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- Vermunt, L., et al.
(författare)
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Duration of preclinical, prodromal, and dementia stages of Alzheimer's disease in relation to age, sex, and APOE genotype
- 2019
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Ingår i: Alzheimers & Dementia. - : Wiley. - 1552-5260 .- 1552-5279. ; 15:7, s. 888-898
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: We estimated the age-specific duration of the preclinical, prodromal, and dementia stages of Alzheimer's disease (AD) and the influence of sex, setting, apolipoprotein E (APOE) genotype, and cerebrospinal fluid tau on disease duration. Methods: We performed multistate modeling in a combined sample of 6 cohorts (n = 3268) with death as the end stage and estimated the preclinical, prodromal, and dementia stage duration. Results: The overall AD duration varied between 24 years (age 60) and 15 years (age 80). For individuals presenting with preclinical AD, age 70, the estimated preclinical AD duration was 10 years, prodromal AD 4 years, and dementia 6 years. Male sex, clinical setting, APOE epsilon 4 allele carriership, and abnormal cerebrospinal fluid tau were associated with a shorter duration, and these effects depended on disease stage. Discussion: Estimates of AD disease duration become more accurate if age, sex, setting, APOE, and cerebrospinal fluid tau are taken into account. This will be relevant for clinical practice and trial design. (C) 2019 the Alzheimer's Association. Published by Elsevier Inc. All rights reserved.
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- Beishuizen, Cathrien R. L., et al.
(författare)
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Web-Based Interventions Targeting Cardiovascular Risk Factors in Middle-Aged and Older People : A Systematic Review and Meta-Analysis
- 2016
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Ingår i: Journal of Medical Internet Research. - : JMIR Publications Inc.. - 1438-8871. ; 18:3
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Forskningsöversikt (refereegranskat)abstract
- Background: Web-based interventions can improve single cardiovascular risk factors in adult populations. In view of global aging and the associated increasing burden of cardiovascular disease, older people form an important target population as well.Objective: In this systematic review and meta-analysis, we evaluated whether Web-based interventions for cardiovascular risk factor management reduce the risk of cardiovascular disease in older people.Methods: Embase, Medline, Cochrane and CINAHL were systematically searched from January 1995 to November 2014. Search terms included cardiovascular risk factors and diseases (specified), Web-based interventions (and synonyms) and randomized controlled trial. Two authors independently performed study selection, data-extraction and risk of bias assessment. In a meta-analysis, outcomes regarding treatment effects on cardiovascular risk factors (blood pressure, glycated hemoglobin A1c (HbA1C), low-density lipoprotein (LDL) cholesterol, smoking status, weight and physical inactivity) and incident cardiovascular disease were pooled with random effects models.Results: A total of 57 studies (N=19,862) fulfilled eligibility criteria and 47 studies contributed to the meta-analysis. A significant reduction in systolic blood pressure (mean difference -2.66 mmHg, 95% CI -3.81 to -1.52), diastolic blood pressure (mean difference -1.26 mmHg, 95% CI -1.92 to -0.60), HbA1c level (mean difference -0.13%, 95% CI -0.22 to -0.05), LDL cholesterol level (mean difference -2.18 mg/dL, 95% CI -3.96 to -0.41), weight (mean difference -1.34 kg, 95% CI -1.91 to -0.77), and an increase of physical activity (standardized mean difference 0.25, 95% CI 0.10-0.39) in the Web-based intervention group was found. The observed effects were more pronounced in studies with short (<12 months) follow-up and studies that combined the Internet application with human support (blended care). No difference in incident cardiovascular disease was found between groups (6 studies).Conclusions: Web-based interventions have the potential to improve the cardiovascular risk profile of older people, but the effects are modest and decline with time. Currently, there is insufficient evidence for an effect on incident cardiovascular disease. A focus on long-term effects, clinical endpoints, and strategies to increase sustainability of treatment effects is recommended for future studies.
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- Gandouin, E., et al.
(författare)
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Environmental and climate reconstruction of the late-glacial-Holocene transition from a lake sediment sequence in Aubrac, French Massif Central : Chironomid and diatom evidence
- 2016
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Ingår i: Palaeogeography, Palaeoclimatology, Palaeoecology. - : Elsevier BV. - 0031-0182. ; 461, s. 292-309
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Tidskriftsartikel (refereegranskat)abstract
- The analysis of fossil chironomid and diatom assemblages from a sedimentary record from Les Roustières peat bog (Massif Central, France, 1196 m asl) allows the reconstruction of past environmental and climate changes during the late-glacial and early Holocene. Chironomid assemblages showed that the infilling of the palaeolake had commenced during the Oldest Dryas (GS-2b) as suggested by the rapid decrease in chironomid species associated with the cold and deep zone of lakes and by their replacement by littoral and eutrophic taxa. Quantitative July temperature reconstructions, based on the chironomid data, suggest that mean July air temperature (Tjul) ranged between 6 °C and 11 °C at the termination of the Oldest Dryas period (GS-2b). Climate began to warm at the start of the Bølling period (GI-1e), between 15,000 and 14,800 cal yr BP, with a rise in Tjul of about 4 °C. This climate warming is contemporaneous with lake eutrophication as suggested by diatoms and chironomids. Maximum temperatures of 13–14 °C were reached around 13,600 cal yr BP during the Allerød period (GI-1c–GI-1a). The Younger Dryas period (GS-1) is marked by a return to cold conditions with Tjul of about 10 °C during a first phase, then 13 °C in its terminal part. A probable increase in the duration of the ice-cover may have favoured arctic and alpine diatom species. The early-Holocene climate improvement is marked by a rise in Tjul of about 3 °C.
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- Kuchenbaecker, Karoline B., et al.
(författare)
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Risks of breast, ovarian, and contralateral breast cancer for BRCA1 and BRCA2 mutation carriers
- 2017
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Ingår i: JAMA - Journal of the American Medical Association. - : American Medical Association (AMA). - 0098-7484. ; 317:23, s. 2402-2416
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Tidskriftsartikel (refereegranskat)abstract
- IMPORTANCE The clinical management of BRCA1 and BRCA2 mutation carriers requires accurate, prospective cancer risk estimates. OBJECTIVES To estimate age-specific risks of breast, ovarian, and contralateral breast cancer for mutation carriers and to evaluate risk modification by family cancer history and mutation location. DESIGN, SETTING, AND PARTICIPANTS Prospective cohort study of 6036 BRCA1 and 3820 BRCA2 female carriers (5046 unaffected and 4810 with breast or ovarian cancer or both at baseline) recruited in 1997-2011 through the International BRCA1/2 Carrier Cohort Study, the Breast Cancer Family Registry and the Kathleen Cuningham Foundation Consortium for Research into Familial Breast Cancer, with ascertainment through family clinics (94%) and population-based studies (6%). The majority were from large national studies in the United Kingdom (EMBRACE), the Netherlands (HEBON), and France (GENEPSO). Follow-up ended December 2013; median follow-up was 5 years. EXPOSURES BRCA1/2 mutations, family cancer history, and mutation location. MAIN OUTCOMES AND MEASURES Annual incidences, standardized incidence ratios, and cumulative risks of breast, ovarian, and contralateral breast cancer. RESULTS Among 3886 women (median age, 38 years; interquartile range [IQR], 30-46 years) eligible for the breast cancer analysis, 5066 women (median age, 38 years; IQR, 31-47 years) eligible for the ovarian cancer analysis, and 2213 women (median age, 47 years; IQR, 40-55 years) eligible for the contralateral breast cancer analysis, 426 were diagnosed with breast cancer, 109 with ovarian cancer, and 245 with contralateral breast cancer during follow-up. The cumulative breast cancer risk to age 80 years was 72%(95%CI, 65%-79%) for BRCA1 and 69%(95%CI, 61%-77%) for BRCA2 carriers. Breast cancer incidences increased rapidly in early adulthood until ages 30 to 40 years for BRCA1 and until ages 40 to 50 years for BRCA2 carriers, then remained at a similar, constant incidence (20-30 per 1000 person-years) until age 80 years. The cumulative ovarian cancer risk to age 80 years was 44%(95%CI, 36%-53%) for BRCA1 and 17%(95%CI, 11%-25%) for BRCA2 carriers. For contralateral breast cancer, the cumulative risk 20 years after breast cancer diagnosis was 40% (95%CI, 35%-45%) for BRCA1 and 26%(95%CI, 20%-33%) for BRCA2 carriers (hazard ratio [HR] for comparing BRCA2 vs BRCA1, 0.62; 95%CI, 0.47-0.82; P=.001 for difference). Breast cancer risk increased with increasing number of first- and second-degree relatives diagnosed as having breast cancer for both BRCA1 (HR for 2 vs 0 affected relatives, 1.99; 95%CI, 1.41-2.82; P<.001 for trend) and BRCA2 carriers (HR, 1.91; 95%CI, 1.08-3.37; P=.02 for trend). Breast cancer risk was higher if mutations were located outside vs within the regions bounded by positions c.2282-c.4071 in BRCA1 (HR, 1.46; 95%CI, 1.11-1.93; P=.007) and c.2831-c.6401 in BRCA2 (HR, 1.93; 95%CI, 1.36-2.74; P<.001). CONCLUSIONS AND RELEVANCE These findings provide estimates of cancer risk based on BRCA1 and BRCA2 mutation carrier status using prospective data collection and demonstrate the potential importance of family history and mutation location in risk assessment.
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- Richard, Edo, et al.
(författare)
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Healthy ageing through internet counselling in the elderly (HATICE) : a multinational, randomised controlled trial
- 2019
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Ingår i: The Lancet Digital Health. - 2589-7500. ; 1:8, s. e424-e434
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Tidskriftsartikel (refereegranskat)abstract
- Background Although web-based interventions have been promoted for cardiovascular risk management over the past decade, there is limited evidence for effectiveness of these interventions in people older than 65 years. The healthy ageing through internet counselling in the elderly (HATICE) trial aimed to determine whether a coach-supported internet intervention for self-management can reduce cardiovascular risk in community-dwelling older people.Methods This prospective open-label, blinded endpoint clinical trial among people age 65 years or over at increased risk of cardiovascular disease randomly assigned participants in the Netherlands, Finland, and France to an interactive internet intervention stimulating coach-supported self-management or a control platform. Primary outcome was the difference from baseline to 18 months on a standardised composite score (Z score) of systolic blood pressure, LDL cholesterol, and body-mass index (BMI). Secondary outcomes included individual risk factors and cardiovascular endpoints. This trial is registered with the ISRCTN registry, 48151589, and is closed to accrual.Findings Among 2724 participants, complete primary outcome data were available for 2398 (88%). After 18 months, the primary outcome improved in the intervention group versus the control group (0.09 vs 0.04, respectively; mean difference -0.05, 95% CI -0.08 to -0.01; p=0.008). For individual components of the primary outcome, mean differences (intervention vs control) were systolic blood pressure -1.79 mm Hg versus -0.67 mm Hg (-1.12, -2.51 to 0.27); BMI -0.23 kg/m(2) versus -0.08 kg/m(2) (-0.15, -0.28 to -0.01); and LDL -0.12 mmol/L versus -0.07 mmol/L (-0.05, -0.11 to 0.01). Cardiovascular disease occurred in 30 (2.2%) of 1382 patients in the intervention versus 32 (2.4%) of 1333 patients in the control group (hazard ratio 0.86, 95% CI 0.52 to 1.43).Interpretation Coach-supported self-management of cardiovascular risk factors using an interactive internet intervention is feasible in an older population, and leads to a modest improvement of cardiovascular risk profile. When implemented on a large scale this could potentially reduce the burden of cardiovascular disease.
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