Brief Exercise at Work (BE@Work): A Mixed-Methods Pilot Trial of a Workplace High-Intensity Interval Training Intervention

Introduction: The efficacy of high-intensity interval training (HIIT) for improving markers of physical fitness and cardiometabolic health is promising. The workplace is one non-laboratory setting where the effectiveness of HIIT could be explored. The aim of this study was to undertake a mixed-methods exploratory pilot trial of a workplace HIIT intervention named Brief Exercise at Work (BE@Work).Methods: Fifty-four healthy employees (mean ± standard deviation [SD] age 46 ± 10 years) from two workplaces in Northeast England were allocated to 8 weeks of thrice-weekly workplace HIIT based on boxing, stair climbing and stepping, comprising 4–7 60 s high-intensity intervals interspersed with 75 s rest (n = 30), or a no-intervention control (n = 24). The primary outcome was the change SD of predicted maximal oxygen consumption (VO2max). Markers of physical fitness, cardiometabolic health and mental well-being were also measured at baseline and follow-up. Participant perceptions of the intervention were explored in post-intervention focus groups (n = 9).Results: Mean (±SD) session attendance was 82% (±15%). Mean peak heart rate across the intervention was 87% of age-predicted maximal heart rate with a within- and between-subject SD of 5.5% and 3.7%, respectively. The SD of changes in predicted VO2max was 6.6 mL·kg−1·min−1 across both groups, which can be used to inform sample size estimations for a future full trial. The control-adjusted mean increase (95% confidence interval) in predicted VO2max was 3.9 (−0.2 to 8.1) mL·kg−1·min−1, corresponding to a Cohen's D of 0.47. We also observed preliminary evidence of small to moderate effects in favour of the intervention group for non-dominant leg extensor muscle power, markers of health-related quality of life, well-being and perceived stress and small to moderate effects in favour of the controls in perceived pain, physical activity and high-density lipoprotein cholesterol. During HIIT, focus group participants reported physiological responses they perceived as unpleasant or tiring (e.g., breathlessness, local muscular fatigue), but also that they felt alert and energised afterwards.Conclusion: The findings of this exploratory pilot trial support the implementation of a definitive randomised controlled trial to quantify the effectiveness of a workplace HIIT intervention

The association between physical fitness, sports club participation and body mass index on health-related quality of life in primary school children from a socioeconomically deprived area of England

We examined associations between physical fitness components, body mass index (BMI) and sports club participation on health-related quality of life (HRQoL) in 8- to 11-year-old children from a socioeconomically deprived region of England. From May-October 2019, 432 children completed the HRQoL questionnaire Kidscreen-27 and Leisure Time Physical Activity Survey, and a physical fitness testing battery of 20 m shuttle run test (20mSRT), handgrip strength (Handgrip), standing broad jump (Broad Jump), and sit-and-reach. Height, body mass, BMI and somatic maturity data were collected. Comparisons with reference populations were undertaken using a quintile framework. Linear and quantile regression assessed associations between physical fitness components and HRQoL variables. Using English Indices of Multiple Deprivation, 90% of children were from the most deprived quintile and 39% were overweight or obese. More children scored poorly on the Physical Wellbeing (40%) and Psychological Wellbeing (45%) HRQoL domains than the reference population (31%). Physical fitness scores were generally classed as ‘low’-’very low’ (42–58%). 20mSRT and Broad Jump performance explained an additional 10.7% of variance in Physical Wellbeing after adjusting for BMI z-score, sex and age (total R2 21.2%). Quantile regression identified a subset of children who rated Physical Wellbeing as high regardless of 20mSRT performance. Sports club participation was associated with better 20mSRT and Broad Jump performance, and all domains of HRQoL. Our data indicate that some physical fitness components and sports club participation are positively associated with HRQoL of children from socioeconomically deprived areas, irrespective of BMI z-score. Interventions to improve HRQoL should consider both aspects

Changes in children’s physical fitness, BMI and health-related quality of life after the first 2020 COVID-19 lockdown in England: A longitudinal study

We aimed to assess one-year changes in physical fitness, health-related quality of life (HRQoL) and body mass index (BMI), encompassing the 2020 COVID-19 UK lockdowns. Data were collected (October 2019, November 2020) from 178 8–10–year-olds in Newcastle-upon-Tyne, England, 85% from England’s most deprived quintile. Twenty-metre shuttle run test performance (20mSRT), handgrip strength (HGS), standing broad jump (SBJ), sit-and-reach, height, body mass, HRQoL (Kidscreen-27 questionnaire) and sports club participation were measured. BMI z-scores and overweight/obesity were calculated (≥85th centile). Paired t-tests and linear regression assessed change, adjusting for baseline BMI. Significant (p<0.001) changes were observed: increases in mean BMI (+1.5kg·m−2), overweight/obesity (33% to 47%), SBJ (+6.8cm) and HGS (+1.5kg); decreases in 20mSRT performance (−3 shuttles), sit-and-reach (−1.8cm). More children at follow-up were categorized “very low” for 20mSRT performance (35% baseline v 51%). Increased BMI z-score was associated with decreased “Physical Wellbeing” HRQoL. Follow-up sports club participation was associated with better 20mSRT performance (p=0.032), and “Autonomy & Parents” (p=0.011), “Social Support & Peers” (p=0.038) HRQoL. Children’s 20mSRT performance and BMI changed adversely over one year; national lockdowns potentially made negative contributions. Physical fitness, physical activity and sports programmes should be part of children’s physical and mental recovery from the pandemic

Changes in children’s physical fitness, BMI and health-related quality of life after the first 2020 COVID-19 lockdown in England: A longitudinal study

We aimed to assess one-year changes in physical fitness, health-related quality of life (HRQoL) and body mass index (BMI), encompassing the 2020 COVID-19 UK lockdowns. Data were collected (October 2019, November 2020) from 178 8–10–year-olds in Newcastle-upon-Tyne, England, 85% from England’s most deprived quintile. Twenty-metre shuttle run test performance (20mSRT), handgrip strength (HGS), standing broad jump (SBJ), sit-and-reach, height, body mass, HRQoL (Kidscreen-27 questionnaire) and sports club participation were measured. BMI z-scores and overweight/obesity were calculated (≥85th centile). Paired t-tests and linear regression assessed change, adjusting for baseline BMI. Significant (p<0.001) changes were observed: increases in mean BMI (+1.5kg·m−2), overweight/obesity (33% to 47%), SBJ (+6.8cm) and HGS (+1.5kg); decreases in 20mSRT performance (−3 shuttles), sit-and-reach (−1.8cm). More children at follow-up were categorized “very low” for 20mSRT performance (35% baseline v 51%). Increased BMI z-score was associated with decreased “Physical Wellbeing” HRQoL. Follow-up sports club participation was associated with better 20mSRT performance (p=0.032), and “Autonomy & Parents” (p=0.011), “Social Support & Peers” (p=0.038) HRQoL. Children’s 20mSRT performance and BMI changed adversely over one year; national lockdowns potentially made negative contributions. Physical fitness, physical activity and sports programmes should be part of children’s physical and mental recovery from the pandemic

Spectrum, risk factors and outcomes of neurological and psychiatric complications of COVID-19: a UK-wide cross-sectional surveillance study.

SARS-CoV-2 is associated with new-onset neurological and psychiatric conditions. Detailed clinical data, including factors associated with recovery, are lacking, hampering prediction modelling and targeted therapeutic interventions. In a UK-wide cross-sectional surveillance study of adult hospitalized patients during the first COVID-19 wave, with multi-professional input from general and sub-specialty neurologists, psychiatrists, stroke physicians, and intensivists, we captured detailed data on demographics, risk factors, pre-COVID-19 Rockwood frailty score, comorbidities, neurological presentation and outcome. A priori clinical case definitions were used, with cross-specialty independent adjudication for discrepant cases. Multivariable logistic regression was performed using demographic and clinical variables, to determine the factors associated with outcome. A total of 267 cases were included. Cerebrovascular events were most frequently reported (131, 49%), followed by other central disorders (95, 36%) including delirium (28, 11%), central inflammatory (25, 9%), psychiatric (25, 9%), and other encephalopathies (17, 7%), including a severe encephalopathy (n = 13) not meeting delirium criteria; and peripheral nerve disorders (41, 15%). Those with the severe encephalopathy, in comparison to delirium, were younger, had higher rates of admission to intensive care and a longer duration of ventilation. Compared to normative data during the equivalent time period prior to the pandemic, cases of stroke in association with COVID-19 were younger and had a greater number of conventional, modifiable cerebrovascular risk factors. Twenty-seven per cent of strokes occurred in patients 60 years old, the younger stroke patients presented with delayed onset from respiratory symptoms, higher rates of multi-vessel occlusion (31%) and systemic thrombotic events. Clinical outcomes varied between disease groups, with cerebrovascular disease conferring the worst prognosis, but this effect was less marked than the pre-morbid factors of older age and a higher pre-COVID-19 frailty score, and a high admission white cell count, which were independently associated with a poor outcome. In summary, this study describes the spectrum of neurological and psychiatric conditions associated with COVID-19. In addition, we identify a severe COVID-19 encephalopathy atypical for delirium, and a phenotype of COVID-19 associated stroke in younger adults with a tendency for multiple infarcts and systemic thromboses. These clinical data will be useful to inform mechanistic studies and stratification of patients in clinical trials

Safety and efficacy of the ChAdOx1 nCoV-19 vaccine (AZD1222) against SARS-CoV-2: an interim analysis of four randomised controlled trials in Brazil, South Africa, and the UK.

BACKGROUND: A safe and efficacious vaccine against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), if deployed with high coverage, could contribute to the control of the COVID-19 pandemic. We evaluated the safety and efficacy of the ChAdOx1 nCoV-19 vaccine in a pooled interim analysis of four trials. METHODS: This analysis includes data from four ongoing blinded, randomised, controlled trials done across the UK, Brazil, and South Africa. Participants aged 18 years and older were randomly assigned (1:1) to ChAdOx1 nCoV-19 vaccine or control (meningococcal group A, C, W, and Y conjugate vaccine or saline). Participants in the ChAdOx1 nCoV-19 group received two doses containing 5 × 1010 viral particles (standard dose; SD/SD cohort); a subset in the UK trial received a half dose as their first dose (low dose) and a standard dose as their second dose (LD/SD cohort). The primary efficacy analysis included symptomatic COVID-19 in seronegative participants with a nucleic acid amplification test-positive swab more than 14 days after a second dose of vaccine. Participants were analysed according to treatment received, with data cutoff on Nov 4, 2020. Vaccine efficacy was calculated as 1 - relative risk derived from a robust Poisson regression model adjusted for age. Studies are registered at ISRCTN89951424 and ClinicalTrials.gov, NCT04324606, NCT04400838, and NCT04444674. FINDINGS: Between April 23 and Nov 4, 2020, 23 848 participants were enrolled and 11 636 participants (7548 in the UK, 4088 in Brazil) were included in the interim primary efficacy analysis. In participants who received two standard doses, vaccine efficacy was 62·1% (95% CI 41·0-75·7; 27 [0·6%] of 4440 in the ChAdOx1 nCoV-19 group vs71 [1·6%] of 4455 in the control group) and in participants who received a low dose followed by a standard dose, efficacy was 90·0% (67·4-97·0; three [0·2%] of 1367 vs 30 [2·2%] of 1374; pinteraction=0·010). Overall vaccine efficacy across both groups was 70·4% (95·8% CI 54·8-80·6; 30 [0·5%] of 5807 vs 101 [1·7%] of 5829). From 21 days after the first dose, there were ten cases hospitalised for COVID-19, all in the control arm; two were classified as severe COVID-19, including one death. There were 74 341 person-months of safety follow-up (median 3·4 months, IQR 1·3-4·8): 175 severe adverse events occurred in 168 participants, 84 events in the ChAdOx1 nCoV-19 group and 91 in the control group. Three events were classified as possibly related to a vaccine: one in the ChAdOx1 nCoV-19 group, one in the control group, and one in a participant who remains masked to group allocation. INTERPRETATION: ChAdOx1 nCoV-19 has an acceptable safety profile and has been found to be efficacious against symptomatic COVID-19 in this interim analysis of ongoing clinical trials. FUNDING: UK Research and Innovation, National Institutes for Health Research (NIHR), Coalition for Epidemic Preparedness Innovations, Bill & Melinda Gates Foundation, Lemann Foundation, Rede D'Or, Brava and Telles Foundation, NIHR Oxford Biomedical Research Centre, Thames Valley and South Midland's NIHR Clinical Research Network, and AstraZeneca

Safety and efficacy of the ChAdOx1 nCoV-19 vaccine (AZD1222) against SARS-CoV-2: an interim analysis of four randomised controlled trials in Brazil, South Africa, and the UK

Background A safe and efficacious vaccine against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), if deployed with high coverage, could contribute to the control of the COVID-19 pandemic. We evaluated the safety and efficacy of the ChAdOx1 nCoV-19 vaccine in a pooled interim analysis of four trials. Methods This analysis includes data from four ongoing blinded, randomised, controlled trials done across the UK, Brazil, and South Africa. Participants aged 18 years and older were randomly assigned (1:1) to ChAdOx1 nCoV-19 vaccine or control (meningococcal group A, C, W, and Y conjugate vaccine or saline). Participants in the ChAdOx1 nCoV-19 group received two doses containing 5 × 1010 viral particles (standard dose; SD/SD cohort); a subset in the UK trial received a half dose as their first dose (low dose) and a standard dose as their second dose (LD/SD cohort). The primary efficacy analysis included symptomatic COVID-19 in seronegative participants with a nucleic acid amplification test-positive swab more than 14 days after a second dose of vaccine. Participants were analysed according to treatment received, with data cutoff on Nov 4, 2020. Vaccine efficacy was calculated as 1 - relative risk derived from a robust Poisson regression model adjusted for age. Studies are registered at ISRCTN89951424 and ClinicalTrials.gov, NCT04324606, NCT04400838, and NCT04444674. Findings Between April 23 and Nov 4, 2020, 23 848 participants were enrolled and 11 636 participants (7548 in the UK, 4088 in Brazil) were included in the interim primary efficacy analysis. In participants who received two standard doses, vaccine efficacy was 62·1% (95% CI 41·0–75·7; 27 [0·6%] of 4440 in the ChAdOx1 nCoV-19 group vs71 [1·6%] of 4455 in the control group) and in participants who received a low dose followed by a standard dose, efficacy was 90·0% (67·4–97·0; three [0·2%] of 1367 vs 30 [2·2%] of 1374; pinteraction=0·010). Overall vaccine efficacy across both groups was 70·4% (95·8% CI 54·8–80·6; 30 [0·5%] of 5807 vs 101 [1·7%] of 5829). From 21 days after the first dose, there were ten cases hospitalised for COVID-19, all in the control arm; two were classified as severe COVID-19, including one death. There were 74 341 person-months of safety follow-up (median 3·4 months, IQR 1·3–4·8): 175 severe adverse events occurred in 168 participants, 84 events in the ChAdOx1 nCoV-19 group and 91 in the control group. Three events were classified as possibly related to a vaccine: one in the ChAdOx1 nCoV-19 group, one in the control group, and one in a participant who remains masked to group allocation. Interpretation ChAdOx1 nCoV-19 has an acceptable safety profile and has been found to be efficacious against symptomatic COVID-19 in this interim analysis of ongoing clinical trials

Bi-allelic Loss-of-Function CACNA1B Mutations in Progressive Epilepsy-Dyskinesia.

The occurrence of non-epileptic hyperkinetic movements in the context of developmental epileptic encephalopathies is an increasingly recognized phenomenon. Identification of causative mutations provides an important insight into common pathogenic mechanisms that cause both seizures and abnormal motor control. We report bi-allelic loss-of-function CACNA1B variants in six children from three unrelated families whose affected members present with a complex and progressive neurological syndrome. All affected individuals presented with epileptic encephalopathy, severe neurodevelopmental delay (often with regression), and a hyperkinetic movement disorder. Additional neurological features included postnatal microcephaly and hypotonia. Five children died in childhood or adolescence (mean age of death: 9 years), mainly as a result of secondary respiratory complications. CACNA1B encodes the pore-forming subunit of the pre-synaptic neuronal voltage-gated calcium channel Cav2.2/N-type, crucial for SNARE-mediated neurotransmission, particularly in the early postnatal period. Bi-allelic loss-of-function variants in CACNA1B are predicted to cause disruption of Ca2+ influx, leading to impaired synaptic neurotransmission. The resultant effect on neuronal function is likely to be important in the development of involuntary movements and epilepsy. Overall, our findings provide further evidence for the key role of Cav2.2 in normal human neurodevelopment.MAK is funded by an NIHR Research Professorship and receives funding from the Wellcome Trust, Great Ormond Street Children's Hospital Charity, and Rosetrees Trust. E.M. received funding from the Rosetrees Trust (CD-A53) and Great Ormond Street Hospital Children's Charity. K.G. received funding from Temple Street Foundation. A.M. is funded by Great Ormond Street Hospital, the National Institute for Health Research (NIHR), and Biomedical Research Centre. F.L.R. and D.G. are funded by Cambridge Biomedical Research Centre. K.C. and A.S.J. are funded by NIHR Bioresource for Rare Diseases. The DDD Study presents independent research commissioned by the Health Innovation Challenge Fund (grant number HICF-1009-003), a parallel funding partnership between the Wellcome Trust and the Department of Health, and the Wellcome Trust Sanger Institute (grant number WT098051). We acknowledge support from the UK Department of Health via the NIHR comprehensive Biomedical Research Centre award to Guy's and St. Thomas' National Health Service (NHS) Foundation Trust in partnership with King's College London. This research was also supported by the NIHR Great Ormond Street Hospital Biomedical Research Centre. J.H.C. is in receipt of an NIHR Senior Investigator Award. The research team acknowledges the support of the NIHR through the Comprehensive Clinical Research Network. The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR, Department of Health, or Wellcome Trust. E.R.M. acknowledges support from NIHR Cambridge Biomedical Research Centre, an NIHR Senior Investigator Award, and the University of Cambridge has received salary support in respect of E.R.M. from the NHS in the East of England through the Clinical Academic Reserve. I.E.S. is supported by the National Health and Medical Research Council of Australia (Program Grant and Practitioner Fellowship)

Back to ‘normal’? BMI, physical fitness and health-related quality of life of children from North East England before, during and after the COVID-19 lockdowns

We assessed whether changes in children’s body mass index (BMI), physical fitness and health-related quality of life observed post-2020 United Kingdom COVID-19 lockdown remained 12 and 18 months later. Twenty-metre shuttle run test (20mSRT), handgrip strength, standing broad jump, sit-and-reach, height, body mass, and health-related quality of life (Kidscreen27 questionnaire) were measured in 90 children (8–9 years) during October 2019 (“T0”), November 2020 (“T1”), November 2021 (“T2”) and June 2022 (“T3”). Mixed-effects models showed age- and sex-normalised BMI increased from T0 (mean: 0.71) to T1 (0.97), remaining elevated at T2 (0.95) and T3 (0.89). Decreases in 20mSRT performance were observed from T0 (22.0) to T1 (19.3), then increased at T2 (23.5) and T3 (28.3). Standing broad jump and handgrip strength increased over time. The proportion of children with overweight/obesity increased from T0 (32%) to T3 (48%). Health-related quality of life decreased for “Physical Wellbeing” yet increased for “Autonomy & Parents”. Our findings highlight that lockdowns may have had lasting implications for children’s health, and the urgent need to reduce overweight and obesity in North East England. Improving health and fitness behaviours to maximise long-term health outcomes and build resilience to future emergencies and disruptions to health behaviours is also paramount