Ronan Ryan

Development and validation of an electronic frailty index using routine primary care electronic health record data

Background: frailty is an especially problematic expression of population ageing. International guidelines recommend routine identification of frailty to provide evidence-based treatment, but currently available tools require additional resource. Objectives: to develop and validate an electronic frailty index (eFI) using routinely available primary care electronic health record data. Study design and setting: retrospective cohort study. Development and internal validation cohorts were established using a randomly split sample of the ResearchOne primary care database. External validation cohort established using THIN database. Participants: patients aged 65–95, registered with a ResearchOne or THIN practice on 14 October 2008. Predictors: we constructed the eFI using the cumulative deficit frailty model as our theoretical framework. The eFI score is calculated by the presence or absence of individual deficits as a proportion of the total possible. Categories of fit, mild, moderate and severe frailty were defined using population quartiles. Outcomes: outcomes were 1-, 3- and 5-year mortality, hospitalisation and nursing home admission. Statistical analysis: hazard ratios (HRs) were estimated using bivariate and multivariate Cox regression analyses. Discrimination was assessed using receiver operating characteristic (ROC) curves. Calibration was assessed using pseudo-R2 estimates. Results: we include data from a total of 931,541 patients. The eFI incorporates 36 deficits constructed using 2,171 CTV3 codes. One-year adjusted HR for mortality was 1.92 (95% CI 1.81–2.04) for mild frailty, 3.10 (95% CI 2.91–3.31) for moderate frailty and 4.52 (95% CI 4.16–4.91) for severe frailty. Corresponding estimates for hospitalisation were 1.93 (95% CI 1.86–2.01), 3.04 (95% CI 2.90–3.19) and 4.73 (95% CI 4.43–5.06) and for nursing home admission were 1.89 (95% CI 1.63–2.15), 3.19 (95% CI 2.73–3.73) and 4.76 (95% CI 3.92–5.77), with good to moderate discrimination but low calibration estimates. Conclusions: the eFI uses routine data to identify older people with mild, moderate and severe frailty, with robust predictive validity for outcomes of mortality, hospitalisation and nursing home admission. Routine implementation of the eFI could enable delivery of evidence-based interventions to improve outcomes for this vulnerable group.

Evaluation of the management of heart failure in primary care

BACKGROUND The extent to which guidelines for the treatment of heart failure are currently followed in primary care in the UK is unclear. OBJECTIVE To evaluate the prevalence of heart failure and the pharmacological management of heart failure in relation to European Society of Cardiology (ESC) and National Institute for Health and Clinical Excellence guidelines. METHODS Retrospective cohort study using routinely collected data from 163 general practices across Great Britain contributing data to the Doctors Independent Network (DIN-LINK) database over a 5-year period until December 31, 2006. RESULTS From a patient population of nearly 1.43 million, 9311 patients with heart failure were identified [mean age 78 years (SD 12)], giving an estimated prevalence of 0.7%. Of these, 7410 (79.6%) were prescribed a loop diuretic, 6620 (71.1%) were prescribed an angiotensin-converting enzyme (ACE) inhibitor or ARB, 3403 (36.6%) were prescribed beta-blockers but only 2732 (29.3%) were prescribed an ACE inhibitor or ARB and a beta-blocker in combination. Thirty-five per cent of patients prescribed ACE inhibitor and 11.5% of those prescribed beta-blockers met ESC guideline target doses. Age, gender and comorbidity predicted whether patients received beta-blocker or ACE inhibitor with younger males being more likely to receive maximal therapy. CONCLUSIONS These data suggest that while most patients with heart failure receive an ACE inhibitor/ARB in primary care, few are titrated to target dose and many do not receive a beta-blocker. Optimum treatment appears to be most likely for young men. New strategies are required to ensure equitable and optimal treatment for all.

The association between smoking cessation and glycaemic control in patients with type 2 diabetes: A THIN database cohort study

BACKGROUND Smoking increases the risk of developing type 2 diabetes. However, several population studies also show a higher risk in people 3-5 years after smoking cessation than in continuing smokers. After 10-12 years the risk equates to that of never-smokers. Small cohort studies suggest diabetes control deteriorates temporarily during the first year after quitting. We examined whether or not quitting smoking was associated with altered diabetes control in a population study, for how long this association persisted, and whether or not this association was mediated by weight change. METHODS We did a retrospective cohort study (Jan 1, 2005, to Dec 31, 2010) of adult smokers with type 2 diabetes using The Health Improvement Network (THIN), a large UK primary care database. We developed adjusted multilevel regression models to investigate the association between a quit event, smoking abstinence duration, change in HbA1c, and the mediating effect of weight change. FINDINGS 10 692 adult smokers with type 2 diabetes were included. 3131 (29%) quit smoking and remained abstinent for at least 1 year. After adjustment for potential confounders, HbA1c increased by 0·21% (95% CI 0·17-0·25; p<0·001; [2·34 mmol/mol (95% CI 1·91-2·77)]) within the first year after quitting. HbA1c decreased as abstinence continued and became comparable to that of continual smokers after 3 years. This increase in HbA1c was not mediated by weight change. INTERPRETATION In type 2 diabetes, smoking cessation is associated with deterioration in glycaemic control that lasts for 3 years and is unrelated to weight gain. At a population level, this temporary rise could increase microvascular complications. FUNDING National Institute for Health Research School for Primary Care Research.

Use of name recognition software, census data and multiple imputation to predict missing data on ethnicity: application to cancer registry records

BackgroundInformation on ethnicity is commonly used by health services and researchers to plan services, ensure equality of access, and for epidemiological studies. In common with other important demographic and clinical data it is often incompletely recorded. This paper presents a method for imputing missing data on the ethnicity of cancer patients, developed for a regional cancer registry in the UK.MethodsRoutine records from cancer screening services, name recognition software (Nam Pehchan and Onomap), 2001 national Census data, and multiple imputation were used to predict the ethnicity of the 23% of cases that were still missing following linkage with self-reported ethnicity from inpatient hospital records.ResultsThe name recognition software were good predictors of ethnicity for South Asian cancer cases when compared with data on ethnicity derived from hospital inpatient records, especially when combined (sensitivity 90.5%; specificity 99.9%; PPV 93.3%). Onomap was a poor predictor of ethnicity for other minority ethnic groups (sensitivity 4.4% for Black cases and 0.0% for Chinese/Other ethnic groups). Area-based data derived from the national Census was also a poor predictor non-White ethnicity (sensitivity: South Asian 7.4%; Black 2.3%; Chinese/Other 0.0%; Mixed 0.0%).ConclusionsCurrently, neither method for assigning individuals to an ethnic group (name recognition and ethnic distribution of area of residence) performs well across all ethnic groups. We recommend further development of name recognition applications and the identification of additional methods for predicting ethnicity to improve their precision and accuracy for comparisons of health outcomes. However, real improvements can only come from better recording of ethnicity by health services.

Can analyses of electronic patient records be independently and externally validated? The effect of statins on the mortality of patients with ischaemic heart disease: a cohort study with nested case-control analysis.

Objective To conduct a fully independent and external validation of a research study based on one electronic health record database, using a different electronic database sampling the same population. Design Using the Clinical Practice Research Datalink (CPRD), we replicated a published investigation into the effects of statins in patients with ischaemic heart disease (IHD) by a different research team using QResearch. We replicated the original methods and analysed all-cause mortality using: (1) a cohort analysis and (2) a case-control analysis nested within the full cohort. Setting Electronic health record databases containing longitudinal patient consultation data from large numbers of general practices distributed throughout the UK. Participants CPRD data for 34 925 patients with IHD from 224 general practices, compared to previously published results from QResearch for 13 029 patients from 89 general practices. The study period was from January 1996 to December 2003. Results We successfully replicated the methods of the original study very closely. In a cohort analysis, risk of death was lower by 55% for patients on statins, compared with 53% for QResearch (adjusted HR 0.45, 95% CI 0.40 to 0.50; vs 0.47, 95% CI 0.41 to 0.53). In case-control analyses, patients on statins had a 31% lower odds of death, compared with 39% for QResearch (adjusted OR 0.69, 95% CI 0.63 to 0.75; vs OR 0.61, 95% CI 0.52 to 0.72). Results were also close for individual statins. Conclusions Database differences in population characteristics and in data definitions, recording, quality and completeness had a minimal impact on key statistical outputs. The results uphold the validity of research using CPRD and QResearch by providing independent evidence that both datasets produce very similar estimates of treatment effect, leading to the same clinical and policy decisions. Together with other non-independent replication studies, there is a nascent body of evidence for wider validity.

Bisphosphonates and Glucose Homeostasis: A Population-Based, Retrospective Cohort Study

CONTEXT Evidence suggests that the human skeleton might be involved in the regulation of glucose homeostasis. OBJECTIVE The objective of the study was to investigate the effect of exposure to bisphosphonates on the risk of incident type 2 diabetes mellitus (T2DM). DESIGN This was a population-based, retrospective, open cohort study over the period 1995-2010. SETTING The study was conducted from The Health Improvement Network database from the United Kingdom in a primary care setting. PATIENTS A total of 35 998 individuals aged older than 60 years, without diabetes at baseline and with more than 1 years exposure to bisphosphonates, and 126 459 age-, gender-, body mass index- and general practice-matched unexposed individuals participated in the study. INTERVENTIONS There were no interventions. MAIN OUTCOME MEASURE A new diagnosis of T2DM during the 16-year-long observation period, determined by Read codes and adjusted incidence rate ratio in bisphosphonate-exposed compared with unexposed groups, was the main outcome measure. RESULTS The risk of incident T2DM was significantly lower in patients exposed to bisphosphonates compared with matched controls [adjusted incidence rate ratio 0.52, 95% confidence interval (CI) 0.48-0.56, P < .0001]. In subgroup analyses, the findings remained consistent in males [0.77 (95% CI 0.66-0.89)], females [0.49 (95% CI 0.45-0.53)], obese [0.54 (95% CI 0.50-0.59)], individuals exposed to steroid treatment [0.47 (95% CI 0.34-0.64)], and over different types of bisphosphonate medication. Analysis of duration of treatment suggested a brief increase in the risk of T2DM (1 to 2.5 y of exposure), followed by a progressive, sustained decrease as the years of exposure accumulated. CONCLUSIONS This observational evidence suggests exposure to bisphosphonates was associated with a significant 50% reduction in the risk of incident T2DM.

Iron deficiency anaemia and delayed diagnosis of colorectal cancer : a retrospective cohort study

Aim  The extent to which different referral pathways following a primary care diagnosis of iron deficiency anaemia (IDA) are associated with delay in diagnosis of colorectal cancer (CRC) was determined.

Survival following a diagnosis of heart failure in primary care

Abstract Background. Heart failure is a common long term condition affecting around 900 000 people in the UK and patients commonly present to primary care. The prognosis of patients with a code of heart failure in their primary care record is unknown. Objective. The study sought to determine the overall survival rates for patients with heart failure in a primary care population from the time of diagnosis. Methods. Survival analysis was carried out using UK primary care records from The Health Improvement Network (THIN) between 1 January 1998 and 31 December 2012. Patients age 45 or over with a first diagnostic label of heart failure were matched by age, sex and practice to people without heart failure. Outcome was death in the heart failure and no heart failure cohorts. Kaplan-Meier curves were used to compare survival. Age-specific survival rates at 1, 5 and 10 years were determined for men and women with heart failure. Survival rates by year of diagnosis and case definition were also calculated. Results. During the study period, 54313 patients had a first diagnostic code of heart failure. Overall survival rates for the heart failure group were 81.3% (95%CI 80.9–81.6), 51.5% (95%CI 51.0–52.0) and 29.5% (95%CI 28.9–30.2) at 1, 5 and 10 years respectively and did not change over time. Conclusions. In a primary care population, the survival of patients diagnosed with heart failure did not improved over time. Further research is needed to explain these trends and to find strategies to improve outlook.

Assessing the predictive value of HIV indicator conditions in general practice: a case–control study using the THIN database

BACKGROUND UK HIV guidelines identify 37 clinical indicator conditions for adult HIV infection that should prompt an HIV test. However, few data currently exist to show their predictive value in identifying undiagnosed HIV. AIM To identify symptoms and clinical diagnoses associated with HIV infection and assess their relative importance in identifying HIV cases, using data from The Health Improvement Network (THIN) general practice database. DESIGN AND SETTING A case-control study in primary care. METHOD Cases (HIV-positive patients) were matched to controls (not known to have HIV). Data from 939 cases and 2576 controls were included (n = 3515). Statistical analysis assessed the incidence of the 37 clinical conditions in cases and controls, and their predictive value in indicating HIV infection, and derived odds ratios (ORs) for each indicator condition. RESULTS Twelve indicator conditions were significantly associated with HIV infection; 74.2% of HIV cases (n = 697) presented with none of the HIV indicator conditions prior to diagnosis. The conditions most strongly associated with HIV infection were bacterial pneumonia (OR = 47.7; 95% confidence interval [CI] = 5.6 to 404.2) and oral candidiasis (OR = 29.4; 95% CI = 6.9 to 125.5). The signs and symptoms most associated with HIV were weight loss (OR = 13.4; 95% CI = 5.0 to 36.0), pyrexia of unknown origin (OR = 7.2; 95% CI = 2.8 to 18.7), and diarrhoea (one or two consultations). CONCLUSION This is the first study to quantify the predictive value of clinical diagnoses related to HIV infection in primary care. In identifying the conditions most strongly associated with HIV, this study could aid GPs in offering targeted HIV testing to those at highest risk.

The effect of seeking consent on the representativeness of patient cohorts: iron-deficiency anaemia and colorectal cancer

Aim  The study aimed to establish the level of selection bias that may occur should individual patient consent be sought, by comparing characteristics of consenters and nonconsenters to a request for access to medical records within a cohort of patients diagnosed with iron‐deficiency anaemia (IDA).