scholarly journals Metabolic subgroups and cardiometabolic multimorbidity in the UK Biobank

2021 ◽  
Author(s):  
Anwar Mulugeta ◽  
Elina Hypponen ◽  
Mika Ala-Korpela ◽  
Ville-Petteri Makinen
Keyword(s):  
Cox Regression ◽  
Population Based ◽  
Self Organizing Map ◽  
Metabolic Dysfunction ◽  
Uk Biobank ◽  
Metabolic Diversity ◽  
Hazard Ratios ◽  
Random Expectation ◽  
The Uk ◽  
Aggregate Burden

Background: Ischemic heart disease (IHD), diabetes, cancer and dementia share features of age-associated metabolic dysfunction. We hypothesized that metabolic diversity explains the diversity of morbidity later in life. Methods: We analyzed data from the UK Biobank (N = 329,908). A self-organizing map (SOM, an artificial neural network) was trained with 51 metabolic traits adjusted for age and sex. The SOM analyses produced six subgroups that summarized the multi-variable metabolic diversity. The subgroup with the lowest adiposity and disease burden was chosen as the reference. Hazard ratios (HR) were modeled by Cox regression (P < 0.0001 unless otherwise indicated). Enrichment of multi-morbidity over random expectation was tested by permutation analysis. Results: The subgroup with the highest sex hormones was not associated with IHD (HR = 1.04, P = 0.14). The subgroup with high urinary excretion without kidney stress (HR = 1.24) and the subgroup with the highest apolipoprotein B and blood pressure (HR = 1.52) were associated with IHD. The subgroup with high adiposity, inflammation and kidney stress was associated with IHD (HR = 2.11), cancer (HR= 1.29), dementia (HR = 1.70) and mortality (HR = 2.12). The subgroup with high triglycerides and liver enzymes was at risk of diabetes (HR = 15.6). Paradoxical enrichment of multimorbidity in young individuals and in favorable subgroups was observed. Conclusions: These results support metabolic diversity as an explanation to diverging morbidity and demonstrate the potential value of population-based metabolic subgroups as public health targets for reducing aggregate burden of chronic diseases in ageing populations.

scholarly journals Use of SNP chips to detect rare pathogenic variants: retrospective, population based diagnostic evaluation

BMJ ◽  
2021 ◽  
pp. n214
Author(s):  
Weedon MN ◽  
Jackson L ◽  
Harrison JW ◽  
Ruth KS ◽  
Tyrrell J ◽  
...  
Keyword(s):  
Positive Predictive Value ◽  
Predictive Value ◽  
Population Based ◽  
Genome Project ◽  
Personal Genome ◽  
Uk Biobank ◽  
Sequencing Data ◽  
Snp Chip ◽  
Pathogenic Variants ◽  
The Uk

Abstract Objective To determine whether the sensitivity and specificity of SNP chips are adequate for detecting rare pathogenic variants in a clinically unselected population. Design Retrospective, population based diagnostic evaluation. Participants 49 908 people recruited to the UK Biobank with SNP chip and next generation sequencing data, and an additional 21 people who purchased consumer genetic tests and shared their data online via the Personal Genome Project. Main outcome measures Genotyping (that is, identification of the correct DNA base at a specific genomic location) using SNP chips versus sequencing, with results split by frequency of that genotype in the population. Rare pathogenic variants in the BRCA1 and BRCA2 genes were selected as an exemplar for detailed analysis of clinically actionable variants in the UK Biobank, and BRCA related cancers (breast, ovarian, prostate, and pancreatic) were assessed in participants through use of cancer registry data. Results Overall, genotyping using SNP chips performed well compared with sequencing; sensitivity, specificity, positive predictive value, and negative predictive value were all above 99% for 108 574 common variants directly genotyped on the SNP chips and sequenced in the UK Biobank. However, the likelihood of a true positive result decreased dramatically with decreasing variant frequency; for variants that are very rare in the population, with a frequency below 0.001% in UK Biobank, the positive predictive value was very low and only 16% of 4757 heterozygous genotypes from the SNP chips were confirmed with sequencing data. Results were similar for SNP chip data from the Personal Genome Project, and 20/21 individuals analysed had at least one false positive rare pathogenic variant that had been incorrectly genotyped. For pathogenic variants in the BRCA1 and BRCA2 genes, which are individually very rare, the overall performance metrics for the SNP chips versus sequencing in the UK Biobank were: sensitivity 34.6%, specificity 98.3%, positive predictive value 4.2%, and negative predictive value 99.9%. Rates of BRCA related cancers in UK Biobank participants with a positive SNP chip result were similar to those for age matched controls (odds ratio 1.31, 95% confidence interval 0.99 to 1.71) because the vast majority of variants were false positives, whereas sequence positive participants had a significantly increased risk (odds ratio 4.05, 2.72 to 6.03). Conclusions SNP chips are extremely unreliable for genotyping very rare pathogenic variants and should not be used to guide health decisions without validation.

Fracture Risk in Patients with Myasthenia Gravis: A Population-Based Cohort Study

2021 ◽  
pp. 1-8
Author(s):  
Charles Kassardjian ◽  
Jessica Widdifield ◽  
J. Michael Paterson ◽  
Alexander Kopp ◽  
Chenthila Nagamuthu ◽  
...  
Keyword(s):  
Myasthenia Gravis ◽  
Lower Risk ◽  
Cox Regression ◽  
Large Population ◽  
Population Based ◽  
Osteoporosis Prevention ◽  
Inception Cohort ◽  
Hazard Ratios ◽  
Multiple Covariates ◽  
Region Of Residence

Background: Prednisone is a common treatment for myasthenia gravis (MG), and osteoporosis is a known potential risk of chronic prednisone therapy. Objective: Our aim was to evaluate the risk of serious fractures in a population-based cohort of MG patients. Methods: An inception cohort of patients with MG was identified from administrative health data in Ontario, Canada between April 1, 2002 and December 31, 2015. For each MG patient, we matched 4 general population comparators based on age, sex, and region of residence. Fractures were identified through emergency department and hospitalization data. Crude overall rates and sex-specific rates of fractures were calculated for the MG and comparator groups, as well as rates of specific fractures. Adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox regression. Results: Among 3,823 incident MG patients (followed for a mean of 5 years), 188 (4.9%) experienced a fracture compared with 741 (4.8%) fractures amongst 15,292 matched comparators. Crude fracture rates were not different between the MG cohort and matched comparators (8.71 vs. 7.98 per 1000 patient years), overall and in men and women separately. After controlling for multiple covariates, MG patients had a significantly lower risk of fracture than comparators (HR 0.74, 95% CI 0.63–0.88). Conclusions: In this large, population-based cohort of incident MG patients, MG patients were at lower risk of a major fracture than comparators. The reasons for this finding are unclear but may highlight the importance osteoporosis prevention.

scholarly journals Gender- and age-related differences of statin use on incident dementia in patients with rheumatoid arthritis: a Nationwide population-based cohort study

2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Tsung-Kun Lin ◽  
Jing-Yang Huang ◽  
Lung-Fa Pan ◽  
Gwo-Ping Jong
Keyword(s):  
Rheumatoid Arthritis ◽  
Cohort Study ◽  
Subgroup Analysis ◽  
Cox Regression ◽  
Population Based ◽  
Age Related ◽  
Hazard Ratios ◽  
Incident Dementia ◽  
Gender And Age ◽  
New Onset

Abstract Background Some observational studies have found a significant association between the use of statin and a reduced risk of dementia. However, the results of these studies are unclear in patients with rheumatoid arthritis (RA). This study is to determine the association between the use of statins and the incidence of dementia according to sex and age-related differences in patients with RA. Methods We conducted a nationwide retrospective cohort study using the Taiwan Health Insurance Review and Assessment Service database (2003–2016). The primary outcome assessed was the risk of dementia by estimating hazard ratios (HRs) and 95% confidence intervals (CIs). Multiple Cox regression was used to estimate the adjusted hazard ratio of new-onset dementia. Subgroup analysis was also conducted. Results Among the 264,036 eligible patients with RA aged > 40 years, statin users were compared with non-statin users by propensity score matching at a ratio of 1:1 (25,764 in each group). However, no association was found between the use of statins and the risk of new-onset dementia (NOD) in patients with RA (HR: 1.01; 95% CI: 0.97–1.06). The subgroup analysis identified the use of statin as having a protective effect against developing NOD in male and older patients. Conclusion No association was observed between the use of a statin and the risk of NOD in patients with RA, including patients of both genders and aged 40–60 years, but these parameters were affected by gender and age. The decreased risk of NOD in patients with RA was greater among older male patients. Use of a statin in older male (> 60 years) patients with RA may be needed in clinical practice to prevent dementia.

scholarly journals All coffee types decrease the risk of adverse clinical outcomes in chronic liver disease: a UK Biobank study

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Oliver J. Kennedy ◽  
Jonathan A. Fallowfield ◽  
Robin Poole ◽  
Peter C. Hayes ◽  
Julie Parkes ◽  
...  
Keyword(s):  
Liver Disease ◽  
Chronic Liver Disease ◽  
Cox Regression ◽  
Coffee Consumption ◽  
Chronic Liver ◽  
Hospital Death ◽  
Uk Biobank ◽  
Middle Income ◽  
Hazard Ratios ◽  
Ground Coffee

Abstract Background Chronic liver disease (CLD) is a growing cause of morbidity and mortality worldwide, particularly in low to middle-income countries with high disease burden and limited treatment availability. Coffee consumption has been linked with lower rates of CLD, but little is known about the effects of different coffee types, which vary in chemical composition. This study aimed to investigate associations of coffee consumption, including decaffeinated, instant and ground coffee, with chronic liver disease outcomes. Methods A total of 494,585 UK Biobank participants with known coffee consumption and electronic linkage to hospital, death and cancer records were included in this study. Cox regression was used to estimate hazard ratios (HR) of incident CLD, incident CLD or steatosis, incident hepatocellular carcinoma (HCC) and death from CLD according to coffee consumption of any type as well as for decaffeinated, instant and ground coffee individually. Results Among 384,818 coffee drinkers and 109,767 non-coffee drinkers, there were 3600 cases of CLD, 5439 cases of CLD or steatosis, 184 cases of HCC and 301 deaths from CLD during a median follow-up of 10.7 years. Compared to non-coffee drinkers, coffee drinkers had lower adjusted HRs of CLD (HR 0.79, 95% CI 0.72–0.86), CLD or steatosis (HR 0.80, 95% CI 0.75–0.86), death from CLD (HR 0.51, 95% CI 0.39–0.67) and HCC (HR 0.80, 95% CI 0.54–1.19). The associations for decaffeinated, instant and ground coffee individually were similar to all types combined. Conclusion The finding that all types of coffee are protective against CLD is significant given the increasing incidence of CLD worldwide and the potential of coffee as an intervention to prevent CLD onset or progression.

scholarly journals Plasma Vitamin B12 Levels, High-Dose Vitamin B12 Treatment, and Risk of Dementia

2021 ◽  
Vol 79 (4) ◽  
pp. 1601-1612
Author(s):  
Johan Frederik Håkonsen Arendt ◽  
Erzsébet Horváth-Puhó ◽  
Henrik Toft Sørensen ◽  
Ebba Nexø ◽  
Lars Pedersen ◽  
...  
Keyword(s):  
Vitamin B12 ◽  
Vascular Dementia ◽  
Cox Regression ◽  
Population Based ◽  
High Dose ◽  
Plasma Vitamin ◽  
Hazard Ratios ◽  
B12 Deficiency ◽  
First Time

Background: It is controversial whether B12 deficiency causes dementia or B12 treatment can prevent dementia. Objective: To assess associations between low plasma (P-)B12 levels, B12 treatment, and risk of Alzheimer’s disease (AD; primary outcome) and all-cause or vascular dementia (secondary outcomes). Methods: We conducted a population-based cohort study using Danish registry data to assess associations between low P-B12 levels, high-dose injection or oral B12 treatment, and risk of dementia (study period 2000–2013). The primary P-B12 cohort included patients with a first-time P-B12 measurement whose subsequent B12 treatment was recorded. The secondary B12 treatment cohort included patients with a first-time B12 prescription and P-B12 measurement within one year before this prescription. For both cohorts, patients with low P-B12 levels (<200 pmol/L) were propensity score-matched 1:1 with patients with normal levels (200–600 pmol/L). We used multivariable Cox regression to compute 0–15-year hazard ratios for dementia. Results: For low P-B12 and normal P-B12 level groups, we included 53,089 patients in the primary P-B12 cohort and 13,656 patients in the secondary B12 treatment cohort. In the P-B12 cohort, hazard ratios for AD centered around one, regardless of follow-up period or treatment during follow-up. In the B12 treatment cohort, risk of AD was unaffected by low pre-treatment P-B12 levels, follow-up period and type of B12 treatment. Findings were similar for all-cause and vascular dementia. Conclusion: We found no associatio1n between low P-B12 levels and dementia. Associations were unaffected by B12 treatment. Results do not support routine screening for B12 deficiency in patients with suspected dementia.

scholarly journals A population-wide analysis of the familial risk of suicide in Utah, USA

2021 ◽  
pp. 1-10
Author(s):  
Amanda V. Bakian ◽  
Danli Chen ◽  
Chong Zhang ◽  
Heidi A. Hanson ◽  
Anna R. Docherty ◽  
...  
Keyword(s):  
Suicide Risk ◽  
Cox Regression ◽  
Familial Risk ◽  
Risk Groups ◽  
Population Based ◽  
Unified Framework ◽  
Population Database ◽  
First Degree Relatives ◽  
Hazard Ratios ◽  
History Of

Abstract Background The degree to which suicide risk aggregates in US families is unknown. The authors aimed to determine the familial risk of suicide in Utah, and tested whether familial risk varies based on the characteristics of the suicides and their relatives. Methods A population-based sample of 12 160 suicides from 1904 to 2014 were identified from the Utah Population Database and matched 1:5 to controls based on sex and age using at-risk sampling. All first through third- and fifth-degree relatives of suicide probands and controls were identified (N = 13 480 122). The familial risk of suicide was estimated based on hazard ratios (HR) from an unsupervised Cox regression model in a unified framework. Moderation by sex of the proband or relative and age of the proband at time of suicide (<25 v. ⩾25 years) was examined. Results Significantly elevated HRs were observed in first- (HR 3.45; 95% CI 3.12–3.82) through fifth-degree relatives (HR 1.07; 95% CI 1.02–1.12) of suicide probands. Among first-degree relatives of female suicide probands, the HR of suicide was 6.99 (95% CI 3.99–12.25) in mothers, 6.39 in sisters (95% CI 3.78–10.82), and 5.65 (95% CI 3.38–9.44) in daughters. The HR in first-degree relatives of suicide probands under 25 years at death was 4.29 (95% CI 3.49–5.26). Conclusions Elevated familial suicide risk in relatives of female and younger suicide probands suggests that there are unique risk groups to which prevention efforts should be directed – namely suicidal young adults and women with a strong family history of suicide.

Gender- and Age-related Differences of Statin Use on Incident Dementia in Patients with Rheumatoid Arthritis: A Nationwide Population-based Cohort Study

2021 ◽  
Author(s):  
Tsung-Kun Lin ◽  
Jing-Yang Huang ◽  
Lung-Fa Pan ◽  
Gwo-Ping Jong
Keyword(s):  
Rheumatoid Arthritis ◽  
Cohort Study ◽  
Subgroup Analysis ◽  
Older Patients ◽  
Cox Regression ◽  
Population Based ◽  
Age Related ◽  
Hazard Ratios ◽  
Gender And Age ◽  
New Onset

Abstract Background: Some observational studies have found a significant association between the use of statin and a reduced risk of dementia. However, the results of these studies are unclear in patients with rheumatoid arthritis (RA). This study is to determine the association between the use of statins and the incidence of dementia according to sex and age-related differences in patients with RA.Methods: We conducted a nationwide retrospective cohort study using the Taiwan Health Insurance Review and Assessment Service database (2003–2016). The primary outcome assessed was the risk of dementia by estimating hazard ratios (HRs) and 95% confidence intervals (CIs). Multiple Cox regression was used to estimate the adjusted hazard ratio of new-onset dementia. Subgroup analysis was also conducted.Results: Among the 264,036 eligible patients with RA aged > 40 years, statin users were compared with non-statin users by propensity score matching at a ratio of 1:1 (25,764 in each group). However, no association was found between the use of statins and the risk of new-onset dementia (NOD) in patients with RA (HR: 1.01; 95%CI: 0.97–1.06). The subgroup analysis identified the use of statin as having a protective effect against developing NOD in male and older patients.Conclusion: There is no association between the use of statin and the risk of NOD in patients with RA, but these parameters are influenced by gender and age. The decreased risk of NOD in patients with RA was greater among male and older patients. The use of statin in older male patients with RA for the prevention of dementia may be needed in clinical practice.

Headache as a risk factor for dementia: A prospective population-based study

Cephalalgia ◽  
2013 ◽  
Vol 34 (5) ◽  
pp. 327-335 ◽  
Author(s):  
Knut Hagen ◽  
Eystein Stordal ◽  
Mattias Linde ◽  
Timothy J Steiner ◽  
John-Anker Zwart ◽  
...  
Keyword(s):  
Risk Factor ◽  
Cohort Study ◽  
Cox Regression ◽  
Subsequent Development ◽  
Population Based ◽  
Health Study ◽  
Cox Regression Analysis ◽  
Hazard Ratios ◽  
Increased Risk

Background Headache has not been established as a risk factor for dementia. The aim of this study was to determine whether any headache was associated with subsequent development of vascular dementia (VaD), Alzheimer’s disease (AD) or other types of dementia. Methods This prospective population-based cohort study used baseline data from the Nord-Trøndelag Health Study (HUNT 2) performed during 1995–1997 and, from the same Norwegian county, a register of cases diagnosed with dementia during 1997–2010. Participants aged ≥20 years who responded to headache questions in HUNT 2 were categorized (headache free; with any headache; with migraine; with nonmigrainous headache). Hazard ratios (HRs) for later inclusion in the dementia register were estimated using Cox regression analysis. Results Of 51,383 participants providing headache data in HUNT 2, 378 appeared in the dementia register during the follow-up period. Compared to those who were headache free, participants with any headache had increased risk of VaD ( n = 63) (multivariate-adjusted HR = 2.3, 95% CI 1.4–3.8, p = 0.002) and of mixed dementia (VaD and AD ( n = 52)) (adjusted HR = 2.0, 95% CI 1.1–3.5, p = 0.018). There was no association between any headache and later development of AD ( n = 180). Conclusion In this prospective population-based cohort study, any headache was a risk factor for development of VaD.

scholarly journals Complementary Chinese Herbal Medicine Therapy Improves Survival of Patients With Pancreatic Cancer in Taiwan: A Nationwide Population-Based Cohort Study

2017 ◽  
Vol 17 (2) ◽  
pp. 411-422 ◽  
Author(s):  
Yi-Ting Kuo ◽  
Hou-Hsun Liao ◽  
Jen-Huai Chiang ◽  
Mei-Yao Wu ◽  
Bor-Chyuan Chen ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Herbal Medicine ◽  
Chinese Herbal Medicine ◽  
Mortality Risk ◽  
Cox Regression ◽  
Population Based ◽  
Hazard Ratio ◽  
Chinese Herbal ◽  
Hazard Ratios ◽  
Lower Hazard

Background: Pancreatic cancer is a difficult-to-treat cancer with a late presentation and poor prognosis. Some patients seek traditional Chinese medicine (TCM) consultation. We aimed to investigate the benefits of complementary Chinese herbal medicine (CHM) among patients with pancreatic cancer in Taiwan. Methods: We included all patients with pancreatic cancer who were registered in the Taiwanese Registry for Catastrophic Illness Patients Database between 1997 and 2010. We used 1:1 frequency matching by age, sex, the initial diagnostic year of pancreatic cancer, and index year to enroll 386 CHM users and 386 non-CHM users. A Cox regression model was used to compare the hazard ratios (HRs) of the risk of mortality. The Kaplan-Meier curve was used to compare the difference in survival time. Results: According to the Cox hazard ratio model mutually adjusted for CHM use, age, sex, urbanization level, comorbidity, and treatments, we found that CHM users had a lower hazard ratio of mortality risk (adjusted HR = 0.67, 95% CI = 0.56-0.79). Those who received CHM therapy for more than 90 days had significantly lower hazard ratios of mortality risk than non-CHM users (90- to 180-day group: adjusted HR = 0.56, 95% CI = 0.42-0.75; >180-day group: HR = 0.33, 95% CI = 0.24-0.45). The survival probability was higher for patients in the CHM group. Bai-hua-she-she-cao (Herba Oldenlandiae; Hedyotis diffusa Spreng) and Xiang-sha-liu-jun-zi-tang (Costus and Chinese Amomum Combination) were the most commonly used single herb and Chinese herbal formula, respectively. Conclusions: Complementary Chinese herbal therapy might be associated with reduced mortality among patients with pancreatic cancer. Further prospective clinical trial is warranted.

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