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    Burden of disease scenarios for 204 countries and territories, 2022–2050: a forecasting analysis for the Global Burden of Disease Study 2021

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    Background Future trends in disease burden and drivers of health are of great interest to policy makers and the public at large. This information can be used for policy and long-term health investment, planning, and prioritisation. We have expanded and improved upon previous forecasts produced as part of the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) and provide a reference forecast (the most likely future), and alternative scenarios assessing disease burden trajectories if selected sets of risk factors were eliminated from current levels by 2050. Methods Using forecasts of major drivers of health such as the Socio-demographic Index (SDI; a composite measure of lag-distributed income per capita, mean years of education, and total fertility under 25 years of age) and the full set of risk factor exposures captured by GBD, we provide cause-specific forecasts of mortality, years of life lost (YLLs), years lived with disability (YLDs), and disability-adjusted life-years (DALYs) by age and sex from 2022 to 2050 for 204 countries and territories, 21 GBD regions, seven super-regions, and the world. All analyses were done at the cause-specific level so that only risk factors deemed causal by the GBD comparative risk assessment influenced future trajectories of mortality for each disease. Cause-specific mortality was modelled using mixed-effects models with SDI and time as the main covariates, and the combined impact of causal risk factors as an offset in the model. At the all-cause mortality level, we captured unexplained variation by modelling residuals with an autoregressive integrated moving average model with drift attenuation. These all-cause forecasts constrained the cause-specific forecasts at successively deeper levels of the GBD cause hierarchy using cascading mortality models, thus ensuring a robust estimate of cause-specific mortality. For non-fatal measures (eg, low back pain), incidence and prevalence were forecasted from mixed-effects models with SDI as the main covariate, and YLDs were computed from the resulting prevalence forecasts and average disability weights from GBD. Alternative future scenarios were constructed by replacing appropriate reference trajectories for risk factors with hypothetical trajectories of gradual elimination of risk factor exposure from current levels to 2050. The scenarios were constructed from various sets of risk factors: environmental risks (Safer Environment scenario), risks associated with communicable, maternal, neonatal, and nutritional diseases (CMNNs; Improved Childhood Nutrition and Vaccination scenario), risks associated with major non-communicable diseases (NCDs; Improved Behavioural and Metabolic Risks scenario), and the combined effects of these three scenarios. Using the Shared Socioeconomic Pathways climate scenarios SSP2-4.5 as reference and SSP1-1.9 as an optimistic alternative in the Safer Environment scenario, we accounted for climate change impact on health by using the most recent Intergovernmental Panel on Climate Change temperature forecasts and published trajectories of ambient air pollution for the same two scenarios. Life expectancy and healthy life expectancy were computed using standard methods. The forecasting framework includes computing the age-sex-specific future population for each location and separately for each scenario. 95% uncertainty intervals (UIs) for each individual future estimate were derived from the 2·5th and 97·5th percentiles of distributions generated from propagating 500 draws through the multistage computational pipeline. Findings In the reference scenario forecast, global and super-regional life expectancy increased from 2022 to 2050, but improvement was at a slower pace than in the three decades preceding the COVID-19 pandemic (beginning in 2020). Gains in future life expectancy were forecasted to be greatest in super-regions with comparatively low life expectancies (such as sub-Saharan Africa) compared with super-regions with higher life expectancies (such as the high-income super-region), leading to a trend towards convergence in life expectancy across locations between now and 2050. At the super-region level, forecasted healthy life expectancy patterns were similar to those of life expectancies. Forecasts for the reference scenario found that health will improve in the coming decades, with all-cause age-standardised DALY rates decreasing in every GBD super-region. The total DALY burden measured in counts, however, will increase in every super-region, largely a function of population ageing and growth. We also forecasted that both DALY counts and age-standardised DALY rates will continue to shift from CMNNs to NCDs, with the most pronounced shifts occurring in sub-Saharan Africa (60·1% [95% UI 56·8–63·1] of DALYs were from CMNNs in 2022 compared with 35·8% [31·0–45·0] in 2050) and south Asia (31·7% [29·2–34·1] to 15·5% [13·7–17·5]). This shift is reflected in the leading global causes of DALYs, with the top four causes in 2050 being ischaemic heart disease, stroke, diabetes, and chronic obstructive pulmonary disease, compared with 2022, with ischaemic heart disease, neonatal disorders, stroke, and lower respiratory infections at the top. The global proportion of DALYs due to YLDs likewise increased from 33·8% (27·4–40·3) to 41·1% (33·9–48·1) from 2022 to 2050, demonstrating an important shift in overall disease burden towards morbidity and away from premature death. The largest shift of this kind was forecasted for sub-Saharan Africa, from 20·1% (15·6–25·3) of DALYs due to YLDs in 2022 to 35·6% (26·5–43·0) in 2050. In the assessment of alternative future scenarios, the combined effects of the scenarios (Safer Environment, Improved Childhood Nutrition and Vaccination, and Improved Behavioural and Metabolic Risks scenarios) demonstrated an important decrease in the global burden of DALYs in 2050 of 15·4% (13·5–17·5) compared with the reference scenario, with decreases across super-regions ranging from 10·4% (9·7–11·3) in the high-income super-region to 23·9% (20·7–27·3) in north Africa and the Middle East. The Safer Environment scenario had its largest decrease in sub-Saharan Africa (5·2% [3·5–6·8]), the Improved Behavioural and Metabolic Risks scenario in north Africa and the Middle East (23·2% [20·2–26·5]), and the Improved Nutrition and Vaccination scenario in sub-Saharan Africa (2·0% [–0·6 to 3·6]). Interpretation Globally, life expectancy and age-standardised disease burden were forecasted to improve between 2022 and 2050, with the majority of the burden continuing to shift from CMNNs to NCDs. That said, continued progress on reducing the CMNN disease burden will be dependent on maintaining investment in and policy emphasis on CMNN disease prevention and treatment. Mostly due to growth and ageing of populations, the number of deaths and DALYs due to all causes combined will generally increase. By constructing alternative future scenarios wherein certain risk exposures are eliminated by 2050, we have shown that opportunities exist to substantially improve health outcomes in the future through concerted efforts to prevent exposure to well established risk factors and to expand access to key health interventions.publishedVersio

    Revisiting the past, being in the present, preparing for the future: Making sense of a digital-free holiday camp for adults

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    In this chapter, we explore how participants experience disconnection in practice at a digital-free summer camp for adults. Underleir is an annual week-long camp originating from discussions on the Norwegian social network Underskog and draws inspiration both from Silicon Valley disconnectionist ideology and Scandinavian traditions of friluftsliv [outdoor recreation]. When the camp was f irst organised in 2014, digital detoxing was not a well-known concept in the Norwegian context, and such camps are still rare in Scandinavia. The study is based on fieldwork, interviews, and online material. In the chapter, we discuss how camp experiences relate to the participants’ life course along three temporal dimensions: the past (nostalgia, play), the present (freedom from status games, relaxation), and the future (survivalism, utopianism). The study contributes to the disconnection literature by moving beyond the media-centred issue of how users relate to their gadgets. Instead, the chapter explores how being digital-free is made meaningful within a concrete and unusual holiday setting and relates to the societal and personal values of those attending.publishedVersio

    Angiogenic and vasoactive proteins in the maternal-fetal interface in healthy pregnancies and preeclampsia

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    Background Preeclampsia is characterized by maternal endothelial activation and placental dysfunction. Imbalance in maternal angiogenic and vasoactive factors has been linked to the pathophysiology. The contribution of the placenta as a source of these factors remains unclear. Furthermore, little is known about fetal angiogenic and vasoactive proteins and the relation between maternal and fetal levels. Objective We describe placental growth factor, soluble Fms-like tyrosine kinase 1, soluble endoglin, and endothelin 1–3 in 5 vessels in healthy pregnancies, early- and late-onset preeclampsia. Specifically, we aimed to (1) compare protein abundance in vessels at the maternal-fetal interface between early- and late-onset preeclampsia, and healthy pregnancies, (2) describe placental uptake and release of proteins, and (3) describe protein abundance in the maternal vs fetal circulations. Study Design Samples were collected from the maternal radial artery, uterine vein and antecubital vein, and fetal umbilical vein and artery in 75 healthy and 37 preeclamptic mother-fetus pairs (including 19 early-onset preeclampsia and 18 late-onset preeclampsia), during scheduled cesarean delivery. This method allows estimation of placental release and uptake of proteins by calculation of venoarterial differences on each side of the placenta. The microarray-based SomaScan assay quantified the proteins. Results The abundance of soluble Fms-like tyrosine kinase 1 and endothelin 1 was higher in the maternal vessels in preeclampsia than in healthy pregnancies, with the highest abundance in early-onset preeclampsia. Placental growth factor was lower in the maternal vessels in early-onset preeclampsia than in both healthy and late-onset preeclampsia. Maternal endothelin 2 was higher in preeclampsia, with late-onset preeclampsia having the highest abundance. Our model confirmed placental release of placental growth factor and soluble Fms-like tyrosine kinase 1 to the maternal circulation in all groups. The placenta released soluble Fms-like tyrosine kinase 1 into the fetal circulation in healthy and late-onset preeclampsia pregnancies. Fetal endothelin 1 and soluble Fms-like tyrosine kinase 1 were higher in early-onset preeclampsia, whereas soluble endoglin and endothelin 3 were lower in both preeclampsia groups than healthy controls. Across groups, abundances of placental growth factor, soluble Fms-like tyrosine kinase 1, and endothelin 3 were higher in the maternal artery than the fetal umbilical vein, whereas endothelin 2 was lower. Conclusion An increasing abundance of maternal soluble Fms-like tyrosine kinase 1 and endothelin 1 across the groups healthy, late-onset preeclampsia and early-onset combined with a positive correlation may suggest that these proteins are associated with the pathophysiology and severity of the disease. Elevated endothelin 1 in the fetal circulation in early-onset preeclampsia represents a novel finding. The long-term effects of altered protein abundance in preeclampsia on fetal development and health remain unknown. Further investigation of these proteins’ involvement in the pathophysiology and as treatment targets is warranted.publishedVersio

    Global burden and strength of evidence for 88 risk factors in 204 countries and 811 subnational locations, 1990–2021: a systematic analysis for the Global Burden of Disease Study 2021

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    Background Understanding the health consequences associated with exposure to risk factors is necessary to inform public health policy and practice. To systematically quantify the contributions of risk factor exposures to specific health outcomes, the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021 aims to provide comprehensive estimates of exposure levels, relative health risks, and attributable burden of disease for 88 risk factors in 204 countries and territories and 811 subnational locations, from 1990 to 2021. Methods The GBD 2021 risk factor analysis used data from 54 561 total distinct sources to produce epidemiological estimates for 88 risk factors and their associated health outcomes for a total of 631 risk–outcome pairs. Pairs were included on the basis of data-driven determination of a risk–outcome association. Age-sex-location-year-specific estimates were generated at global, regional, and national levels. Our approach followed the comparative risk assessment framework predicated on a causal web of hierarchically organised, potentially combinative, modifiable risks. Relative risks (RRs) of a given outcome occurring as a function of risk factor exposure were estimated separately for each risk–outcome pair, and summary exposure values (SEVs), representing risk-weighted exposure prevalence, and theoretical minimum risk exposure levels (TMRELs) were estimated for each risk factor. These estimates were used to calculate the population attributable fraction (PAF; ie, the proportional change in health risk that would occur if exposure to a risk factor were reduced to the TMREL). The product of PAFs and disease burden associated with a given outcome, measured in disability-adjusted life-years (DALYs), yielded measures of attributable burden (ie, the proportion of total disease burden attributable to a particular risk factor or combination of risk factors). Adjustments for mediation were applied to account for relationships involving risk factors that act indirectly on outcomes via intermediate risks. Attributable burden estimates were stratified by Socio-demographic Index (SDI) quintile and presented as counts, age-standardised rates, and rankings. To complement estimates of RR and attributable burden, newly developed burden of proof risk function (BPRF) methods were applied to yield supplementary, conservative interpretations of risk–outcome associations based on the consistency of underlying evidence, accounting for unexplained heterogeneity between input data from different studies. Estimates reported represent the mean value across 500 draws from the estimate's distribution, with 95% uncertainty intervals (UIs) calculated as the 2·5th and 97·5th percentile values across the draws. Findings Among the specific risk factors analysed for this study, particulate matter air pollution was the leading contributor to the global disease burden in 2021, contributing 8·0% (95% UI 6·7–9·4) of total DALYs, followed by high systolic blood pressure (SBP; 7·8% [6·4–9·2]), smoking (5·7% [4·7–6·8]), low birthweight and short gestation (5·6% [4·8–6·3]), and high fasting plasma glucose (FPG; 5·4% [4·8–6·0]). For younger demographics (ie, those aged 0–4 years and 5–14 years), risks such as low birthweight and short gestation and unsafe water, sanitation, and handwashing (WaSH) were among the leading risk factors, while for older age groups, metabolic risks such as high SBP, high body-mass index (BMI), high FPG, and high LDL cholesterol had a greater impact. From 2000 to 2021, there was an observable shift in global health challenges, marked by a decline in the number of all-age DALYs broadly attributable to behavioural risks (decrease of 20·7% [13·9–27·7]) and environmental and occupational risks (decrease of 22·0% [15·5–28·8]), coupled with a 49·4% (42·3–56·9) increase in DALYs attributable to metabolic risks, all reflecting ageing populations and changing lifestyles on a global scale. Age-standardised global DALY rates attributable to high BMI and high FPG rose considerably (15·7% [9·9–21·7] for high BMI and 7·9% [3·3–12·9] for high FPG) over this period, with exposure to these risks increasing annually at rates of 1·8% (1·6–1·9) for high BMI and 1·3% (1·1–1·5) for high FPG. By contrast, the global risk-attributable burden and exposure to many other risk factors declined, notably for risks such as child growth failure and unsafe water source, with age-standardised attributable DALYs decreasing by 71·5% (64·4–78·8) for child growth failure and 66·3% (60·2–72·0) for unsafe water source. We separated risk factors into three groups according to trajectory over time: those with a decreasing attributable burden, due largely to declining risk exposure (eg, diet high in trans-fat and household air pollution) but also to proportionally smaller child and youth populations (eg, child and maternal malnutrition); those for which the burden increased moderately in spite of declining risk exposure, due largely to population ageing (eg, smoking); and those for which the burden increased considerably due to both increasing risk exposure and population ageing (eg, ambient particulate matter air pollution, high BMI, high FPG, and high SBP). Interpretation Substantial progress has been made in reducing the global disease burden attributable to a range of risk factors, particularly those related to maternal and child health, WaSH, and household air pollution. Maintaining efforts to minimise the impact of these risk factors, especially in low SDI locations, is necessary to sustain progress. Successes in moderating the smoking-related burden by reducing risk exposure highlight the need to advance policies that reduce exposure to other leading risk factors such as ambient particulate matter air pollution and high SBP. Troubling increases in high FPG, high BMI, and other risk factors related to obesity and metabolic syndrome indicate an urgent need to identify and implement interventions.publishedVersio

    Global pattern, trend, and cross-country inequality of early musculoskeletal disorders from 1990 to 2019, with projection from 2020 to 2050

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    Background: This study aims to estimate the burden, trends, forecasts, and disparities of early musculoskeletal (MSK) disorders among individuals ages 15 to 39 years. Methods: The global prevalence, years lived with disabilities (YLDs), disability-adjusted life years (DALYs), projection, and inequality were estimated for early MSK diseases, including rheumatoid arthritis (RA), osteoarthritis (OA), low back pain (LBP), neck pain (NP), gout, and other MSK diseases (OMSKDs). Findings: More adolescents and young adults were expected to develop MSK disorders by 2050. Across five age groups, the rates of prevalence, YLDs, and DALYs for RA, NP, LBP, gout, and OMSKDs sharply increased from ages 15–19 to 35–39; however, these were negligible for OA before age 30 but increased notably at ages 30–34, rising at least 6-fold by 35–39. The disease burden of gout, LBP, and OA attributable to high BMI and gout attributable to kidney dysfunction increased, while the contribution of smoking to LBP and RA and occupational ergonomic factors to LBP decreased. Between 1990 and 2019, the slope index of inequality increased for six MSK disorders, and the relative concentration index increased for gout, NP, OA, and OMSKDs mbut decreased for LBP and RA. Conclusions: Multilevel interventions should be initiated to prevent disease burden related to RA, NP, LBP, gout, and OMSKDs among individuals ages 15–19 and to OA among individuals ages 30–34 to tightly control high BMI and kidney dysfunction. Funding: The Global Burden of Disease study is funded by the Bill and Melinda Gates Foundation. The project is funded by the Scientific Research Fund of Sichuan Academy of Medical Sciences & Sichuan Provincial People’s Hospital (2022QN38publishedVersio

    Promoting Cognitive Brain Health and Sustained Attention in Adults and Older Adults Through e-Games

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    The ability to learn new skills as an adult, cognitive stimulation in the ageing process, and a cognitively active lifestyle interest experts in education, public health, and social studies. The game Scrabble, with its enjoyable nature, has gained recognition as an educational resource that facilitates the acquisition and preservation of vocabulary, thereby augmenting both practical and cognitive abilities. This study implemented a descriptive quantitative research design to assess attentional capacity using the Bourdon Attention Test, specifically utilizing the BoPr (Prague Square Modification of the CSAT), within the cohort of Scrabble League e-players and the broader general population. With a focus on promoting cognitive brain health, this study compares sustained attention levels between these groups. A sample of N = 60 participants (divided into Scrabble e-players who participate in a league [N = 30], and a comparison group of the general population [N = 30]) underwent a study comparing their levels of attention achieved in the Bourdon test. A significant difference (p = 0.050) was found in their attention span, favouring the league e-players. The results suggest that Scrabble e-games can potentially improve the cognitive well-being and attention of adults and older individuals. However, further investigation is necessary to understand their capabilities fully. Utilizing Scrabble in the realms of adult education, gerontology, and medical practice could be beneficial for enhancing cognitive brain health.Promoting Cognitive Brain Health and Sustained Attention in Adults and Older Adults Through e-GamespublishedVersio

    Individual supported work placements (ReISE) for improving sustained return to work in unemployed people with persistent pain: an internal pilot study of a cohort randomised controlled approach

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    Background Persistent pain is a frequent cause of sick leave and work disability in Norway. A return-to-work intervention featuring supported work placements, developed in the UK, demonstrated feasibility, and a return-to-work rate of 20% within 6 months was observed in the sample. We sought to adapt the intervention for delivery in Norway and to confirm feasibility prior to a full-scale trial. Methods In this internal pilot, we used a pragmatic cohort randomised controlled approach with national recruitment in Norway. We recruited people who were unemployed (for at least 1 month), having persistent pain (for at least 3 months), aged between 18 and 64, and wanting to return to work. We initially recruited people to an observational cohort study of the impact of being unemployed with persistent pain. After baseline measurement, we randomly sub-sampled participants to whom we offered the intervention, which featured individual case management and support, work-familiarisation sessions, and the offer of a 6-week part-time unpaid work placement. We assessed recruitment rates (aiming to recruit 66, and sub-sample 17 within 6 months); optimal recruitment pathways; intervention acceptance rates; the feasibility of data collection; using video links for work-familiarisation sessions and remote case manager support. Results The pilot ran from June to November 2022. Of 168 people expressing interest, 94 consented. Recruitment posts on Facebook yielded the most ‘expressions of interest’ (66%, n = 111). After screening for eligibility, we included 55 participants. Of these, 19 were randomised to be offered the intervention. Of these, less than half (n = 8) consented to intervention participation. Remote case manager and work-familiarisation sessions appeared feasible. Following a delay in identifying placements, three participants received offers of work placements, with one starting and completing during the pilot period. Data collection methods were feasible, and no adverse events were reported. Conclusions Recruitment and logistical processes, such as remote management by video link, are feasible. However, delivery of the intervention is challenging. In particular, sourcing placements and the time required for identifying appropriate placements was more challenging than anticipated. A full-scale trial is feasible but will require improvements to the placement identification processes.publishedVersio

    National-level and state-level prevalence of overweight and obesity among children, adolescents, and adults in the USA, 1990–2021, and forecasts up to 2050

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    Background Over the past several decades, the overweight and obesity epidemic in the USA has resulted in a significant health and economic burden. Understanding current trends and future trajectories at both national and state levels is crucial for assessing the success of existing interventions and informing future health policy changes. We estimated the prevalence of overweight and obesity from 1990 to 2021 with forecasts to 2050 for children and adolescents (aged 5–24 years) and adults (aged ≥25 years) at the national level. Additionally, we derived state-specific estimates and projections for older adolescents (aged 15–24 years) and adults for all 50 states and Washington, DC. Methods In this analysis, self-reported and measured anthropometric data were extracted from 134 unique sources, which included all major national surveillance survey data. Adjustments were made to correct for self-reporting bias. For individuals older than 18 years, overweight was defined as having a BMI of 25 kg/m2 to less than 30 kg/m2 and obesity was defined as a BMI of 30 kg/m2 or higher, and for individuals younger than 18 years definitions were based on International Obesity Task Force criteria. Historical trends of overweight and obesity prevalence from 1990 to 2021 were estimated using spatiotemporal Gaussian process regression models. A generalised ensemble modelling approach was then used to derive projected estimates up to 2050, assuming continuation of past trends and patterns. All estimates were calculated by age and sex at the national level, with estimates for older adolescents (aged 15–24 years) and adults aged (≥25 years) also calculated for 50 states and Washington, DC. 95% uncertainty intervals (UIs) were derived from the 2·5th and 97·5th percentiles of the posterior distributions of the respective estimates. Findings In 2021, an estimated 15·1 million (95% UI 13·5–16·8) children and young adolescents (aged 5–14 years), 21·4 million (20·2–22·6) older adolescents (aged 15–24 years), and 172 million (169–174) adults (aged ≥25 years) had overweight or obesity in the USA. Texas had the highest age-standardised prevalence of overweight or obesity for male adolescents (aged 15–24 years), at 52·4% (47·4–57·6), whereas Mississippi had the highest for female adolescents (aged 15–24 years), at 63·0% (57·0–68·5). Among adults, the prevalence of overweight or obesity was highest in North Dakota for males, estimated at 80·6% (78·5–82·6), and in Mississippi for females at 79·9% (77·8–81·8). The prevalence of obesity has outpaced the increase in overweight over time, especially among adolescents. Between 1990 and 2021, the percentage change in the age-standardised prevalence of obesity increased by 158·4% (123·9–197·4) among male adolescents and 185·9% (139·4–237·1) among female adolescents (15–24 years). For adults, the percentage change in prevalence of obesity was 123·6% (112·4–136·4) in males and 99·9% (88·8–111·1) in females. Forecast results suggest that if past trends and patterns continue, an additional 3·33 million children and young adolescents (aged 5–14 years), 3·41 million older adolescents (aged 15–24 years), and 41·4 million adults (aged ≥25 years) will have overweight or obesity by 2050. By 2050, the total number of children and adolescents with overweight and obesity will reach 43·1 million (37·2–47·4) and the total number of adults with overweight and obesity will reach 213 million (202–221). In 2050, in most states, a projected one in three adolescents (aged 15–24 years) and two in three adults (≥25 years) will have obesity. Although southern states, such as Oklahoma, Mississippi, Alabama, Arkansas, West Virginia, and Kentucky, are forecast to continue to have a high prevalence of obesity, the highest percentage changes from 2021 are projected in states such as Utah for adolescents and Colorado for adults. Interpretation Existing policies have failed to address overweight and obesity. Without major reform, the forecasted trends will be devastating at the individual and population level, and the associated disease burden and economic costs will continue to escalate. Stronger governance is needed to support and implement a multifaceted whole-system approach to disrupt the structural drivers of overweight and obesity at both national and local levels. Although clinical innovations should be leveraged to treat and manage existing obesity equitably, population-level prevention remains central to any intervention strategies, particularly for children and adolescents.Bill & Melinda Gates Foundation.publishedVersio

    Stretch of the papillary insertion triggers reentrant arrhythmia: an in silico patient study

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    Background: The electrophysiological mechanism connecting mitral valve prolapse (MVP), premature ventricular complexes and life-threatening ventricular arrhythmia is unknown. A common hypothesis is that stretch activated channels (SACs) play a significant role. SACs can trigger depolarizations or shorten repolarization times in response to myocardial stretch. Through these mechanisms, pathological traction of the papillary muscle (PM), as has been observed in patients with MVP, may induce irregular electrical activity and result in reentrant arrhythmia. Methods: Based on a patient with MVP and mitral annulus disjunction, we modeled the effect of excessive PM traction in a detailed medical image-derived ventricular model by activating SACs in the PM insertion region. By systematically varying the onset of SAC activation following sinus pacing, we identified vulnerability windows for reentry with 1 ms resolution. We explored how reentry was affected by the SAC reversal potential (ESAC) and the size of the region with simulated stretch (SAC region). Finally, the effect of global or focal fibrosis, modeled as reduction in tissue conductivity or mesh splitting (fibrotic microstructure), was investigated. Results: In models with healthy tissue or fibrosis modeled solely as CV slowing, we observed two vulnerable periods of reentry: For ESAC of −10 and −30 mV, SAC activated during the T-wave could cause depolarization of the SAC region which lead to reentry. For ESAC of −40 and −70 mV, SAC activated during the QRS complex could result in early repolarization of the SAC region and subsequent reentry. In models with fibrotic microstructure in the SAC region, we observed micro-reentries and a larger variability in which times of SAC activation triggered reentry. In these models, 86% of reentries were triggered during the QRS complex or T-wave. We only observed reentry for sufficiently large SAC regions (>= 8 mm radius in models with healthy tissue). Conclusion: Stretch of the PM insertion region following sinus activation may initiate ventricular reentry in patients with MVP, with or without fibrosis. Depending on the SAC reversal potential and timing of stretch, reentry may be triggered by ectopy due to SAC-induced depolarizations or by early repolarization within the SAC region.publishedVersio

    Can general exercise training and pelvic floor muscle training be used as an empowering tool among women with endometriosis? Experiences among women with endometriosis participating in the intervention group of a randomized controlled trial

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    Background The potential benefit of exercise in alleviating symptoms of endometriosis is unclear. Still, exercise may be used to empower women and manage disease symptoms. The purpose of this study was to explore how regular supervised group- and individual exercise training, including pelvic floor muscle training (PFMT), is experienced among women with endometriosis after participating in a randomized controlled trial (RCT). Methods Among 41 women randomized to exercise training for four months, ten women were interviewed about their experiences with exercise training after participation in the trial. The weekly group training was led by women’s health physiotherapists and included individualized and progressive muscular strength training of large muscle groups and the pelvic floor muscles, in addition to endurance-, flexibility, and relaxation training. An individual training program followed the same principles as the group training and was to be performed 3–5 times per week, depending on the level of intensity. PFMT was recommended daily. The women also received a group pain management course emphasizing exercise training as self-management. Using inductive reflexive thematic analysis, responses to the question “Did participation in the study change your view of exercise as part of the treatment for endometriosis?“ were analyzed. Results The women brought forward the importance of knowledge about the benefits of exercise to make informed decisions in disease management. Further, the women described how exercise training was perceived as less frightening and manageable when exposed to various intensities, dosages, and types of exercises in a safe and supportive environment. PFMT was especially brought forward as something new and appreciated, and for some of the women, to be performed on days when their bodies could not handle the general exercise training. They also expressed that the supervised exercise brought an extra dimension of belonging through group participation. Conclusions Individualization and regular supervision seem important to empower women with knowledge about exercise training as self-management and to experience exercise training as safe and non-threatening. Further, creating a sense of belonging through group training may improve social support and build active coping strategies that are essential for disease management of endometriosis.publishedVersio

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