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Abstract Background Early Intervention in Psychosis (EIP) services improve health outcomes for young people with psychosis in the medium-long term, but 25% of young people disengage in the first 12 months with costs to their mental health, families, society and health services. This study will evaluate the effectiveness of a team-based motivational engagement intervention, the Early Youth Engagement (EYE-2) intervention. Methods and design The EYE-2 trial is a cluster randomised controlled trial comparing the EYE-2 intervention plus standardised EIP service to standardised EIP service alone, with randomisation at the clinical team (cluster) level. The study aimed to enrol 950 young people (aged 14–35 years) with first episode psychosis in 10 teams per arm. Results The primary outcome is time to disengagement: days from the date of allocation to care coordinator to date of the last contact following either refusal to engage with an EIP team or lack of response to EIP contact for 3 consecutive months which will be analysed using a shared frailty model. Secondary outcomes are Health of the Nation Outcome Scale (HoNOS), Process of Recovery Questionnaire (QPR), DIALOG (a service user-reported measure of quality of life and treatment satisfaction) and service use outcomes which will be analysed using mixed effects regression models. Discussion This paper is the detailed statistical analysis plan for the EYE-2 trial. Any changes to, or deviations from, this plan will be described and justified in the final trial report. Trial registration ISRCTN 51629746 . Prospectively registered on 7 May 2019. Date assigned 10 May 2019.

Abstract Background Early Intervention in Psychosis (EIP) services improve health outcomes for young people with psychosis in the medium–long term, but 25% of young people disengage in the first 12 months with costs to their mental health, families, society and the NHS. This study will evaluate the effectiveness, cost-effectiveness and implementation of a team-based motivational Early Youth Engagement (EYE-2) intervention. Method The study design is a cluster randomised controlled trial (RCT) with economic evaluation, comparing the EYE-2 intervention + standardised EIP service to standardised EIP service alone, with randomisation at the team level. A process evaluation will evaluate the delivery of the intervention qualitatively and quantitatively across contexts. The setting is 20 EIP teams in 5 sites: Manchester, South London, East Anglia, Thames Valley and Hampshire. Participants are young people (14–35 years) with first episode psychosis, and EIP staff. The intervention is the team-based motivational engagement (EYE-2) intervention, delivered alongside standardised EIP services, and supported by additional training, website, booklets and social groups. The comparator is the standardised EIP service. Both interventions are delivered by EIP clinicians. The primary outcome is time to disengagement (time in days from date of allocation to care coordinator to date of last contact following refusal to engage with EIP service, or lack of response to EIP contact for a consecutive 3-month period). Secondary outcomes include mental and physical health, deaths, social and occupational function, recovery, satisfaction and service use at 6, 12, 18 and 24 months. A 12-month within-trial economic evaluation will investigate cost-effectiveness from a societal perspective and from an NHS perspective. Discussion The trial will provide the first test of an engagement intervention in standardised care, with the potential for significant impact on the mental health and wellbeing of young people and their families, and economic benefits for services. The intervention will be highly scalable, supported by the toolkit including manuals, commissioning guide, training and resources, adapted to meet the needs of the diverse EIP population, and based on an in-depth process evaluation. Trial registration ISRCTN 51629746 prospectively registered 7th May 2019. Date assigned 10th May 2019.

Abstract Background Healthcare workers experience higher levels of work-related stress and higher rates of sickness absence than workers in other sectors. Psychological approaches have potential in providing healthcare workers with the knowledge and skills to recognise stress and to manage stress effectively. The strongest evidence for effectiveness in reducing stress in the workplace is for stress-management courses based on cognitive behavioural therapy (CBT) principles and mindfulness-based interventions (MBIs). However, research examining effects of these interventions on sickness absence (an objective indicator of stress) and compassion for others (an indicator of patient care) is limited, as is research on brief CBT stress-management courses (which may be more widely accessible) and on MBIs adapted for workplace settings. Methods/design This protocol is for two randomised controlled trials with participant preference between the two trials and 1:1 allocation to intervention or wait-list within the preferred choice. The first trial is examining a one-day CBT stress-management workshop and the second trial an 8-session Mindfulness-Based Cognitive Therapy for Life (MBCT-L) course, with both trials comparing intervention to wait-list. The primary outcome for both trials is stress post-intervention with secondary outcomes being sickness absence, compassion for others, depression symptoms, anxiety symptoms, wellbeing, work-related burnout, self-compassion, presenteeism, and mindfulness (MBCT-L only). Both trials aim to recruit 234 staff working in the National Health Service in the UK. Discussion This trial will examine whether a one-day CBT stress-management workshop and an 8-session MBCT-L course are effective at reducing healthcare staff stress and other mental health outcomes compared to wait-list, and, whether these interventions are effective at reducing sickness absence and presenteeism and at enhancing wellbeing, self-compassion, mindfulness and compassion for others. Findings will help inform approaches offered to reduce healthcare staff stress and other key variables. A note of caution is that individual-level approaches should only be part of the solution to reducing healthcare staff stress within a broader focus on organisational-level interventions and support. Trial registration ISRCTN Registry, ISRCTN11723441. Registered on 16 June 2017. Protocol Version 1: 24 April 2017. Trial Sponsor: Sussex Partnership NHS Foundation Trust (ResearchGovernance@sussexpartnership.nhs.uk).

Abstract Background Community-acquired respiratory infections are a leading cause of illness and death globally. The aetiologies of community-acquired pneumonia remain poorly defined. The RESPIRO study is an ongoing prospective observational cohort study aimed at developing pragmatic logistical and analytic platforms to accurately identify the causes of moderate-to-severe community-acquired pneumonia in adults and understand the factors influencing disease caused by individual pathogens. The study is currently underway in Singapore and has plans for expansion into the broader region. Methods RESPIRO is being conducted at three major tertiary hospitals in Singapore. Adults hospitalised with acute community-acquired pneumonia or lower respiratory tract infections, based on established clinical, laboratory and radiological criteria, will be recruited. Over the course of the illness, clinical data and biological samples will be collected longitudinally and stored in a biorepository for future analysis. Discussion The RESPIRO study is designed to be hypothesis generating, complementary to and easily integrated with other research projects and clinical trials. The detailed clinical database and biorepository will yield insights into the epidemiology and outcomes of community-acquired lower respiratory tract infections in Singapore and the surrounding region and offers the opportunity to deeply characterise the microbiology and immunopathology of community-acquired pneumonia.

Abstract Background Emergency front-of-neck airway (eFONA) is a life-saving procedure in “cannot intubate, cannot oxygenate” (CICO). The fastest and most reliable method of eFONA has not been determined. We compared two of the most advocated approaches: surgical cricothyroidotomy and percutaneous cricothyroidotomy, in an obese, in vivo porcine hemorrhage model, designed to introduce real-time physiological feedback, relevant and high provider stress. The primary aim was to determine the fastest method to secure airway. Secondary aims were arterial saturation and partial pressure of oxygen, proxy survival and influence of experience. Methods Twelve pigs, mean weight (standard deviation, SD) (60.3 ± 4.1) kg, were anesthetized and exposed to 25–35% total blood volume hemorrhage before extubation and randomization to Seldinger technique “percutaneous cricothyroidotomy” (n = 6) or scalpel-bougie-tube technique “surgical cricothyroidotomy” (n = 6). Specialists in anesthesia and intensive care in a tertiary referral hospital performed the eFONA, simulating an actual CICO-situation. Results In surgical cricothyroidotomy vs. percutaneous cricothyroidotomy, the median (interquartile range, IQR) times to secure airway were 109 (IQR 71–130) s and 298 (IQR 128–360) s (P = 0.0152), arterial blood saturation (SaO2) were 74.7 (IQR 46.6–84.2) % and 7.9 (IQR 4.1–15.6) % (P = 0.0167), pO2 were 7.0 (IQR 4.7–7.7) kPa and 2.0 (IQR 1.1–2.9) kPa (P = 0.0667), and times of cardiac arrest (proxy survival) were 137–233 s, 190 (IQR 143–229), from CICO. All six animals survived surgical cricothyroidotomy, and two of six (33%) animals survived percutaneous cricothyroidotomy. Years in anesthesia, 13.5 (IQR 7.5–21.3), did not influence time to secure airway. Conclusion eFONA by surgical cricothyroidotomy was faster and had increased oxygenation and survival, when performed under stress by board certified anesthesiologists, and may be an indication of preferred method in situations with hemorrhage and CICO, in obese patients.

Abstract Background Patients with headache often seek urgent medical care to treat pain and associated symptoms that do not respond to therapeutic options at home. Urgent Cares (UCs) may be suitable for the evaluation and treatment of such patients but there is little data on how headache is evaluated in UC settings and what types of treatments are available. We conducted a study to evaluate the types of care available for patients with headache presenting to UCs. Design Cross-Sectional. Methods Headache specialists across the United States contacted UCs to collect data on a questionnaire. Questions asked about UC staffing (e.g. number and backgrounds of staff, hours of operation), average length of UC visits for headache, treatments and tests available for patients presenting with headache, and disposition including to the ED. Results Data from 10 UC programs comprised of 61 individual UC sites revealed: The vast majority (8/10; 80%) had diagnostic testing onsite for headache evaluation. A small majority (6/10; 60%) had the American Headache Society recommended intravenous medications for acute migraine available. Half (5/10) had a headache protocol in place. The majority (6/10; 60%) had no follow up policy after UC discharge. Conclusions UCs have the potential to provide expedited care for patients presenting for evaluation and treatment of headache. However, considerable variability exists amongst UCs in their abilities to manage headaches. This study reveals many opportunities for future research including the development of protocols and professional partnerships to help guide the evaluation, triage, and treatment of patients with headache in UC settings.

Abstract Introduction Post stroke management has moved into the focus as it represents the only way to secure acute treatment effects in the long term. Due to individual courses, post stroke management appears rather challenging and is hindered by existing barriers between treatment sectors. As a novel concept, the PostStroke-Manager combines digital and sensor-based technology with personal assistance to enable intersectoral cooperation, best possible reduction of stroke-related disability, optimal secondary prevention, and detection of physical and psychological comorbidities. Methods This prospective single-center observational study aims to investigate the feasibility of the PostStroke-Manager concept in an outpatient setting. Ninety patients who have suffered an ischemic or hemorrhagic stroke or transient ischemic attack will be equipped with a tablet and mobile devices recording physical activity, blood pressure, and electrocardiographic signals. Through a server-based platform, patients will be connected with the primary care physician, a stroke pilot and, if necessary, other specialists who will use web-based platforms. Via the tablet, patients will have access to an application with 10 newly designed components including, for instance, a communication tool, medication schedule, medical records platform, and psychometric screenings (e.g., depression, anxiety symptoms, quality of life, adherence, cognitive impairment). During the 1-year follow-up period, clinical visits are scheduled at three-month intervals. In the interim, communication will be secured by an appropriate tool that includes text messenger, audio, and video telephony. As the primary endpoint, feasibility will be measured by a 14-item questionnaire that addresses digital components, technical support, and personal assistance. The PostStroke-Manager will be judged feasible if at least 50% of these aspects are rated positively by at least 75% of patients. Secondary endpoints include feedback from professionals and longitudinal analyses on clinical and psychometric parameters. Perspective This study will answer the question of whether combined digital and personal support is a feasible approach to post stroke management. Furthermore, the patient perspective gained regarding digital support may help to specify future applications. This study will also provide information regarding the potential use of remote therapies and mobile devices in situations with limited face-to-face contacts. Trial registration German Register for Clinical Trials ( DRKS00023213 .), registered 27 April 2021.

Abstract Background Arterial and venous thrombosis are reported to be common in critically ill COVID-19 patients. Method and results This is a national multicenter retrospective observational study involving all consecutive adult COVID-19 patients who required intensive care units (ICU) admission between 23 January 2020 and 30 April 2020 in Singapore. One hundred eleven patients were included and the venous and arterial thrombotic rates in ICU were 1.8% (n = 2) and 9.9% (n = 11), respectively. Major bleeding rate was 14.8% (n = 16). Conclusions Critically ill COVID-19 patients in Singapore have lower venous thromboembolism but higher arterial thrombosis rates and bleeding manifestations than other reported cohorts.

Abstract Background Since the beginning of the COVID-19 outbreak in December 2019, a substantial body of COVID-19 medical literature has been generated. As of June 2020, gaps and longitudinal trends in the COVID-19 medical literature remain unidentified, despite potential benefits for research prioritisation and policy setting in both the COVID-19 pandemic and future large-scale public health crises. Methods In this paper, we searched PubMed and Embase for medical literature on COVID-19 between 1 January and 24 March 2020. We characterised the growth of the early COVID-19 medical literature using evidence maps and bibliometric analyses to elicit cross-sectional and longitudinal trends and systematically identify gaps. Results The early COVID-19 medical literature originated primarily from Asia and focused mainly on clinical features and diagnosis of the disease. Many areas of potential research remain underexplored, such as mental health, the use of novel technologies and artificial intelligence, pathophysiology of COVID-19 within different body systems, and indirect effects of COVID-19 on the care of non-COVID-19 patients. Few articles involved research collaboration at the international level (24.7%). The median submission-to-publication duration was 8 days (interquartile range: 4–16). Conclusions Although in its early phase, COVID-19 research has generated a large volume of publications. However, there are still knowledge gaps yet to be filled and areas for improvement for the global research community. Our analysis of early COVID-19 research may be valuable in informing research prioritisation and policy planning both in the current COVID-19 pandemic and similar global health crises.

Abstract Background Antimicrobial resistance is a public health problem of global importance. In Singapore, much focus has been given to antibiotic usage patterns in hospital settings. Data on antibiotic use in primary care is lacking. We describe antibiotic usage patterns and assess factors contributing to antibiotic usage among adults presenting with acute febrile illness (AFI) in primary care settings in Singapore. Methods We analyzed data from the Early Dengue infection and outcome study. Adults with AFI presenting at 5 Singapore polyclinics were included. We used multivariable logistic regression to assess demographic, clinical and laboratory factors associated with antibiotic usage among adults with AFI. Results Between December 2007 and February 2013, 1884 adult AFI patients were enrolled. Overall, 16% of adult AFI patients reported antibiotic use. We observed a rise in the use of over-the-counter medications in late 2009 and a decrease in antibiotic use during 2010, possibly related to the outbreak of pandemic influenza A H1N1 virus. After adjusting for age, gender, polyclinic and year of enrolment, the following factors were associated with higher odds of antibiotic use: living in landed property (compared to public housing) (OR = 1.73; 95% CI: 1.06–2.80); body mass index (BMI)

Abstract Background Undifferentiated acute febrile illness (AFI) is a common presentation among adults in primary care settings in Singapore but large gaps exist in the understanding of the characteristics of these patients. We studied clinical and epidemiological characteristics of AFI patients and factors associated with delayed recovery from AFI. Methods We performed a secondary data analysis using data from the Early DENgue infection and outcome (EDEN) study on 2046 adult patients presenting at 5 Singapore polyclinics between December 2007 and February 2013 with a history of fever (≥38 °C) for less than 72 h. We used an accelerated failure time model to investigate factors associated with delayed recovery from AFI. Results The mean age of patients was 36.6 years, 65 % were male, 51 % were of Chinese ethnicity, and 75 % lived in public housing. Median illness duration was 5 days (interquartile range, 3–7). In multivariable analysis, the unemployed and white collar workers had longer illness duration compared with blue collar workers (time ratio (TR), 1.10; 95 % confidence interval (CI), 1.03–1.17 and TR, 1.08; 95 % CI, 1.02–1.15, respectively). Patients with more symptoms at initial consultation had slower recovery (TR, 1.03 per additional symptom; 95 % CI, 1.02–1.03). Other clinical factors were also associated with longer duration of illness, including use of analgesics (TR, 1.21; 95 % CI, 1.15–1.28); use of cough medicines (TR, 1.14; 95 % CI, 1.08–1.20); use of antibiotics (TR, 1.14; 95 % CI, 1.07–1.21); and hospitalization (TR, 1.59; 95 % CI, 1.39–1.82). Compared to patients with normal WBC count at first consultation, those with low WBC count had slower recovery (TR, 1.14; 95 % CI, 1.07–1.21), while the reverse was observed among patients with high WBC count (TR, 0.94; 95 % CI, 0.88–1.00). Conclusions Differences in illness duration among different types of employment may reflect differences in their underlying general health status. Early identification of factors delaying recovery could help triage management in a primary care setting. In-depth characterization of fever etiology in Singapore will improve surveillance and control activities.