Comparison of device-based physical activity and sedentary behaviour following percutaneous coronary intervention in a cohort from Sweden and Australia:A harmonised, exploratory study

Background Few studies have measured device-based physical activity and sedentary behaviour following a percutaneous coronary intervention (PCI), with no studies comparing these behaviours between countries using the same methods. The aim of the study was to compare device-based physical activity and sedentary behaviour, using a harmonised approach, following a PCI on-entry into centre-based cardiac rehabilitation in two countries. Methods A cross-sectional study was conducted at two outpatient cardiac rehabilitation centres in Australia and Sweden. Participants were adults following a PCI and commencing cardiac rehabilitation (Australia n = 50, Sweden n = 133). Prior to discharge from hospital, Australian participants received brief physical activity advice (&amp;lt; 5 mins), while Swedish participants received physical activity counselling for 30 min. A triaxial accelerometer (Actigraph GT3X/ActiSleep) was used to objectively assess physical activity (light (LPA), moderate-to-vigorous (MVPA)) and sedentary behaviour. Outcomes included daily minutes of physical activity and sedentary behaviour, and the proportion and distribution of time spent in each behaviour. Results There was no difference in age, gender or relationship status between countries. Swedish (S) participants commenced cardiac rehabilitation later than Australian (A) participants (days post-PCI A 16 vs S 22, p &amp;lt; 0.001). Proportionally, Swedish participants were significantly more physically active and less sedentary than Australian participants (LPA A 27% vs S 30%, p &amp;lt; 0.05; MVPA A 5% vs S 7%, p &amp;lt; 0.01; sedentary behaviour A 68% vs S 63%, p &amp;lt; 0.001). When adjusting for wear-time, Australian participants were doing less MVPA minutes (A 42 vs S 64, p &amp;lt; 0.001) and more sedentary behaviour minutes (A 573 vs S 571, p &amp;lt; 0.001) per day. Both Swedish and Australian participants spent a large part of the day sedentary, accumulating 9.5 h per day in sedentary behaviour. Conclusion Swedish PCI participants when commencing cardiac rehabilitation are more physically active than Australian participants. Potential explanatory factors are differences in post-PCI in-hospital physical activity education between countries and pre-existing physical activity levels. Despite this, sedentary behaviour is high in both countries. Internationally, interventions to address sedentary behaviour are indicated post-PCI, in both the acute setting and cardiac rehabilitation, in addition to traditional physical activity and cardiac rehabilitation recommendations.Funding Agencies|University of Canberra (Early Career Academic Research Development Grant); ACT Health Chief Allied Health Office (Allied Health Research Support Grant); Swedish Heart and Lung AssociationSwedish Heart-Lung Foundation; Swedish Society for Medical Research</p

Pathway-Based Analysis of a Melanoma Genome-Wide Association Study: Analysis of Genes Related to Tumour-Immunosuppression

Systemic immunosuppression is a risk factor for melanoma, and sunburn-induced immunosuppression is thought to be causal. Genes in immunosuppression pathways are therefore candidate melanoma-susceptibility genes. If variants within these genes individually have a small effect on disease risk, the association may be undetected in genome-wide association (GWA) studies due to low power to reach a high significance level. Pathway-based approaches have been suggested as a method of incorporating a priori knowledge into the analysis of GWA studies. In this study, the association of 1113 single nucleotide polymorphisms (SNPs) in 43 genes (39 genomic regions) related to immunosuppression have been analysed using a gene-set approach in 1539 melanoma cases and 3917 controls from the GenoMEL consortium GWA study. The association between melanoma susceptibility and the whole set of tumour-immunosuppression genes, and also predefined functional subgroups of genes, was considered. The analysis was based on a measure formed by summing the evidence from the most significant SNP in each gene, and significance was evaluated empirically by case-control label permutation. An association was found between melanoma and the complete set of genes (pemp = 0.002), as well as the subgroups related to the generation of tolerogenic dendritic cells (pemp = 0.006) and secretion of suppressive factors (pemp = 0.0004), thus providing preliminary evidence of involvement of tumour-immunosuppression gene polymorphisms in melanoma susceptibility. The analysis was repeated on a second phase of the GenoMEL study, which showed no evidence of an association. As one of the first attempts to replicate a pathway-level association, our results suggest that low power and heterogeneity may present challenges

Novel Role for p110β PI 3-Kinase in Male Fertility through Regulation of Androgen Receptor Activity in Sertoli Cells

We thank Anna-Lena Berg (AstraZeneca, Lund) and Cheryl Scudamore (MRC, Harwell, UK) for histological analysis, Julie Foster (Barts Cancer Institute, London) for CT scans, Johan Swinnen and Frank Claessens (Leuven University, Belgium) for discussion and AR-luciferase reporter plasmids, Florian Guillou (INRA, CNRS, Université de Tours, France) for the AMH-Cre mouse line and Laura Milne (MRC Centre for Reproductive Health, The University of Edinburgh) for technical support. We thank the members of the Cell Signalling group for critical input.International audienceThe organismal roles of the ubiquitously expressed class I PI3K isoform p110β remain largely unknown. Using a new kinase-dead knockin mouse model that mimics constitutive pharmacological inactivation of p110β, we document that full inactivation of p110β leads to embryonic lethality in a substantial fraction of mice. Interestingly, the homozygous p110β kinase-dead mice that survive into adulthood (maximum ~26% on a mixed genetic background) have no apparent phenotypes, other than subfertility in females and complete infertility in males. Systemic inhibition of p110β results in a highly specific blockade in the maturation of spermatogonia to spermatocytes. p110β was previously suggested to signal downstream of the c-kit tyrosine kinase receptor in germ cells to regulate their proliferation and survival. We now report that p110β also plays a germ cell-extrinsic role in the Sertoli cells (SCs) that support the developing sperm, with p110β inactivation dampening expression of the SC-specific Androgen Receptor (AR) target gene Rhox5, a homeobox gene critical for spermatogenesis. All extragonadal androgen-dependent functions remain unaffected by global p110β inactivation. In line with a crucial role for p110β in SCs, selective inactivation of p110β in these cells results in male infertility. Our study is the first documentation of the involvement of a signalling enzyme, PI3K, in the regulation of AR activity during spermatogenesis. This developmental pathway may become active in prostate cancer where p110β and AR have previously been reported to functionally interac

Retrospective evaluation of whole exome and genome mutation calls in 746 cancer samples

Funder: NCI U24CA211006Abstract: The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) curated consensus somatic mutation calls using whole exome sequencing (WES) and whole genome sequencing (WGS), respectively. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole genome sequencing data from 2,658 cancers across 38 tumour types, we compare WES and WGS side-by-side from 746 TCGA samples, finding that ~80% of mutations overlap in covered exonic regions. We estimate that low variant allele fraction (VAF < 15%) and clonal heterogeneity contribute up to 68% of private WGS mutations and 71% of private WES mutations. We observe that ~30% of private WGS mutations trace to mutations identified by a single variant caller in WES consensus efforts. WGS captures both ~50% more variation in exonic regions and un-observed mutations in loci with variable GC-content. Together, our analysis highlights technological divergences between two reproducible somatic variant detection efforts

Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

Abstract Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries

Exercise-Based Cardiac Rehabilitation in Patients with Coronary Artery Disease : Attendance, Adherence and the Added Value of a Behavioural Medicine Intervention

Background: Coronary artery disease (CAD) is the leading global cause of death. After an index event related to CAD, exercise-based cardiac rehabilitation (exCR) is strongly recommended as part of the secondary prevention. Despite the well-established beneficial effects of exCR in patients with CAD, attendance at and adherence to the programme are low, and remain a matter of major concern. One strategy that may increase adherence and rehabilitation outcomes in patients with CAD is to add a behavioural medicine intervention to routine exCR care. The added value of such interventions needs to be further explored. Although several factors associated with non-attendance at exCR appear to be similar between different countries, patterns of attendance may differ due to differences in contextual aspects. The factors that affect attendance at exCR in a Swedish context remain to be explored. Overall aim: To investigate barriers for exCR attendance and to evaluate the added value of a behavioural medicine intervention in physiotherapy on exercise adherence and rehabilitation outcomes in patients with CAD. Methods: The three papers in this thesis are based on two studies of patients with CAD, one registrybased cohort study of 31,297 patients included from the SWEDEHEART registry (Paper I), and one randomised controlled trial of 170 patients included at a Swedish university hospital (Papers II and III). In the first paper, several individual and structural variables were compared for attenders and nonattenders, using multivariable analysis in a logistic regression model. In Papers II and III, patients were randomised 1:1 either to a behavioural medicine intervention in physiotherapy in addition to routine exCR care or to routine exCR care alone for four months. The behaviour change techniques used in the behavioural medicine intervention – specific goal-setting, re-evaluation of the goals, and selfmonitoring and feedback – were based on control theory. Outcome assessment took place at baseline, four and 12 months, and included physical fitness, psychological outcomes and health-related quality of life. Exercise adherence was evaluated at the end of the four-month intervention. An intention-to-treat and a per-protocol analysis were performed. Results: Individual and structural factors associated with non-attendance at exCR in a Swedish context were identified as having a distance greater than 16 km to the hospital, belonging to a county hospital, having a higher burden of comorbidities, being male, and being retired. Exercise adherence was higher for patients who received the behavioural medicine intervention in physiotherapy together with routine exCR (31%) than it was for those who received routine exCR care alone (19%). Rehabilitation outcomes did not differ significantly between the two groups, either between baseline and four months or between four and 12 months. Both groups improved significantly in all measures of physical fitness, and in several measures of health-related quality of life and anxiety at the four-month follow-up. Sufficient enablement remained for patients in both groups at the 12-months follow-up. Conclusions: Distance to the hospital was the strongest predictor for non-attendance at exCR in a Swedish context. The individual factors associated with non-attendance at exCR identified in this thesis confirm previous results, with the exception that female gender was associated with a higher attendance at exCR. The results of this thesis confirm what others have pointed out: it is challenging to achieve behavioural change in patients with the aim to improve rehabilitation outcomes. Even though adherence was higher when a behavioural medicine intervention was added, it was low in both groups. The current behavioural medicine intervention in physiotherapy did not give any improvements over routine exCR care alone in physical fitness, psychological outcomes or health-related quality of life. As such, there is still room for further development and evaluation of behavioural medicine interventions within the context of exCR. A greater tailoring of these interventions to individual needs in a broader population of patients with CAD is suggested.Bakgrund: Kranskärlssjukdom är den ledande dödsorsaken i världen. Efter en hjärthändelse till följd av kranskärlssjukdom är träningsbaserad hjärtrehabilitering högt rekommenderad som en del av sekundärpreventionen. Trots att träningsbaserad hjärtrehabilitering har väletablerade positiva effekter hos patienter med kranskärlssjukdom är deltagande och följsamhet till behandlingen låg och ett fortsatt stort bekymmer. En beteendemedicinsk intervention i tillägg till sedvanlig träningsbaserad hjärtrehabilitering kan vara en strategi för att öka följsamheten och förbättra rehabiliteringsutfallet hos patienter med kranskärlssjukdom. Betydelsen av sådana interventioner behöver dock undersökas ytterligare. Även om det finns faktorer associerade med icke-deltagande i träningsbaserad hjärtrehabilitering som är likartade mellan olika länder, kan mönster för deltagande också skilja sig åt på grund av skillnader i kontextuella aspekter. Faktorer som påverkar deltagande i träningsbaserad hjärtrehabilitering i en svensk kontext är understuderat. Övergripande syfte: Att undersöka barriärer för deltagande i träningsbaserad hjärtrehabilitering samt utvärdera mervärdet av en beteendemedicinsk intervention inom träningsbaserad hjärtrehabilitering avseende följsamhet samt rehabiliteringsutfall hos patienter med kranskärlssjukdom. Metod: De tre delarbeten som ingår i den här avhandlingen baseras på två studier innefattande patienter med kranskärlssjukdom, en registerbaserad kohortstudie med 31 297 patienter inkluderade från SWEDEHEART-registret (delarbete I) och en randomiserad kontrollerad studie med 170 patienter inkluderade på ett svenskt universitetssjukhus (delarbete II och III). I det första delarbetet jämfördes deltagare och icke-deltagare i träningsbaserad hjärtrehabilitering avseende samtliga inkluderade individuella och strukturella variabler och en multivariabel analys med logistisk regressionsmodell utfördes. I delarbete II och III randomiserades patienterna 1:1 till en beteendemedicinsk intervention i tillägg till sedvanlig träningsbaserad hjärtrehabilitering eller till enbart sedvanlig träningsbaserad hjärtrehabilitering under fyra månader. De beteendeförändringstekniker som användes i den beteendemedicinska interventionen innefattade specifik målsättning, omvärdering av målen, självmonitorering och feedback och baserades på kontrollteorin. Test av utfallsmått ägde rum vid baslinjen och efter fyra och 12 månader och inkluderade fysisk kapacitet, psykologiska utfallsmått samt hälsorelaterad livskvalitet. Följsamhet till det träningsbaserade hjärtrehabiliteringsprogrammet utvärderades efter avslutad intervention vid fyra månader. En intention-to-treat och en per-protokoll analys utfördes. Resultat: Individuella och strukturella faktorer associerade med icke-deltagande i träningsbaserad hjärtrehabilitering i en svensk kontext var ett avstånd längre än 16 km till sjukhuset, att tillhöra ett länssjukhus, ha en högre grad av komorbiditet, vara av manligt kön samt att vara pensionär. Följsamheten till träningsprogrammet var bättre för de patienter som erhöll en beteendemedicinsk intervention i tillägg till sedvanlig träningsbaserad hjärtrehabilitering (31%) jämfört med de som enbart erhöll sedvanlig träningsbaserad hjärtrehabilitering (19%). Utfallsmåtten skilde sig inte signifikant mellan de två grupperna, varken mellan baslinjen och fyra månader eller mellan fyra och 12 månader. Båda grupperna förbättrades dock signifikant i samtliga utfallsmått för fysisk kapacitet, ångest samt i flera mått av hälsorelaterad livskvalitet mellan baslinjen och fyra månader. Patienterna i båda grupperna uppvisade en kvarstående förmåga att förstå och hantera sin sjukdom (enablement) vid 12 månadersuppföljningen. Konklusion: Avstånd till sjukhuset var den starkaste prediktorn för icke-deltagande i träningsbaserad hjärtrehabilitering. Individuella faktorer som associerades med icke-deltagande i en svensk kontext var i linje med resultat från tidigare studier, med undantaget att kvinnligt kön var associerat med högre deltagande i träningsbaserad hjärtrehabilitering. Resultaten av denna avhandling bekräftar tidigare rapporterade utmaningar med att lyckas uppnå beteendeförändringar hos patienter i syfte att förbättra rehabiliteringsutfall. Trots att följsamheten var bättre med ett tillägg av en beteendemedicinsk intervention, så var den låg i båda grupperna. Den aktuella beteendemedicinska interventionen gav inget mervärde avseende effekter av fysisk kapacitet, psykologiska utfallsmått och hälsorelaterad livskvalitet jämfört med enbart sedvanlig träningsbaserad hjärtrehabilitering. Således finns det fortfarande utrymme för vidareutveckling och utvärdering av beteendemedicinska interventioner inom ramen för träningsbaserad hjärtrehabilitering. En större anpassning av dessa interventioner utifrån individuella behov i en bredare population av patienter med kranskärlssjukdom föreslås

Outdoor activity/learning and outdoor recreation in physical education? : A quantitative study with high school students in Danderyd

Syfte och frågeställningar: Studien avser att undersöka om högstadieelever får prova på friluftsliv och utevistelse i sin idrottsundervisning utifrån kunskapsmålen i Lgr 11 samt hur nöjda de är med momentet friluftsliv och utevistelse. Frågeställningar: Vilka moment inom ämnet friluftsliv och utevistelse får eleverna prova på i sin idrottsundervisning utifrån kursplanen? Hur ser de inbördes förhållandena ut mellan momenten inom friluftsliv och utevistelse i idrottsundervisningen enligt eleverna? Metod Totalt deltog 124 högstadieelever från en skola i Danderyds kommun. Eleverna fick besvara en pilottestad enkät med frågor om deras undervisning i friluftsliv och utevistelse. Enkäten utformades efter kunskapsmålen i Lgr 11. Insamlad data bearbetades i Excel och Statistica. Resultat: Resultatet visade att de flesta elever upplever att de fått prova på samtliga moment inom friluftsliv och utevistelse i skolan enligt Lgr 11. Eleverna fick till största del ta lärdom av orientering i okänd miljö med olika hjälpmedel. Även andra moment inom friluftsliv såsom livräddning under olika årstider fick eleverna ta del av men inte i lika stor utsträckning. De moment som eleverna upplevde de fått prova på minst var att själva planera, organisera och genomföra en friluftsaktivitet samt friluftslivets kulturella traditioner. Slutsats: Studien talar emot tidigare forskning om att friluftsliv är ett bristande moment i skolan. Skolan vi undersökte hade bra förutsättningar för att kunna undervisa och uppnå målen i friluftsliv och utevistelse utifrån Lgr11 med deras geografiska läge. Studiens resultat visar att eleverna fått prova på samtliga kunskapsmål.Aim The aim with the study is to investigate if high school students get to experience outdoor teaching and outdoor activities based on its content within the curriculum Lgr 11 and how satisfied they are with the specific segment as a whole. Research questions: What part of outdoor teaching and outdoor activities do the students get to experience in physical education based on the curriculum Lgr 11? According to the students, how does the interrelation between the different segments of outdoor teaching and outdoor activity look like? Method A total of 124 students from the eight and ninth grade in Danderyd took part in the study. The students were asked to answer a pilot-tested questionnaire regarding their education in outdoor teaching and outdoors activities. The questionnaire was based on the learning goals from Lgr 11. The collected data were processed in Excel and Statistica. Results The result shows that the majority of students feel that they have got to experience all segments from outdoor teaching and outdoor activity as stated in the curriculum Lgr 11. The dominating segment according to the students was orientation in unknown environment with the help of different resources. Other segments within outdoor teaching and outdoor activity, e.g, life-saving training throughout the different seasons was mentioned as well, but not to the same extent. The minority of activities within the segment of outdoor teaching and outdoor activity, i.e, the activities that the students had experienced the least, were to plan, organize and perform outdoor activity, as well as being taught about the cultural traditions that come with outdoor teaching and outdoor activites. Conclusions The study argues against previous research that outdoor teaching and outdoor activities is lacking in presence in school. The school where the study took place had good opportunities to teach and to achieve the goals of outdoor teaching stated in Lgr 11, much thanks to their geographical location. The result demonstrates that the students have got to practice all segments within the curriculum Lgr 11

The role of a behavioural medicine intervention in physiotherapy for the effects of rehabilitation outcomes in exercise-based cardiac rehabilitation (ECRA) - the study protocol of a randomised, controlled trial

Background: To help patients with coronary artery disease (CAD) benefit from the positive health effects attained by exercise-based cardiac rehabilitation (CR), adherence to these programmes according to international guidelines is important. Strategies to increase adherence to exercise-based CR are mainly an unexplored area. The objective of this study is to investigate the effects of a behavioural medicine intervention in physiotherapy, containing goal-setting, self-monitoring and feedback, with the aim of improving rehabilitation outcomes for exercise-based CR, compared with usual care. Methods: This is a randomised, controlled trial. A total of 160 patients with CAD will be included consecutively at the Coronary Care Unit at a university hospital in Sweden. Patients are randomised 1:1 using sealed envelopes to usual care or a behavioural medicine intervention in physiotherapy, in addition to usual care for 4 months. Outcome assessment at baseline, 4 and 12 months includes submaximal aerobic capacity (primary outcome), exercise adherence, muscle endurance, level of physical activity, biomarkers, anxiety and depression, health-related quality of life, patient enablement and self-efficacy (secondary outcomes). Discussion: This is the first study to evaluate the role of an integrated behavioural medicine intervention in exercise-based CR in the effects of rehabilitation outcomes. The results of this study will provide valuable information about the effect of these interventions in exercise-based CR and it has the potential to inform and assist in further treatment in secondary prevention for patients with CAD.Funding Agencies|Heart and Lung Association [E133/15, E 118/16]</p

The Added Value of a Behavioral Medicine Intervention in Physiotherapy on Adherence and Physical Fitness in Exercise-Based Cardiac Rehabilitation (ECRA): A Randomised, Controlled Trial

Purpose: Despite beneficial effects, adherence to exercise-based cardiac rehabilitation (exCR) is low in patients with coronary artery disease (CAD). The aim of this study was to investigate adherence to and the effects of a behavioral medicine intervention in physiotherapy (BMW) added to routine exCR care on the primary outcome of physical fitness compared with routine exCR care. Patients and Methods: In a randomized, controlled trial, 170 patients with CAD (136 men), mean age 62.3 (7.9) years, were included at a Swedish university hospital. Patients were randomized 1:1 to routine exCR care (RC) or to a BMIP added to routine exCR care for four months, with a long-term follow-up at 12 months. The outcome assessment included submaximal aerobic exercise capacity, muscle endurance and self-reported physical activity and physical capacity. Results: The four-month follow-up showed improvements in all outcomes for both groups, but changes did not differ significantly between the groups. Patients in the BMIP group were more adherent to exCR recommendations compared with the RC group (31% vs 19%) and a non-significant tendency towards the maintenance of submaximal aerobic exercise capacity over time was seen in the BMIP group, whereas patients in the RC group appeared to deteriorate. Conclusion: Both groups improved significantly at the four-month follow-up, while the 12-month follow-up showed a non-significant tendency towards better long-term effects on submaximal aerobic exercise capacity and exercise adherence for a BMIP compared with RC. In spite of this, a better understanding of the role of a BMIP in enhancing adherence is needed.Funding Agencies|Swedish Heart and Lung AssociationSwedish Heart-Lung Foundation; Swedish Society of Medical Research; Region Ostergotland</p

Correction:Factors associated with non-attendance at exercise-based cardiac rehabilitation (vol 11, 13, 2019)

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