| 21. |
- Peters, Ruth, et al.
(författare)
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An investigation of antihypertensive class, dementia, and cognitive decline: A meta-analysis.
- 2020
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Ingår i: Neurology. - 1526-632X. ; 94:3, s. e267-e281
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Tidskriftsartikel (refereegranskat)abstract
- High blood pressure is one of the main modifiable risk factors for dementia. However, there is conflicting evidence regarding the best antihypertensive class for optimizing cognition. Our objective was to determine whether any particular antihypertensive class was associated with a reduced risk of cognitive decline or dementia using comprehensive meta-analysis including reanalysis of original participant data.To identify suitable studies, MEDLINE, Embase, and PsycINFO and preexisting study consortia were searched from inception to December 2017. Authors of prospective longitudinal human studies or trials of antihypertensives were contacted for data sharing and collaboration. Outcome measures were incident dementia or incident cognitive decline (classified using the reliable change index method). Data were separated into mid and late-life (>65 years) and each antihypertensive class was compared to no treatment and to treatment with other antihypertensives. Meta-analysis was used to synthesize data.Over 50,000 participants from 27 studies were included. Among those aged >65 years, with the exception of diuretics, we found no relationship by class with incident cognitive decline or dementia. Diuretic use was suggestive of benefit in some analyses but results were not consistent across follow-up time, comparator group, and outcome. Limited data precluded meaningful analyses in those ≤65 years of age.Our findings, drawn from the current evidence base, support clinical freedom in the selection of antihypertensive regimens to achieve blood pressure goals.The review was registered with the international prospective register of systematic reviews (PROSPERO), registration number CRD42016045454.
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| 22. |
- Pikkemaat, Miriam, et al.
(författare)
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C-peptide predicts all-cause and cardiovascular death in a cohort of individuals with newly diagnosed type 2 diabetes. The Skaraborg diabetes register
- 2019
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Ingår i: Diabetes Research and Clinical Practice. - : Elsevier BV. - 0168-8227 .- 1872-8227. ; 150, s. 174-183
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Tidskriftsartikel (refereegranskat)abstract
- Aims: To study the association between baseline level of C-peptide and all-cause death, cardiovascular death and cardiovascular complications among persons with newly diagnosed type 2 diabetes. Methods: The Skaraborg Diabetes Register contains data on baseline C-peptide concentrations among 398 persons <65 years with newly diagnosed type 2 diabetes 1996–1998. National registries were used to determine all-cause death, cardiovascular death and incidence of myocardial infarction and ischemic stroke until 31 December 2014. The association between baseline C-peptide and outcomes were evaluated with adjustment for multiple confounders by Cox regression analysis. Missing data were handled by multiple imputation. Results: In the imputed and fully adjusted model there was a significant association between 1 nmol/l increase in C-peptide concentration and all-cause death (HR 2.20, 95% CI 1.49–3.25, p < 0.001, number of events = 104), underlying cardiovascular death (HR 2.69, 1.49–4.85, p = 0.001, n = 35) and the composite outcome of underlying cardiovascular death, myocardial infarction or ischemic stroke (HR 1.61, 1.06–2.45, p = 0.027, n = 90). Conclusions: Elevated C-peptide levels at baseline in persons with newly diagnosed type 2 diabetes are associated with increased risk of all-cause and cardiovascular mortality. C-peptide might be used to identify persons at high risk of cardiovascular complications and premature death.
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| 23. |
- Pinho-Gomes, Ana-Catarina, et al.
(författare)
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Blood pressure-lowering treatment for the prevention of cardiovascular events in patients with atrial fibrillation : An individual participant data meta-analysis
- 2021
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Ingår i: PLoS Medicine. - : Public Library of Science (PLoS). - 1549-1277 .- 1549-1676. ; 18:6
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Tidskriftsartikel (refereegranskat)abstract
- Background Randomised evidence on the efficacy of blood pressure (BP)-lowering treatment to reduce cardiovascular risk in patients with atrial fibrillation (AF) is limited. Therefore, this study aimed to compare the effects of BP-lowering drugs in patients with and without AF at baseline. Methods and findings The study was based on the resource provided by the Blood Pressure Lowering Treatment Trialists' Collaboration (BPLTTC), in which individual participant data (IPD) were extracted from trials with over 1,000 patient-years of follow-up in each arm, and that had randomly assigned patients to different classes of BP-lowering drugs, BP-lowering drugs versus placebo, or more versus less intensive BP-lowering regimens. For this study, only trials that had collected information on AF status at baseline were included. The effects of BP-lowering treatment on a composite endpoint of major cardiovascular events (stroke, ischaemic heart disease or heart failure) according to AF status at baseline were estimated using fixed-effect one-stage IPD meta-analyses based on Cox proportional hazards models stratified by trial. Furthermore, to assess whether the associations between the intensity of BP reduction and cardiovascular outcomes are similar in those with and without AF at baseline, we used a meta-regression. From the full BPLTTC database, 28 trials (145,653 participants) were excluded because AF status at baseline was uncertain or unavailable. A total of 22 trials were included with 188,570 patients, of whom 13,266 (7%) had AF at baseline. Risk of bias assessment showed that 20 trials were at low risk of bias and 2 trials at moderate risk. Meta-regression showed that relative risk reductions were proportional to trial-level intensity of BP lowering in patients with and without AF at baseline. Over 4.5 years of median follow-up, a 5-mm Hg systolic BP (SBP) reduction lowered the risk of major cardiovascular events both in patients with AF (hazard ratio [HR] 0.91, 95% confidence interval [CI] 0.83 to 1.00) and in patients without AF at baseline (HR 0.91, 95% CI 0.88 to 0.93), with no difference between subgroups. There was no evidence for heterogeneity of treatment effects by baseline SBP or drug class in patients with AF at baseline. The findings of this study need to be interpreted in light of its potential limitations, such as the limited number of trials, limitation in ascertaining AF cases due to the nature of the arrhythmia and measuring BP in patients with AF. Conclusions In this meta-analysis, we found that BP-lowering treatment reduces the risk of major cardiovascular events similarly in individuals with and without AF. Pharmacological BP lowering for prevention of cardiovascular events should be recommended in patients with AF. Author summary Why was this study done? Atrial fibrillation (AF) is the most common cardiac arrhythmia across the world and is strongly associated with future vascular disease, particularly stroke. Blood pressure (BP) lowering is an established strategy for prevention of vascular disease, but whether patients with AF benefit similarly from pharmacological BP reduction is not well understood. What did the researchers do and find? We compared the preventive effect of BP-lowering treatment on cardiovascular outcomes in patients with and without AF at baseline. We conducted an individual participant data meta-analysis using published and unpublished data from large randomised clinical trials (22 trials involving 188,570 patients). We showed that BP-lowering treatment reduced the risk of a major cardiovascular events with no evidence that effects differed according to the presence or absence of AF at baseline. The relative risk reductions were proportional to the intensity of BP reduction in individuals with and without AF. In individuals with AF, the relative risk reduction was comparable irrespective of whether baseline systolic BP was under or over the conventional treatment threshold of 140 mm Hg. What do these findings mean? BP-lowering treatment reduces the risk of major cardiovascular events in patients with AF to a similar extent to that of patients without AF. Pharmacological BP-lowering treatment for prevention of cardiovascular events should be recommended as part of care for patients with AF.
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| 24. |
- Prinsen, Cecilia A C, et al.
(författare)
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Navigating the landscape of core outcome set development in dermatology.
- 2019
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Ingår i: The Journal of American Academy of Dermatology. - : Elsevier. - 0190-9622 .- 1097-6787. ; 81:1, s. 297-305
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Tidskriftsartikel (refereegranskat)abstract
- The development of core outcome sets (COSs; ie, a minimum set of core outcomes that should be measured and reported in all trials or in clinical practice for a specific condition) in dermatology is increasing in pace. A total of 44 dermatology-related COS projects have been registered in the online Core Outcome Measures in Effectiveness Trials database (http://www.comet-initiative.org/studies/search) and include studies on 26 different skin diseases. With the increasing number of COSs in dermatology, care is needed to ensure the delivery of high-quality COSs that meet quality standards when using state-of-the-art methods. In 2015, the Cochrane Skin-Core Outcome Set Initiative (CS-COUSIN) was established. CS-COUSIN is an international, multidisciplinary working group aiming to improve the development and implementation of COSs in dermatology. CS-COUSIN has developed guidance on how to develop high-quality COSs for skin diseases and supports dermatology-specific COS initiatives. Currently, 17 COS development groups are affiliated with CS-COUSIN and following standardized COS development processes. To ensure successful uptake of COSs in dermatology, researchers, clinicians, systematic reviewers, guideline developers, and other stakeholders should use existing COSs in their work.
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| 25. |
- Rådholm, Karin, 1976-, et al.
(författare)
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Dog ownership, glycaemic control and all-cause death in patients with newly diagnosed type 2 diabetes: a national cohort study
- 2023
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Ingår i: Frontiers In Public Health. - : FRONTIERS MEDIA SA. - 2296-2565. ; 11
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Tidskriftsartikel (refereegranskat)abstract
- Aims: To evaluate whether dog ownership from the time of type 2 diabetes diagnosis improved glycaemic control, increased achievement of major guideline treatment goals or reduced the risk of all-cause death.Methods: Patients diagnosed with type 2 diabetes were followed by linkage of four Swedish national registers covering diabetes, dog ownership, socioeconomics, and mortality. Linear regression was used to estimate the mean yearly change in glycated haemoglobin (HbA1c). Cox survival analysis and logistic regression were used to analyse associations between dog ownership and all-cause death and achievement of treatment goals, respectively.Results: Of 218,345 individuals included, 8,352 (3.8%) were dog-owners. Median follow-up was 5.2 years. Dog-owners had worse yearly change in HbA1c, and were less likely to reach HbA1c, low-density lipoprotein (LDL), and systolic blood pressure (SBP) treatment goals than non-dog-owners (adjusted odds ratios [95% CI] of 0.93 [0.88–0.97], 0.91 [0.86–0.95], and 0.95 [0.90–1.00], respectively). There was no difference in the risk of all-cause death (adjusted hazard ratio [95% CI] 0.92 [0.81–1.04], dog owners versus not).Conclusion: Owning a dog when diagnosed with diabetes did not lead to better achievement of treatment goals or reduced mortality, but was in fact associated with a smaller reduction in HbA1c and reduced likelihood of achieving treatment goals.
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| 26. |
- Rådholm, Karin, et al.
(författare)
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Older age is a strong predictor for poor outcome in intracerebral haemorrhage : the INTERACT2 study
- 2015
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Ingår i: Age and Ageing. - : Oxford University Press. - 0002-0729 .- 1468-2834. ; 44:3, s. 422-427
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND AND PURPOSE:: Global ageing contributes greatly to the burden of stroke. We investigated the influence of age on the baseline profile and on outcomes in acute intracerebral haemorrhage (ICH) among participants of the INTERACT2 study.METHODS:: INTERACT2 was an international, randomised controlled trial in 2839 patients with spontaneous ICH within 6 h of onset and elevated systolic blood pressure (SBP; 150-220 mmHg) who were allocated to receive intensive (target SBP <140 mmHg within 1 h) or guideline-recommended (target SBP <180 mmHg) blood pressure lowering treatment. Stroke severity was assessed with the National Institutes of Health Stroke Scale. Poor outcome was defined as death or major disability ('dependency', modified Rankin Scale scores 3-6) at 90 days. Health-related quality of life (HRQoL) was assessed with the European Quality of Life-5 Dimensions (EQ-5D) questionnaire. Associations between age and outcomes were analysed in multivariable logistic regression models.RESULTS:: Stroke severity increased in categories of older age (P-trend 0.002). Stroke patients over 75 years old were four times more likely to die or be disabled at 90 days than those <52 years when other confounders were accounted for (odds ratio 4.36, 95% confidence interval 3.12-6.08). Older age was also associated with decreasing HRQoL, across mobility, self-care, usual activities and depression (all P-trend <0.001), and pain or discomfort (P-trend 0.022).CONCLUSION:: In the INTERACT2 cohort, older people had more severe ICH and worse outcomes (death, major disability and HRQoL). These data will help guide clinicians manage older people with haemorrhagic stroke. Clinical Trial Registration: http://www.clinicaltrials.gov (NCT00716079).
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| 27. |
- Rådholm, Karin, et al.
(författare)
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Use of the waist-to-height ratio to predict cardiovascular risk in patients with diabetes: Results from the ADVANCE-ON study
- 2018
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Ingår i: Diabetes, obesity and metabolism. - : WILEY. - 1462-8902 .- 1463-1326. ; 20:8, s. 1903-1910
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Tidskriftsartikel (refereegranskat)abstract
- Aims Patients with type 2 diabetes have a high risk of cardiovascular disease (CVD). Central obesity has been particularly associated with this risk relationship. We aimed to evaluate waist to height ratio (WHtR) as a predictor of risk in such patients. Methods WHtR was evaluated as a predictor of the risk of CVD and mortality amongst 11125 participants with type 2 diabetes in the ADVANCE and ADVANCE-ON studies, and was compared with body mass index (BMI), waist circumference and waist hip ratio (WHR). Primary outcome was a composite of death from CVD, non-fatal myocardial infarction or non-fatal stroke. Secondary outcomes were myocardial infarction, stroke, cardiovascular death and death from any cause. Cox models were used, with bootstrapping to compare associations between anthropometric measures for the primary outcome. Results Median follow-up time was 9.0 years. There was a positive association between WHtR and adverse outcomes. The hazard ratio (HR) (confidence interval), per SD higher WHtR, was 1.16 (1.11-1.22) for the primary endpoint, with no heterogeneity by sex or region, but a stronger effect in individuals aged 66 years or older. The other 3 anthropometric measurements showed similar associations, although there was evidence that WHtR marginally outperformed BMI and WHR. Based on commonly used BMI cut-points, the equivalent WHtR cut-points were estimated to be 0.55 and 0.6, with no evidence of a difference across subgroups. Conclusions In patients with diabetes, WHtR is a useful indicator of future adverse risk, with similar effects in different population subgroups.
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| 28. |
- Salam, Abdul, et al.
(författare)
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Effects of blood pressure lowering on cardiovascular events, in the context of regression to the mean : a systematic review of randomized trials
- 2019
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Ingår i: Journal of Hypertension. - : Lippincott Williams & Wilkins. - 0263-6352 .- 1473-5598. ; 37:1, s. 16-23
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Forskningsöversikt (refereegranskat)abstract
- Objective: To assess the clinical relevance of regression to the mean for clinical trials and clinical practice. Methods: MEDLINE was searched until February 2018 for randomized trials of BP lowering with over 1000 patient-years follow-up per group. We estimated baseline mean BP, follow-up mean (usual) BP amongst patients grouped by 10 mmHg strata of baseline BP, and assessed effects of BP lowering on coronary heart disease (CHD) and stroke according to these BP levels. Results: Eighty-six trials (349 488 participants), with mean follow-up of 3.7 years, were included. Most mean BP change was because of regression to the mean rather than treatment. At high baseline BP levels, even after rigorous hypertension diagnosis, downwards regression to the mean caused much of the fall in BP. At low baseline BP levels, upwards regression to the mean increased BP levels, even in treatment groups. Overall, a BP reduction of 6/3 mmHg lowered CHD by 14% (95% CI 11-17%) and stroke by 18% (15-22%), and these treatment effects occurred at follow-up BP levels much closer to the mean than baseline BP levels. In particular, more evidence was available in the SBP 130-139 mmHg range than any other range. Benefits were apparent in numerous high-risk patient groups with baseline mean SBP less than 140 mmHg. Conclusion: Clinical practice should focus less on pretreatment BP levels, which rarely predict future untreated BP levels or rule out capacity to benefit from BP lowering in high cardiovascular risk patients. Instead, focus should be on prompt, empirical treatment to maintain lower BP for those with high BP and/or high risk.
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| 29. |
- Salvi, Erika, et al.
(författare)
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Genomewide Association Study Using a High-Density Single Nucleotide Polymorphism Array and Case-Control Design Identifies a Novel Essential Hypertension Susceptibility Locus in the Promoter Region of Endothelial NO Synthase.
- 2012
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Ingår i: Hypertension. - 1524-4563. ; 59:2, s. 248-248
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Tidskriftsartikel (refereegranskat)abstract
- Essential hypertension is a multifactorial disorder and is the main risk factor for renal and cardiovascular complications. The research on the genetics of hypertension has been frustrated by the small predictive value of the discovered genetic variants. The HYPERGENES Project investigated associations between genetic variants and essential hypertension pursuing a 2-stage study by recruiting cases and controls from extensively characterized cohorts recruited over many years in different European regions. The discovery phase consisted of 1865 cases and 1750 controls genotyped with 1M Illumina array. Best hits were followed up in a validation panel of 1385 cases and 1246 controls that were genotyped with a custom array of 14 055 markers. We identified a new hypertension susceptibility locus (rs3918226) in the promoter region of the endothelial NO synthase gene (odds ratio: 1.54 [95% CI: 1.37-1.73]; combined P=2.58 · 10(-13)). A meta-analysis, using other in silico/de novo genotyping data for a total of 21 714 subjects, resulted in an overall odds ratio of 1.34 (95% CI: 1.25-1.44; P=1.032 · 10(-14)). The quantitative analysis on a population-based sample revealed an effect size of 1.91 (95% CI: 0.16-3.66) for systolic and 1.40 (95% CI: 0.25-2.55) for diastolic blood pressure. We identified in silico a potential binding site for ETS transcription factors directly next to rs3918226, suggesting a potential modulation of endothelial NO synthase expression. Biological evidence links endothelial NO synthase with hypertension, because it is a critical mediator of cardiovascular homeostasis and blood pressure control via vascular tone regulation. This finding supports the hypothesis that there may be a causal genetic variation at this locus.
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| 30. |
- Squires, Janet E., et al.
(författare)
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The Implementation in Context (ICON) Framework: A meta-framework of context domains, attributes and features in healthcare
- 2023
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Ingår i: Health Research Policy and Systems. - 1478-4505 .- 1478-4505. ; 21:1
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Tidskriftsartikel (refereegranskat)abstract
- Background There is growing evidence that context mediates the effects of implementation interventions intended to increase healthcare professionals’ use of research evidence in clinical practice. However, conceptual clarity about what comprises context is elusive. The purpose of this study was to advance conceptual clarity on context by developing the Implementation in Context Framework, a meta-framework of the context domains, attributes and features that can facilitate or hinder healthcare professionals’ use of research evidence and the effectiveness of implementation interventions in clinical practice.Methods We conducted a meta-synthesis of data from three interrelated studies: (1) a concept analysis of published literature on context (n = 70 studies), (2) a secondary analysis of healthcare professional interviews (n = 145) examining context across 11 unique studies and (3) a descriptive qualitative study comprised of interviews with heath system stakeholders (n = 39) in four countries to elicit their tacit knowledge on the attributes and features of context. A rigorous protocol was followed for the meta-synthesis, resulting in development of the Implementation in Context Framework. Following this meta-synthesis, the framework was further refined through feedback from experts in context and implementation science.Results In the Implementation in Context Framework, context is conceptualized in three levels: micro (individual), meso (organizational), and macro (external). The three levels are composed of six contextual domains: (1) actors (micro), (2) organizational climate and structures (meso), (3) organizational social behaviour (meso), (4) organizational response to change (meso), (5) organizational processes (meso) and (6) external influences (macro). These six domains contain 22 core attributes of context and 108 features that illustrate these attributes.Conclusions The Implementation in Context Framework is the only meta-framework of context available to guide implementation efforts of healthcare professionals. It provides a comprehensive and critically needed understanding of the context domains, attributes and features relevant to healthcare professionals’ use of research evidence in clinical practice. The Implementation in Context Framework can inform implementation intervention design and delivery to better interpret the effects of implementation interventions, and pragmatically guide implementation efforts that enhance evidence uptake and sustainability by healthcare professionals.
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