Paula Dhiman

Antidepressant use and risk of adverse outcomes in older people: population based cohort study

Objectives To investigate the association between antidepressant treatment and risk of several potential adverse outcomes in older people with depression and to examine risks by class of antidepressant, duration of use, and dose. Design Cohort study of people aged 65 and over diagnosed as having depression. Setting 570 general practices in the United Kingdom supplying data to the QResearch primary care database. Participants 60 746 patients diagnosed as having a new episode of depression between the ages of 65 and 100 years from 1 January 1996 to 31 December 2007 and followed up until 31 December 2008. Main outcome measures Hazard ratios associated with antidepressant use for all cause mortality, attempted suicide/self harm, myocardial infarction, stroke/transient ischaemic attack, falls, fractures, upper gastrointestinal bleeding, epilepsy/seizures, road traffic accidents, adverse drug reactions, and hyponatraemia, adjusted for a range of potential confounding variables. Hazard ratios were calculated for antidepressant class (tricyclic and related antidepressants, selective serotonin reuptake inhibitors, other antidepressants), dose, and duration of use and for commonly prescribed individual drugs. Results 54 038 (89.0%) patients received at least one prescription for an antidepressant during follow-up. A total of 1 398 359 antidepressant prescriptions were issued: 764 659 (54.7%) for selective serotonin reuptake inhibitors, 442 192 (31.6%) for tricyclic antidepressants, 2203 (0.2%) for monoamine oxidase inhibitors, and 189 305 (13.5%) for the group of other antidepressants. The associations with the adverse outcomes differed significantly between the antidepressant classes for seven outcomes. Selective serotonin reuptake inhibitors were associated with the highest adjusted hazard ratios for falls (1.66, 95% confidence interval 1.58 to 1.73) and hyponatraemia (1.52, 1.33 to 1.75) compared with when antidepressants were not being used. The group of other antidepressants was associated with the highest adjusted hazard ratios for all cause mortality (1.66, 1.56 to 1.77), attempted suicide/self harm (5.16, 3.90 to 6.83), stroke/transient ischaemic attack (1.37, 1.22 to 1.55), fracture (1.64, 1.46 to 1.84), and epilepsy/seizures (2.24, 1.60 to 3.15), compared with when antidepressants were not being used. Tricyclic antidepressants did not have the highest hazard ratio for any of the outcomes. Significantly different associations also existed between the individual drugs for the same seven outcomes; trazodone (tricyclic antidepressant), mirtazapine, and venlafaxine (both in the group of other antidepressants) were associated with the highest rates for some of these outcomes. Absolute risks over 1 year for all cause mortality were 7.04% for patients while not taking antidepressants, 8.12% for those taking tricyclic antidepressants, 10.61% for selective serotonin reuptake inhibitors, and 11.43% for other antidepressants. Conclusions Selective serotonin reuptake inhibitors and drugs in the group of other antidepressants were associated with an increased risk of several adverse outcomes compared with tricyclic antidepressants. Among individual drugs, trazodone, mirtazapine, and venlafaxine were associated with the highest risks for some outcomes. As this is an observational study, it is susceptible to confounding by indication, channelling bias, and residual confounding, so differences in characteristics between patients prescribed different antidepressant drugs that could account for some of the associations between the drugs and the adverse outcomes may remain. Further research is needed to confirm these findings, but the risks and benefits of different antidepressants should be carefully evaluated when these drugs are prescribed to older people.

Effect of Adding Systematic Family History Enquiry to Cardiovascular Disease Risk Assessment in Primary Care : A Matched-Pair, Cluster Randomized Trial

BACKGROUND Evidence of the value of systematically collecting family history in primary care is limited. OBJECTIVE To evaluate the feasibility of systematically collecting family history of coronary heart disease in primary care and the effect of incorporating these data into cardiovascular risk assessment. DESIGN Pragmatic, matched-pair, cluster randomized, controlled trial. (International Standardized Randomized Controlled Trial Number Register: ISRCTN 17943542). SETTING 24 family practices in the United Kingdom. PARTICIPANTS 748 persons aged 30 to 65 years with no previously diagnosed cardiovascular risk, seen between July 2007 and March 2009. INTERVENTION Participants in control practices had the usual Framingham-based cardiovascular risk assessment with and without use of existing family history information in their medical records. Participants in intervention practices also completed a questionnaire to systematically collect their family history. All participants were informed of their risk status. Participants with high cardiovascular risk were invited for a consultation. MEASUREMENTS The primary outcome was the proportion of participants with high cardiovascular risk (10-year risk ≥ 20%). Other measures included questionnaire completion rate and anxiety score. RESULTS 98% of participants completed the family history questionnaire. The mean increase in proportion of participants classified as having high cardiovascular risk was 4.8 percentage points in the intervention practices, compared with 0.3 percentage point in control practices when family history from patient records was incorporated. The 4.5-percentage point difference between groups (95% CI, 1.7 to 7.2 percentage points) remained significant after adjustment for participant and practice characteristics (P = 0.007). Anxiety scores were similar between groups. LIMITATIONS Relatively few participants were from ethnic minority or less-educated groups. The potential to explore behavioral change and clinical outcomes was limited. Many data were missing for anxiety scores. CONCLUSION Systematically collecting family history increases the proportion of persons identified as having high cardiovascular risk for further targeted prevention and seems to have little or no effect on anxiety. PRIMARY FUNDING SOURCE Genetics Health Services Research program of the United Kingdom Department of Health.

A study of the safety and harms of antidepressant drugs for older people: a cohort study using a large primary care database

OBJECTIVES The aim of this study was to establish the relative safety and balance of risks for antidepressant treatment in older people. The study objectives were to (1) determine relative and absolute risks of predefined adverse events in older people with depression, comparing classes of antidepressant drugs [tricyclic and related antidepressants (TCAs), selective serotonin reuptake inhibitors (SSRIs), monoamine oxidase inhibitors (MAOIs) and other antidepressants] and commonly prescribed individual drugs with non-use of antidepressant drugs; (2) directly compare the risk of adverse events for SSRIs with TCAs; (3) determine associations with dose and duration of antidepressant medication; (4) describe patterns of antidepressant use in older people with depression; and (5) estimate costs of antidepressant medication and primary care visits. DESIGN A cohort study of patients aged 65 years and over diagnosed with depression. SETTING The study was based in 570 general practices in the UK supplying data to the QResearch database. PARTICIPANTS Patients diagnosed with a new episode of depression between the ages of 65 and 100 years, from 1 January 1996 to 31 December 2007. Participants were followed up until 31 December 2008. INTERVENTIONS The exposure of interest was treatment with antidepressant medication. Antidepressant drugs were grouped into the major classes and commonly prescribed individual drugs were identified. MAIN OUTCOME MEASURES There were 13 predefined outcome measures: all-cause mortality, sudden cardiac death, suicide, attempted suicide/self-harm, myocardial infarction, stroke/transient ischaemic attack (TIA), falls, fractures, upper gastrointestinal bleeding, epilepsy/seizures, road traffic accidents, adverse drug reactions and hyponatraemia. RESULTS In total, 60,746 patients were included in the study cohort. Of these, 54,038 (89.0%) received at least one prescription for an antidepressant during follow-up. The associations with the adverse outcomes were significantly different between the classes of antidepressant drugs for seven outcomes. SSRIs were associated with the highest adjusted hazard ratios (HRs) for falls [1.66, 95% confidence interval (CI) 1.58 to 1.73] and hyponatraemia (1.52, 95% CI 1.33 to 1.75), and the group of other antidepressants was associated with the highest HRs for all-cause mortality (1.66, 95% CI 1.56 to 1.77), attempted suicide/self-harm (5.16, 95% CI 3.90 to 6.83), stroke/TIA (1.37, 95% CI 1.22 to 1.55), fracture (1.63, 95% CI 1.45 to 1.83) and epilepsy/seizures (2.24, 95% CI 1.60 to 3.15) compared with when antidepressants were not being used. TCAs did not have the highest HR for any of the outcomes. There were also significantly different associations between the individual drugs for seven outcomes, with trazodone, mirtazapine and venlafaxine associated with the highest rates for several of these outcomes. The mean incremental cost (for all antidepressant prescriptions) ranged between £51.58 (amitriptyline) and £641.18 (venlafaxine) over the 5-year post-diagnosis period. CONCLUSIONS This study found associations between use of antidepressant drugs and a number of adverse events in older people. There was no evidence that SSRIs or drugs in the group of other antidepressants were associated with a reduced risk of any of the adverse outcomes compared with TCAs; however, they may be associated with an increased risk for certain outcomes. Among individual drugs trazodone, mirtazapine and venlafaxine were associated with the highest rates for some outcomes. Indication bias and residual confounding may explain some of the study findings. The risks of prescribing antidepressants need to be weighed against the potential benefits of these drugs. FUNDING The National Institute for Health Research Health Technology Assessment programme.

Availability and quality of coronary heart disease family history in primary care medical records: implications for cardiovascular risk assessment.

Background The potential to use data on family history of premature disease to assess disease risk is increasingly recognised, particularly in scoring risk for coronary heart disease (CHD). However the quality of family health information in primary care records is unclear. Aim To assess the availability and quality of family history of CHD documented in electronic primary care records Design Cross-sectional study Setting 537 UK family practices contributing to The Health Improvement Network database. Method Data were obtained from patients aged 20 years or more, registered with their current practice between 1st January 1998 and 31st December 2008, for at least one year. The availability and quality of recorded CHD family history was assessed using multilevel logistic and ordinal logistic regression respectively. Results In a cross-section of 1,504,535 patients, 19% had a positive or negative family history of CHD recorded. Multilevel logistic regression showed patients aged 50–59 had higher odds of having their family history recorded compared to those aged 20–29 (OR:1.23 (1.21 to 1.25)), however most deprived patients had lower odds compared to those least deprived (OR: 0.86 (0.85 to 0.88)). Of the 140,058 patients with a positive family history recorded (9% of total cohort), age of onset was available in 45%; with data specifying both age of onset and relative affected available in only 11% of records. Multilevel ordinal logistic regression confirmed no statistical association between the quality of family history recording and age, gender, deprivation and year of registration. Conclusion Family history of CHD is documented in a small proportion of primary care records; and where positive family history is documented the details are insufficient to assess familial risk or populate cardiovascular risk assessment tools. Data capture needs to be improved particularly for more disadvantaged patients who may be most likely to benefit from CHD risk assessment.

Psychological morbidity and return to work after injury: multicentre cohort study

BACKGROUND The benefits of work for physical, psychological, and financial wellbeing are well documented. Return to work (RTW) after unintentional injury is often delayed, and psychological morbidity may contribute to this delay. The impact of psychological morbidity on RTW after a wide range of unintentional injuries in the UK has not been adequately quantified. AIM To quantify the role of psychological factors, including anxiety, depression, and post-traumatic distress, on RTW following unintentional injuries. DESIGN AND SETTING A longitudinal multicentre prospective study was undertaken in Nottingham, Bristol, Leicester, and Guildford, UK. METHOD Participants (n = 273) were 16-69-year-olds admitted to hospital following unintentional injury, who were in paid employment prior to injury. They were surveyed at baseline, then at 1, 2, 4, and 12 months following injury; demographic data were collected along with injury characteristics, psychological morbidity, and RTW status. Associations between demographic, injury and psychological factors, and RTW between 2 and 12 months after injury were quantified using random effects logistic regression. RESULTS The odds of RTW between 2 and 12 months after injury reduced as depression scores early in the recovery period (1 month after injury) increased (odds ratio [OR] 0.87, 95% confidence interval [CI] = 0.79 to 0.95) and as length of hospital stay increased (OR 0.91, 95% CI] = 0.86 to 0.96). For those experiencing threatening life events following injury (OR 0.27, 95% CI = 0.10 to 0.72) and with higher scores on the Crisis Support Scale (OR 0.93, 95% CI] = 0.88 to 0.99), the odds of RTW between 2 and 12 months after injury were lower. Multiple imputation analysis found similar results, but those relating to crisis support did not remain statistically significant. CONCLUSION Primary care professionals can identify patients at risk of delayed RTW who may benefit from management of psychological morbidity and support to RTW.

Does bone mineral density improve the predictive accuracy of fracture risk assessment? A prospective cohort study in Northern Denmark

Objective To evaluate the added predictive accuracy of bone mineral density (BMD) to fracture risk assessment. Design Prospective cohort study using data between 01 January 2010 and 31 December 2012. Setting North Denmark Osteoporosis Clinic of referred patients presenting with at least one fracture risk factor to the referring doctor. Participants Patients aged 40–90 years; had BMD T-score recorded at the hip and not taking osteoporotic preventing drugs for more than 1 year prior to baseline. Main outcome measures Incident diagnoses of osteoporotic fractures (hip, spine, forearm, humerus and pelvis) were identified using the National Patient Registry of Denmark during 01 January 2012–01 January 2014. Cox regression was used to develop a fracture model based on predictors in the Fracture Risk Assessment Tool (FRAX®), with and without, binary and continuous BMD. Change in Harrell’s C-Index and Reclassification tables were used to describe the added statistical value of BMD. Results Adjusting for predictors included in FRAX®, patients with osteoporosis (T-score ≤−2.5) had 75% higher hazard of a fracture compared with patients with higher BMD (HR: 1.75 (95% CI 1.28 to 2.38)). Forty per cent lower hazard was found per unit increase in continuous BMD T-score (HR: 0.60 (95% CI 0.52 to 0.69)). Accuracy improved marginally, and Harrell’s C-Index increased by 1.2% when adding continuous BMD (0.76 to 0.77). Reclassification tables showed continuous BMD shifted 529 patients into different risk categories; 292 of these were reclassified correctly (57%; 95% CI 55% to 64%). Adding binary BMD however no improvement: Harrell’s C-Index decreased by 0.6%. Conclusions Continuous BMD marginally improves fracture risk assessment. Importantly, this was only found when using continuous BMD measurement for osteoporosis. It is suggested that future focus should be on evaluation of this risk factor using routinely collected data and on the development of more clinically relevant methodology to assess the added value of a new risk factor.

Comparison of coronary heart disease genetic assessment with conventional cardiovascular risk assessment in primary care: reflections on a feasibility study.

AIM This study assesses the feasibility of collecting genetic samples and self-reported outcome measures after cardiovascular risk assessment, and presenting the genetic test results to participants. BACKGROUND Coronary heart disease (CHD) genetic tests are increasingly available through direct-to-consumer marketing, but their potential clinical impact on cardiovascular risk assessment is unclear. METHODS Observational study in 10 British general practices in Central England. A total of 320 individuals, who had completed conventional cardiovascular risk assessment, were offered CHD genetic test, with follow-up outcome questionnaire at eight months for lifestyle change and State-Trait Anxiety. FINDINGS A total of 119 (37%) participants returned genetic test specimens, with over a third reporting family history of CHD in a specified relative; 79 (66.4%) were categorized above-average risk on conventional cardiovascular risk assessment, 65 of whom (82.3%) were only average risk on genetic assessment. The dietary fat questionnaire was poorly completed while study participation was not associated with increased anxiety (mean increase in anxiety score=2.1; 95% CI -0.1-4.3; P=0.06). CONCLUSION As a feasibility study, over a third of individuals offered genetic testing in primary care, as part of CVD risk assessment, took up the offer. Although intervention did not appear to increase anxiety, this needs further evaluation. To improve generalizability and effect size, future studies should actively engage individuals from wider socio-economic backgrounds who may not have already contemplated lifestyle change. The current research suggests general practitioners will face the clinical challenge of patients presenting with direct-to-consumer genetic results that are inconsistent with conventional cardiovascular risk assessment.

Decision analytic models to evaluate the cost-effectiveness of strategies for preventing fire-related injuries in children

Aim To develop decision analytic models to evaluate the cost-effectiveness of strategies for preventing fire-related injuries in children, for use in Childrens Centres in the UK. Methods Decision models will be developed to characterise the impact of different interventions to prevent fire related injuries (eg, possession of functional smoke alarms, fire guards and fire extinguishers) in terms of costs and quality of life. These models will be populated using relevant data obtained from a variety of sources including: (i) effectiveness of the different interventions in preventing fire related injury obtained from systematic review of existing experimental and observational studies, (ii) costs obtained from existing economic evaluations and other published data and (iii) effectiveness of a range of interventions on the use (and functioning) of equipment from existing trials and systematic reviews This decision analysis will identify the most cost effective strategies to increase the prevalence of functioning equipment and prevent fire related injuries. All model parameters will be estimated with uncertainty and correlation between parameters will be accounted for within a comprehensive modelling framework using Bayesian methods. Results and Conclusions The decision analysis models for fire prevention interventions will be used to develop injury guidance for Childrens Centres (injury prevention briefing, (IPB)). The implementation of the IPB will be tested using a cluster randomised control trial.