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Sökning: WFRF:(Baron John A)

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31.
  • Farahmand, Bahman Y., et al. (författare)
  • Survival after hip fracture
  • 2005
  • Ingår i: Osteoporosis International. - : Springer Science and Business Media LLC. - 0937-941X .- 1433-2965. ; 16:12, s. 1583-90
  • Tidskriftsartikel (refereegranskat)abstract
    • Although it is known that overall mortality is increased after hip fracture, the influence of hip fracture risk factors on the subsequent mortality and cause of death has not been well studied. The objective of this study was to establish the survival after hip fracture in women and to assess the impact of comorbidity on mortality. We identified a complete population-based set of 2,245 incident hip fracture cases and 4,035 randomly selected population-based controls among women 50-81 years old in Sweden and followed these subjects for an average of 5 years through the Swedish National Inpatient and Cause-of-Death Registers. Information on factors related to hip fracture was obtained through linkage to hospital discharge data and through a mailed questionnaire. We studied excess mortality of hip fracture patients compared to controls using survival curves and proportional hazard regression models. During follow-up, 896 hip fracture patients (40%) and 516 (13%) controls died. The relative risk (RR) of death, adjusted for age and previous hospitalization for serious disease, was 2.3 (95% CI 2.0-2.5). Although the highest mortality risks were in the 1st 6 months post-fracture, RRs for fractures versus controls were increased for at least 6 years. Increased mortality was apparent both in those with evidence of comorbidity and those without. Hip fracture patients have a substantially increased risk of death that persists for at least 6 years post-fracture. The relative excess mortality is independent of comorbidity and known hip fracture risk factors.
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32.
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33.
  • Holmberg, Lars, et al. (författare)
  • Alcohol intake and breast cancer risk : effect of exposure from 15 years of age
  • 1995
  • Ingår i: Cancer Epidemiology, Biomarkers and Prevention. - 1055-9965 .- 1538-7755. ; 4:8, s. 843-847
  • Tidskriftsartikel (refereegranskat)abstract
    • Research regarding the relationship between alcohol intake and breast cancer risk has suggested an association between the two, although the data are inconsistent regarding dose effects and susceptible populations. To clarify these issues, we investigated the association of breast cancer risk with alcohol intake at various ages in a population-based case-control study nested within a screening cohort in Sweden. Subjects were women 40-75 years old who participated in a screening program in central Sweden. Information about personal characteristics, diet, and alcohol intake was obtained by a questionnaire sent out at the invitation to the screening interview and at a supplementary interview conducted among a sample of women who did and did not develop breast cancer. Alcohol intake did not affect breast cancer risk among women under 50 years old. However, among those over 50 years of age, ever-drinking conferred a relative risk of 1.8 (95% confidence interval = 1.2-2.6). Current and former drinkers had similar increases in risk. No particular latent period of alcohol effect was identified, but drinking later in life to have a bigger effect than did drinking earlier in life.
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34.
  • Kasimova, Marina A., et al. (författare)
  • Helix breaking transition in the S4 of HCN channel is critical for hyperpolarization- dependent gating
  • 2019
  • Ingår i: eLIFE. - : NLM (Medline). - 2050-084X. ; 8
  • Tidskriftsartikel (refereegranskat)abstract
    • In contrast to most voltage-gated ion channels, hyperpolarization- and cAMP gated (HCN) ion channels open on hyperpolarization. Structure-function studies show that the voltagesensor of HCN channels are unique but the mechanisms that determine gating polarity remain poorly understood. All-atom molecular dynamics simulations (similar to 20 mu s) of HCN1 channel under hyperpolarization reveals an initial downward movement of the S4 voltage-sensor but following the transfer of last gating charge, the S4 breaks into two sub-helices with the lower sub-helix becoming parallel to the membrane. Functional studies on bipolar channels show that the gating polarity strongly correlates with helical turn propensity of the substituents at the breakpoint. Remarkably, in a proto-HCN background, the replacement of breakpoint serine with a bulky hydrophobic amino acid is sufficient to completely flip the gating polarity from inward to outward-rectifying. Our studies reveal an unexpected mechanism of inward rectification involving a linker sub-helix emerging from HCN S4 during hyperpolarization.
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35.
  • Larsson, Susanna C., et al. (författare)
  • Genetically predicted plasma phospholipid arachidonic acid concentrations and 10 site-specific cancers in UK biobank and genetic consortia participants : A mendelian randomization study
  • 2021
  • Ingår i: Clinical Nutrition. - : Elsevier. - 0261-5614 .- 1532-1983. ; 40:5, s. 3332-3337
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND & AIMS: Arachidonic acid (AA) is metabolized by cyclooxygenases and lipoxygenases to pro-inflammatory eicosanoids, which according to experimental research modulate tumor cell proliferation, differentiation, and apoptosis. We employed the Mendelian randomization design to test the hypothesis that higher plasma phospholipid AA concentrations are associated with increased risk of 10 site-specific cancers.METHODS: Two genetic variants associated with plasma phospholipid concentrations of AA (rs174547 in FADS1 [P = 3.0 × 10-971] and rs16966952 in PDXDC1 [P = 2.4 × 10-10]) in the Cohorts for Heart and Aging Research in Genomic Epidemiology Consortium were used as genetic instruments. The associations of those variants with cancer were taken from the UK Biobank (n = 367,643), FinnGen consortium (n = 135,638), International Lung Cancer Consortium (n = 27,209), Prostate Cancer Association Group to Investigate Cancer Associated Alterations in the Genome consortium (n = 140,254), Breast Cancer Association Consortium (n = 228,951), Ovarian Cancer Association Consortium (n = 66,450), and BioBank Japan (n = 212,453).RESULTS: Higher genetically predicted plasma phospholipid AA concentrations were associated with increased risk of colorectal and lung cancer. Results were consistent across data sources and variants. The combined odds ratios per standard deviation increase of AA concentrations were 1.08 (95% CI 1.05-1.11; P = 6.3 × 10-8) for colorectal cancer and 1.07 (95%CI 1.05-1.10; P = 3.5 × 10-7) for lung cancer. Genetically predicted AA concentrations had a suggestive positive association with esophageal cancer (odds ratio 1.09; 95% CI 1.02-1.17; P = 0.016) but were not associated with cancers of the stomach, pancreas, bladder, prostate, breast, uterus, or ovary.CONCLUSION: These results indicate that AA may be implicated in the development of colorectal and lung cancer and possibly esophageal cancer. Treatments with plasma AA-lowering properties should be evaluated for clinical benefit.
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36.
  • Larsson, Susanna C., et al. (författare)
  • Genetically proxied milk consumption and risk of colorectal, bladder, breast, and prostate cancer : a two-sample Mendelian randomization study
  • 2020
  • Ingår i: BMC Medicine. - : Springer Science and Business Media LLC. - 1741-7015. ; 18:1
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Observational studies have shown that milk consumption is inversely associated with colorectal, bladder, and breast cancer risk, but positively associated with prostate cancer. However, whether the associations reflect causality remains debatable. We investigated the potential causal associations of milk consumption with the risk of colorectal, bladder, breast, and prostate cancer using a genetic variant near the LCT gene as proxy for milk consumption.METHODS: We obtained genetic association estimates for cancer from the UK Biobank (n = 367,643 women and men), FinnGen consortium (n = 135,638 women and men), Breast Cancer Association Consortium (n = 228,951 women), and Prostate Cancer Association Group to Investigate Cancer Associated Alterations in the Genome consortium (n = 140,254 men). Milk consumption was proxied by a genetic variant (rs4988235 or rs182549) upstream of the gene encoding lactase, which catalyzes the breakdown of lactose.RESULTS: Genetically proxied milk consumption was associated with a reduced risk of colorectal cancer. The odds ratio (OR) for each additional milk intake increasing allele was 0.95 (95% confidence interval [CI] 0.91-0.99; P = 0.009). There was no overall association of genetically predicted milk consumption with bladder (OR 0.99; 95% CI 0.94-1.05; P = 0.836), breast (OR 1.01; 95% CI 1.00-1.02; P = 0.113), and prostate cancer (OR 1.01; 95% CI 0.99-1.02; P = 0.389), but a positive association with prostate cancer was observed in the FinnGen consortium (OR 1.07; 95% CI 1.01-1.13; P = 0.026).CONCLUSIONS: Our findings strengthen the evidence for a protective role of milk consumption on colorectal cancer risk. There was no or limited evidence that milk consumption affects the risk of bladder, breast, and prostate cancer.
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37.
  • Michaëlsson, Karl, 1959-, et al. (författare)
  • Combined associations of body mass index and adherence to a Mediterranean-like diet with all-cause and cardiovascular mortality : A cohort study
  • 2020
  • Ingår i: PLoS Medicine. - : Public Library of Science (PLoS). - 1549-1277 .- 1549-1676. ; 17:9
  • Tidskriftsartikel (refereegranskat)abstract
    • BackgroundIt is unclear whether the effect on mortality of a higher body mass index (BMI) can be compensated for by adherence to a healthy diet and whether the effect on mortality by a low adherence to a healthy diet can be compensated for by a normal weight. We aimed to evaluate the associations of BMI combined with adherence to a Mediterranean-like diet on all-cause and cardiovascular disease (CVD) mortality.Methods and findingsOur longitudinal cohort design included the Swedish Mammography Cohort (SMC) and the Cohort of Swedish Men (COSM) (1997–2017), with a total of 79,003 women (44%) and men (56%) and a mean baseline age of 61 years. BMI was categorized into normal weight (20–24.9 kg/m2), overweight (25–29.9 kg/m2), and obesity (30+ kg/m2). Adherence to a Mediterranean-like diet was assessed by means of the modified Mediterranean-like diet (mMED) score, ranging from 0 to 8; mMED was classified into 3 categories (0 to <4, 4 to <6, and 6–8 score points), forming a total of 9 BMI × mMED combinations. We identified mortality by use of national Swedish registers. Cox proportional hazard models with time-updated information on exposure and covariates were used to calculate the adjusted hazard ratios (HRs) of mortality with their 95% confidence intervals (CIs). Our HRs were adjusted for age, baseline educational level, marital status, leisure time physical exercise, walking/cycling, height, energy intake, smoking habits, baseline Charlson’s weighted comorbidity index, and baseline diabetes mellitus. During up to 21 years of follow-up, 30,389 (38%) participants died, corresponding to 22 deaths per 1,000 person-years. We found the lowest HR of all-cause mortality among overweight individuals with high mMED (HR 0.94; 95% CI 0.90, 0.98) compared with those with normal weight and high mMED. Using the same reference, obese individuals with high mMED did not experience significantly higher all-cause mortality (HR 1.03; 95% CI 0.96–1.11). In contrast, compared with those with normal weight and high mMED, individuals with a low mMED had a high mortality despite a normal BMI (HR 1.60; 95% CI 1.48–1.74). We found similar estimates among women and men. For CVD mortality (12,064 deaths) the findings were broadly similar, though obese individuals with high mMED retained a modestly increased risk of CVD death (HR 1.29; 95% CI 1.16–1.44) compared with those with normal weight and high mMED. A main limitation of the present study is the observational design with self-reported lifestyle information with risk of residual or unmeasured confounding (e.g., genetic liability), and no causal inferences can be made based on this study alone.ConclusionsThese findings suggest that diet quality modifies the association between BMI and all-cause mortality in women and men. A healthy diet may, however, not completely counter higher CVD mortality related to obesity.
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38.
  • Michaëlsson, Karl, 1959-, et al. (författare)
  • Differences in Risk Factor Patterns Between Cervical and Trochanteric Hip Fractures
  • 1999
  • Ingår i: Osteoporosis International. - : Springer Science and Business Media LLC. - 0937-941X .- 1433-2965. ; 10:6, s. 487-494
  • Tidskriftsartikel (refereegranskat)abstract
    • The two types of hip fracture--cervical and trochanteric femoral fractures--are generally considered together in etiologic studies. However, women with a trochanteric fracture may be more osteoporotic than those with cervical hip fractures, and have higher post-fracture mortality. To explore differences in risk factor patterns between the two types of hip fracture we used data from a large population-based case-control study in Swedish women, 50-81 years of age. Data were collected by questionnaire, to which more than 80% of subjects responded. Of the cases included, 811 had had a cervical fracture and 483 a trochanteric fracture during the study period; these cases were compared with 3312 randomly selected controls. Height and hormonal factors appeared to affect the risk of the two types of hip fracture differently. For every 5 cm of current height, women with a cervical fracture had an adjusted odds ratio (OR) of 1.23 (95% CI 1.15-1.32) compared with an OR of 1.06 (95% CI 0.97-1.15) for women with trochanteric fractures. Later menopausal age was protective for trochanteric fractures (OR 0.95, 95% CI 0. 91-0.99 per 2 years) but no such association was found for cervical fractures. Compared with never smokers, current smokers had an OR of 1.48 (95% CI 1.12-1.95) for trochanteric fractures and 1.22 (95% CI 0.98-1.52) for cervical fractures. Current hormone replacement therapy was similarly protective for both fracture types, but former use substantially reduced risk only for trochanteric fractures: OR 0. 55 (95% CI 0.33-0.92) compared with 1.00 (95% CI 0.71-1.39) for cervical fractures. These risk factor patterns suggest etiologic differences between the fracture types which have to be considered when planning preventive interventions.
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39.
  • Michaëlsson, Karl, 1959-, et al. (författare)
  • Hormone replacement therapy and hip fracture risk : population based case-control study
  • 1998
  • Ingår i: BMJ - British Medical Journal. - 1756-1833. ; 316:7148, s. 1858-63
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVE: To determine the relative risk of hip fracture associated with postmenopausal hormone replacement therapy including the effect of duration and recency of treatment, the addition of progestins, route of administration, and dose. DESIGN: Population based case-control study. Setting: Six counties in Sweden. SUBJECTS: 1327 women aged 50-81 years with hip fracture and 3262 randomly selected controls. MAIN OUTCOME MEASURE: Use of hormone replacement therapy. RESULTS: Compared with women who had never used hormone replacement therapy, current users had an odds ratio of 0.35 (95 % confidence interval 0.24 to 0.53) for hip fracture and former users had an odds ratio of 0.76 (0.57 to 1.01). For every year of therapy, the overall risk decreased by 6% (3% to 9%): 4% (1% to 8%) for regimens without progestin and 11% (6% to 16%) for those with progestin. Last use between one and five years previously, with a duration of use more than five years, was associated with an odds ratio of 0.27 (0.08 to 0.94). After five years without hormone replacement therapy the protective effect was substantially diminished (-7% to 48%). With current use, an initiation of therapy nine or more years after the menopause gave equally strong reduction in risk for hip fracture as an earlier start. Oestrogen treatment with skin patches gave similar risk estimates as oral regimens. CONCLUSIONS: Recent use of hormone replacement therapy is required for optimum fracture protection, but therapy can be started several years after the menopause. The protective effect increases with duration of use, and an oestrogen-sparing effect is achieved when progestins are included in the regimen.
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40.
  • Michaëlsson, Karl, 1959-, et al. (författare)
  • Influence of parity and lactation on hip fracture risk
  • 2001
  • Ingår i: American Journal of Epidemiology. - : Oxford University Press (OUP). - 0002-9262 .- 1476-6256. ; 153:12, s. 1166-1172
  • Tidskriftsartikel (refereegranskat)abstract
    • Several studies indicate that parity and lactation are associated with modest, short-term bone loss, but the long-term effect on osteoporotic fracture risk is uncertain. The authors therefore analyzed data from a population-based case-control study among Swedish postmenopausal women aged 50-81 years between October 1993 and February 1995. Mailed questionnaires and telephone interviews were used to collect data on 1,328 incident cases with hip fracture and 3,312 randomly selected controls. In age-adjusted analyses, the risk of hip fracture among all women was reduced by 10% per child (95% confidence interval (CI): 5, 14). After multivariate adjustment including body mass index as a covariate, the risk reduction was 5% per child (95% CI: 0, 10). Oral contraceptive use modified the association of parity with hip fracture risk. Among never users of oral contraceptives, the risk of hip fracture was reduced by 8% per child (95% CI: 2, 13), whereas among ever users of oral contraceptives, the risk was in the opposite direction, with an increase in risk by 19% per child (95% CI: 0, 41). After parity was considered, there was no association of duration of lactation period with fracture risk. The authors conclude that parity is modestly associated with a reduced hip fracture risk among women who had not used oral contraceptives previously.
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