCLUSIONS: This study demonstrated that treatment with three infusions of ketamine was well tolerated in patients with alcohol use disorder and was associated with more days of abstinence from alcohol at 6-month follow-up. The findings suggest a possible beneficial effect of adding psychological therapy alongside ketamine treatment.

Time trends in autism diagnosis over 20 years: a UK population-based cohort study.

BACKGROUND: Autism spectrum disorder is a diagnosis that is increasingly applied; however, previous studies have conflicting findings whether rates of diagnosis rates continue to grow in the UK. This study tested whether the proportion of people receiving a new autism diagnosis has been increasing over a twenty-year period, both overall and by subgroups. METHOD: Population-based study utilizing the Clinical Practice Research Datalink (CPRD) primary care database, which contains patients registered with practices contributing data to the CPRD between 1998 and 2018 (N = 6,786,212 in 1998 to N = 9,594,598 in 2018). 65,665 patients had a diagnosis of autism recorded in 2018. Time trend of new (incident) cases of autism diagnosis was plotted for all, and stratified by gender, diagnostic subtypes, and developmental stage: infancy and preschool, 0-5 years old; childhood, 6-11 years old; adolescence, 12-19 years old; adults, over 19 years old. RESULTS: There was a 787%, exponential increase in recorded incidence of autism diagnoses between 1998 and 2018; R2 = 0.98, exponentiated coefficient = 1.07, 95% CI [1.06, 1.08], p < .001. The increase in diagnoses was greater for females than males (exponentiated interaction coefficient = 1.02, 95% CI [1.01, 1.03], p < .001) and moderated by age band, with the greatest rises in diagnostic incidence among adults (exponentiated interaction coefficient = 1.06, 95% CI [1.04, 1.07], p < .001). CONCLUSIONS: Increases could be due to growth in prevalence or, more likely, increased reporting and application of diagnosis. Rising diagnosis among adults, females and higher functioning individuals suggest augmented recognition underpins these changes.

Economic evaluation of a complex intervention (Engager) for prisoners with common mental health problems, near to and after release: a cost-utility and cost-consequences analysis.

BACKGROUND: People in prison experience a range of physical and mental health problems. Evaluating the effectiveness and efficiency of prison-based interventions presents a number of methodological challenges. We present a case study of an economic evaluation of a prison-based intervention ("Engager") to address common mental health problems. METHODS: Two hundred and eighty people were recruited from prisons in England and randomised to Engager plus usual care or usual care. Participants were followed up for 12 months following release from prison. The primary analysis is the cost per quality-adjusted life year (QALY) gained of Engager compared to usual care from a National Health Service (NHS) perspective with QALYs calculated using the CORE 6 Dimension. A cost-consequences analysis evaluated cross-sectoral costs and a range of outcomes. RESULTS: From an NHS perspective, Engager cost an additional £2737 per participant (95% of iterations between £1029 and £4718) with a mean QALY difference of - 0.014 (95% of iterations between - 0.045 and 0.017). For the cost-consequences, there was evidence of improved access to substance misuse services 12 months post-release (odds ratio 2.244, 95% confidence Interval 1.304-3.861). CONCLUSION: Engager provides a rare example of a cost-utility analysis conducted in prisons and the community using patient-completed measures. Although the results from this trial show no evidence that Engager is cost-effective, the results of the cost-consequences analysis suggest that follow-up beyond 12 months post-release using routine data may provide additional insights into the effectiveness of the intervention and the importance of including a wide range of costs and outcomes in prison-based economic evaluations. TRIAL REGISTRATION: (ISRCTN11707331).

An Observational Cohort Study on the Incidence of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Infection and B.1.1.7 Variant Infection in Healthcare Workers by Antibody and Vaccination Status.

BACKGROUND: Natural and vaccine-induced immunity will play a key role in controlling the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic. SARS-CoV-2 variants have the potential to evade natural and vaccine-induced immunity. METHODS: In a longitudinal cohort study of healthcare workers (HCWs) in Oxfordshire, United Kingdom, we investigated the protection from symptomatic and asymptomatic polymerase chain reaction (PCR)-confirmed SARS-CoV-2 infection conferred by vaccination (Pfizer-BioNTech BNT162b2, Oxford-AstraZeneca ChAdOx1 nCOV-19) and prior infection (determined using anti-spike antibody status), using Poisson regression adjusted for age, sex, temporal changes in incidence and role. We estimated protection conferred after 1 versus 2 vaccinations and from infections with the B.1.1.7 variant identified using whole genome sequencing. RESULTS: In total, 13 109 HCWs participated; 8285 received the Pfizer-BioNTech vaccine (1407 two doses), and 2738 the Oxford-AstraZeneca vaccine (49 two doses). Compared to unvaccinated seronegative HCWs, natural immunity and 2 vaccination doses provided similar protection against symptomatic infection: no HCW vaccinated twice had symptomatic infection, and incidence was 98% lower in seropositive HCWs (adjusted incidence rate ratio 0.02 [95% confidence interval {CI} < .01-.18]). Two vaccine doses or seropositivity reduced the incidence of any PCR-positive result with or without symptoms by 90% (0.10 [95% CI .02-.38]) and 85% (0.15 [95% CI .08-.26]), respectively. Single-dose vaccination reduced the incidence of symptomatic infection by 67% (0.33 [95% CI .21-.52]) and any PCR-positive result by 64% (0.36 [95% CI .26-.50]). There was no evidence of differences in immunity induced by natural infection and vaccination for infections with S-gene target failure and B.1.1.7. CONCLUSIONS: Natural infection resulting in detectable anti-spike antibodies and 2 vaccine doses both provide robust protection against SARS-CoV-2 infection, including against the B.1.1.7 variant.

Time of Day of Vaccination Affects SARS-CoV-2 Antibody Responses in an Observational Study of Health Care Workers.

The COVID-19 pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a global crisis with unprecedented challenges for public health. Vaccinations against SARS-CoV-2 have slowed the incidence of new infections and reduced disease severity. As the time of day of vaccination has been reported to influence host immune responses to multiple pathogens, we quantified the influence of SARS-CoV-2 vaccination time, vaccine type, participant age, sex, and days post-vaccination on anti-Spike antibody responses in health care workers. The magnitude of the anti-Spike antibody response is associated with the time of day of vaccination, vaccine type, participant age, sex, and days post-vaccination. These results may be relevant for optimising SARS-CoV-2 vaccine efficacy.

'Rich' and 'poor' in mentalizing: Do expert mentalizers exist?

Mentalization theory is concerned with the capacity to notice, and make sense of, thoughts and feelings in self and others. This development may be healthy or impaired and therefore, by extension, it may be theorized that expertise in mentalizing can exist. Furthermore, a continuum from impairment to expertise should exist within separate dimensions of mentalizing: of self and of others. This study hypothesized that three groups would be distinguishable on the basis of their mentalizing capacities. In a cross-sectional design, Psychological Therapists ('expert' mentalizers; n = 51), individuals with a diagnosis of Borderline Personality Disorder ('poor' mentalizers; n = 43) and members of the general population ('non-clinical controls'; n = 35) completed a battery of self-report measures. These assessed the mentalizing of self and of others (using an extended version of the Reflective Function Questionnaire (RFQ18)), alexithymia and cognitive empathy. As hypothesized, Psychological Therapists' scores were higher than controls on self-mentalizing and control group scores were higher than those with BPD. Cognitive empathy scores in the BPD group indicated markedly lower capacities than the other two groups. Contrary to predictions, no significant differences were found between groups on mentalizing others in RFQ18 scores. The Psychological Therapist and BPD profiles were characterized by differential impairment with regards to mentalizing self and others but in opposing directions. Results suggest that the RFQ18 can identify groups with expertise in mentalizing. Implications of these results for the effectiveness of psychological therapy and of Psychological Therapists are discussed.

Psychological therapy for mood instability within bipolar spectrum disorder: a randomised, controlled feasibility trial of a dialectical behaviour therapy-informed approach (the ThrIVe-B programme).

BACKGROUND: A subgroup of those with bipolar spectrum disorders experience ongoing mood fluctuations outside of full episodes. We conducted a randomised, controlled feasibility study of a Dialectical Behavioural Therapy-informed approach for bipolar mood fluctuations (Therapy for Inter-episode mood Variability in Bipolar [ThrIVe-B]). Our study aimed to examine the feasibility and acceptability of a future definitive trial evaluating the clinical and cost effectiveness of the ThrIVe-B programme. Participants were required to meet diagnostic criteria for a bipolar spectrum disorder and report frequent mood swings outside of acute episodes. They were randomised to treatment as usual (control arm) or the ThrIVe-B intervention plus treatment as usual (intervention arm). Follow-up points were at 3, 6, 9 and 15 months after baseline, with 9 months as the primary end point. To evaluate feasibility and acceptability we examined recruitment and retention rates, completion rates for study measures, adverse events and feedback from participants on their experience of study participation and therapy. RESULTS: Of the target 48 participants, 43 were recruited (22 in the intervention arm; 21 in the control arm), with a recruitment rate of 3.9 participants per month. At 9 months 74% of participants engaged in research follow-up assessment, exceeding the pre-specified criterion of 60%. There were no serious concerns about the safety of the research procedures or the intervention. On one of the four candidate primary outcome measures, the 95% CI for the between-group mean difference score excluded the null effect and included the minimal clinically important difference, favouring the intervention arm, whilst on no measure was there evidence of deterioration in the intervention arm relative to the control arm. Attendance of the intervention (50% attending at least half of the mandatory sessions) was below the pre-specified continuation criterion of 60%, and qualitative feedback from participants indicated areas that may have hampered or facilitated engagement. CONCLUSIONS: It is broadly feasible to conduct a trial of this design within the population of people with frequent bipolar mood swings. Changes should be made to the therapy to increase uptake, such as simplifying content and considering individual rather than group delivery. Trial registration ISRCTN: ISRCTN54234300. Registered 14th July 2017, http://www.isrctn.com/ISRCTN54234300.

Epidemiological data and genome sequencing reveals that nosocomial transmission of SARS-CoV-2 is underestimated and mostly mediated by a small number of highly infectious individuals.

OBJECTIVES: Despite robust efforts, patients and staff acquire SARS-CoV-2 infection in hospitals. We investigated whether whole-genome sequencing enhanced the epidemiological investigation of healthcare-associated SARS-CoV-2 acquisition. METHODS: From 17-November-2020 to 5-January-2021, 803 inpatients and 329 staff were diagnosed with SARS-CoV-2 infection at four Oxfordshire hospitals. We classified cases using epidemiological definitions, looked for a potential source for each nosocomial infection, and evaluated genomic evidence supporting transmission. RESULTS: Using national epidemiological definitions, 109/803(14%) inpatient infections were classified as definite/probable nosocomial, 615(77%) as community-acquired and 79(10%) as indeterminate. There was strong epidemiological evidence to support definite/probable cases as nosocomial. Many indeterminate cases were likely infected in hospital: 53/79(67%) had a prior-negative PCR and 75(95%) contact with a potential source. 89/615(11% of all 803 patients) with apparent community-onset had a recent hospital exposure. Within 764 samples sequenced 607 genomic clusters were identified (>1 SNP distinct). Only 43/607(7%) clusters contained evidence of onward transmission (subsequent cases within ≤ 1 SNP). 20/21 epidemiologically-identified outbreaks contained multiple genomic introductions. Most (80%) nosocomial acquisition occurred in rapid super-spreading events in settings with a mix of COVID-19 and non-COVID-19 patients. CONCLUSIONS: Current surveillance definitions underestimate nosocomial acquisition. Most nosocomial transmission occurs from a relatively limited number of highly infectious individuals.

COVID-NURSE: evaluation of a fundamental nursing care protocol compared with care as usual on experience of care for noninvasively ventilated patients in hospital with the SARS-CoV-2 virus-protocol for a cluster randomised controlled trial.

INTRODUCTION: Patient experience of nursing care is correlated with safety, clinical effectiveness, care quality, treatment outcomes and service use. Effective nursing care includes actions to develop nurse-patient relationships and deliver physical and psychosocial care to patients. The high risk of transmission of the SARS-CoV-2 virus compromises nursing care. No evidence-based nursing guidelines exist for patients infected with SARS-CoV-2, leading to potential variations in patient experience, outcomes, quality and costs. METHODS AND ANALYSIS: we aim to recruit 840 in-patient participants treated for infection with the SARS-CoV-2 virus from 14 UK hospitals, to a cluster randomised controlled trial, with embedded process and economic evaluations, of care as usual and a fundamental nursing care protocol addressing specific areas of physical, relational and psychosocial nursing care where potential variation may occur, compared with care as usual. Our coprimary outcomes are patient-reported experience (Quality from the Patients' Perspective; Relational Aspects of Care Questionnaire); secondary outcomes include care quality (pressure injuries, falls, medication errors); functional ability (Barthell Index); treatment outcomes (WHO Clinical Progression Scale); depression Patient Health Questionnaire-2 (PHQ-2), anxiety General Anxiety Disorder-2 (GAD-2), health utility (EQ5D) and nurse-reported outcomes (Measure of Moral Distress for Health Care Professionals). For our primary analysis, we will use a standard generalised linear mixed-effect model adjusting for ethnicity of the patient sample and research intensity at cluster level. We will also undertake a planned subgroup analysis to compare the impact of patient-level ethnicity on our primary and secondary outcomes and will undertake process and economic evaluations. ETHICS AND DISSEMINATION: Research governance and ethical approvals are from the UK National Health Service Health Research Authority Research Ethics Service. Dissemination will be open access through peer-reviewed scientific journals, study website, press and online media, including free online training materials on the Open University's FutureLearn web platform. TRIAL REGISTRATION NUMBER: ISRCTN13177364; Pre-results.

Continuation of Antidepressants vs Sequential Psychological Interventions to Prevent Relapse in Depression: An Individual Participant Data Meta-analysis.

Importance: Depression frequently recurs. To prevent relapse, antidepressant medication is often taken in the long term. Sequentially delivering a psychological intervention while undergoing tapering of antidepressant medication might be an alternative to long-term antidepressant use. However, evidence is lacking on which patients may benefit from tapering antidepressant medication while receiving a psychological intervention and which should continue the antidepressant therapy. A meta-analysis of individual patient data with more power and precision than individual randomized clinical trials or a standard meta-analysis is warranted. Objectives: To compare the associations between use of a psychological intervention during and/or after antidepressant tapering vs antidepressant use alone on the risk of relapse of depression and estimate associations of individual clinical factors with relapse. Data Sources: PubMed, the Cochrane Library, Embase, and PsycInfo were last searched on January 23, 2021. Requests for individual participant data from included randomized clinical trials (RCTs) were sent. Study Selection: Randomized clinical trials that compared use of a psychological intervention while tapering antidepressant medication with antidepressant monotherapy were included. Patients had to be in full or partial remission from depression. Two independent assessors conducted screening and study selection. Data Extraction and Synthesis: Of 15 792 screened studies, 236 full-text articles were retrieved, and 4 RCTs that provided individual participant data were included. Main Outcomes and Measures: Time to relapse and relapse status over 15 months measured via a blinded assessor using a diagnostic clinical interview. Results: Individual data from 714 participants (mean [SD] age, 49.2 [11.5] years; 522 [73.1%] female) from 4 RCTs that compared preventive cognitive therapy or mindfulness-based cognitive therapy during and/or after antidepressant tapering vs antidepressant monotherapy were available. Two-stage random-effects meta-analysis found no significant difference in time to depressive relapse between use of a psychological intervention during tapering of antidepressant medication vs antidepressant therapy alone (hazard ratio [HR], 0.86; 95% CI, 0.60-1.23). Younger age at onset (HR, 0.98; 95% CI, 0.97-0.99), shorter duration of remission (HR, 0.99; 95% CI, 0.98-1.00), and higher levels of residual depressive symptoms at baseline (HR, 1.07; 95% CI, 1.04-1.10) were associated with a higher overall risk of relapse. None of the included moderators were associated with risk of relapse. Conclusions and Relevance: The findings of this individual participant data meta-analysis suggest that regardless of the clinical factors included in these studies, the sequential delivery of a psychological intervention during and/or after tapering may be an effective relapse prevention strategy instead of long-term use of antidepressants. These results could be used to inform shared decision-making in clinical practice.