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- 2019
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Tidskriftsartikel (refereegranskat)
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| 4. |
- Hudson, Thomas J., et al.
(författare)
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International network of cancer genome projects
- 2010
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 464:7291, s. 993-998
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Tidskriftsartikel (refereegranskat)abstract
- The International Cancer Genome Consortium (ICGC) was launched to coordinate large-scale cancer genome studies in tumours from 50 different cancer types and/or subtypes that are of clinical and societal importance across the globe. Systematic studies of more than 25,000 cancer genomes at the genomic, epigenomic and transcriptomic levels will reveal the repertoire of oncogenic mutations, uncover traces of the mutagenic influences, define clinically relevant subtypes for prognosis and therapeutic management, and enable the development of new cancer therapies.
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| 5. |
- Pattaro, Cristian, et al.
(författare)
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Genetic associations at 53 loci highlight cell types and biological pathways relevant for kidney function
- 2016
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 7
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Tidskriftsartikel (refereegranskat)abstract
- Reduced glomerular filtration rate defines chronic kidney disease and is associated with cardiovascular and all-cause mortality. We conducted a meta-analysis of genome-wide association studies for estimated glomerular filtration rate (eGFR), combining data across 133,413 individuals with replication in up to 42,166 individuals. We identify 24 new and confirm 29 previously identified loci. Of these 53 loci, 19 associate with eGFR among individuals with diabetes. Using bioinformatics, we show that identified genes at eGFR loci are enriched for expression in kidney tissues and in pathways relevant for kidney development and transmembrane transporter activity, kidney structure, and regulation of glucose metabolism. Chromatin state mapping and DNase I hypersensitivity analyses across adult tissues demonstrate preferential mapping of associated variants to regulatory regions in kidney but not extra-renal tissues. These findings suggest that genetic determinants of eGFR are mediated largely through direct effects within the kidney and highlight important cell types and biological pathways.
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| 6. |
- Lee, Crystal, et al.
(författare)
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Association of anthropometry and weight change with risk of dementia and its major subtypes: a meta-analysis consisting 2.8 million adults with 57,294 cases of dementia
- 2020
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Ingår i: Obesity Reviews. - : Wiley. - 1467-7881 .- 1467-789X. ; 21:4
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Tidskriftsartikel (refereegranskat)abstract
- Uncertainty exists regarding the relation of body size and weight change with dementia risk. As populations continue to age and the global obesity epidemic shows no sign of waning, reliable quantification of such associations is important. We examined the relationship of body mass index, waist circumference, and annual percent weight change with risk of dementia and its subtypes by pooling data from 19 prospective cohort studies and four clinical trials using meta-analysis. Compared with body mass index-defined lower-normal weight (18.5–22.4 kg/m2), the risk of all-cause dementia was higher among underweight individuals but lower among those with upper-normal (22.5–24.9 kg/m2) levels. Obesity was associated with higher risk in vascular dementia. Similarly, relative to the lowest fifth of waist circumference, those in the highest fifth had non-significant higher vascular dementia risk. Weight loss was associated with higher all-cause dementia risk relative to weight maintenance. Weight gain was weakly associated with higher vascular dementia risk. The relationship between body size, weight change and dementia is complex and exhibits nonlinear associations depending on dementia subtype under scrutiny. Weight loss was associated with an elevated risk most likely due to reverse causality and/or pathophysiological changes in the brain, although the latter remains speculative.
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| 7. |
- af Geijerstam, Peder, Doktorand, 1983-, et al.
(författare)
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Orthostatic Hypotension and Cognitive Function in Individuals 85 Years of Age: A Longitudinal Cohort Study in Sweden
- 2024
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Ingår i: Aging and Disease. - Fort Wortht, TX, United States : Buck Institute for Age Research. - 2152-5250.
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Tidskriftsartikel (refereegranskat)abstract
- Background: Orthostatic hypotension (OH) is more common in the elderly, and associated with increased mortality. However, its implications in 85-year-olds are not known.Methods: In the prospective observational cohort study Elderly in Linköping Screening Assessment (ELSA 85), 496 individuals in Linköping, Sweden, were followed from age 85 years with cognitive assessments. Blood pressure (BP) was measured supine and after 1, 3, 5, and 10 minutes of standing. Participants with a BP fall of ≥20 mmHg systolic or ≥10 mmHg diastolic after 1 or 3 minutes were classified as classical continuous or classical transient OH depending on whether the BP fall was sustained or not, at subsequent measurements. Those with a BP fall of the same magnitude, but only after 5 or 10 minutes were classified as delayed OH.Results: Of participants, 329 took part in BP measurements and were included. Of these, 156 (47.4%) had classical OH (113 [34.3%] continuous classical, 38 [11.6%] transient classical), and 15 (4.6%) had delayed OH. Cognitive assessments were not markedly different between groups. After 8.6 years, 195 (59.3%) of the participants had died, and delayed vs no OH was associated with twice the risk of all-cause mortality, HR 2.15 (95% CI 1.12-4.12). Transient classical OH was associated with reduced mortality, HR 0.58 (95% CI 0.33-0.99), but not after multiple adjustments, and continuous classical OH was not associated with mortality.Conclusion: OH may have different implications for morbidity and mortality in 85-year-olds compared with younger populations.
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| 8. |
- af Geijerstam, Peder, Doktorand, 1983-, et al.
(författare)
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Prescription and dispensing duration of medicines for hypertension and other chronic conditions: a review of international policies and evidence to inform the Australian setting
- 2024
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Ingår i: Hypertension Research. - : Springer Nature. - 0916-9636 .- 1348-4214.
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Forskningsöversikt (refereegranskat)abstract
- The duration of treatment for which a physician may prescribe a medicine, ‘prescription duration’, is often dispensed at the pharmacy on multiple occasions of shorter time periods, ‘dispensing duration’. These durations vary significantly between and within countries. In Australia, the quantity of medication supplied at each dispensing has recently been extended from 30 to 60 days for a selection of medicines used for chronic health conditions, such as diabetes and hypertension. Dispensing durations vary between countries, with 30, 60 or 90 days being the most common—with 90 days aligning with the recommendation of the 2023 Global Report on Hypertension from the World Health Organization. The full impact of shorter vs longer prescription durations on health costs and outcomes is unknown, but current evidence suggests that 90-day dispensing could reduce costs and improve patient convenience and adherence. More rigorous research is needed.
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| 9. |
- Andersson, Ulrika, et al.
(författare)
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Variability in home blood pressure and its association with renal function and pulse pressure in patients with treated hypertension in primary care
- 2023
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Ingår i: Journal of Human Hypertension. - : SPRINGERNATURE. - 0950-9240 .- 1476-5527.
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Tidskriftsartikel (refereegranskat)abstract
- Blood pressure variability (BPV) represents a cardiovascular risk factor, regardless of mean level of blood pressure (BP). In this post-hoc analysis from the PERson-centredness in Hypertension management using Information Technology (PERHIT) study, we aimed to explore BPV in daily home measurements in hypertensive patients from primary care, to identify factors associated with high BPV and to investigate whether estimated glomerular filtration rate (eGFR) and pulse pressure, as markers of target organ damage (TOD), are associated with BPV. For eight consecutive weeks, 454 participants reported their daily BP and heart rate in their mobile phone, along with reports of lifestyle and hypertension-related factors. Systolic BP (SBP) values were used to calculate BPV with coefficient of variation (CV) as primary estimate. Background characteristics and self-reports were tested between fifths of CV in a linear regression model, adjusted for age and sex. Associations between BPV and eGFR and pulse pressure were tested with linear and logistic regression models. Higher home BPV was associated with higher age, BP, heart rate, and smoking. BPV was lower for participants with low alcohol consumption and treatment with calcium channel blockers. There was a significant association between BPV and pulse pressure (P = 0.015), and between BPV and eGFR (P = 0.049). Participants with high BPV reported more dizziness and palpitations. In conclusion, pulse pressure and eGFR were significantly associated with home BPV. Older age, high BP, heart rate, and smoking were associated with high BPV, but treatment with calcium channel blockers and low alcohol consumption was associated with low BPV. Trial registration: The study was registered with ClinicalTrials.gov [NCT03554382].
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| 10. |
- Bolmsjö, Beata Borgström, et al.
(författare)
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Risk factors and consequences of decreased kidney function in nursing home residents : A longitudinal study
- 2017
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Ingår i: Geriatrics & Gerontology International. - : Wiley. - 1444-1586 .- 1447-0594. ; 17:5, s. 791-797
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Tidskriftsartikel (refereegranskat)abstract
- Aim: The aim of the present study was to study the renal function and the relationship of deterioration in renal function with major outcomes in elderly nursing home residents. A second aim was to compare the internationally recommended formulae for estimated glomerular filtration rate (eGFR) consisting of both creatinine and cystatinC in a nursing home population. Methods: A total of 429 patients from 11 nursing homes were included during 2008-2011. GFR was estimated, from formulae based on both creatinine and cystatinC, at baseline and after 1 and 2years. The patients were divided into groups based on chronic kidney disease level, and comparisons were made for mortality, morbidity, the use of medications and between the different formulae for eGFR. Results: Survival was lower in the groups with lower renal function. Over 60% of the residents had impaired renal function. Those with impaired renal function were older, had a higher number of medications and a higher prevalence of heart failure. Higher number of medications was associated with a greater risk of rapid decline in renal function with an odds ratio of 1.2 (95% confidence interval 1.06-1.36, P=0.003). The compared eGFR formulae based on both cystatinC and creatinine were in excellent concordance with each other. Conclusions: Decreased renal function was associated with increased mortality. A majority of nursing home residents had declining renal function, which should be considered when prescribing medications. The more medications, the higher the risk for rapidly declining renal function.
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| 11. |
- Caleres, Gabriella, et al.
(författare)
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Medication Discrepancies in Discharge Summaries and Associated Risk Factors for Elderly Patients with Many Drugs
- 2020
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Ingår i: Drugs - Real World Outcomes. - : Springer Science and Business Media LLC. - 2199-1154 .- 2198-9788. ; 7:1, s. 53-62
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND AND OBJECTIVE: Elderly patients are at high risk for medication errors in care transitions. The discharge summary aims to counteract drug-related problems due to insufficient information transfer in care transitions, hence the accuracy of its medication information is of utmost importance. The purpose of this study was to describe the medication discrepancy rate and associated risk factors in discharge summaries for elderly patients.METHODS: Pharmacists collected random samples of discharge summaries from ten hospitals in southern Sweden. Medication discrepancies, organisational, and patient- and care-specific factors were noted. Patients aged ≥ 75 years with five or more drugs were further included. Descriptive and logistic regression analyses were performed.RESULTS: Discharge summaries for a total of 933 patients were included. Average age was 83.1 years, and 515 patients (55%) were women. Medication discrepancies were noted for 353 patients (38%) (mean 0.87 discrepancies per discharged patient, 95% confidence interval 0.76-0.98). Unintentional addition of a drug was the most common discrepancy type. Central nervous system drugs/analgesics were most commonly affected. Major risk factors for the presence of discrepancies were multi-dose drug dispensing (adjusted odds ratio 3.42, 95% confidence interval 2.48-4.74), an increasing number of drugs in the discharge summary (adjusted odds ratio 1.09, 95% confidence interval 1.05-1.13) and discharge from departments of surgery (adjusted odds ratio 2.96, 95% confidence interval 1.55-5.66). By contrast, an increasing number of drug changes reduced the odds of a discrepancy (adjusted odds ratio 0.93, 95% confidence interval 0.88-0.99).CONCLUSIONS: Medication discrepancies were common. In addition, we identified certain circumstances in which greater vigilance may be of considerable value for increased medication safety for elderly patients in care transitions.
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| 12. |
- Copland, Emma, et al.
(författare)
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Antihypertensive treatment and risk of cancer : an individual participant data meta-analysis
- 2021
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Ingår i: The Lancet Oncology. - : Elsevier. - 1470-2045 .- 1474-5488. ; 22:4, s. 558-570
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Tidskriftsartikel (refereegranskat)abstract
- Findings 33 trials met the inclusion criteria, and included 260 447 participants with 15 012 cancer events. Median follow-up of included participants was 4?2 years (IQR 3?0?5?0). In the individual participant data meta-analysis comparing each drug class with all other comparators, no associations were identified between any antihypertensive drug class and risk of any cancer (HR 0?99 [95% CI 0?95?1?04] for ACEIs; 0?96 [0?92?1?01] for ARBs; 0?98 [0?89?1?07] for 13 blockers; 1?01 [0?95?1?07] for thiazides), with the exception of calcium channel blockers (1?06 [1?01?1?11]). In the network meta-analysis comparing drug classes against placebo, we found no excess cancer risk with any drug class (HR 1?00 [95% CI 0?93?1?09] for ACEIs; 0?99 [0?92?1?06] for ARBs; 0?99 [0?89?1?11] for 13 blockers; 1?04 [0?96?1?13] for calcium channel blockers; 1?00 [0?90?1?10] for thiazides). Summary Background Some studies have suggested a link between antihypertensive medication and cancer, but the evidence is so far inconclusive. Thus, we aimed to investigate this association in a large individual patient data meta-analysis of randomised clinical trials. Methods We searched PubMed, MEDLINE, The Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov from Jan 1, 1966, to Sept 1, 2019, to identify potentially eligible randomised controlled trials. Eligible studies were randomised controlled trials comparing one blood pressure lowering drug class with a placebo, inactive control, or other blood pressure lowering drug. We also required that trials had at least 1000 participant years of follow-up in each treatment group. Trials without cancer event information were excluded. We requested individual participant data from the authors of eligible trials. We pooled individual participant-level data from eligible trials and assessed the effects of angiotensin-converting enzyme inhibitors (ACEIs), angiotensin II receptor blockers (ARBs), 13 blockers, calcium channel blockers, and thiazide diuretics on cancer risk in one-stage individual participant data and network meta-analyses. Cause-specific fixed-effects Cox regression models, stratified by trial, were used to calculate hazard ratios (HRs). The primary outcome was any cancer event, defined as the first occurrence of any cancer diagnosed after randomisation. This study is registered with PROSPERO (CRD42018099283). Findings 33 trials met the inclusion criteria, and included 260 447 participants with 15 012 cancer events. Median follow-up of included participants was 4 & middot;2 years (IQR 3 & middot;0 & ndash;5 & middot;0). In the individual participant data meta-analysis comparing each drug class with all other comparators, no associations were identified between any antihypertensive drug class and risk of any cancer (HR 0 & middot;99 [95% CI 0 & middot;95 & ndash;1 & middot;04] for ACEIs; 0 & middot;96 [0 & middot;92 & ndash;1 & middot;01] for ARBs; 0 & middot;98 [0 & middot;89 & ndash;1 & middot;07] for 13 blockers; 1 & middot;01 [0 & middot;95 & ndash;1 & middot;07] for thiazides), with the exception of calcium channel blockers (1 & middot;06 [1 & middot;01 & ndash;1 & middot;11]). In the network meta-analysis comparing drug classes against placebo, we found no excess cancer risk with any drug class (HR 1 & middot;00 [95% CI 0 & middot;93 & ndash;1 & middot;09] for ACEIs; 0 & middot;99 [0 & middot;92 & ndash;1 & middot;06] for ARBs; 0 & middot;99 [0 & middot;89 & ndash;1 & middot;11] for 13 blockers; 1 & middot;04 [0 & middot;96 & ndash;1 & middot;13] for calcium channel blockers; 1 & middot;00 [0 & middot;90 & ndash;1 & middot;10] for thiazides). Interpretation We found no consistent evidence that antihypertensive medication use had any effect on cancer risk. Although such findings are reassuring, evidence for some comparisons was insufficient to entirely rule out excess risk, in particular for calcium channel blockers.
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| 13. |
- Coulman, Karen D., et al.
(författare)
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Development of a Bariatric Surgery Core Data Set for an International Registry
- 2023
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Ingår i: Obesity Surgery. - : Springer. - 0960-8923 .- 1708-0428. ; 33:5, s. 1463-1475
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: Bariatric and metabolic surgery is an effective treatment for severe and complex obesity; however, robust long-term data comparing operations is lacking. Clinical registries complement clinical trials in contributing to this evidence base. Agreement on standard data for bariatric registries is needed to facilitate comparisons. This study developed a Core Registry Set (CRS) - core data to include in bariatric surgery registries globally.MATERIALS AND METHODS: Relevant items were identified from a bariatric surgery research core outcome set, a registry data dictionary project, systematic literature searches, and a patient advisory group. This comprehensive list informed a questionnaire for a two-round Delphi survey with international health professionals. Participants rated each item's importance and received anonymized feedback in round 2. Using pre-defined criteria, items were then categorized for voting at a consensus meeting to agree the CRS.RESULTS: Items identified from all sources were grouped into 97 questionnaire items. Professionals (n = 272) from 56 countries participated in the round 1 survey of which 45% responded to round 2. Twenty-four professionals from 13 countries participated in the consensus meeting. Twelve items were voted into the CRS including demographic and bariatric procedure information, effectiveness, and safety outcomes.CONCLUSION: This CRS is the first step towards unifying bariatric surgery registries internationally. We recommend the CRS is included as a minimum dataset in all bariatric registries worldwide. Adoption of the CRS will enable meaningful international comparisons of bariatric operations. Future work will agree definitions and measures for the CRS including incorporating quality-of-life measures defined in a parallel project.
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| 14. |
- Fox, Caroline S, et al.
(författare)
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Associations of kidney disease measures with mortality and end-stage renal disease in individuals with and without diabetes : a meta-analysis
- 2012
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Ingår i: The Lancet. - 0140-6736 .- 1474-547X. ; 380:9854, s. 1662-73
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Chronic kidney disease is characterised by low estimated glomerular filtration rate (eGFR) and high albuminuria, and is associated with adverse outcomes. Whether these risks are modified by diabetes is unknown.METHODS: We did a meta-analysis of studies selected according to Chronic Kidney Disease Prognosis Consortium criteria. Data transfer and analyses were done between March, 2011, and June, 2012. We used Cox proportional hazards models to estimate the hazard ratios (HR) of mortality and end-stage renal disease (ESRD) associated with eGFR and albuminuria in individuals with and without diabetes.FINDINGS: We analysed data for 1,024,977 participants (128,505 with diabetes) from 30 general population and high-risk cardiovascular cohorts and 13 chronic kidney disease cohorts. In the combined general population and high-risk cohorts with data for all-cause mortality, 75,306 deaths occurred during a mean follow-up of 8·5 years (SD 5·0). In the 23 studies with data for cardiovascular mortality, 21,237 deaths occurred from cardiovascular disease during a mean follow-up of 9·2 years (SD 4·9). In the general and high-risk cohorts, mortality risks were 1·2-1·9 times higher for participants with diabetes than for those without diabetes across the ranges of eGFR and albumin-to-creatinine ratio (ACR). With fixed eGFR and ACR reference points in the diabetes and no diabetes groups, HR of mortality outcomes according to lower eGFR and higher ACR were much the same in participants with and without diabetes (eg, for all-cause mortality at eGFR 45 mL/min per 1·73 m(2) [vs 95 mL/min per 1·73 m(2)], HR 1·35; 95% CI 1·18-1·55; vs 1·33; 1·19-1·48 and at ACR 30 mg/g [vs 5 mg/g], 1·50; 1·35-1·65 vs 1·52; 1·38-1·67). The overall interactions were not significant. We identified much the same findings for ESRD in the chronic kidney disease cohorts.INTERPRETATION: Despite higher risks for mortality and ESRD in diabetes, the relative risks of these outcomes by eGFR and ACR are much the same irrespective of the presence or absence of diabetes, emphasising the importance of kidney disease as a predictor of clinical outcomes.FUNDING: US National Kidney Foundation.
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| 15. |
- Gorski, Mathias, et al.
(författare)
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Genetic loci and prioritization of genes for kidney function decline derived from a meta-analysis of 62 longitudinal genome-wide association studies
- 2022
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Ingår i: Kidney International. - : Elsevier. - 0085-2538 .- 1523-1755. ; 102:3, s. 624-639
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Tidskriftsartikel (refereegranskat)abstract
- Estimated glomerular filtration rate (eGFR) reflects kidney function. Progressive eGFR-decline can lead to kidney failure, necessitating dialysis or transplantation. Hundreds of loci from genome-wide association studies (GWAS) for eGFR help explain population cross section variability. Since the contribution of these or other loci to eGFR-decline remains largely unknown, we derived GWAS for annual eGFR-decline and meta-analyzed 62 longitudinal studies with eGFR assessed twice over time in all 343,339 individuals and in high-risk groups. We also explored different covariate adjustment. Twelve genomewide significant independent variants for eGFR-decline unadjusted or adjusted for eGFR- baseline (11 novel, one known for this phenotype), including nine variants robustly associated across models were identified. All loci for eGFR-decline were known for cross-sectional eGFR and thus distinguished a subgroup of eGFR loci. Seven of the nine variants showed variant- by-age interaction on eGFR cross section (further about 350,000 individuals), which linked genetic associations for eGFR-decline with agedependency of genetic cross- section associations. Clinically important were two to four-fold greater genetic effects on eGFR-decline in high-risk subgroups. Five variants associated also with chronic kidney disease progression mapped to genes with functional in- silico evidence (UMOD, SPATA7, GALNTL5, TPPP). An unfavorable versus favorable nine-variant genetic profile showed increased risk odds ratios of 1.35 for kidney failure (95% confidence intervals 1.03- 1.77) and 1.27 for acute kidney injury (95% confidence intervals 1.08-1.50) in over 2000 cases each, with matched controls). Thus, we provide a large data resource, genetic loci, and prioritized genes for kidney function decline, which help inform drug development pipelines revealing important insights into the age-dependency of kidney function genetics.
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| 16. |
- Gorski, Mathias, et al.
(författare)
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Meta-analysis uncovers genome-wide significant variants for rapid kidney function decline
- 2021
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Ingår i: Kidney International. - : Elsevier. - 0085-2538 .- 1523-1755. ; 99:4, s. 926-939
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Tidskriftsartikel (refereegranskat)abstract
- Rapid decline of glomerular filtration rate estimated from creatinine (eGFRcrea) is associated with severe clinical endpoints. In contrast to cross-sectionally assessed eGFRcrea, the genetic basis for rapid eGFRcrea decline is largely unknown. To help define this, we meta-analyzed 42 genome-wide association studies from the Chronic Kidney Diseases Genetics Consortium and United Kingdom Biobank to identify genetic loci for rapid eGFRcrea decline. Two definitions of eGFRcrea decline were used: 3 mL/min/1.73m2/year or more ("Rapid3"; encompassing 34,874 cases, 107,090 controls) and eGFRcrea decline 25% or more and eGFRcrea under 60 mL/min/1.73m2 at follow-up among those with eGFRcrea 60 mL/min/1.73m2 or more at baseline ("CKDi25"; encompassing 19,901 cases, 175,244 controls). Seven independent variants were identified across six loci for Rapid3 and/or CKDi25: consisting of five variants at four loci with genome-wide significance (near UMOD-PDILT (2), PRKAG2, WDR72, OR2S2) and two variants among 265 known eGFRcrea variants (near GATM, LARP4B). All these loci were novel for Rapid3 and/or CKDi25 and our bioinformatic follow-up prioritized variants and genes underneath these loci. The OR2S2 locus is novel for any eGFRcrea trait including interesting candidates. For the five genome-wide significant lead variants, we found supporting effects for annual change in blood urea nitrogen or cystatin-based eGFR, but not for GATM or LARP4B. Individuals at high compared to those at low genetic risk (8-14 vs 0-5 adverse alleles) had a 1.20-fold increased risk of acute kidney injury (95% confidence interval 1.08-1.33). Thus, our identified loci for rapid kidney function decline may help prioritize therapeutic targets and identify mechanisms and individuals at risk for sustained deterioration of kidney function.
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| 17. |
- Huang, Liping, et al.
(författare)
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The impact of baseline potassium intake on the dose-response relation between sodium reduction and blood pressure change : systematic review and meta-analysis of randomized trials.
- 2021
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Ingår i: Journal of Human Hypertension. - : Springer Nature. - 0950-9240 .- 1476-5527. ; 35:11, s. 946-957
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Tidskriftsartikel (refereegranskat)abstract
- Sodium and potassium appear to interact with each other in their effects on blood pressure with potassium supplementation having a greater blood pressure lowering-effect when sodium intake is high. Whether the effect of sodium reduction on blood pressure varies according to potassium intake levels is unclear. We carried out a systematic review and meta-analysis to examine the impact of baseline potassium intake on blood pressure response to sodium reduction in randomized trials in adult populations, with sodium and potassium intake estimated from 24-h urine samples. We included 68 studies involving 5708 participants and conducted univariable and multivariable meta-regression. The median intake of baseline potassium was 67.7 mmol (Interquartile range: 54.6-76.4 mmol), and the mean reduction in sodium intake was 128 mmol (95% CI: 107-148). Multivariable meta-regression that included baseline 24-h urinary potassium excretion, age, ethnicity, baseline blood pressure, change in 24-h urinary sodium excretion, as well as the interaction between baseline 24-h urinary potassium excretion and change in 24-h urinary sodium excretion did not identify a significant association of baseline potassium intake levels with the blood pressure reduction achieved with a 50 mmol lowering of sodium intake (p > 0.05 for both systolic and diastolic blood pressure). A higher starting level of blood pressure was consistently associated with a greater blood pressure reduction from reduced sodium consumption. However, the nonsignificant findings may subject to the limitations of the data available. Additional studies with more varied potassium intake levels would allow a more confident exclusion of an interaction.
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| 18. |
- Karmali, Kunal N., et al.
(författare)
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Blood pressure-lowering treatment strategies based on cardiovascular risk versus blood pressure : A meta-analysis of individual participant data
- 2018
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Ingår i: PLoS Medicine. - : PUBLIC LIBRARY SCIENCE. - 1549-1277 .- 1549-1676. ; 15:3
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Tidskriftsartikel (refereegranskat)abstract
- Background: Clinical practice guidelines have traditionally recommended blood pressure treatment based primarily on blood pressure thresholds. In contrast, using predicted cardiovascular risk has been advocated as a more effective strategy to guide treatment decisions for cardiovascular disease (CVD) prevention. We aimed to compare outcomes from a blood pressure-lowering treatment strategy based on predicted cardiovascular risk with one based on systolic blood pressure (SBP) level.Methods and findings: We used individual participant data from the Blood Pressure Lowering Treatment Trialists' Collaboration (BPLTTC) from 1995 to 2013. Trials randomly assigned participants to either blood pressure-lowering drugs versus placebo or more intensive versus less intensive blood pressure-lowering regimens. We estimated 5-y risk of CVD events using a multivariable Weibull model previously developed in this dataset. We compared the two strategies at specific SBP thresholds and across the spectrum of risk and blood pressure levels studied in BPLTTC trials. The primary outcome was number of CVD events avoided per persons treated. We included data from 11 trials (47,872 participants). During a median of 4.0 y of follow-up, 3,566 participants (7.5%) experienced a major cardiovascular event. Areas under the curve comparing the two treatment strategies throughout the range of possible thresholds for CVD risk and SBP demonstrated that, on average, a greater number of CVD events would be avoided for a given number of persons treated with the CVD risk strategy compared with the SBP strategy (area under the curve 0.71 [95% confidence interval (CI) 0.70-0.72] for the CVD risk strategy versus 0.54 [95% CI 0.53-0.55] for the SBP strategy). Compared with treating everyone with SBP >= 150 mmHg, a CVD risk strategy would require treatment of 29% (95% CI 26%-31%) fewer persons to prevent the same number of events or would prevent 16% (95% CI 14%-18%) more events for the same number of persons treated. Compared with treating everyone with SBP >= 140 mmHg, a CVD risk strategy would require treatment of 3.8% (95% CI 12.5% fewer to 7.2% more) fewer persons to prevent the same number of events or would prevent 3.1% (95% CI 1.5%-5.0%) more events for the same number of persons treated, although the former estimate was not statistically significant. In subgroup analyses, the CVD risk strategy did not appear to be more beneficial than the SBP strategy in patients with diabetes mellitus or established CVD.Conclusions: A blood pressure-lowering treatment strategy based on predicted cardiovascular risk is more effective than one based on blood pressure levels alone across a range of thresholds. These results support using cardiovascular risk assessment to guide blood pressure treatment decision-making in moderate- to high-risk individuals, particularly for primary prevention.
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| 19. |
- Lenander, Cecilia, et al.
(författare)
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Use of Antipsychotic Drugs by Elderly Primary Care Patients and the Effects of Medication Reviews: A Cross-Sectional Study in Sweden
- 2017
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Ingår i: Drugs - Real World Outcomes. - : Springer Science and Business Media LLC. - 2199-1154 .- 2198-9788. ; 4:3, s. 159-165
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Tidskriftsartikel (refereegranskat)abstract
- Background Antipsychotics form a class of drugs that should be used with caution among elderly people because of a high risk of adverse events. Despite the risks and modest effects, their use is estimated to be high, especially in nursing homes. Objective The aim was to explore the effects of medication reviews on antipsychotic drug use for elderly primary care patients and describe the extent of, and reasons for, the prescription of antipsychotics.Methods In this cross-sectional study in primary care in Skane, Sweden, patients aged >75 years living in nursing homes or in their own homes with home care were included. The effects of medication reviews were documented, as were the use of antipsychotics and the differences in characteristics between patients receiving or not receiving antipsychotics.Results A total of 1683 patients aged 87.6 (±5.7) years were included in the analysis. Medication reviews reduced the use of antipsychotics by 23% (p\0.001) in this study. Of the 206 patients using antipsychotics, 43% (n = 93) had an approved indication, while for 15% (n = 32) the indication was not given. Antipsychotic drug use was more common with increasing number of drugs (p = 0.001), and in nursing home residents (p\0.01). It was also morefrequent in patients with cognitive impairment, depressive symptoms or sleeping problems.Conclusion The use of antipsychotic drugs is high in elderly patients in nursing homes. They are often given for indications that are not officially approved or are poorly documented. Medication reviews appear to offer one usefulstrategy for reducing excessive use of these drugs.
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| 20. |
- Matsushita, Kunihiro, et al.
(författare)
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Estimated glomerular filtration rate and albuminuria for prediction of cardiovascular outcomes : a collaborative meta-analysis of individual participant data
- 2015
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Ingår i: LANCET DIABETES & ENDOCRINOLOGY. - 2213-8587. ; 3:7, s. 514-525
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Tidskriftsartikel (refereegranskat)abstract
- Background The usefulness of estimated glomerular filtration rate (eGFR) and albuminuria for prediction of cardiovascular outcomes is controversial. We aimed to assess the addition of creatinine-based eGFR and albuminuria to traditional risk factors for prediction of cardiovascular risk with a meta-analytic approach. Methods We meta-analysed individual-level data for 637 315 individuals without a history of cardiovascular disease from 24 cohorts (median follow-up 4.2-19.0 years) included in the Chronic Kidney Disease Prognosis Consortium. We assessed C statistic difference and reclassification improvement for cardiovascular mortality and fatal and non-fatal cases of coronary heart disease, stroke, and heart failure in a 5 year timeframe, contrasting prediction models for traditional risk factors with and without creatinine-based eGFR, albuminuria (either albumin-to-creatinine ratio [ACR] or semi-quantitative dipstick proteinuria), or both. Findings The addition of eGFR and ACR significantly improved the discrimination of cardiovascular outcomes beyond traditional risk factors in general populations, but the improvement was greater with ACR than with eGFR, and more evident for cardiovascular mortality (C statistic difference 0.0139 [95% CI 0.0105- 0.0174] for ACR and 0.0065 [0.0042-0.0088] for eGFR) and heart failure (0.0196 [0.0108-0.0284] and 0.0109 [0.0059-0.0159]) than for coronary disease (0.0048 [0.0029-0.0067] and 0.0036 [0.0019-0.0054]) and stroke (0.0105 [0.0058-0.0151]and 0.0036 [0.0004-0.0069]). Dipstick proteinuria showed smaller improvement than ACR. The discrimination improvement with eGFR or ACR was especially evident in individuals with diabetes or hypertension, but remained significant with ACR for cardiovascular mortality and heart failure in those without either of these disorders. In individuals with chronic kidney disease, the combination of eGFR and ACR for risk discrimination outperformed most single traditional predictors; the C statistic for cardiovascular mortality fell by 0.0227 (0.0158-0.0296) after omission of eGFR and ACR compared with less than 0.007 for any single modifiable traditional predictor. Interpretation Creatinine-based eGFR and albuminuria should be taken into account for cardiovascular prediction, especially when these measures are already assessed for clinical purpose or if cardiovascular mortality and heart failure are outcomes of interest. ACR could have particularly broad implications for cardiovascular prediction. In populations with chronic kidney disease, the simultaneous assessment of eGFR and ACR could facilitate improved classification of cardiovascular risk, supporting current guidelines for chronic kidney disease. Our results lend some support to also incorporating eGFR and ACR into assessments of cardiovascular risk in the general population.
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| 21. |
- Nazarzadeh, Milad, et al.
(författare)
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Blood pressure lowering and risk of new-onset type 2 diabetes : an individual participant data meta-analysis
- 2021
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Ingår i: The Lancet. - : Elsevier. - 0140-6736 .- 1474-547X. ; 398:10313, s. 1803-1810
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundBlood pressure lowering is an established strategy for preventing microvascular and macrovascular complications of diabetes, but its role in the prevention of diabetes itself is unclear. We aimed to examine this question using individual participant data from major randomised controlled trials.MethodsWe performed a one-stage individual participant data meta-analysis, in which data were pooled to investigate the effect of blood pressure lowering per se on the risk of new-onset type 2 diabetes. An individual participant data network meta-analysis was used to investigate the differential effects of five major classes of antihypertensive drugs on the risk of new-onset type 2 diabetes. Overall, data from 22 studies conducted between 1973 and 2008, were obtained by the Blood Pressure Lowering Treatment Trialists' Collaboration (Oxford University, Oxford, UK). We included all primary and secondary prevention trials that used a specific class or classes of antihypertensive drugs versus placebo or other classes of blood pressure lowering medications that had at least 1000 persons-years of followup in each randomly allocated arm. Participants with a known diagnosis of diabetes at baseline and trials conducted in patients with prevalent diabetes were excluded. For the one-stage individual participant data meta-analysis we used stratified Cox proportional hazards model and for the individual participant data network meta-analysis we used logistic regression models to calculate the relative risk (RR) for drug class comparisons.Findings145 939 participants (88 500 [60.6%] men and 57 429 [39.4%] women) from 19 randomised controlled trials were included in the one-stage individual participant data meta-analysis. 22 trials were included in the individual participant data network meta-analysis. After a median follow-up of 4.5 years (IQR 2.0), 9883 participants were diagnosed with new-onset type 2 diabetes. Systolic blood pressure reduction by 5 mm Hg reduced the risk of type 2 diabetes across all trials by 11% (hazard ratio 0.89 [95% CI 0.84-0.95]). Investigation of the effects of five major classes of antihypertensive drugs showed that in comparison to placebo, angiotensin-converting enzyme inhibitors (RR 0.84 [95% 0.76-0.93]) and angiotensin II receptor blockers (RR 0.84 [0.76-0.92]) reduced the risk of new-onset type 2 diabetes; however, the use of beta blockers (RR 1.48 [1.27-1.72]) and thiazide diuretics (RR 1.20 [1.07-1.35]) increased this risk, and no material effect was found for calcium channel blockers (RR 1.02 [0.92-1.13]).InterpretationBlood pressure lowering is an effective strategy for the prevention of new-onset type 2 diabetes. Established pharmacological interventions, however, have qualitatively and quantitively different effects on diabetes, likely due to their differing off-target effects, with angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers having the most favourable outcomes. This evidence supports the indication for selected classes of antihypertensive drugs for the prevention of diabetes, which could further refine the selection of drug choice according to an individual's clinical risk of diabetes.
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| 22. |
- 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
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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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| 23. |
- 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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| 24. |
- 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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| 25. |
- 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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