Does access to cardiac investigation and treatment contribute to social and ethnic differences in coronary heart disease? Whitehall II prospective cohort study

Objective: To determine whether access to cardiac procedures and drugs contributes to social and ethnic differences in coronary heart disease in a population setting. Design: Prospective study with follow up over 15 years. Civil service employment grade was used as a measure of individual socioeconomic position. Need for cardiac care was determined by the presence of angina, myocardial infarction, and coronary risk factors. Setting: 20 civil service departments originally located in London. Participants: 10 308 civil servants (3414 women; 560 South Asian) aged 35-55 years at baseline in 1985-8. Main outcome measures: Use of exercise electrocardiography, coronary angiography, and coronary revascularisation procedures and secondary prevention drugs. Results: Inverse social gradients existed in incident coronary morbidity and mortality. South Asian participants also had higher rates than white participants. After adjustment for clinical need, social position showed no association with the use of cardiac procedures or secondary prevention drugs. For example, men in the low versus high employment grade had an age adjusted odds ratio for angiography of 1.87 (95% confidence interval 1.32 to 2.64), which decreased to 1.27 (0.83 to 1.94) on adjustment for clinical need. South Asians tended to be more likely to have cardiac procedures and to be taking more secondary prevention drugs than white participants, even after adjustment for clinical need. Conclusion: This population based study, which shows the widely observed social and ethnic patterning of coronary heart disease, found no evidence that low social position or South Asian ethnicity was associated with lower use of cardiac procedures or drugs, independently of clinical need. Differences in medical care are unlikely to contribute to social or ethnic differences in coronary heart disease in this cohort

Recruiting patients to medical research: double blind randomised trial of "opt-in" versus "opt-out" strategies

Objective To evaluate the effect of opt-in compared with opt-out recruitment strategies on response rate and selection bias. Design Double blind randomised controlled trial. Setting Two general practices in England. Participants 510 patients with angina. Intervention Patients were randomly allocated to an opt-in (asked to actively signal willingness to participate in research) or opt-out (contacted repeatedly unless they signalled unwillingness to participate) approach for recruitment to an observational prognostic study of patients with angina. Main outcome measures Recruitment rate and clinical characteristics of patients. Results The recruitment rate, defined by clinic attendance, was 38% (96/252) in the opt-in arm and 50% (128/258) in the opt-out arm (P = 0.014). Once an appointment had been made, non-attendance at the clinic was similar (20% opt-in arm v 17% opt-out arm; P = 0.86). Patients in the opt-in arm had fewer risk factors (44% v 60%; P = 0.053), less treatment for angina (69% v 82%; P = 0.010), and less functional impairment (9% v 20%; P = 0.023) than patients in the opt-out arm. Conclusions The opt-in approach to participant recruitment, increasingly required by ethics committees, resulted in lower response rates and a biased sample. We propose that the opt-out approach should be the default recruitment strategy for studies with low risk to participants

Organisational downsizing and musculoskeletal problems in employees: a prospective study

Objectives: To study the association between organisational downsizing and subsequent musculoskeletal problems in employees and to determine the association with changes in psychosocial and behavioural risk factors. Methods: Participants were 764 municipal employees working in Raisio, Finland before and after an organisational downsizing carried out between 1991 and 1993. The outcome measures were self reports of severity and sites of musculoskeletal pain at the end of 1993 and medically certified musculoskeletal sickness absence for 1993-5. The contribution of changes in psychosocial work characteristics and health related behaviour between the 1990 and 1993 surveys was assessed by adjustment. Results: After adjustment for age, sex, and income, the odds ratio (OR) for severe musculoskeletal pain between major and minor downsizing and the corresponding rate ratios for musculoskeletal sickness absence were 2.59 (95% confidence interval (95% CI) 1.5 to 4.5) and 5.50 (3.6 to 7.6), respectively. Differences between the mean number of sites of pain after major and minor downsizing was 0.99 (0.4 to 1.6). The largest contribution from changes in work characteristics and health related behaviour to the association between downsizing and musculoskeletal problems was from increases in physical demands, particularly in women and low income employees. Additional contributory factors were reduction of skill discretion (relative to musculoskeletal pain) and job insecurity. The results were little different when analyses were confined to initially healthy participants. Conclusions: Downsizing is a risk factor for musculoskeletal problems among those who remain in employment. Much of this risk is attributable to increased physical demands, but adverse changes in other psychosocial factors may also play a part

Does autonomic function link social position to coronary risk? The Whitehall II study.

BACKGROUND: Laboratory and clinical studies suggest that the autonomic nervous system responds to chronic behavioral and psychosocial stressors with adverse metabolic consequences and that this may explain the relation between low social position and high coronary risk. We sought to test this hypothesis in a healthy occupational cohort. METHODS AND RESULTS: This study comprised 2197 male civil servants 45 to 68 years of age in the Whitehall II study who were undergoing standardized assessments of social position (employment grade) and the psychosocial, behavioral, and metabolic risk factors for coronary disease previously found to be associated with low social position. Five-minute recordings of heart rate variability (HRV) were used to assess cardiac parasympathetic function (SD of N-N intervals and high-frequency power [0.15 to 0.40 Hz]) and the influence of sympathetic and parasympathetic function (low-frequency power [0.04 to 0.15 Hz]). Low employment grade was associated with low HRV (age-adjusted trend for each modality, P< or =0.02). Adverse behavioral factors (smoking, exercise, alcohol, and diet) and psychosocial factors (job control) showed age-adjusted associations with low HRV (P<0.03). The age-adjusted mean low-frequency power was 319 ms2 among those participants in the bottom tertile of job control compared with 379 ms2 in the other participants (P=0.004). HRV showed strong (P<0.001) linear associations with components of the metabolic syndrome (waist circumference, systolic blood pressure, HDL cholesterol, triglycerides, and fasting and 2-hour postload glucose). The social gradient in prevalence of metabolic syndrome was explained statistically by adjustment for low-frequency power, behavioral factors, and job control. CONCLUSIONS: Chronically impaired autonomic function may link social position to different components of coronary risk in the general population

Genome-wide and Mendelian randomisation studies of liver MRI yield insights into the pathogenesis of steatohepatitis

Background A non-invasive method to grade the severity of steatohepatitis and liver fibrosis is magnetic resonance imaging (MRI) based corrected T1 (cT1). We aimed to identify genetic variants influencing liver cT1 and use genetics to understand mechanisms underlying liver fibroinflammatory disease and its link with other metabolic traits and diseases. Methods First, we performed a genome-wide association study (GWAS) in 14,440 Europeans in UK Biobank with liver cT1 measures. Second, we explored the effects of the cT1 variants on liver blood tests, and a range of metabolic traits and diseases. Third, we used Mendelian randomisation to test the causal effects of 24 predominantly metabolic traits on liver cT1 measures. Results We identified six independent genetic variants associated with liver cT1 that reached GWAS significance threshold (p<5x10-8). Four of the variants (rs75935921 in SLC30A10, rs13107325 in SLC39A8, rs58542926 in TM6SF2, rs738409 in PNPLA3) were also associated with elevated transaminases and had variable effects on liver fat and other metabolic traits. Insulin resistance, type 2 diabetes, non-alcoholic fatty liver and BMI were causally associated with elevated cT1 whilst favourable adiposity (instrumented by variants associated with higher adiposity but lower risk of cardiometabolic disease and lower liver fat) was found to be protective. Conclusion The association between two metal ion transporters and cT1 indicates an important new mechanism in steatohepatitis. Future studies are needed to determine whether interventions targeting the identified transporters might prevent liver disease in at risk individuals

Analyzing the heterogeneity of rule-based EHR phenotyping algorithms in CALIBER and the UK Biobank

Electronic Health Records (EHR) are data generated during routine interactions across healthcare settings and contain rich, longitudinal information on diagnoses, symptoms, medications, investigations and tests. A primary use-case for EHR is the creation of phenotyping algorithms used to identify disease status, onset and progression or extraction of information on risk factors or biomarkers. Phenotyping however is challenging since EHR are collected for different purposes, have variable data quality and often require significant harmonization. While considerable effort goes into the phenotyping process, no consistent methodology for representing algorithms exists in the UK. Creating a national repository of curated algorithms can potentially enable algorithm dissemination and reuse by the wider community. A critical first step is the creation of a robust minimum information standard for phenotyping algorithm components (metadata, implementation logic, validation evidence) which involves identifying and reviewing the complexity and heterogeneity of current UK EHR algorithms. In this study, we analyzed all available EHR phenotyping algorithms (n=70) from two large-scale contemporary EHR resources in the UK (CALIBER and UK Biobank). We documented EHR sources, controlled clinical terminologies, evidence of algorithm validation, representation and implementation logic patterns. Understanding the heterogeneity of UK EHR algorithms and identifying common implementation patterns will facilitate the design of a minimum information standard for representing and curating algorithms nationally and internationally

Underuse of coronary revascularization procedures in patients considered appropriate candidates for revascularization.

Background: Ratings by an expert panel of the appropriateness of treatments may offer better guidance for clinical practice than the variable decisions of individual clinicians, yet there have been no prospective studies of clinical outcomes. We compared the clinical outcomes of patients treated medically after angiography with those of patients who underwent revascularization, within groups defined by ratings of the degree of appropriateness of revascularization in varying clinical circumstances.Methods: This was a prospective study of consecutive patients undergoing coronary angiography at three London hospitals. Before patients were recruited, a nine-member expert panel rated the appropriateness of percutaneous transluminal coronary angioplasty (PTCA) and coronary-artery bypass grafting (CABG) on a nine-point scale (with 1 denoting highly inappropriate and 9 denoting highly appropriate) for specific clinical indications. These ratings were then applied to a population of patients with coronary artery disease. However, the patients were treated without regard to the ratings. A total of 2552 patients were followed for a median of 30 months after angiography.Results: Of 908 patients with indications for which PTCA was rated appropriate (score, 7 to 9), 34 percent were treated medically; these patients were more likely to have angina at follow-up than those who underwent PTCA (odds ratio, 1.97; 95 percent confidence interval, 1.29 to 3.00). Of 1353 patients with indications for which CABG was considered appropriate, 26 percent were treated medically; they were more likely than those who underwent CABG to die or have a nonfatal myocardial infarction - the composite primary outcome (hazard ratio, 4.08; 95 percent confidence interval, 2.82 to 5.93) - and to have angina (odds ratio, 3.03; 95 percent confidence interval, 2.08 to 4.42). Furthermore, there was a graded relation between rating and outcome over the entire scale of appropriateness (P for linear trend = 0.002).Conclusions: On the basis of the ratings of the expert panel, we identified substantial underuse of coronary revascularization among patients who were considered appropriate candidates for these procedures. Underuse was associated with adverse clinical outcomes. (N Engl J Med 2001;344:645-54.) Copyright (C) 2001 Massachusetts Medical Society

Neutrophil Counts and Initial Presentation of 12 Cardiovascular Diseases: A CALIBER Cohort Study

BACKGROUND: Neutrophil counts are a ubiquitous measure of inflammation, but previous studies on their association with cardiovascular disease (CVD) were limited by small numbers of patients or a narrow range of endpoints. OBJECTIVES: This study investigated associations of clinically recorded neutrophil counts with initial presentation for a range of CVDs. METHODS: We used linked primary care, hospitalization, disease registry, and mortality data in England. We included people 30 years or older with complete blood counts performed in usual clinical care and no history of CVD. We used Cox models to estimate cause-specific hazard ratios (HRs) for 12 CVDs, adjusted for cardiovascular risk factors and acute conditions affecting neutrophil counts (such as infections and cancer). RESULTS: Among 775,231 individuals in the cohort, 154,179 had complete blood counts performed under acute conditions and 621,052 when they were stable. Over a median 3.8 years of follow-up, 55,004 individuals developed CVD. Adjusted HRs comparing neutrophil counts 6 to 7 versus 2 to 3 × 10(9)/l (both within the 'normal' range) showed strong associations with heart failure (HR: 2.04; 95% confidence interval [CI]: 1.82 to 2.29), peripheral arterial disease (HR: 1.95; 95% CI: 1.72 to 2.21), unheralded coronary death (HR: 1.78; 95% CI: 1.51 to 2.10), abdominal aortic aneurysm (HR: 1.72; 95% CI: 1.34 to 2.21), and nonfatal myocardial infarction (HR: 1.58; 95% CI: 1.42 to 1.76). These associations were linear, with greater risk even among individuals with neutrophil counts of 3 to 4 versus 2 to 3 × 10(9)/l. There was a weak association with ischemic stroke (HR: 1.36; 95% CI: 1.17 to 1.57), but no association with stable angina or intracerebral hemorrhage. CONCLUSIONS: Neutrophil counts were strongly associated with the incidence of some CVDs, but not others, even within the normal range, consistent with underlying disease mechanisms differing across CVDs. (White Blood Cell Counts and Onset of Cardiovascular Diseases: a CALIBER Study [CALIBER]; NCT02014610)

Low eosinophil and low lymphocyte counts and the incidence of 12 cardiovascular diseases: a CALIBER cohort study

BACKGROUND: Eosinophil and lymphocyte counts are commonly performed in clinical practice. Previous studies provide conflicting evidence of association with cardiovascular diseases. METHODS: We used linked primary care, hospitalisation, disease registry and mortality data in England (the CALIBER (CArdiovascular disease research using LInked Bespoke studies and Electronic health Records) programme). We included people aged 30 or older without cardiovascular disease at baseline, and used Cox models to estimate cause-specific HRs for the association of eosinophil or lymphocyte counts with the first occurrence of cardiovascular disease. RESULTS: The cohort comprised 775 231 individuals, of whom 55 004 presented with cardiovascular disease over median follow-up 3.8 years. Over the first 6 months, there was a strong association of low eosinophil counts (<0.05 compared with 0.15-0.25×10(9)/L) with heart failure (adjusted HR 2.05; 95% CI 1.72 to 2.43), unheralded coronary death (HR 1.94, 95% CI 1.40 to 2.69), ventricular arrhythmia/sudden cardiac death and subarachnoid haemorrhage, but not angina, non-fatal myocardial infarction, transient ischaemic attack, ischaemic stroke, haemorrhagic stroke, subarachnoid haemorrhage or abdominal aortic aneurysm. Low eosinophil count was inversely associated with peripheral arterial disease (HR 0.63, 95% CI 0.44 to 0.89). There were similar associations with low lymphocyte counts (<1.45 vs 1.85-2.15×10(9)/L); adjusted HR over the first 6 months for heart failure was 2.25 (95% CI 1.90 to 2.67). Associations beyond the first 6 months were weaker. CONCLUSIONS: Low eosinophil counts and low lymphocyte counts in the general population are associated with increased short-term incidence of heart failure and coronary death. TRIAL REGISTRATION NUMBER: NCT02014610; results

Evaluating a natural horsemanship program in relation to the ISES first principles of horse training.

The ISES training principles provide an excellent starting point for professionals and horse owners. Currently, there does not seem to be an accepted protocol for evaluating horse training programs against the ISES principles. We suggest an approach to this, using Parelli Natural Horsemanship as our subject for evaluation. This initial pilot study (single-subject / n=1), trials two analytical methods, as applied to the current, video-based teaching materials from Parelli (latest DVD set, published and commercially available from 2015, supplied by Parelli for use in this study). The two methods used were: (i) ethology-based video observation / logging and (ii) discourse analysis of the language used to teach. The ethology-based approach uses an ethogram, which lists the behavioural characteristics of a human trainer adhering to the ISES principles. Computer-based ‘continuous sampling’ of Parelli video clips was used to log the frequencies of ISES principles. Inter Observer Reliability of the analysis to date was assessed using a two-way, mixed, absolute agreement, average-measures ICC (Intra Class Correlation). This evaluated observer agreement in the frequency count ratings for the ISES principles. Discourse analysis is a qualitative research methodology, applied across many domains including politics and health. Discourse analysis allows us to study transcripts of horse training materials, codifying the words, phrases and linguistic structures. Understanding the context within which training language is used, and its meaning to both the speaker and audience, makes it possible to evaluate compatibility with the ISES principles. Results for the ethology-based observations found all ISES principles present (1-10). High frequency counts for principles 2 & 10. Low counts for principles 5 & 7. Inter Observer Reliability (2 observers) was in the ‘excellent’ range (ICC=0.79). The high ICC value suggests that a minimal amount of measurement error was introduced by the independent observers, and therefore statistical power is not substantially reduced. At this stage (without an ICC value closer to 1.0 or further calibrating observers), increasing the evidence against random effects would require more extensive trials (p=0.16). The interim results from the discourse analysis shows consistent congruence between the Parelli materials and the ISES principles, particularly in the areas of: training according to the horse’s ethology and cognition, using learning theory appropriately, forming consistent habits, avoiding flight responses and ensuring that the horse should always be as calm as possible (1, 2, 7, 9 and 10)