scholarly journals A semi-supervised approach for rapidly creating clinical biomarker phenotypes in the UK Biobank using different primary care EHR and clinical terminology systems

JAMIA Open ◽  
2020 ◽  
Author(s):  
Spiros Denaxas ◽  
Anoop D Shah ◽  
Bilal A Mateen ◽  
Valerie Kuan ◽  
Jennifer K Quint ◽  
...  
Keyword(s):  
Primary Care ◽  
Proportional Hazards ◽  
Biomarker Discovery ◽  
Data Extraction ◽  
Cox Proportional Hazards ◽  
Research Quality ◽  
Uk Biobank ◽  
Expert Review ◽  
Cox Proportional Hazards Models ◽  
The Uk

Abstract Objectives The UK Biobank (UKB) is making primary care electronic health records (EHRs) for 500 000 participants available for COVID-19-related research. Data are extracted from four sources, recorded using five clinical terminologies and stored in different schemas. The aims of our research were to: (a) develop a semi-supervised approach for bootstrapping EHR phenotyping algorithms in UKB EHR, and (b) to evaluate our approach by implementing and evaluating phenotypes for 31 common biomarkers. Materials and Methods We describe an algorithmic approach to phenotyping biomarkers in primary care EHR involving (a) bootstrapping definitions using existing phenotypes, (b) excluding generic, rare, or semantically distant terms, (c) forward-mapping terminology terms, (d) expert review, and (e) data extraction. We evaluated the phenotypes by assessing the ability to reproduce known epidemiological associations with all-cause mortality using Cox proportional hazards models. Results We created and evaluated phenotyping algorithms for 31 biomarkers many of which are directly related to COVID-19 complications, for example diabetes, cardiovascular disease, respiratory disease. Our algorithm identified 1651 Read v2 and Clinical Terms Version 3 terms and automatically excluded 1228 terms. Clinical review excluded 103 terms and included 44 terms, resulting in 364 terms for data extraction (sensitivity 0.89, specificity 0.92). We extracted 38 190 682 events and identified 220 978 participants with at least one biomarker measured. Discussion and conclusion Bootstrapping phenotyping algorithms from similar EHR can potentially address pre-existing methodological concerns that undermine the outputs of biomarker discovery pipelines and provide research-quality phenotyping algorithms.

scholarly journals A semi-supervised approach for rapidly creating clinical biomarker phenotypes in the UK Biobank using different primary care EHR and clinical terminology systems.

2020 ◽  
Author(s):  
Spiros Denaxas ◽  
Anoop Shah ◽  
Bilal Mateen ◽  
Valerie Kuan ◽  
Jennifer Quint ◽  
...  
Keyword(s):  
Primary Care ◽  
Proportional Hazards ◽  
Biomarker Discovery ◽  
Data Extraction ◽  
Cox Proportional Hazards ◽  
Research Quality ◽  
Uk Biobank ◽  
Expert Review ◽  
Cox Proportional Hazards Models ◽  
The Uk

Objectives The UK Biobank (UKB) is making primary care Electronic Health Records (EHR) for 500,000 participants available for COVID-19-related research. Data are extracted from four sources, recorded using five clinical terminologies and stored in different schemas. The aims of our research were to: a) develop a semi-supervised approach for bootstrapping EHR phenotyping algorithms in UKB EHR, and b) to evaluate our approach by implementing and evaluating phenotypes for 31 common biomarkers. Materials and Methods We describe an algorithmic approach to phenotyping biomarkers in primary care EHR involving a) bootstrapping definitions using existing phenotypes, b) excluding generic, rare or semantically distant terms, c) forward-mapping terminology terms, d) expert review, and e) data extraction. We evaluated the phenotypes by assessing the ability to reproduce known epidemiological associations with all-cause mortality using Cox proportional hazards models. Results We created and evaluated phenotyping algorithms for 31 biomarkers many of which are directly related to COVID-19 complications e.g. diabetes, cardiovascular disease, respiratory disease. Our algorithm identified 1651 Read v2 and Clinical Terms Version 3 terms and automatically excluded 1228 terms. Clinical review excluded 103 terms and included 44 terms, resulting in 364 terms for data extraction (sensitivity 0.89, specificity 0.92). We extracted 38,190,682 events and identified 220,978 participants with at least one biomarker measured. Discussion and conclusion Bootstrapping phenotyping algorithms from similar EHR can potentially address pre-existing methodological concerns that undermine the outputs of biomarker discovery pipelines and provide research-quality phenotyping algorithms.

scholarly journals Haematological abnormalities in new-onset rheumatoid arthritis and risk of common infections: a population-based study

Rheumatology ◽  
2019 ◽  
Vol 59 (5) ◽  
pp. 997-1005 ◽  
Author(s):  
Elena Nikiphorou ◽  
Simon de Lusignan ◽  
Christian Mallen ◽  
Kaivan Khavandi ◽  
Jacqueline Roberts ◽  
...  
Keyword(s):  
Primary Care ◽  
Influenza Vaccination ◽  
Proportional Hazards ◽  
Population Based ◽  
Infection Risk ◽  
Cox Proportional Hazards ◽  
Population Based Study ◽  
Cox Proportional Hazards Models ◽  
The Uk ◽  
Common Infections

Abstract Objectives To describe the prevalence of haematological abnormalities in individuals with RA at the point of diagnosis in primary care and the associations between haematological abnormalities, vaccinations and subsequent risk of common infections. Methods We studied 6591 individuals with newly diagnosed RA between 2004 and 2016 inclusive using the UK Royal College of General Practitioners Research and Surveillance Centre primary care database. The prevalence of haematological abnormalities at diagnosis (anaemia, neutropenia and lymphopenia) was established. Cox proportional hazards models were used to evaluate the association between each haematological abnormality and time to common infections and the influence of vaccination status (influenza and pneumococcal vaccine) on time to common infections in individuals with RA compared with a matched cohort of individuals without RA. Results Anaemia was common at RA diagnosis (16.1% of individuals), with neutropenia (0.6%) and lymphopenia (1.4%) less so. Lymphopenia and anaemia were associated with increased infection risk [hazard ratio (HR) 1.18 (95% CI 1.08, 1.29) and HR 1.37 (95% CI 1.08, 1.73), respectively]. There was no evidence of an association between neutropenia and infection risk [HR 0.94 (95% CI 0.60, 1.47)]. Pneumonia was much more common in individuals with early RA compared with controls. Influenza vaccination was associated with reduced risk of influenza-like illness only for individuals with RA [HR 0.58 (95% CI 0.37, 0.90)]. Conclusion At diagnosis, anaemia and lymphopenia, but not neutropenia, increase the risk of common infections in individuals with RA. Our data support the effectiveness of the influenza vaccination in individuals with RA.

Risk of over- and undertreatment with levothyroxine in primary care in Copenhagen, Denmark

2021 ◽  
Author(s):  
Jeppe Lerche la Cour ◽  
Bjarke Røssner Medici ◽  
Mia Klinten Grand ◽  
Dagny Ros Nicolaisdottir ◽  
Bent Lind ◽  
...  
Keyword(s):  
Primary Care ◽  
Proportional Hazards ◽  
Cumulative Risk ◽  
Thyroid Stimulating Hormone ◽  
Primary Objective ◽  
Cox Proportional Hazards ◽  
Cox Proportional Hazards Models ◽  
Time Period ◽  
Primary Care Patients ◽  
Tsh Levels

Objective: A decrease over time in thyroid stimulating hormone (TSH) levels when initiating levothyroxine (L-T4) therapy for hypothyroidism has been reported, where treatment most often is initiated with TSH levels below 10 mIU/L. The primary objective of this study was to investigate whether this lower TSH threshold resulted in an increased number of overtreated patients. Design and Method: Retrospective cohort study comprising inhabitants in Copenhagen who had TSH measurements requested by general practitioners which led to a new prescription of L-T4 between 2001 and 2012. Over- and undertreatment were defined as TSH < 0.1 mIU/L or above 10 mIU/mL, respectively, in three consecutive measurements. Data were analysed by Aalen-Johansen estimators and Cox proportional hazards models. Results: In total, 14,533 initiations of L-T4 in the study. The cumulative risk of being over- or undertreated, was 4.7% and 7.4% after 10 years. The hazard of overtreatment was higher among women, younger adults and with lower initial TSH levels. The hazard of overtreatment decreased over the time period from 2001 to 2012. Among overtreated individuals, the chance of returning to a normal TSH was about 55% after 10 years. In 18% of the cases, L-T4 therapy was initiated on TSH levels less than 5 mIU/L. Conclusion: Although a still decreasing threshold for initiating L-T4 therapy is known, the risk of overtreatment (and undertreatment) was low and lessened in the period 2001 – 2012 among Danish primary care patients. Nevertheless, as many as 18% were started on L-T4 with normal TSH levels.

scholarly journals Association of poor sleep burden in middle age and older adults with risk for delirium during hospitalization

2021 ◽  
Author(s):  
Ma Cherrysse Ulsa ◽  
Xi Zheng ◽  
Peng Li ◽  
Arlen Gaba ◽  
Patricia M Wong ◽  
...  
Keyword(s):  
Sleep Disturbances ◽  
Proportional Hazards ◽  
Time Lag ◽  
Cox Proportional Hazards ◽  
Poor Sleep ◽  
Cardiovascular Risks ◽  
Cox Proportional Hazards Models ◽  
Increased Risk ◽  
The Uk

Abstract Background Delirium is a distressing neurocognitive disorder recently linked to sleep disturbances. However, the longitudinal relationship between sleep and delirium remains unclear. This study assessed the associations of poor sleep burden, and its trajectory, with delirium risk during hospitalization. Methods 321,818 participants from the UK Biobank (mean age 58±8y[SD]; range 37-74y) reported (2006-2010) sleep traits (sleep duration, excessive daytime sleepiness, insomnia-type complaints, napping, and chronotype–a closely-related circadian measure for sleep timing), aggregated into a sleep burden score (0-9). New-onset delirium (n=4,775) was obtained from hospitalization records during 12y median follow-up. 42,291 (mean age 64±8; range 44-83y) had repeat sleep assessment on average 8y after their first. Results In the baseline cohort, Cox proportional hazards models showed that moderate (aggregate scores=4-5) and severe (scores=6-9) poor sleep burden groups were 18% (hazard ratio 1.18 [95% confidence interval 1.08-1.28], p&lt;0.001) and 57% (1.57 [1.38-1.80], p&lt;0.001), more likely to develop delirium respectively. The latter risk magnitude is equivalent to two additional cardiovascular risks. These findings appeared robust when restricted to postoperative delirium and after exclusion of underlying dementia. Higher sleep burden was also associated with delirium in the follow-up cohort. Worsening sleep burden (score increase ≥2 vs. no change) further increased the risk for delirium (1.79 [1.23-2.62], p=0.002) independent of their baseline sleep score and time-lag. The risk was highest in those under 65y at baseline (p for interaction &lt;0.001). Conclusion Poor sleep burden and worsening trajectory were associated with increased risk for delirium; promotion of sleep health may be important for those at higher risk.

scholarly journals Transthyretin-stabilizing mutation T119M is not associated with protection against vascular disease or death in the UK Biobank

2019 ◽  
Author(s):  
Margaret M. Parker ◽  
Simina Ticau ◽  
James Butler ◽  
David Erbe ◽  
Madeline Merkel ◽  
...  
Keyword(s):  
Cardiovascular Disease ◽  
Cerebrovascular Disease ◽  
Vascular Disease ◽  
Prospective Cohort ◽  
Proportional Hazards ◽  
Disease Diagnosis ◽  
Cox Proportional Hazards ◽  
Uk Biobank ◽  
The Uk ◽  
Large Prospective Cohort

AbstractBackgroundDestabilized transthyretin (TTR) can result in the progressive, fatal disease transthyretin-mediated (ATTR) amyloidosis. A stabilizing TTR mutation, T119M, is the basis for a therapeutic strategy to reduce destabilized TTR. Recently, T119M was associated with extended lifespan and lower risk of cerebrovascular disease in a Danish cohort. We aimed to determine whether this finding could be replicated in the UK Biobank.MethodsTTR T119M carriers were identified in the UK Biobank, a large prospective cohort of ∼500,000 individuals. Association between T119M genotype and inpatient diagnosis of vascular disease, cardiovascular disease, cerebrovascular disease, and mortality was analyzed.ResultsFrequency of T119M within the white UK Biobank population (n=337,148) was 0.4%. Logistic regression comparing T119M carriers to non-carriers found no association between T119M and vascular disease (odds ratio [OR]=1.08; p=.27), cardiovascular disease (OR=1.08; p=.31), cerebrovascular disease (OR=1.1; p=.42), or death (OR=1.2; p=.06). Cox proportional hazards regression showed similar results (hazard ratio>1, p>.05). Age at death and vascular disease diagnosis were similar between T119M carriers and non-carriers (p=.12 and p=.38, respectively).ConclusionsThere was no association between the TTR T119M genotype and risk of vascular disease or death in a large prospective cohort study, indicating that TTR tetramer stabilization through T119M is not protective in this setting.

scholarly journals Visual impairment and risk of dementia in two population-based prospective cohorts: UK Biobank and EPIC-Norfolk

2021 ◽  
Author(s):  
Thomas J Littlejohns ◽  
Shabina Hayat ◽  
Robert Luben ◽  
Carol Brayne ◽  
Megan Conroy ◽  
...  
Keyword(s):  
Visual Impairment ◽  
Proportional Hazards ◽  
Population Based ◽  
Cox Proportional Hazards ◽  
Uk Biobank ◽  
Cox Proportional Hazards Models ◽  
Hazard Ratios ◽  
Promising Target ◽  
Increased Risk

Abstract Visual impairment has emerged as a potential modifiable risk factor for dementia. However, there are a lack of large studies with objective measures of vison and with more than ten years of follow-up. We investigated whether visual impairment is associated with an increased risk of incident dementia in UK Biobank and EPIC-Norfolk. In both cohorts, visual acuity was measured using a “logarithm of the minimum angle of resolution” (LogMAR) chart and categorised as no (≤0.30 LogMAR), mild (&gt;0.3 - ≤0.50 LogMAR), and moderate to severe (&gt;0.50 LogMAR) impairment. Dementia was ascertained through linkage to electronic medical records. After restricting to those aged ≥60 years, without prevalent dementia and with eye measures available, the analytic samples consisted of 62,206 UK Biobank and 7,337 EPIC-Norfolk participants, respectively. In UK Biobank and EPIC-Norfolk. respectively, 1,113 and 517 participants developed dementia over 11 and 15 years of follow-up. Using multivariable cox proportional-hazards models, the hazard ratios for mild and moderate to severe visual impairment were 1.26 (95% Confidence Interval [CI] 0.92-1.72) and 2.16 (95% CI 1.37-3.40), in UK Biobank, and 1.05 (95% CI 0.72-1.53) and 1.93 (95% CI 1.05-3.56) in EPIC-Norfolk, compared to no visual impairment. When excluding participants censored within 5 years of follow-up or with prevalent poor or fair self-reported health, the direction of the associations remained similar for moderate impairment but were not statistically significant. Our findings suggest visual impairment might be a promising target for dementia prevention, however the possibility of reverse causation cannot be excluded.

scholarly journals Association between anticholinergic burden and dementia in UK Biobank

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. 936-936
Author(s):  
Jure Mur ◽  
Simon Cox ◽  
Riccardo Marioni ◽  
Tom Russ ◽  
Graciela Muniz-Terrera
Keyword(s):  
Proportional Hazards ◽  
Cox Proportional Hazards ◽  
Anticholinergic Drugs ◽  
Uk Biobank ◽  
General Measure ◽  
Future Studies ◽  
Cox Proportional Hazards Models ◽  
Dementia Risk ◽  
Anticholinergic Burden

Abstract Previous studies on the association between the long-term use of anticholinergic drugs and dementia report heterogenous results. This variability could be due to, among other factors, different anticholinergic scales used, and differential effects of distinct classes of anticholinergic drugs. Here, we use 171,775 participants of UK Biobank with linked GP prescription records to calculate the cumulative annual anticholinergic burden (ACB) and ascertain dementia diagnoses through GP- and inpatient records. We then use Cox proportional hazards models to compare 13 anticholinergic scales and anticholinergic burden (ACB) due to different classes of drugs in their association with dementia. We find dementia to be more strongly predicted by ACB than by polypharmacy across most anticholinergic scales (standardised ORs range: 1.027-1.125). Furthermore, not only the baseline ACB, but the slope of the longitudinal trajectory of ACB (HR=1.094; 95% CI: 1.068-1.119) is predictive of dementia. However, the association between ACB and dementia holds only for some classes of drugs – especially antidepressants, antiepileptics, and high-ceiling antidiuretics. Moreover, we do not find a clear relationship between reported anticholinergic potency and dementia risk. The heterogeneity in findings on the association between ACB and dementia may in part be due to different effects for different classes of drugs. Future studies should establish such differences in more detail and further examine the practicality of using a general measure of anticholinergic potency as it relates to the risk of dementia.

scholarly journals Effectiveness of Statins as Primary Prevention in People With Gout: A Population-Based Cohort Study

2019 ◽  
Vol 24 (6) ◽  
pp. 542-550
Author(s):  
Maria Garcia-Gil ◽  
Marc Comas-Cufí ◽  
Rafel Ramos ◽  
Ruth Martí ◽  
Lia Alves-Cabratosa ◽  
...  
Keyword(s):  
Primary Care ◽  
Cohort Study ◽  
Primary Prevention ◽  
Statin Therapy ◽  
Proportional Hazards ◽  
Population Based ◽  
Cox Proportional Hazards ◽  
Research Quality ◽  
All Cause Mortality ◽  
Clinically Significant

Background: Cardiovascular guidelines do not give firm recommendations on statin therapy in patients with gout because evidence is lacking. Aim: To analyze the effectiveness of statin therapy in primary prevention of coronary heart disease (CHD), ischemic stroke (IS), and all-cause mortality in a population with gout. Methods: A retrospective cohort study (July 2006 to December 2017) based on Information System for the Development of Research in Primary Care (SIDIAPQ), a research-quality database of electronic medical records, included primary care patients (aged 35-85 years) without previous cardiovascular disease (CVD). Participants were categorized as nonusers or new users of statins (defined as receiving statins for the first time during the study period). Index date was first statin invoicing for new users and randomly assigned to nonusers. The groups were compared for the incidence of CHD, IS, and all-cause mortality, using Cox proportional hazards modeling adjusted for propensity score. Results: Between July 2006 and December 2008, 8018 individuals were included; 736 (9.1%) were new users of statins. Median follow-up was 9.8 years. Crude incidence of CHD was 8.16 (95% confidence interval [CI]: 6.25-10.65) and 6.56 (95% CI: 5.85-7.36) events per 1000 person-years in new users and nonusers, respectively. Hazard ratios were 0.84 (95% CI: 0.60-1.19) for CHD, 0.68 (0.44-1.05) for IS, and 0.87 (0.67-1.12) for all-cause mortality. Hazard for diabetes was 1.27 (0.99-1.63). Conclusions: Statin therapy was not associated with a clinically significant decrease in CHD. Despite higher risk of CVD in gout populations compared to general population, patients with gout from a primary prevention population with a low-to-intermediate incidence of CHD should be evaluated according to their cardiovascular risk assessment, lifestyle recommendations, and preferences, in line with recent European League Against Rheumatism recommendations.

Glucosamine use, smoking and risk of incident chronic obstructive pulmonary disease: A large prospective cohort study

2021 ◽  
pp. 1-35
Author(s):  
Xi-Ru Zhang ◽  
Pei-Dong Zhang ◽  
Zhi-Hao Li ◽  
Pei Yang ◽  
Xiao-Meng Wang ◽  
...  
Keyword(s):  
Chronic Obstructive Pulmonary Disease ◽  
Pulmonary Disease ◽  
Proportional Hazards ◽  
Smoking Status ◽  
Cox Proportional Hazards ◽  
Chronic Obstructive ◽  
Obstructive Pulmonary Disease ◽  
Cox Proportional Hazards Models ◽  
Large Prospective Cohort Study ◽  
The Uk

Abstract Chronic inflammation exerts pleiotropic effects in the etiology and progression of chronic obstructive pulmonary disease (COPD). Glucosamine is widely used in many countries and may have anti-inflammatory properties. We aimed to prospectively evaluate the association of regular glucosamine use with incident COPD risk and explore whether such association could be modified by smoking in the UK Biobank cohort, which recruited more than half a million participants aged 40–69 years from across the UK between 2006 and 2010. Cox proportional hazards models with adjustment for potential confounding factors were used to calculate hazard ratios (HRs) as well as 95% confidence intervals (95% CIs) for the risk of incident COPD. During a median follow-up of 8.96 years (interquartile range 8.29 to 9.53 years), 9016 new-onset events of COPD were documented. We found that regular use of glucosamine was associated with a significantly lower risk of incident COPD with multivariable adjusted HR of 0.80 (95% CI, 0.75 to 0.85; P<0.001). When subgroup analyses were performed by smoking status, the adjusted HRs for the association of regular glucosamine use with incident COPD were 0.84 (0.73 to 0.96), 0.84 (0.77 to 0.92), and 0.71 (0.62 to 0.80) among never smokers, former smokers and current smokers, respectively. No significant interaction was observed between glucosamine use and smoking status (P for interaction=0.078). Incident COPD could be reduced by 14% to 84% through a combination of regular glucosamine use and smoking cessation

scholarly journals Resting Heartbeat Complexity Predicts All‐Cause and Cardiorespiratory Mortality in Middle‐ to Older‐Aged Adults From the UK Biobank

2021 ◽  
Vol 10 (3) ◽  
Author(s):  
Lei Gao ◽  
Arlen Gaba ◽  
Longchang Cui ◽  
Hui‐Wen Yang ◽  
Richa Saxena ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Heart Rate ◽  
Proportional Hazards ◽  
Large Population ◽  
Cox Proportional Hazards ◽  
Uk Biobank ◽  
Cardiovascular Risks ◽  
Prior Myocardial Infarction ◽  
Risk Of Death ◽  
Cox Proportional Hazards Models

Background Spontaneous heart rate fluctuations contain rich information related to health and illness in terms of physiological complexity, an accepted indicator of plasticity and adaptability. However, it is challenging to make inferences on complexity from shorter, more practical epochs of data. Distribution entropy (DistEn) is a recently introduced complexity measure that is designed specifically for shorter duration heartbeat recordings. We hypothesized that reduced DistEn predicted increased mortality in a large population cohort. Method and Results The prognostic value of DistEn was examined in 7631 middle‐older–aged UK Biobank participants who had 2‐minute resting ECGs conducted (mean age, 59.5 years; 60.4% women). During a median follow‐up period of 7.8 years, 451 (5.9%) participants died. In Cox proportional hazards models with adjustment for demographics, lifestyle factors, physical activity, cardiovascular risks, and comorbidities, for each 1‐SD decrease in DistEn, the risk increased by 36%, 56%, and 73% for all‐cause, cardiovascular, and respiratory disease–related mortality, respectively. These effect sizes were equivalent to the risk of death from being >5 years older, having been a former smoker, or having diabetes mellitus. Lower DistEn was most predictive of death in those <55 years with a prior myocardial infarction, representing an additional 56% risk for mortality compared with older participants without prior myocardial infarction. These observations remained after controlling for traditional mortality predictors, resting heart rate, and heart rate variability. Conclusions Resting heartbeat complexity from short, resting ECGs was independently associated with mortality in middle‐ to older‐aged adults. These risks appear most pronounced in middle‐aged participants with prior MI, and may uniquely contribute to mortality risk screening.

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