Background Associations between human herpesviruses (HHVs) and cardiovascular disease/mortality have been reported, but evidence is inconsistent. We investigated associations between three common herpesviruses and i) incident stroke or myocardial infarction (MI) and ii) all-cause mortality. Methods We included participants from the UK Biobank Infectious Disease pilot study with valid serum antibody (IgG) measurements taken at cohort entry (2006-2010) for herpes simplex virus type 1 (HSV1), varicella zoster virus (VZV), and cytomegalovirus (CMV). Linked hospital and mortality records up to 30/12/2019 provided information on rates of i) incident first stroke or MI and ii) all-cause mortality. Hazard ratios (HRs) from Cox proportional hazards regression models were used to assess relationships between (i) HHV seropositivity, (ii) HHV titre and incident stroke/MI and death outcomes. Fully adjusted models accounted for sociodemographic information (age, sex, ethnicity, education, deprivation quintile, birthplace, population density), baseline comorbidities (including diabetes and hypertension), smoking status, body mass index and serum cholesterol. Results Of 9429 study participants (56% female, 95% White, median age 58 years), 41% were seropositive for all three HHVs. HHV seropositivity was not associated with stroke/MI (fully-adjusted HRs and 95% confidence intervals: HSV1; 0.93 [0.72–1.22], VZV; 0.78 [0.51–1.20], CMV; 0.91 [0.71–1.16]) or all-cause mortality (HSV1; 1.21 [1.00–1.47], VZV: 0.79 [0.58–1.07], CMV: 0.90 [0.76–1.06]). HHV titres were not associated with outcomes. Conclusions In this mostly White UK Biobank subset, neither HHV seropositivity nor titres were associated with stroke/MI or all-cause mortality.

Background The Structured E-Parenting Support (STEPS) app provides support for parents of children with elevated hyperactivity, impulsivity, inattention, and conduct problems who are awaiting clinical assessment. STEPS will be evaluated in a randomized controlled trial (RCT) within the Online Parent Training for the Initial Management of ADHD Referrals (OPTIMA) research program in the United Kingdom. Phase 1 of the OPTIMA tested the feasibility of participants’ recruitment and the app’s usability. Objective This study aimed to adapt a digital routine clinical monitoring system, myHealthE, for research purposes to facilitate waitlist recruitment; test using remote methods to screen and identify participants quickly and systematically; pilot the acceptability of the recruitment and assessment protocol; and explore the usability of STEPS. Methods myHealthE was adapted to screen patients’ data. Parents’ and clinicians’ feedback on myHealthE was collected, and information governance reviews were conducted in clinical services planning to host the RCT. Potential participants for the observational feasibility study were identified from new referrals using myHealthE and non-myHealthE methods. Descriptive statistics were used to summarize the demographic and outcome variables. We estimated whether the recruitment rate would meet the planned RCT sample size requirement (n=352). In addition to the feasibility study participants, another group of parents was recruited to assess the STEPS usability. They completed the adapted System Usability Scale and responded to open-ended questions about the app, which were coded using the Enlight quality construct template. Results Overall, 124 potential participants were identified as eligible: 121 (97.6%) via myHealthE and 3 (2.4%) via non-myHealthE methods. In total, 107 parents were contacted, and 48 (44.9%) consented and were asked if, hypothetically, they would be willing to participate in the OPTIMA RCT. Of the 28 feasibility study participants who provided demographic data, 21 (75%) identified as White. Their children had an average age of 8.4 (SD 1.7) years and 65% (31/48) were male. During the primary recruitment period (June to July 2021) when 45 participants had consented, 38 (84%) participants agreed hypothetically to take part in the RCT (rate of 19/mo, 95% CI 13.5-26.1), meeting the stop-go criterion of 18 participants per month to proceed with the RCT. All parents were satisfied or very satisfied with the study procedures. Parents (n=12) recruited to assess STEPS’ usability described it as easy to navigate and use and as having an attractive combination of colors and visual design. They described the content as useful, pitched at the right level, and sensitively presented. Suggested improvements included adding captions to videos or making the recorded reflections editable. Conclusions Remote recruitment and study procedures for testing a parenting intervention app are feasible and acceptable for parents. The parents felt that STEPS was a useful and easy-to-use digital parenting support tool. International Registered Report Identifier (IRRID) RR2-10.1186/s40814-021-00959-0

• Background Peer support is effective in improving psychological well-being of family caregivers of people with conditions such as dementia, cancer, and brain injury. However, there are limited data on effective psychological interventions for family caregivers of people living with motor neurone disease. Our objective is to evaluate the efficacy of a virtual peer support programme for improving caregiver psychological wellbeing and caregiving related outcomes. • Methods We will conduct a multi-centre parallel group randomised controlled superiority trial. Using a multi-modal recruitment strategy, we will recruit informal caregivers from UK MND clinics, in-patient units, and hospices. We will randomise (1:1, stratified by gender) participants to either a 12-week virtual peer support programme or usual care comprising provision of online information resources publicly available via the MND Association website. Peer support programme elements will be delivered via a secure digital e-platform aTouchAway™ (Aetonix, Canada). Our target sample size is 160 (80 each arm). Our primary outcome is the Hospital Anxiety and Depression Scale (HADS) assessed at 12-weeks (primary endpoint). Secondary outcomes that will also be assessed at 12 weeks include the Zarit Burden Interview, Pearlin Mastery Scale, Personal Gain Scale, Positive Affect Scale and the Brief COPE. Outcome assessors will be blinded to allocation. Tertiary outcomes include perceived usability (1 item 9-point Likert scale) and acceptability (semi-structured qualitative interviews) of the peer support programme. Intervention fidelity measures will comprise frequency, type (text, audio, video), and duration (audio and video) of peer support contact downloaded from the aTouchAway AWS server. We will use a mixed-effects linear model to test the effect of the intervention on the primary outcome. Secondary outcomes will be analysed using linear regression. We have ethical approval (21/NW/0269) from the North-West Research Ethics Committee, UK. • Discussion This single blinded randomised controlled trial will determine the effect of a virtual peer support programme on caregiver psychological wellbeing and caregiver burden. This study will examine the impact of a virtual peer support intervention on quality-of-life measures in informal caregivers of individuals with MND living in the community. Trial registration ClinicalTrials.gov: NCT04695210

Background Peer support is effective in improving psychological well-being of family caregivers of people with conditions such as dementia, cancer, and brain injury. However, there are limited data on effective psychological interventions for family caregivers of people living with motor neurone disease. Our objective is to evaluate the efficacy of a virtual peer support programme for improving caregiver psychological wellbeing and caregiving related outcomes. Methods We will conduct a multi-centre parallel group randomised controlled superiority trial. Using a multi-modal recruitment strategy, we will recruit informal caregivers from UK MND clinics, in-patient units, and hospices. We will randomise (1:1, stratified by gender) participants to either a 12-week virtual peer support programme or usual care comprising provision of online information resources publicly available via the MND Association website. Peer support programme elements will be delivered via a secure digital e-platform aTouchAway™ (Aetonix, Canada). Our target sample size is 160 (80 each arm). Our primary outcome is the Hospital Anxiety and Depression Scale (HADS) assessed at 12 weeks (primary endpoint). Secondary outcomes that will also be assessed at 12 weeks include the Zarit Burden Interview, Pearlin Mastery Scale, Personal Gain Scale, Positive Affect Scale, and the Brief COPE. Outcome assessors will be blinded to allocation. Tertiary outcomes include perceived usability (1 item 9-point Likert scale) and acceptability (semi-structured qualitative interviews) of the peer support programme. Intervention fidelity measures will comprise frequency, type (text, audio, video), and duration (audio and video) of peer support contact downloaded from the aTouchAway AWS server. We will use a mixed-effects linear model to test the effect of the intervention on the primary outcome. Secondary outcomes will be analysed using linear regression. We have ethical approval (21/NW/0269) from the North-West Research Ethics Committee, UK. Discussion This single-blinded randomised controlled trial will determine the effect of a virtual peer support programme on caregiver psychological wellbeing and caregiver burden. This study will examine the impact of a virtual peer support intervention on quality-of-life measures in informal caregivers of individuals with MND living in the community. Trial registration ClinicalTrials.gov: NCT04695210