Predicting prognosis for adults with depression using individual symptom data: a comparison of modelling approaches.

BACKGROUND: This study aimed to develop, validate and compare the performance of models predicting post-treatment outcomes for depressed adults based on pre-treatment data. METHODS: Individual patient data from all six eligible randomised controlled trials were used to develop (k = 3, n = 1722) and test (k = 3, n = 918) nine models. Predictors included depressive and anxiety symptoms, social support, life events and alcohol use. Weighted sum scores were developed using coefficient weights derived from network centrality statistics (models 1-3) and factor loadings from a confirmatory factor analysis (model 4). Unweighted sum score models were tested using elastic net regularised (ENR) and ordinary least squares (OLS) regression (models 5 and 6). Individual items were then included in ENR and OLS (models 7 and 8). All models were compared to one another and to a null model (mean post-baseline Beck Depression Inventory Second Edition (BDI-II) score in the training data: model 9). Primary outcome: BDI-II scores at 3-4 months. RESULTS: Models 1-7 all outperformed the null model and model 8. Model performance was very similar across models 1-6, meaning that differential weights applied to the baseline sum scores had little impact. CONCLUSIONS: Any of the modelling techniques (models 1-7) could be used to inform prognostic predictions for depressed adults with differences in the proportions of patients reaching remission based on the predicted severity of depressive symptoms post-treatment. However, the majority of variance in prognosis remained unexplained. It may be necessary to include a broader range of biopsychosocial variables to better adjudicate between competing models, and to derive models with greater clinical utility for treatment-seeking adults with depression.

The importance of transdiagnostic symptom level assessment to understanding prognosis for depressed adults: analysis of data from six randomised control trials.

BACKGROUND: Depression is commonly perceived as a single underlying disease with a number of potential treatment options. However, patients with major depression differ dramatically in their symptom presentation and comorbidities, e.g. with anxiety disorders. There are also large variations in treatment outcomes and associations of some anxiety comorbidities with poorer prognoses, but limited understanding as to why, and little information to inform the clinical management of depression. There is a need to improve our understanding of depression, incorporating anxiety comorbidity, and consider the association of a wide range of symptoms with treatment outcomes. METHOD: Individual patient data from six RCTs of depressed patients (total n = 2858) were used to estimate the differential impact symptoms have on outcomes at three post intervention time points using individual items and sum scores. Symptom networks (graphical Gaussian model) were estimated to explore the functional relations among symptoms of depression and anxiety and compare networks for treatment remitters and those with persistent symptoms to identify potential prognostic indicators. RESULTS: Item-level prediction performed similarly to sum scores when predicting outcomes at 3 to 4 months and 6 to 8 months, but outperformed sum scores for 9 to 12 months. Pessimism emerged as the most important predictive symptom (relative to all other symptoms), across these time points. In the network structure at study entry, symptoms clustered into physical symptoms, cognitive symptoms, and anxiety symptoms. Sadness, pessimism, and indecision acted as bridges between communities, with sadness and failure/worthlessness being the most central (i.e. interconnected) symptoms. Connectivity of networks at study entry did not differ for future remitters vs. those with persistent symptoms. CONCLUSION: The relative importance of specific symptoms in association with outcomes and the interactions within the network highlight the value of transdiagnostic assessment and formulation of symptoms to both treatment and prognosis. We discuss the potential for complementary statistical approaches to improve our understanding of psychopathology.

Prioritising physical and psychological symptoms: what are the barriers and facilitators to the discussion of anxiety in the primary care consultation?

BACKGROUND: Anxiety is under-recorded and under-treated in the UK and is under-represented in research compared with depression. Detecting anxiety can be difficult because of co-existing conditions. GPs can be reluctant to medicalise anxiety symptoms and patients can be reluctant to disclose them, for a variety of reasons. This research addresses the gap in evidence of real-life consultations of patients with anxiety and explores how physical and psychological symptoms are discussed and prioritised by patients and GPs in primary care consultations. METHODS: A mixed methods study using a baseline questionnaire, video-recorded primary care consultations and interview data with patients and GPs. RESULTS: Seventeen patients with anxiety symptoms (GAD-7 score ≥ 10) completed a questionnaire, had their consultation video-recorded and took part in a semi-structured interview. Four GPs were interviewed. The main themes that emerged from GP and patients accounts as barriers and facilitators to discussing anxiety mostly mirrored each other. The GP/patient relationship and continuity of care was the main facilitator for the discussion of anxiety in the consultation. The main barriers were: attribution of or unacknowledged symptoms; co-morbidities; and time constraints. GPs overcame these barriers by making repeat appointments and employing prioritising techniques; patients by choosing an empathetic GP. CONCLUSIONS: The findings add to the evidence base concerning the management of anxiety in primary care. The findings suggest that the discussion around anxiety is a process negotiated between the patient and the GP influenced by a range of barriers and facilitators. Co-existing depression and health anxieties can mask anxiety symptoms in patients. Good practice techniques such as bringing back patients for appointments to foster continuity of care and understanding can help disclosure and detection of anxiety symptoms. Future research could investigate this longitudinally and should include a wider range of GPs practices and GPs.

Variation in the recall of socially rewarding information and depressive symptom severity: a prospective cohort study.

OBJECTIVE: To test the association between recall for socially rewarding (positive) and/or socially critical (negative) information and depressive symptoms. METHOD: Cohort study of people who had visited UK primary care in the past year reporting depressive symptoms (N = 558, 69% female). Positive and negative recall was assessed at three time-points, 2 weeks apart, using a computerised task. Depressive symptoms were assessed at four time-points using the Beck Depression Inventory (BDI). Analyses were conducted using multilevel models. RESULTS: Concurrently we found evidence that, for every increase in two positive words recalled, depressive symptoms reduced by 0.6 (95% CI -1.0 to -0.2) BDI points. This association was not affected by adjustment for confounders. There was no evidence of an association between negative recall and depressive symptoms (-0.1, 95% CI -0.5 to 0.3). Longitudinally, we found more evidence that positive recall was associated with reduced depressive symptoms than vice versa. CONCLUSION: People with more severe depressive symptoms recall less positive information, even if their recall of negative information is unaltered. Clinicians could put more emphasis on encouraging patients to recall positive, socially rewarding information, rather than trying to change negative interpretations of events that have already occurred.

Minimal clinically important difference on the Beck Depression Inventory--II according to the patient's perspective.

BACKGROUND: The Beck Depression Inventory, 2nd edition (BDI-II) is widely used in research on depression. However, the minimal clinically important difference (MCID) is unknown. MCID can be estimated in several ways. Here we take a patient-centred approach, anchoring the change on the BDI-II to the patient's global report of improvement. METHOD: We used data collected (n = 1039) from three randomized controlled trials for the management of depression. Improvement on a 'global rating of change' question was compared with changes in BDI-II scores using general linear modelling to explore baseline dependency, assessing whether MCID is best measured in absolute terms (i.e. difference) or as percent reduction in scores from baseline (i.e. ratio), and receiver operator characteristics (ROC) to estimate MCID according to the optimal threshold above which individuals report feeling 'better'. RESULTS: Improvement in BDI-II scores associated with reporting feeling 'better' depended on initial depression severity, and statistical modelling indicated that MCID is best measured on a ratio scale as a percentage reduction of score. We estimated a MCID of a 17.5% reduction in scores from baseline from ROC analyses. The corresponding estimate for individuals with longer duration depression who had not responded to antidepressants was higher at 32%. CONCLUSIONS: MCID on the BDI-II is dependent on baseline severity, is best measured on a ratio scale, and the MCID for treatment-resistant depression is larger than that for more typical depression. This has important implications for clinical trials and practice.

Allowing for non-adherence to treatment in a randomized controlled trial of two antidepressants (citalopram versus reboxetine): an example from the GENPOD trial.

BACKGROUND: Meta-analyses suggest that reboxetine may be less effective than other antidepressants. Such comparisons may be biased by lower adherence to reboxetine and subsequent handling of missing outcome data. This study illustrates how to adjust for differential non-adherence and hence derive an unbiased estimate of the efficacy of reboxetine compared with citalopram in primary care patients with depression. METHOD: A structural mean modelling (SMM) approach was used to generate adherence-adjusted estimates of the efficacy of reboxetine compared with citalopram using GENetic and clinical Predictors Of treatment response in Depression (GENPOD) trial data. Intention-to-treat (ITT) analyses were performed to compare estimates of effectiveness with results from previous meta-analyses. RESULTS: At 6 weeks, 92% of those randomized to citalopram were still taking their medication, compared with 72% of those randomized to reboxetine. In ITT analysis, there was only weak evidence that those on reboxetine had a slightly worse outcome than those on citalopram [adjusted difference in mean Beck Depression Inventory (BDI) scores: 1.19, 95% confidence interval (CI) -0.52 to 2.90, p = 0.17]. There was no evidence of a difference in efficacy when differential non-adherence was accounted for using the SMM approach for mean BDI (-0.29, 95% CI -3.04 to 2.46, p = 0.84) or the other mental health outcomes. CONCLUSIONS: There was no evidence of a difference in the efficacy of reboxetine and citalopram when these drugs are taken and tolerated by depressed patients. The SMM approach can be implemented in standard statistical software to adjust for differential non-adherence and generate unbiased estimates of treatment efficacy for comparisons of two (or more) active interventions.

Common versus psychopathology-specific risk factors for psychotic experiences and depression during adolescence.

BACKGROUND: An argument often used to support the view that psychotic experiences (PEs) in general population samples are a valid phenotype for studying the aetiology of schizophrenia is that risk factors for schizophrenia show similar patterns of association with PEs. However, PEs often co-occur with depression, and no study has explicitly tested whether risk factors for schizophrenia are shared between PEs and depression, or are psychopathology specific, while jointly modelling both outcomes. METHOD: We used data from 7030 subjects from a birth cohort study. Depression and PEs at age 18 years were assessed using self-report questionnaires and semi-structured interviews. We compared the extent to which risk factors for schizophrenia across sociodemographic, familial, neurodevelopmental, stress-adversity, emotional-behavioural and substance use domains showed different associations with PEs and depression within bivariate models that allowed for their correlation. RESULTS: Most of the exposures examined were associated, to a similar degree, with an increased risk of both outcomes. However, whereas female sex and family history of depression showed some discrimination as potential risk factors for depression and PEs, with stronger associations in the former, markers of abnormal neurodevelopment showed stronger associations with PEs. CONCLUSIONS: The argument that PEs are valid markers for studying the aetiology of schizophrenia, made simply on the basis that they share risk factors in common, is not well supported. PEs seem to be a weak index of genetic and environmental risk for schizophrenia; however, studies disentangling aetiological pathways to PEs from those impacting upon co-morbid psychopathology might provide important insights into the aetiology of psychotic disorders.

Role of age, gender and marital status in prognosis for adults with depression: An individual patient data meta-analysis.

AIMS: To determine whether age, gender and marital status are associated with prognosis for adults with depression who sought treatment in primary care. METHODS: Medline, Embase, PsycINFO and Cochrane Central were searched from inception to 1st December 2020 for randomised controlled trials (RCTs) of adults seeking treatment for depression from their general practitioners, that used the Revised Clinical Interview Schedule so that there was uniformity in the measurement of clinical prognostic factors, and that reported on age, gender and marital status. Individual participant data were gathered from all nine eligible RCTs (N = 4864). Two-stage random-effects meta-analyses were conducted to ascertain the independent association between: (i) age, (ii) gender and (iii) marital status, and depressive symptoms at 3-4, 6-8, and 9-12 months post-baseline and remission at 3-4 months. Risk of bias was evaluated using QUIPS and quality was assessed using GRADE. PROSPERO registration: CRD42019129512. Pre-registered protocol https://osf.io/e5zup/. RESULTS: There was no evidence of an association between age and prognosis before or after adjusting for depressive 'disorder characteristics' that are associated with prognosis (symptom severity, durations of depression and anxiety, comorbid panic disorderand a history of antidepressant treatment). Difference in mean depressive symptom score at 3-4 months post-baseline per-5-year increase in age = 0(95% CI: -0.02 to 0.02). There was no evidence for a difference in prognoses for men and women at 3-4 months or 9-12 months post-baseline, but men had worse prognoses at 6-8 months (percentage difference in depressive symptoms for men compared to women: 15.08% (95% CI: 4.82 to 26.35)). However, this was largely driven by a single study that contributed data at 6-8 months and not the other time points. Further, there was little evidence for an association after adjusting for depressive 'disorder characteristics' and employment status (12.23% (-1.69 to 28.12)). Participants that were either single (percentage difference in depressive symptoms for single participants: 9.25% (95% CI: 2.78 to 16.13) or no longer married (8.02% (95% CI: 1.31 to 15.18)) had worse prognoses than those that were married, even after adjusting for depressive 'disorder characteristics' and all available confounders. CONCLUSION: Clinicians and researchers will continue to routinely record age and gender, but despite their importance for incidence and prevalence of depression, they appear to offer little information regarding prognosis. Patients that are single or no longer married may be expected to have slightly worse prognoses than those that are married. Ensuring this is recorded routinely alongside depressive 'disorder characteristics' in clinic may be important.

Predictors of persistent neck pain after whiplash injury.

OBJECTIVE: To establish the aetiological influences of persistent neck pain following a motor vehicle collision and to construct a model for use in the emergency department for identifying patients at high risk of persistent symptoms. DESIGN: Prospective cohort study. Patients recruited from hospital emergency departments were sent a questionnaire to gather information on various exposures. They were followed up at 1, 3, and 12 months to identify those with persistent symptoms. MAIN OUTCOME MEASURE: Persistent neck pain (pain at 1, 3, and 12 months after collision). RESULTS: The baseline survey included 765 patients. Subsequently, 480 completed a questionnaire at each follow up time point, of whom 128 (27%) reported neck pain on each occasion. Few collision specific factors predicted persistent neck pain. In contrast, a high level of general psychological distress, pre-collision history of widespread body pain, type of vehicle, whiplash associated symptoms, and initial neck disability best predicted the persistence of symptoms. Furthermore, these factors, in combination, accounted for more than a fivefold increase in the risk of persistent neck pain. CONCLUSION: The greatest predictors of persistent neck pain following a motor vehicle collision relate to psychological distress and aspects of pre-collision health rather than to various attributes of the collision itself. With these factors, and those relating to initial injury severity, it is possible to identify a subgroup of patients presenting with neck pain with the highest risk of persistent symptoms. Thus, it is possible to identify whiplash patients with a poor prognosis and to provide closer follow up and specific attention to management in these individuals.

Associations between demographic and disease-related variables and disability over the first five years of inflammatory polyarthritis: a longitudinal analysis using generalized estimating equations.

OBJECTIVES: To investigate whether the relationship between demographic and disease-related variables and disability is constant during the first five years of inflammatory polyarthritis (IP) and to identify the contribution from involvement of specific joint areas to overall disability. METHODS: 684 patients referred to the Norfolk Arthritis Register were followed for five years using the Health Assessment Questionnaire (HAQ). The relationship between disability and demographic and clinical variables was analyzed using a multi-level modelling approach. RESULTS: Female gender, older age at symptom onset (> or = 64 years), joint involvement at six specific sites, joint tenderness and the number of deformed joints were all independently associated with disability (HAQ > or = 1.00). Similar results were obtained using a more stringent cut-off (HAQ > or = 1.50) or when analysis was restricted to the 325 patients who satisfied the 1987 ARA list criteria for rheumatoid arthritis. CONCLUSION: Disability, as measured by the HAQ, was associated with a large number of independent factors over the first five years of disease.

A pragmatic randomised controlled trial to evaluate the cost-effectiveness of a physical activity intervention as a treatment for depression: the treating depression with physical activity (TREAD) trial.

OBJECTIVE: The TREAting Depression with physical activity (TREAD) study investigated the cost-effectiveness of a physical activity intervention, in addition to usual general practitioner care, as a treatment for people with depression. DESIGN: An individually randomised, pragmatic, multicentre randomised controlled trial with follow-up at 4, 8 and 12 months. A subset of participants took part in a qualitative study that investigated the acceptability and perceived benefits of the intervention. SETTING: General practices in the Bristol and Exeter areas. PARTICIPANTS: Aged 18-69 years with an International Statistical Classification of Diseases and Related Health Problems, 10th Edition (ICD-10) diagnosis of depression and scoring ≥ 14 on the Beck Depression Inventory (BDI). Those who were unable to complete self-administered questionnaires in English, with medical contraindications to physical activity or with psychosis, bipolar disorder or serious drug abuse were excluded. INTERVENTIONS: We devised an intervention designed to encourage choice and autonomy in the adoption of physical activity. It consisted of up to three face-to-face and ten telephone contacts delivered by a trained physical activity facilitator over an 8-month period. MAIN OUTCOME MEASURES: The primary outcome was the BDI score measured at 4 months. Secondary outcomes included depressive symptoms over the 12 months and quality of life, antidepressant use and level of physical activity. RESULTS: The study recruited 361 patients, with 182 randomised to the intervention arm and 179 to the usual care arm; there was 80% retention at the 4-month follow-up. The intervention group had a slightly lower BDI score at 4 months [-0.54, 95% confidence interval (CI) -3.06 to 1.99] but there was no evidence that the intervention improved outcome for depression. Neither was there any evidence to suggest a difference in the prescription of or self-reported use of antidepressants. However, the amount of physical activity undertaken by those who had received the intervention was increased (odds ratio 2.3, 95% CI 1.3 to 3.9) and was sustained beyond the end of the intervention. From a health-care perspective, the intervention group was more costly than the usual care group, with the cost of the intervention £220 per person on average. It is therefore extremely unlikely that the intervention is cost-effective as a treatment for depression using current willingness-to-pay thresholds. CONCLUSIONS: This physical activity intervention is very unlikely to lead to any clinical benefit in terms of depressive symptoms or to be a cost-effective treatment for depression. Previous research has reported some benefit and there are three possible reasons for this discrepancy: first, even though the intervention increased self-reported physical activity, the increase in activity was not sufficiently large to lead to a measurable influence; second, only more vigorous activity might be of benefit; and third, previous studies had recruited individuals with a pre-existing commitment to physical activity. Future research is needed to identify and explain the mechanisms by which depression might be effectively treated, including, in particular, specific guidance on the optimum type, intensity and duration of physical activity required to produce a therapeutic effect. TRIAL REGISTRATION: Current Controlled Trials ISRCTN16900744. FUNDING: This project was funded by the NIHR Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 16, No. 10. See the HTA programme website for further project information.

Childhood diet and behavioural problems: results from the ALSPAC cohort.

OBJECTIVE: To investigate whether a 'junk food' diet at 81 months of age is associated with the development of behavioural problems over the following 16 months. SUBJECTS/METHODS: The study used data from the Avon Longitudinal Study of Parents and Children (ALSPAC) and 12,942 children were included. The main outcome measure was behavioural problems, measured using the Strengths and Difficulties Questionnaire (SDQ). SDQ scores were available at 81 and 97 months of age. Child-based dietary data were collected at 81 months by food frequency questionnaire; from this a 'junk food' score was derived, and mean weekly non-milk extrinsic sugar (NMES) intake estimated. Statistical analyses examined the associations between dietary exposures at 81 months and SDQ outcomes at 97 months. Children with SDQ scores suggesting behavioural problems at baseline were excluded in order to identify new cases. Adjustments were made for potential confounders such as socioeconomic status. RESULTS: Unadjusted analyses suggested associations between the 'junk food' score at 81 months and both total difficulties and pro-social behaviour at 97 months. However, adjustment for baseline SDQ scores attenuated these associations, with confidence intervals including the null for both total difficulties (OR (95% CI): 1.05 (0.92, 1.21); P=0.45) and pro-social behaviour (1.13 (1.00, 1.26); P=0.04). Adjustment for other potential confounders further attenuated the effects. Adjustment for confounders similarly attenuated modest associations between NMES intake and behavioural problems. CONCLUSIONS: There was no evidence to support an association between a 'junk food' diet at 81 months of age and behavioural problems after 16 months.

'Junk food' diet and childhood behavioural problems: results from the ALSPAC cohort.

BACKGROUND/OBJECTIVES: To determine whether a 'junk food' diet at age 4(1/2) is associated with behavioural problems at age 7. SUBJECTS/METHODS: Data on approximately 4000 children participating in the Avon Longitudinal Study of Parents and Children, a birth cohort recruited in Avon, UK in 1991/92 were used. Behavioural problems were measured at age 7 using the Strengths and Difficulties Questionnaire (SDQ; maternal completion). Total difficulties and scores for the five sub-scales (hyperactivity, conduct and peer problems, emotional symptoms and pro-social behaviour) were calculated. Principal components analysis of dietary data (frequency of consumption of 57 foods/drinks) collected at age 4(1/2) by maternal report was used to generate a 'junk food' factor. Data on confounders were available from questionnaires. RESULTS: A one standard deviation increase in 'junk food' intake at age 4(1/2) years was associated with increased hyperactivity at age 7 (odds ratio: 1.19; 95% confidence interval: 1.10, 1.29). This persisted after adjustment for confounders including intelligence quotient score (odds ratio: 1.13; 95% confidence interval: 1.01, 1.15). There was little evidence to support an association between 'junk food' intake and overall behavioural difficulties or other sub-scales of the SDQ. CONCLUSIONS: Children eating a diet high in 'junk food' in early childhood were more likely to be in the top 33% on the SDQ hyperactivity sub-scale at age 7. This may reflect a long-term nutritional imbalance, or differences in parenting style. This finding requires replication before it can provide an avenue for intervention.

Alcohol consumption as a risk factor for non-recovery from common mental disorder: results from the longitudinal follow-up of the National Psychiatric Morbidity Survey.

BACKGROUND: Alcohol is commonly considered to be associated with persistence of common mental disorder (CMD; anxiety/depression). However no community-based longitudinal studies have investigated the direction of causality. METHOD: We examined the association between alcohol consumption and recovery from CMD using data on 706 community-based subjects with CMD who were followed for 18 months. Alcohol consumption at baseline was defined as hazardous drinking [Alcohol Use Disorders Identification Test (AUDIT) 8], binge drinking (defined as six or more units of alcohol on one occasion, approximately two to three pints of commercially sold beer) and dependence. RESULTS: When compared with a non-binge-drinking group, non-recovery at follow-up was associated with binge drinking on at least a monthly basis at baseline, although the confidence interval (CI) included unity [adjusted odds ratio (OR) 1.47, 95% CI 0.89-2.45]. There was also weak evidence that alcohol dependence was associated with non-recovery (adjusted OR 1.37, 95% CI 0.67-2.81). There was little evidence to support hazardous drinking as a risk factor for non-recovery (adjusted OR 1.12, 95% CI 0.67-1.88). CONCLUSIONS: Binge drinking may be a potential risk factor for non-recovery from CMD, although the possibility of no effect cannot be excluded. Larger studies are required to refute or confirm this finding.

GPs' experiences of primary care mental health research: a qualitative study of the barriers to recruitment.

OBJECTIVE: To investigate the perceived barriers among GPs towards introducing participation in randomized controlled trials (RCTs) to patients presenting with depression during consultations. METHODS: Qualitative study using semi-structured interviews. Interviews were recorded using a digital voice recorder, transcribed verbatim and analysed using the Framework Approach. The participants were 41 GPs from five primary care trusts in the South West who were collaborating with the University of Bristol on an RCT recruiting patients with depression. RESULTS: Three themes were identified: (i) concern about protecting the vulnerable patient and the impact on the doctor-patient relationship; (ii) the perceived lack of skill and confidence of GPs to introduce a request for research participation within a potentially sensitive consultation; and (iii) the priority given to clinical and administrative issues over research participation. These themes were underpinned by GPs' observations that consultations with people about depression differed in content, style and perceived difficulty compared to other types of consultations. CONCLUSION: Depressed patients were often viewed as vulnerable and in need of protection and it was seen as difficult and intrusive to introduce research. Patients were not always given the choice to participate in research in the same way that they are encouraged to participate in treatment decision making. A lack of skills in introducing research could be addressed with training through the new Primary Care Research Network. A more radical change in clinician attitudes and policy may be needed in order to give research a higher priority within primary care.

Anticoagulation via anti-Factor Xa inhibition.

Hospital-acquired deep vein thrombosis (DVT) affects 10-25% of medical patients and up to 60% of surgical patients. While thromboprophylaxis is without a doubt under utilized in the hospital setting, there is also a need for more efficacious agents. Fondaparinux, the first of a new class of agents Factor Xa inhibitiors, has recently come into clinical use. It is a synthetic pentasaccharide and indirect Factor Xa inhibitor with a predictable antithrombotic action. Being a synthetic product, there are no concerns about supply, nor viral or prion protein contamination. Initial large international trials in orthopaedic patients demonstrated its superior efficacy to standard thromboprophylaxis. Further trials confirmed its superior efficacy in venous thromboembolism (VTE) prevention, both in medical and surgical patient groups, as well as treatment of pulmonary embolism and DVT. Its use has also recently been evaluated in acute coronary syndromes and angioplasty. Fondaparinux currently has licenses in the UK for thromboprophylaxis and treatment of VTE and a license for the management of acute coronary syndrome is likely to be forthcoming. It has a favourable side effect profile and if the price is acceptable, is likely to take over from low molecular weight heparins in these indications as the drug of choice on the grounds of efficacy and safety.

The impact of rheumatoid arthritis on employment status in the early years of disease: a UK community-based study.

OBJECTIVE: To establish the prevalence of work disability and predictors of change in employment status in patients with early rheumatoid arthritis (RA). SETTING: The Norfolk Arthritis Register (NOAR), a primary-care based inception cohort of patients with recent-onset inflammatory arthritis. METHODS: Two cohorts of patients notified to NOAR, who satisfied the 1987 ACR criteria for RA at the time of notification (baseline) and who were economically active at the time of RA symptom onset, were identified. Cohort 1 consisted of 160 patients with an onset of RA between 1989 and 1992, and was followed for a mean of 8.6 yr from symptom onset. For 110 of these cases, a control group, matched for age, gender and employment status at baseline, was identified from the local population. Their employment histories were compared in 1995. Cohort 2 consisted of 134 patients with an onset of RA between 1994 and 1997, and was followed for a mean of 4.1 yr from symptom onset. RESULTS: One-third of RA cohort 1 had stopped working on the grounds of ill health by 1995. The baseline health assessment questionnaire (HAQ) score was the most important predictor of work disability. These patients were 32 times more likely to stop work on health grounds than the matched controls. The rates for work disability for the RA cases 1, 2, 5 and 10 yr after symptom onset were 14, 26, 33 and 39% respectively. For cohort 2, the rates for work disability 1 and 2 yr from onset were 23 and 33% respectively. CONCLUSION: Work disability is an important outcome in RA patients of working age. Many people stop working very early in the disease process, often before they are referred to hospital or started on disease-modifying anti-rheumatic drugs. Although the peak rates for work disability are in the early years, people with RA continue to leave the work force several years after onset. Thus, the recent move to earlier, more aggressive treatment has had no effect on the rates of work disability.

Disability in patients with early inflammatory polyarthritis cannot be "tracked" from year to year: an examination of the hypothesis underlying percentile reference charts.

OBJECTIVE: To determine whether disability in patients with early inflammatory polyarthritis (IP) can be charted or "tracked" over time. The disability score was also adjusted in an attempt to exclude the influence of current disease activity, with the aim of ascertaining that component of disability relating to other factors such as psychosocial factors and joint damage. METHODS: Four hundred thirty-three patients with early IP referred to the Norfolk Arthritis Register (NOAR) were followed annually using the Health Assessment Questionnaire (HAQ) for 5 years. HAQ scores at each year were divided into quartiles. The number of patients remaining in the same quartile from year to year was examined. The relationship between disease activity, assessed by swollen and tender joint counts, and HAQ was modelled, with the residual HAQ attributed to psychosocial factors and joint damage. RESULTS: From year to year, there was considerable within-individual variation in quartile, with only 48-65% of patients remaining in the same quartile. With increasing time, a greater proportion of patients remained in the same quartile. A statistically valid activity-adjusted HAQ score could not be computed. CONCLUSION: Disability in patients with early IP cannot be easily tracked over time. It is therefore not appropriate to construct longitudinal reference charts for disability in the early years, although it may be feasible for more established disease.

The NOAR Damaged Joint Count (NOAR-DJC): a clinical measure for assessing articular damage in patients with early inflammatory polyarthritis including rheumatoid arthritis.

OBJECTIVES: To evaluate the reliability and validity of the Norfolk Arthritis Register Damaged Joint Count (NOAR-DJC) in patients with early inflammatory polyarthritis (IP). METHODS: The NOAR-DJC examines deformity in 51 joints. Deformity is defined as inability to adopt the anatomical position, reduction in range of movement by at least one-third, and/or surgical alteration of the joint. Reliability was investigated by assessing intra- and inter-observer agreement in 40 and 32 patients, respectively. Validity was assessed by correlating the NOAR-DJC with the eroded joint count (criterion validity), the Health Assessment Questionnaire (HAQ) (convergent construct validity) and tender and swollen joint counts (divergent construct validity) and by discriminating between those who did and did not satisfy criteria for rheumatoid arthritis (discriminant validity). RESULTS: The intraclass correlation coefficient for the intra- and inter-rater studies were 0.88 [95% confidence interval (CI) 0.79, 0.94, P<0.00001] and 0.74 (95% CI 0.53, 0.86, P<0.00001), respectively. Correlations with eroded joint counts and HAQ scores after 5 yr follow-up were r(s) = 0.42 (95% CI 0.35, 0.49, P<0.01) and r(s) = 0.45 (95% CI 0.4, 0.5, P<0.01), respectively. Correlations with tender and swollen joint counts were weak (r(s) = 0.28 and r(s) = 0.33). CONCLUSION: The NOAR-DJC is a quick, reliable and valid tool for assessing articular damage in patients with early IP.

One year followup variables predict disability 5 years after presentation with inflammatory polyarthritis with greater accuracy than at baseline.

OBJECTIVE: To compare the accuracy of simple demographic and clinical variables recorded at baseline with those recorded after one year followup, in predicting self-reported functional disability recorded 5 years after initial assessment in patients with early inflammatory polyarthritis (IP). METHODS: We followed annually for 5 years 528 patients registered by the Norfolk Arthritis Register (a primary care based cohort of patients with early IP) using the Health Assessment Questionnaire (HAQ). Backward stepwise logistic regression was used to determine the clinical and demographic variables, collected at either baseline or first followup, that were associated with disability (HAQ > or = 1.00/> or =1.50) at 5 years. RESULTS: At the 5th anniversary assessment, the prevalence of moderate disability (HAQ > or = 1.00) was 47%. Twenty-nine percent reported more severe disability (HAQ > or = 1.50). Variables recorded at first anniversary assessment were better able to predict patients at risk of developing a poor outcome than baseline variables. Multivariate methods identified age at symptom onset, HAQ score, presence of nodules, and a statistically derived factor describing joint tenderness recorded at first year as important predictors of both moderate disability (HAQ > or =1.00) and a higher level of disability (HAQ > or = 1.50). When tested in an independent validation sample, the accuracy of the models generated from data recorded at the first year was 76% (HAQ > or = 1.00) and 83% (HAQ > or = 1.50). CONCLUSION: It was possible to predict disability at 5 years with high accuracy using simple clinical variables and demographic data collected 4 or 5 years previously. First year HAQ score was the strongest predictor of future disability. HAQ score at 5 years could be predicted more accurately using data collected at first anniversary visit than using data recorded at baseline.