Heard, valued, supported? : Doctors' wellbeing during transitions triggered by COVID-19

Funding Information: The authors would like to thank all study participants who invested significant time and energy into participating in this study in exceptional circumstances. The authors would also like to thank study funders: Chief Scientist Office (Scotland) and Scottish Medical Education Research Consortium (SMERC). Publisher Copyright: © 2021 The Authors. Medical Education published by Association for the Study of Medical Education and John Wiley & Sons Ltd.Peer reviewedPublisher PD

Walk with Me: a protocol for a pilot RCT of a peer-led walking programme to increase physical activity in inactive older adults

Background: Levels of physical activity decline with age. Some of the most disadvantaged individuals in society, such as those from lower socio-economic position, are also the most inactive. Increasing physical activity levels, particularly among those most inactive, is a public health priority. Peer-led physical activity interventions may offer a model to increase physical activity in the older adult population. This study aims to test the feasibility of a peer-led, multicomponent physical activity intervention in socio-economically disadvantaged community dwelling older adults. Methods: The Medical Research Council framework for developing and evaluating complex interventions will be used to design and test the feasibility of a randomised controlled trial (RCT) of a multicomponent peer-led physical activity intervention. Data will be collected at baseline, immediately after the intervention (12 weeks) and 6 months after baseline measures. The pilot RCT will provide information on recruitment of peer mentors and participants and attrition rates, intervention fidelity, and data on the variability of the primary outcome (minutes of moderate to vigorous physical activity measured with an accelerometer). The pilot trail will also assess the acceptability of the intervention and identify potential resources needed to undertake a definitive study. Data analyses will be descriptive and include an evaluation of eligibility, recruitment, and retention rates. The findings will be used to estimate the sample size required for a definitive trial. A detailed process evaluation using qualitative and quantitative methods will be conducted with a variety of stakeholders to identify areas of success and necessary improvements. Discussion: This paper describes the protocol for the ‘Walk with Me’ pilot RCT which will provide the information necessary to inform the design and delivery of a fully powered trial should the Walk with Me intervention prove feasible

Colorectal cancer linkage on chromosomes 4q21, 8q13, 12q24, and 15q22

A substantial proportion of familial colorectal cancer (CRC) is not a consequence of known susceptibility loci, such as mismatch repair (MMR) genes, supporting the existence of additional loci. To identify novel CRC loci, we conducted a genome-wide linkage scan in 356 white families with no evidence of defective MMR (i.e., no loss of tumor expression of MMR proteins, no microsatellite instability (MSI)-high tumors, or no evidence of linkage to MMR genes). Families were ascertained via the Colon Cancer Family Registry multi-site NCI-supported consortium (Colon CFR), the City of Hope Comprehensive Cancer Center, and Memorial University of Newfoundland. A total of 1,612 individuals (average 5.0 per family including 2.2 affected) were genotyped using genome-wide single nucleotide polymorphism linkage arrays; parametric and non-parametric linkage analysis used MERLIN in a priori-defined family groups. Five lod scores greater than 3.0 were observed assuming heterogeneity. The greatest were among families with mean age of diagnosis less than 50 years at 4q21.1 (dominant HLOD = 4.51, α = 0.84, 145.40 cM, rs10518142) and among all families at 12q24.32 (dominant HLOD = 3.60, α = 0.48, 285.15 cM, rs952093). Among families with four or more affected individuals and among clinic-based families, a common peak was observed at 15q22.31 (101.40 cM, rs1477798; dominant HLOD = 3.07, α = 0.29; dominant HLOD = 3.03, α = 0.32, respectively). Analysis of families with only two affected individuals yielded a peak at 8q13.2 (recessive HLOD = 3.02, α = 0.51, 132.52 cM, rs1319036). These previously unreported linkage peaks demonstrate the continued utility of family-based data in complex traits and suggest that new CRC risk alleles remain to be elucidated. © 2012 Cicek et al

An enhanced toolkit for the generation of knockout and marker-free fluorescent Plasmodium chabaudi.

The rodent parasite Plasmodium chabaudi is an important in vivo model of malaria. The ability to produce chronic infections makes it particularly useful for investigating the development of anti- Plasmodium immunity, as well as features associated with parasite virulence during both the acute and chronic phases of infection. P. chabaudi also undergoes asexual maturation (schizogony) and erythrocyte invasion in culture, so offers an experimentally-amenable in vivo to in vitro model for studying gene function and drug activity during parasite replication. To extend the usefulness of this model, we have further optimised transfection protocols and plasmids for P. chabaudi and generated stable, fluorescent lines that are free from drug-selectable marker genes. These mother-lines show the same infection dynamics as wild-type parasites throughout the lifecycle in mice and mosquitoes; furthermore, their virulence can be increased by serial blood passage and reset by mosquito transmission. We have also adapted the large-insert, linear PlasmoGEM vectors that have revolutionised the scale of experimental genetics in another rodent malaria parasite and used these to generate barcoded P. chabaudi gene-deletion and -tagging vectors for transfection in our fluorescent P. chabaudi mother-lines. This produces a tool-kit of P. chabaudi lines, vectors and transfection approaches that will be of broad utility to the research community

Sexual and drug use risk behaviour trajectories among people treated for recent HCV infection: the REACT study.

INTRODUCTION Exploration of sexual and drug use behaviours following treatment for recent hepatitis C virus (HCV) is limited. This analysis modelled behavioural trajectories following treatment for recent HCV and assessed reinfection. METHODS Participants treated for recent HCV in an international trial (enrolled 2017-2019) were followed at 3-monthly intervals for up to 2 years to assess longitudinal behaviours. Population-averaged changes were assessed using generalized estimating equations. Distinct behavioural trajectories were identified using group-based trajectory modelling. HCV reinfection incidence was calculated using person-years (PY) of observation. RESULTS During the follow-up of 212 participants (84% gay and bisexual men [GBM]; 69% HIV; 26% current injecting drug use [IDU]), behavioural trajectories for IDU and stimulant use (past month) did not change. However, population-averaged decreases in the likelihood of daily IDU (adjusted odds ratio [AOR] 0.83; 95% CI 0.72, 0.95) and opioid use (AOR 0.84; 95% CI 0.75, 0.93) were observed. Among GBM, behavioural trajectories for chemsex did not change. Population-averaged decreases in condomless anal intercourse with casual male partners (CAI-CMP) (AOR 0.95; 95% CI 0.90, 0.99) and group-sex (AOR 0.86; 95% CI 0.80, 0.93) were observed, but masked distinct trajectories. While a proportion had a decreased probability of CAI-CMP (23%) and group-sex (59%) post-treatment, a substantial proportion retained a high probability of these behaviours. High HCV reinfection incidence was observed for the sustained high probability IDU (33.0/100 PY; 95% CI 17.7, 61.3) and chemsex (23.3/100 PY; 95% CI 14.5, 37.5) trajectories. CONCLUSIONS Limited sexual and drug use behavioural change was observed following treatment for recent HCV, supporting access to surveillance and (re)treatment

Peer-led walking programme to increase physical activity in inactive 60- to 70-year-olds: Walk with Me pilot RCT

Background Levels of physical activity decline with age. Some of the most disadvantaged individuals in society, such as those with a lower rather than a higher socioeconomic position, are also the most inactive. Peer-led physical activity interventions may offer a model to increase physical activity in these older adults and thus help reduce associated health inequalities. This study aims to develop and test the feasibility of a peer-led, multicomponent physical activity intervention in socioeconomically disadvantaged community-dwelling older adults. Objectives The study aimed to develop a peer-led intervention through a rapid review of previous peer-led interventions and interviews with members of the target population. A proposed protocol to evaluate its effectiveness was tested in a pilot randomised controlled trial (RCT). Design A rapid review of the literature and the pilot study informed the intervention design; a pilot RCT included a process evaluation of intervention delivery. Setting Socioeconomically disadvantaged communities in the South Eastern Health and Social Care Trust and the Northern Health and Social Care Trust in Northern Ireland. Participants Fifty adults aged 60–70 years, with low levels of physical activity, living in socioeconomically disadvantaged communities, recruited though community organisations and general practices. Interventions ‘Walk with Me’ is a 12-week peer-led walking intervention based on social cognitive theory. Participants met weekly with peer mentors. During the initial period (weeks 1–4), each intervention group participant wore a pedometer and set weekly step goals with their mentor’s support. During weeks 5–8 participants and mentors met regularly to walk and discuss step goals and barriers to increasing physical activity. In the final phase (weeks 9–12), participants and mentors continued to set step goals and planned activities to maintain their activity levels beyond the intervention period. The control group received only an information booklet on active ageing. Main outcome measures Rates of recruitment, retention of participants and completeness of the primary outcome [moderate- and vigorous-intensity physical activity measured using an ActiGraph GT3X+ accelerometer (ActiGraph, LLC, Pensacola, FL, USA) at baseline, 12 weeks (post intervention) and 6 months]; acceptability assessed through interviews with participants and mentors. Results The study planned to recruit 60 participants. In fact, 50 eligible individuals participated, of whom 66% (33/50) were female and 80% (40/50) were recruited from general practices. At 6 months, 86% (43/50) attended for review, 93% (40/43) of whom returned valid accelerometer data. Intervention fidelity was assessed by using weekly step diaries, which were completed by both mentors and participants for all 12 weeks, and checklists for the level of delivery of intervention components, which was high for the first 3 weeks (range 49–83%). However, the rate of return of checklists by both mentors and participants diminished thereafter. Outcome data indicate that a sample size of 214 is required for a definitive trial. Limitations The sample was predominantly female and somewhat active. Conclusions The ‘Walk with Me’ intervention is acceptable to a socioeconomically disadvantaged community of older adults and a definitive RCT to evaluate its effectiveness is feasible. Some modifications are required to ensure fidelity of intervention delivery is optimised. Future research needs to identify methods to recruit males and less active older adults into physical activity interventions

Atypical cortical networks in children at high-genetic risk of psychiatric and eurodevelopmental disorders

Although many genetic risk factors for psychiatric and neurodevelopmental disorders have been identified, the neurobiological route from genetic risk to neuropsychiatric outcome remains unclear. 22q11.2 deletion syndrome (22q11.2DS) is a copy number variant (CNV) syndrome associated with high rates of neurodevelopmental and psychiatric disorders including autism spectrum disorder (ASD), attention deficit hyperactivity disorder (ADHD) and schizophrenia. Alterations in neural integration and cortical connectivity have been linked to the spectrum of neuropsychiatric disorders seen in 22q11.2DS and may be a mechanism by which the CNV acts to increase risk. In this study, magnetoencephalography (MEG) was used to investigate electrophysiological markers of local and global network function in 34 children with 22q11.2DS and 25 controls aged 10–17 years old. Resting-state oscillatory activity and functional connectivity across six frequency bands were compared between groups. Regression analyses were used to explore the relationships between these measures, neurodevelopmental symptoms and IQ. Children with 22q11.2DS had altered network activity and connectivity in high and low frequency bands, reflecting modified local and long-range cortical circuitry. Alpha and theta band connectivity were negatively associated with ASD symptoms while frontal high frequency (gamma band) activity was positively associated with ASD symptoms. Alpha band activity was positively associated with cognitive ability. These findings suggest that haploinsufficiency at the 22q11.2 locus impacts short and long-range cortical circuits, which could be a mechanism underlying neurodevelopmental and psychiatric vulnerability in this high-risk group