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  1. Salway R, Su TT, Ismail R, Glynis Armstrong ME, Foster C, Johnson L
    J Glob Health, 2021;11:05029.
    PMID: 35003716 DOI: 10.7189/jogh.11.05029
    BACKGROUND: The COVID-19 pandemic prompted movement restrictions in countries worldwide, impacting on physical activity (PA), a major non-communicable disease risk factor, and thus may have unintentional long-term health implications. In semi-rural areas of low-middle-income-countries (LMICs), where occupational activity is the main source of PA, changes in PA associated with COVID-19 restrictions are unknown. We investigated the impact of Movement Control Order (MCO) restrictions in a semi-rural region of Malaysia.

    METHODS: The South East Asia Community Observatory (SEACO) is a dynamic prospective community cohort. We contacted a random sample of 1007 adults (18+) who had previously provided PA data in 2018. We asked about PA during the MCO (March-May 2020) and at the time of interview (June 2020).

    RESULTS: During the MCO, PA reduced by a mean of 6.7 hours/week (95% confidence interval (CI) = 5.3, 8.0) compared to 2018, with the largest reductions among those in employment. By June, PA was 3.4 hours/week (95% CI = 2.0, 4.8) less than 2018, leaving 34% of adults currently inactive (20% in 2018). Reductions in occupational PA were not replaced with active travel or activity at home. Despite these observed reductions, most participants did not think the MCO had affected their PA.

    CONCLUSIONS: Movement restrictions are associated with lower PA lasting beyond the period of strict restrictions; such longer-term reductions in PA may have a detrimental impact on health. Future MCOs should encourage people to be active, but may additionally need targeted messaging for those who don't necessarily realise they are at risk. In particular, policies developed in more affluent countries may not easily translate to LMICs.

  2. Alsharqi M, Huckstep OJ, Lapidaire W, Williamson W, Mohamed A, Tan CMJ, et al.
    Echocardiography, 2021 Aug;38(8):1319-1326.
    PMID: 34185918 DOI: 10.1111/echo.15149
    AIMS: To investigate the left ventricular response to exercise in young adults with hypertension, and identify whether this response can be predicted from changes in left atrial function at rest.

    METHODS: A total of 127 adults aged 18-40 years who completed clinical blood pressure assessment and echocardiography phenotyping at rest and during cardiopulmonary exercise testing, were included. Measurements were compared between participants with suboptimal blood pressure ≥120/80mm Hg (n = 68) and optimal blood pressure <120/80mm Hg (n = 59). Left ventricular systolic function during exercise was obtained from an apical four chamber view, while resting left atrial function was assessed from apical four and two chamber views.

    RESULTS: Participants with suboptimal blood pressure had higher left ventricular mass (p = 0.031) and reduced mitral E velocity (p = 0.02) at rest but no other cardiac differences. During exercise, their rise in left ventricular ejection fraction was reduced (p = 0.001) and they had higher left ventricular end diastolic and systolic volumes (p = 0.001 and p = 0.001, respectively). Resting cardiac size predicted left ventricular volumes during exercise but only left atrial booster pump function predicted the left ventricular ejection fraction response ( β = .29, p = 0.011). This association persisted after adjustment for age, sex, body mass index, and mean arterial pressure.

    CONCLUSION: Young adults with suboptimal blood pressure have a reduced left ventricular systolic response to exercise, which can be predicted by their left atrial booster pump function at rest. Echocardiographic measures of left atrial function may provide an early marker of functionally relevant, subclinical, cardiac remodelling in young adults with hypertension.

  3. Lapidaire W, Forkert ND, Williamson W, Huckstep O, Tan CM, Alsharqi M, et al.
    Neuroimage Clin, 2023;37:103337.
    PMID: 36709637 DOI: 10.1016/j.nicl.2023.103337
    IMPORTANCE: Cerebrovascular changes are already evident in young adults with hypertension and exercise is recommended to reduce cardiovascular risk. To what extent exercise benefits the cerebrovasculature at an early stage of the disease remains unclear.

    OBJECTIVE: To investigate whether structured aerobic exercise increases brain vessel lumen diameter or cerebral blood flow (CBF) and whether lumen diameter is associated with CBF.

    DESIGN: Open, parallel, two-arm superiority randomized controlled (1:1) trial in the TEPHRA study on an intention-to-treat basis. The MRI sub-study was an optional part of the protocol. The outcome assessors remained blinded until the data lock.

    SETTING: Single-centre trial in Oxford, UK.

    PARTICIPANTS: Participants were physically inactive (<150 min/week moderate to vigorous physical activity), 18 to 35 years old, 24-hour ambulatory blood pressure 115/75 mmHg-159/99 mmHg, body mass index below 35 kg/m2 and never been on prescribed hypertension medications. Out of 203 randomized participants, 135 participated in the MRI sub-study. Randomisation was stratified for sex, age (<24, 24-29, 30-35 years) and gestational age at birth (<32, 32-37, >37 weeks).

    INTERVENTION: Study participants were randomised to a 16 week aerobic exercise intervention targeting 3×60 min sessions per week at 60 to 80 % peak heart rate.

    MAIN OUTCOMES AND MEASURES: cerebral blood flow (CBF) maps from ASL MRI scans, internal carotid artery (ICA), middle cerebral artery (MCA) M1 and M2 segments, anterior cerebral artery (ACA), basilar artery (BA), and posterior cerebral artery (PCA) diameters extracted from TOF MRI scans.

    RESULTS: Of the 135 randomized participants (median age 28 years, 58 % women) who had high quality baseline MRI data available, 93 participants also had high quality follow-up data available. The exercise group showed an increase in ICA (0.1 cm, 95 % CI 0.01 to 0.18, p =.03) and MCA M1 (0.05 cm, 95 % CI 0.01 to 0.10, p =.03) vessel diameter compared to the control group. Differences in the MCA M2 (0.03 cm, 95 % CI 0.0 to 0.06, p =.08), ACA (0.04 cm, 95 % CI 0.0 to 0.08, p =.06), BA (0.02 cm, 95 % CI -0.04 to 0.09, p =.48), and PCA (0.03 cm, 95 % CI -0.01 to 0.06, p =.17) diameters or CBF were not statistically significant. The increase in ICA vessel diameter in the exercise group was associated with local increases in CBF.

    CONCLUSIONS AND RELEVANCE: Aerobic exercise induces positive cerebrovascular remodelling in young people with early hypertension, independent of blood pressure. The long-term benefit of these changes requires further study.

    TRIAL REGISTRATION: Clinicaltrials.gov NCT02723552, 30 March 2016.

  4. Bradbury K, Steele M, Corbett T, Geraghty AWA, Krusche A, Heber E, et al.
    NPJ Digit Med, 2019;2:85.
    PMID: 31508496 DOI: 10.1038/s41746-019-0163-4
    This paper illustrates a rigorous approach to developing digital interventions using an evidence-, theory- and person-based approach. Intervention planning included a rapid scoping review that identified cancer survivors' needs, including barriers and facilitators to intervention success. Review evidence (N = 49 papers) informed the intervention's Guiding Principles, theory-based behavioural analysis and logic model. The intervention was optimised based on feedback on a prototype intervention through interviews (N = 96) with cancer survivors and focus groups with NHS staff and cancer charity workers (N = 31). Interviews with cancer survivors highlighted barriers to engagement, such as concerns about physical activity worsening fatigue. Focus groups highlighted concerns about support appointment length and how to support distressed participants. Feedback informed intervention modifications, to maximise acceptability, feasibility and likelihood of behaviour change. Our systematic method for understanding user views enabled us to anticipate and address important barriers to engagement. This methodology may be useful to others developing digital interventions.
  5. Williamson W, Lewandowski AJ, Huckstep OJ, Lapidaire W, Ooms A, Tan C, et al.
    EClinicalMedicine, 2022 Jun;48:101445.
    PMID: 35706495 DOI: 10.1016/j.eclinm.2022.101445
    BACKGROUND: Exercise is advised for young adults with elevated blood pressure, but no trials have investigated efficacy at this age. We aimed to determine whether aerobic exercise, self-monitoring and motivational coaching lowers blood pressure in this group.

    METHODS: The study was a single-centre, open, two-arm, parallel superiority randomized clinical trial with open community-based recruitment of physically-inactive 18-35 year old adults with awake 24 h blood pressure 115/75mmHg-159/99 mmHg and BMI<35 kg/m2. The study took place in the Cardiovascular Clinical Research Facility, John Radcliffe Hospital, Oxford, UK. Participants were randomized (1:1) with minimisation factors sex, age (<24, 24-29, 30-35 years) and gestational age at birth (<32, 32-37, >37 weeks) to the intervention group, who received 16-weeks aerobic exercise training (three aerobic training sessions per week of 60 min per session at 60-80% peak heart rate, physical activity self-monitoring with encouragement to do 10,000 steps per day and motivational coaching to maintain physical activity upon completion of the intervention. The control group were sign-posted to educational materials on hypertension and recommended lifestyle behaviours. Investigators performing statistical analyses were blinded to group allocation. The primary outcome was 24 h awake ambulatory blood pressure (systolic and diastolic) change from baseline to 16-weeks on an intention-to-treat basis. Clinicaltrials.gov registered on March 30, 2016 (NCT02723552).

    FINDINGS: Enrolment occurred between 30/06/2016-26/10/2018. Amongst the 203 randomized young adults (n = 102 in the intervention group; n = 101 in the control group), 178 (88%; n = 76 intervention group, n = 84 control group) completed 16-week follow-up and 160 (79%; n = 68 intervention group, n = 69 control group) completed 52-weeks follow-up. There were no group differences in awake systolic (0·0 mmHg [95%CI, -2·9 to 2·8]; P = 0·98) or awake diastolic ambulatory blood pressure (0·6 mmHg [95%CI, -1·4. to 2·6]; P = 0·58). Aerobic training increased peak oxygen uptake (2·8 ml/kg/min [95%CI, 1·6 to 4·0]) and peak wattage (14·2watts [95%CI, 7·6 to 20·9]) at 16-weeks. There were no intervention effects at 52-weeks follow-up.

    INTEPRETATION: These results do not support the exclusive use of moderate to high intensity aerobic exercise training for blood pressure control in young adults.

    FUNDING: Wellcome Trust, British Heart Foundation, National Institute for Health Research, Oxford Biomedical Research Centre.

  6. Washif JA, Farooq A, Krug I, Pyne DB, Verhagen E, Taylor L, et al.
    Sports Med, 2022 04;52(4):933-948.
    PMID: 34687439 DOI: 10.1007/s40279-021-01573-z
    OBJECTIVE: Our objective was to explore the training-related knowledge, beliefs, and practices of athletes and the influence of lockdowns in response to the coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).

    METHODS: Athletes (n = 12,526, comprising 13% world class, 21% international, 36% national, 24% state, and 6% recreational) completed an online survey that was available from 17 May to 5 July 2020 and explored their training behaviors (training knowledge, beliefs/attitudes, and practices), including specific questions on their training intensity, frequency, and session duration before and during lockdown (March-June 2020).

    RESULTS: Overall, 85% of athletes wanted to "maintain training," and 79% disagreed with the statement that it is "okay to not train during lockdown," with a greater prevalence for both in higher-level athletes. In total, 60% of athletes considered "coaching by correspondence (remote coaching)" to be sufficient (highest amongst world-class athletes). During lockdown, 

  7. Page EC, Bancroft EK, Brook MN, Assel M, Hassan Al Battat M, Thomas S, et al.
    Eur Urol, 2019 Dec;76(6):831-842.
    PMID: 31537406 DOI: 10.1016/j.eururo.2019.08.019
    BACKGROUND: Mutations in BRCA2 cause a higher risk of early-onset aggressive prostate cancer (PrCa). The IMPACT study is evaluating targeted PrCa screening using prostate-specific-antigen (PSA) in men with germline BRCA1/2 mutations.

    OBJECTIVE: To report the utility of PSA screening, PrCa incidence, positive predictive value of PSA, biopsy, and tumour characteristics after 3 yr of screening, by BRCA status.

    DESIGN, SETTING, AND PARTICIPANTS: Men aged 40-69 yr with a germline pathogenic BRCA1/2 mutation and male controls testing negative for a familial BRCA1/2 mutation were recruited. Participants underwent PSA screening for 3 yr, and if PSA > 3.0 ng/ml, men were offered prostate biopsy.

    OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: PSA levels, PrCa incidence, and tumour characteristics were evaluated. Statistical analyses included Poisson regression offset by person-year follow-up, chi-square tests for proportion t tests for means, and Kruskal-Wallis for medians.

    RESULTS AND LIMITATIONS: A total of 3027 patients (2932 unique individuals) were recruited (919 BRCA1 carriers, 709 BRCA1 noncarriers, 902 BRCA2 carriers, and 497 BRCA2 noncarriers). After 3 yr of screening, 527 men had PSA > 3.0 ng/ml, 357 biopsies were performed, and 112 PrCa cases were diagnosed (31 BRCA1 carriers, 19 BRCA1 noncarriers, 47 BRCA2 carriers, and 15 BRCA2 noncarriers). Higher compliance with biopsy was observed in BRCA2 carriers compared with noncarriers (73% vs 60%). Cancer incidence rate per 1000 person years was higher in BRCA2 carriers than in noncarriers (19.4 vs 12.0; p =  0.03); BRCA2 carriers were diagnosed at a younger age (61 vs 64 yr; p =  0.04) and were more likely to have clinically significant disease than BRCA2 noncarriers (77% vs 40%; p =  0.01). No differences in age or tumour characteristics were detected between BRCA1 carriers and BRCA1 noncarriers. The 4 kallikrein marker model discriminated better (area under the curve [AUC] = 0.73) for clinically significant cancer at biopsy than PSA alone (AUC = 0.65).

    CONCLUSIONS: After 3 yr of screening, compared with noncarriers, BRCA2 mutation carriers were associated with a higher incidence of PrCa, younger age of diagnosis, and clinically significant tumours. Therefore, systematic PSA screening is indicated for men with a BRCA2 mutation. Further follow-up is required to assess the role of screening in BRCA1 mutation carriers.

    PATIENT SUMMARY: We demonstrate that after 3 yr of prostate-specific antigen (PSA) testing, we detect more serious prostate cancers in men with BRCA2 mutations than in those without these mutations. We recommend that male BRCA2 carriers are offered systematic PSA screening.

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