Linda Nichols

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.

The effect of walking on risk factors for cardiovascular disease: An updated systematic review and meta-analysis of randomised control trials

OBJECTIVE To conduct a systematic review and meta-analysis of randomised control trials that examined the effect of walking on risk factors for cardiovascular disease. METHODS Four electronic databases and reference lists were searched (Jan 1971-June 2012). Two authors identified randomised control trials of interventions ≥ 4 weeks in duration that included at least one group with walking as the only treatment and a no-exercise comparator group. Participants were inactive at baseline. Pooled results were reported as weighted mean treatment effects and 95% confidence intervals using a random effects model. RESULTS 32 articles reported the effects of walking interventions on cardiovascular disease risk factors. Walking increased aerobic capacity (3.04 mL/kg/min, 95% CI 2.48 to 3.60) and reduced systolic (-3.58 mm Hg, 95% CI -5.19 to -1.97) and diastolic (-1.54 mm Hg, 95% CI -2.83 to -0.26) blood pressure, waist circumference (-1.51 cm, 95% CI -2.34 to -0.68), weight (-1.37 kg, 95% CI -1.75 to -1.00), percentage body fat (-1.22%, 95% CI -1.70 to -0.73) and body mass index (-0.53 kg/m(2), 95% CI -0.72 to -0.35) but failed to alter blood lipids. CONCLUSIONS Walking interventions improve many risk factors for cardiovascular disease. This underscores the central role of walking in physical activity for health promotion.

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.

Predicting out-of-office blood pressure level using repeated measurements in the clinic: an observational cohort study.

Objectives: Identification of people with lower (white-coat effect) or higher (masked effect) blood pressure at home compared to the clinic usually requires ambulatory or home monitoring. This study assessed whether changes in SBP with repeated measurement at a single clinic predict subsequent differences between clinic and home measurements. Methods: This study used an observational cohort design and included 220 individuals aged 35–84 years, receiving treatment for hypertension, but whose SBP was not controlled. The characteristics of change in SBP over six clinic readings were defined as the SBP drop, the slope and the quadratic coefficient using polynomial regression modelling. The predictive abilities of these characteristics for lower or higher home SBP readings were investigated with logistic regression and repeated operating characteristic analysis. Results: The single clinic SBP drop was predictive of the white-coat effect with a sensitivity of 90%, specificity of 50%, positive predictive value of 56% and negative predictive value of 88%. Predictive values for the masked effect and those of the slope and quadratic coefficient were slightly lower, but when the slope and quadratic variables were combined, the sensitivity, specificity, positive and negative predictive values for the masked effect were improved to 91, 48, 24 and 97%, respectively. Conclusion: Characteristics obtainable from multiple SBP measurements in a single clinic in patients with treated hypertension appear to reasonably predict those unlikely to have a large white-coat or masked effect, potentially allowing better targeting of out-of-office monitoring in routine clinical practice.

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.

Lack of attentional retraining effects in cigarette smokers attempting cessation: A proof of concept double-blind randomised controlled trial

BACKGROUND Observational studies have shown that attentional bias for smoking-related cues is associated with increased craving and relapse. Laboratory experiments have shown that manipulating attentional bias may change craving. Interventions to reduce attentional bias could reduce relapse in smokers seeking to quit. We report a clinical trial of attentional retraining in treatment-seeking smokers. METHODS This was a double-blind randomised controlled trial that took place in UK smoking cessation clinics. Smokers interested in quitting were randomised to five weekly sessions of attentional retraining (N=60) or placebo training (N = 58) using a modified visual probe task from one week prior to quit day. Both groups received 21 mg nicotine patches (from quit day onwards) and behavioural support. Primary outcomes included change in attentional bias reaction times four weeks after quit day on the visual probe task and craving measured weekly using the Mood and Physical Symptoms Scale. Secondary outcomes were changes in withdrawal symptoms, time to first lapse and prolonged abstinence. RESULTS No attentional bias towards smoking cues was found in the sample at baseline (mean difference = 3 ms, 95% CI = -2, 9). Post-training bias was not significantly lower in the retraining group compared with the placebo group (mean difference = -9 ms, 95% CI = -20, 2). There was no difference between groups in change in craving (p = 0.89) and prolonged abstinence at four weeks (risk ratio = 1.00, 95% CI = 0.70, 1.43). CONCLUSIONS Taken with one other trial, there appears to be no effect from clinic-based attentional retraining using the visual probe task. Attentional retraining conducted out of clinic may prove more effective. CLINICAL TRIAL REGISTRATION UK Clinical Trials ISRCTN 54375405.

Trial Protocol: A randomised controlled trial of extended anticoagulation treatment versus routine anticoagulation treatment for the prevention of recurrent VTE and post thrombotic syndrome in patients being treated for a first episode of unprovoked VTE (The ExACT Study)

BackgroundVenous thromboembolism comprising pulmonary embolism and deep vein thrombosis is a common condition with an incidence of approximately 1 per 1,000 per annum causing both mortality and serious morbidity. The principal aim of treatment of a venous thromboembolism with heparin and warfarin is to prevent extension or recurrence of clot. However, the recurrence rate following a deep vein thrombosis remains approximately 10% per annum following treatment cessation irrespective of the duration of anticoagulation therapy. Patients with raised D-dimer levels after discontinuing oral anticoagulation treatment have also been shown to be at high risk of recurrence.Post thrombotic syndrome is a complication of a deep vein thrombosis which can lead to chronic venous insufficiency and ulceration. It has a cumulative incidence after 2 years of around 25% and it has been suggested that extended oral anticoagulation should be investigated as a possible preventative measure.Methods/designPatients with a first idiopathic venous thromboembolism will be recruited through anticoagulation clinics and randomly allocated to either continuing or discontinuing warfarin treatment for a further 2 years and followed up on a six monthly basis. At each visit D-dimer levels will be measured using a Roche Cobas h 232 POC device. In addition a venous sample will be taken for laboratory D-dimer analysis at the end of the study. Patients will be examined for signs and symptoms of PTS using the Villalta scale and complete VEINES and EQ5D quality of life questionnaires.DiscussionThe primary aim of the study is to investigate whether extending oral anticoagulation treatment (prior to discontinuing treatment) beyond 3–6 months for patients with a first unprovoked proximal deep vein thrombosis or pulmonary embolism prevents recurrence. The study will also determine the role of extending anticoagulation for patients with elevated D-dimer levels prior to discontinuing treatment and identify the potential of D-dimer point of care testing for identification of high risk patients within a primary care setting.Trial registrationISRCTN73819751

Effects of Nutritional Supplementation during Pregnancy on Early Adult Disease Risk: Follow Up of Offspring of Participants in a Randomised Controlled Trial Investigating Effects of Supplementation on Infant Birth Weight

Background Observational evidence suggests that improving fetal growth may improve adult health. Experimental evidence from nutritional supplementation trials undertaken amongst pregnant women in the less developed world does not show strong or consistent effects on adult disease risk and no trials from the more developed world have previously been reported. Objective To test the hypothesis that nutritional supplementation during pregnancy influences offspring disease risk in adulthood Design Clinical assessment of a range of established diseases risk markers in young adult offspring of 283 South Asian mothers who participated in two trials of nutritional supplementation during pregnancy (protein/energy/vitamins; energy/vitamins or vitamins only) at Sorrento Maternity Hospital in Birmingham UK either unselected or selected on the basis of nutritional status. Results 236 (83%) offspring were traced and 118 (50%) of these were assessed in clinic. Protein/energy/vitamins supplementation amongst undernourished mothers was associated with increased infant birthweight. Nutritional supplementation showed no strong association with any one of a comprehensive range of markers of adult disease risk and no consistent pattern of association with risk across markers in offspring of either unselected or undernourished mothers. Conclusions We found no evidence that nutritional supplements given to pregnant women are an important influence on adult disease risk however our study lacked power to estimate small effects. Our findings do not provide support for a policy of nutritional supplementation for pregnant women as an effective means to improve adult health in more developed societies.

Derivation of a prediction model for a diagnosis of depression in young adults: a matched case–control study using electronic primary care records

Approximately 80 000 children and young people in the UK suffer from depression, but many are untreated because of poor identification of early warning signs and risk factors.