Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial

Background Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy

Effect of acute citalopram on self-referential emotional processing and social cognition in healthy volunteers

This study was funded by the UK National Productivity Investment Fund awarded to C.H. through the GW4 BioMed Medical Research Council Doctoral Training Partnership. This study was supported by the National Institute for Health Research (NIHR) Oxford Health Biomedical Research Centre. The views expressed are those of the authors and not necessarily those of the National Health Service, the NIHR or the Department of Health. ICMJE forms are in the supplementary material, available online at https://doi.org/10.1192/bjo.2020.107.Peer reviewedPublisher PD

The impact of point-of-care testing for influenza on antimicrobial stewardship (PIAMS) in UK primary care: protocol for a mixed methods study

Background: Molecular point-of-care testing (POCT) used in primary care can inform whether a patient presenting with an acute respiratory infection has influenza. A confirmed clinical diagnosis, particularly early in the disease, could inform better antimicrobial stewardship. Social distancing and lockdowns during the COVID-19 pandemic have disturbed previous patterns of influenza infections in 2021. However, data from samples taken in the last quarter of 2022 suggest that influenza represents 36% of sentinel network positive virology, compared with 24% for respiratory syncytial virus. Problems with integration into the clinical workflow is a known barrier to incorporating technology into routine care. Objective: This study aims to report the impact of POCT for influenza on antimicrobial prescribing in primary care. We will additionally describe severe outcomes of infection (hospitalization and mortality) and how POCT is integrated into primary care workflows. Methods: The impact of POCT for influenza on antimicrobial stewardship (PIAMS) in UK primary care is an observational study being conducted between December 2022 and May 2023 and involving 10 practices that contribute data to the English sentinel network. Up to 1000 people who present to participating practices with respiratory symptoms will be swabbed and tested with a rapid molecular POCT analyzer in the practice. Antimicrobial prescribing and other study outcomes will be collected by linking information from the POCT analyzer with data from the patient’s computerized medical record. We will collect data on how POCT is incorporated into practice using data flow diagrams, unified modeling language use case diagrams, and Business Process Modeling Notation. Results: We will present the crude and adjusted odds of antimicrobial prescribing (all antibiotics and antivirals) given a POCT diagnosis of influenza, stratifying by whether individuals have a respiratory or other relevant diagnosis (eg, bronchiectasis). We will also present the rates of hospital referrals and deaths related to influenza infection in PIAMS study practices compared with a set of matched practices in the sentinel network and the rest of the network. We will describe any difference in implementation models in terms of staff involved and workflow. Conclusions: This study will generate data on the impact of POCT testing for influenza in primary care as well as help to inform about the feasibility of incorporating POCT into primary care workflows. It will inform the design of future larger studies about the effectiveness and cost-effectiveness of POCT to improve antimicrobial stewardship and any impact on severe outcomes. International Registered Report Identifier (IRRID): DERR1-10.2196/4693

Does device matter? Impacts of food-specific inhibition training on food choice, liking and approach bias when delivered by smartphone or computer.

Food-specific inhibition training (FSIT) requires users to inhibit responses to energy-dense (ED) food stimuli within a reaction time game. FSIT reduces choice and liking of ED foods. Research with the public shows larger effects when FSIT is delivered by computer versus smartphone. This pre-registered study is the first to compare computer-FSIT versus smartphone-FSIT in a controlled setting. Three-hundred-and-thirty-one adults were randomised to computer-FSIT, smartphone-FSIT or non-food control training (computer-delivered). In session 1, participants completed baseline measures of impulsive food choice, food approach bias (approach/avoid implicit association test), and food liking ratings, before completing eight minutes of FSIT/control training. In session 2, participants repeated the same training task, followed by the same measures of food choice, approach bias and liking. We hypothesised that FSIT groups would show healthier food choices, lower ED food liking, and reduced ED food approach bias at post-training compared to control. We expected no statistically significant differences between the two FSIT groups. Post-exclusions, data for 259 participants was analysed. Contrary to predictions, there was no evidence of significant group differences on any of the outcome measures. Baseline measures suggest participants already showed high approach to healthy foods, which may explain these null results

Variation in recognition of happy and sad facial expressions and self-reported depressive symptom severity:A prospective cohort study

Objective: Cognitive theories suggest people with depression interpret self-referential social information negatively. However, it is unclear whether these biases precede or follow depression. We investigated whether facial expression recognition was associated with depressive symptoms cross-sectionally and longitudinally. Methods: Prospective cohort study of people who had visited UK primary care in the past year reporting depressive symptoms (n = 509). Depressive symptoms were measured using the Patient Health Questionnaire (PHQ-9) at four time-points, 2 weeks apart. A computerised task assessed happy and sad facial expression recognition at three time-points (n = 505 at time 1). The unbiased hit rate measured ability to recognise emotions accounting for any general tendency to identify the emotion when it was not present. Results: The sample included the full range of depressive symptom severity, with 45% meeting diagnostic criteria for depression. There was no evidence that happy or sad unbiased hit rates were associated with concurrent or subsequent depressive symptoms. There was weak evidence that, for every additional face incorrectly classified as happy, concurrent PHQ-9 scores reduced by 0.05 of a point (95% CI = -0.10 to 0.002, p = 0.06 after adjustment for confounders). This association was strongest for more ambiguous facial expressions (interaction term p<0.001). Limitations: This was an observational study with relatively short follow-up (6 weeks) and small changes in depressive symptoms and emotion recognition. Only 7% of invited patients consented to participate. Conclusions: Reduced misclassifications of ambiguous faces as happy could be a state marker of depression, but was not associated with subsequent depressive symptoms. Future research should focus on the interpretation of ambiguous social informatio

Antidepressant treatment with sertraline for adults with depressive symptoms in primary care : the PANDA research programme including RCT

Background Despite a growing number of prescriptions for antidepressants (over 70 million in 2018), there is uncertainty about when people with depression might benefit from antidepressant medication and concern that antidepressants are prescribed unnecessarily. Objectives The main objective of the PANDA (What are the indications for Prescribing ANtiDepressAnts that will lead to a clinical benefit?) research programme was to provide more guidance about when antidepressants are likely to benefit people with depression. We aimed to estimate the minimal clinically important difference for commonly used self-administered scales for depression and anxiety, and to understand more about how patients respond to such assessments. We carried out an observational study of patients with depressive symptoms and a placebo-controlled randomised controlled trial of sertraline versus placebo to estimate the treatment effect in UK primary care. The hypothesis was that the severity and duration of symptoms were related to treatment response. Design The programme consisted of three phases. The first phase relied on the secondary analysis of existing data extracted from published trials. The second phase was the PANDA cohort study of patients with depressive symptoms who presented to primary care and were followed up 2, 4 and 6 weeks after a baseline assessment. Both quantitative and qualitative methods were used in the analysis. The third phase was a multicentre randomised placebo-controlled double-blind trial of sertraline versus placebo in patients presenting to primary care with depressive symptoms. Setting UK primary care in Bristol, London, Liverpool and York. Participants Patients aged 18–74 years who were experiencing depressive symptoms in primary care. Eligibility for the PANDA randomised controlled trial included that there was uncertainty about the benefits about treatment with an antidepressant. Interventions In the PANDA randomised controlled trial, patients were individually randomised to 100 mg daily of sertraline or an identical placebo. The PANDA cohort study was an observational study. Main outcome measures Depressive symptoms measured using the Patient Health Questionnaire were the primary outcome for the randomised controlled trial. Other outcomes included anxiety symptoms using the Generalised Anxiety Disorder-7; depressive symptoms using the Beck Depression Inventory, version 2; health-related quality of life; self-reported improvement; and cost-effectiveness. Results The secondary analysis of existing randomised controlled trials [GENetic and clinical Predictors Of treatment response in Depression (GenPod), TREAting Depression with physical activity (TREAD) and Clinical effectiveness and cost-effectiveness of cognitive Behavioural Therapy as an adjunct to pharmacotherapy for treatment-resistant depression in primary care (CoBalT)] found evidence that the minimal clinically important difference increased as the initial severity of depressive symptoms rose. Our estimates of minimal clinically important difference were a 17% and 18% reduction in Beck Depression Inventory scores for GenPod and TREAD, respectively. In CoBalT, a 32% reduction corresponded to the minimal clinically important difference but the participants in this study had depression that had not responded to antidepressants. In the PANDA study cohort, and from our analyses in existing data, we found that the minimal clinically important difference varies considerably with the initial severity of depressive and anxiety symptoms. Expressing the minimal clinically important difference as a percentage reduction reduces this variation at higher scores, but at low scores the percentage reduction increased substantially. The results from the qualitative studies pointed out many limitations of the Patient Health Questionnaire-9 items in assessing change and recovery from depression. In the PANDA randomised controlled trial, there was no evidence that sertraline resulted in a reduction in depressive symptoms within 6 weeks of randomisation, but there was some evidence of a reduction by 12 weeks. However, sertraline led to a reduction in anxiety symptoms, an improvement of mental health-related quality of life and an increased likelihood of reporting improvement. The mean Patient Health Questionnaire-9 items score at 6 weeks was 7.98 (standard deviation 5.63) in the sertraline group and 8.76 (standard deviation 5.86) in the placebo group (5% relative reduction, 95% confidence interval –7% to 15%; p = 0.41). Of the secondary outcomes, there was strong evidence that sertraline reduced anxiety symptoms (Generalised Anxiety Disorder-7 score reduced by 17% (95% confidence interval 9% to 25%; p = 0.00005). Sertraline had a high probability (> 90%) of being cost-effective at 12 weeks. The PANDA randomised controlled trial found no evidence that treatment response or cost-effectiveness was related to severity or duration of depressive symptoms. The minimal clinically important difference estimates suggested that sertraline’s effect on anxiety, but not on depression, was likely to be clinically important. Limitations The results from the randomised controlled trial and the estimates of minimal clinically important difference were not sufficiently precise to provide specific clinical guidance for individuals. We had low power in testing whether or not initial severity and duration of depressive symptoms are related to treatment response. Conclusions The results of the trial support the use of sertraline and probably other selective serotonin reuptake inhibitors because of their action in reducing anxiety symptoms and the likelihood of longer-term benefit on depressive symptoms. Sertraline could be prescribed for anxiety symptoms that commonly occur with depression and many patients will experience a clinical benefit. The Patient Health Questionnaire-9 items and similar self-administered scales should not be used on their own to assess clinical outcome, but should be supplemented with further clinical assessment. Future work We need to examine the longer-term effects of antidepressant treatment. We need more precise estimates of the treatment effects and minimal clinically important difference at different severities to provide more specific guidance for individuals. However, the methods we have developed provide an approach towards providing such detailed guidance. Trial registration Current Controlled Trials ISRCTN84544741 and EudraCT number 2013-003440-22. Funding This project was funded by the National Institute for Health Research (NIHR) Programme Grants for Applied Research programme and will be published in full in Programme Grants for Applied Research; Vol. 7, No. 10. See the NIHR Journals Library website for further project information

The effects of isolated game elements on adherence rates in food response inhibition training

Food response inhibition training (food-RIT) is found to aid weight loss and reduce snacking of foods high in sugar, salt and fat. However, these interventions suffer from a lack of adherence, with gamification proposed as a solution to increase engagement. The effect of gamification is unclear, however, with a lack of research investigating the effects of single game elements in improving adherence to interventions. This study investigates whether isolated game elements (social or feedback) improve adherence, engagement and effectiveness of food-RIT compared to a standard non-gamified intervention. Two hundred and fifty-two participants (169 female) were randomly assigned to either non-gamified F-RIT, a training gamified with feedback elements or a training gamified with social elements. Participants completed measures of snacking frequency and food evaluation before and after a 14-day training period, with adherence and motivation recorded during this time. There were no significant effects of adding either feedback or social gamification elements on training adherence, motivation or effectiveness. There was no meaningful support for adding isolated game elements to food-RIT to improve intervention adherence, raising questions about the magnitude of simple gamification effects. Future research may benefit from systematically assessing the combined effects of multiple gamification elements

A core outcome set for pre-eclampsia research:an international consensus development study

Objective: To develop a core outcome set for pre-eclampsia. Design: Consensus development study. Setting: International. Population: Two hundred and eight-one healthcare professionals, 41 researchers and 110 patients, representing 56 countries, participated. Methods: Modified Delphi method and Modified Nominal Group Technique. Results: A long-list of 116 potential core outcomes was developed by combining the outcomes reported in 79 pre-eclampsia trials with those derived from thematic analysis of 30 in-depth interviews of women with lived experience of pre-eclampsia. Forty-seven consensus outcomes were identified from the Delphi process following which 14 maternal and eight offspring core outcomes were agreed at the consensus development meeting. Maternal core outcomes: death, eclampsia, stroke, cortical blindness, retinal detachment, pulmonary oedema, acute kidney injury, liver haematoma or rupture, abruption, postpartum haemorrhage, raised liver enzymes, low platelets, admission to intensive care required, and intubation and ventilation. Offspring core outcomes: stillbirth, gestational age at delivery, birthweight, small-for-gestational-age, neonatal mortality, seizures, admission to neonatal unit required and respiratory support. Conclusions: The core outcome set for pre-eclampsia should underpin future randomised trials and systematic reviews. Such implementation should ensure that future research holds the necessary reach and relevance to inform clinical practice, enhance women's care and improve the outcomes of pregnant women and their babies. Tweetable abstract: 281 healthcare professionals, 41 researchers and 110 women have developed #preeclampsia core outcomes @HOPEoutcomes @jamesmnduffy. [Correction added on 29 June 2020, after first online publication: the order has been corrected.].</p

A core outcome set for pre-eclampsia research:an international consensus development study

Objective: To develop a core outcome set for pre-eclampsia. Design: Consensus development study. Setting: International. Population: Two hundred and eight-one healthcare professionals, 41 researchers and 110 patients, representing 56 countries, participated. Methods: Modified Delphi method and Modified Nominal Group Technique. Results: A long-list of 116 potential core outcomes was developed by combining the outcomes reported in 79 pre-eclampsia trials with those derived from thematic analysis of 30 in-depth interviews of women with lived experience of pre-eclampsia. Forty-seven consensus outcomes were identified from the Delphi process following which 14 maternal and eight offspring core outcomes were agreed at the consensus development meeting. Maternal core outcomes: death, eclampsia, stroke, cortical blindness, retinal detachment, pulmonary oedema, acute kidney injury, liver haematoma or rupture, abruption, postpartum haemorrhage, raised liver enzymes, low platelets, admission to intensive care required, and intubation and ventilation. Offspring core outcomes: stillbirth, gestational age at delivery, birthweight, small-for-gestational-age, neonatal mortality, seizures, admission to neonatal unit required and respiratory support. Conclusions: The core outcome set for pre-eclampsia should underpin future randomised trials and systematic reviews. Such implementation should ensure that future research holds the necessary reach and relevance to inform clinical practice, enhance women's care and improve the outcomes of pregnant women and their babies. Tweetable abstract: 281 healthcare professionals, 41 researchers and 110 women have developed #preeclampsia core outcomes @HOPEoutcomes @jamesmnduffy. [Correction added on 29 June 2020, after first online publication: the order has been corrected.].</p

Increased Monocyte Turnover from Bone Marrow Correlates with Severity of SIV Encephalitis and CD163 Levels in Plasma

Cells of the myeloid lineage are significant targets for human immunodeficiency virus (HIV) in humans and simian immunodeficiency virus (SIV) in monkeys. Monocytes play critical roles in innate and adaptive immunity during inflammation. We hypothesize that specific subsets of monocytes expand with AIDS and drive central nervous system (CNS) disease. Additionally, there may be expansion of cells from the bone marrow through blood with subsequent macrophage accumulation in tissues driving pathogenesis. To identify monocytes that recently emigrated from bone marrow, we used 5-bromo-2′-deoxyuridine (BrdU) labeling in a longitudinal study of SIV-infected CD8+ T lymphocyte depleted macaques. Monocyte expansion and kinetics in blood was assessed and newly migrated monocyte/macrophages were identified within the CNS. Five animals developed rapid AIDS with differing severity of SIVE. The percentages of BrdU+ monocytes in these animals increased dramatically, early after infection, peaking at necropsy where the percentage of BrdU+ monocytes correlated with the severity of SIVE. Early analysis revealed changes in the percentages of BrdU+ monocytes between slow and rapid progressors as early as 8 days and consistently by 27 days post infection. Soluble CD163 (sCD163) in plasma correlated with the percentage of BrdU+ monocytes in blood, demonstrating a relationship between monocyte activation and expansion with disease. BrdU+ monocytes/macrophages were found within perivascular spaces and SIVE lesions. The majority (80–90%) of the BrdU+ cells were Mac387+ that were not productively infected. There was a minor population of CD68+BrdU+ cells (<10%), very few of which were infected (<1% of total BrdU+ cells). Our results suggest that an increased rate of monocyte recruitment from bone marrow into the blood correlates with rapid progression to AIDS, and the magnitude of BrdU+ monocytes correlates with the severity of SIVE