WITHDRAWN: Selective serotonin reuptake inhibitors (SSRIs) versus other antidepressants for depression.

BACKGROUND: The relatively new class of antidepressant, the selective serotonin reputake inhibitors (SSRIs), may be better tolerated than the older tricyclic antidepressants. This review compares the efficacy of SSRIs with other antidepressants. OBJECTIVES: To examine the relative efficacy of selective serotonin reuptake inhibitors (SSRIs) compared to other antidepressants. SEARCH STRATEGY: The search strategy included a search of (a) Electronic bibliographic databases (MEDLINE, EMBASE); (b) reference lists of related reviews (c) reference lists of all located studies (d) contact with the manufacturer and (e) the Cochrane Group register of controlled trials SELECTION CRITERIA: Randomised controlled trials comparing selective serotonin reuptake inhibitors with other kinds of antidepressants in the treatment of patients with depressive disorders. The outcome measures assessed included measures of the severity of depression. DATA COLLECTION AND ANALYSIS: Data were collected from each study the main outcome measurefrom each study. These included: mean Hamilton depression rating scale, mean Montgomery & Asberg depression rating scale, Clinical Global Impression rating scale. An analysis of standardised mean difference of these scales was performed using Review Manager 3.1 software. The presence of heterogeneity of treatment effect was assessed MAIN RESULTS: Ninety-eight trials contributed data to the analysis of the relative efficacy of SSRIs and related drugs with comparator antidepressants (Figure 3 & Appendix 3). Analysis of efficacy was based upon 5044 patients treated with an SSRI or related drug, and 4510 treated with an alternative antidepressant. The standardised effect size for SSRIs and related drugs together versus alternative antidepressants using a fixed effects model was 0.035 (95% CI -0.006 to 0.076; Q = 149.25, df = 97, p < 0.001). AUTHORS' CONCLUSIONS: There are no clinically significant differences in effectiveness between selective serotonin reuptake inhibitors and tricyclic antidepressants. Treatment decisions need to be based on considerations of relative patient acceptability, toxicity and cost.

WITHDRAWN: Treatment discontinuation with selective serotonin reuptake inhibitors (SSRIs) versus tricyclic antidepressants (TCAs).

BACKGROUND: Selective serotonin reuptake inhibitors are thought to have better discontinuation rates (i.e. less people dropping out) than tricyclic and heterocyclic antidepressant drugs. It is important to quantify the drop-out rates of different antidepressant drugs in order to have a better understanding of the relative tolerability of these drugs. OBJECTIVES: To assess the comparative tolerability of selective serotonin reuptake inhibitors and tricyclic/heterocyclic antidepressant drugs. SEARCH STRATEGY: We searched the Cochrane Collaboration Depression, Anxiety and Neurosis Controlled Trials Registers (1997 to 1999), MEDLINE (1966 to 1999), EMBASE (1974 to 1999) We also searched specialist journals, the reference lists of relevant papers and previous systematic reviews, conference abstracts and government documents. Representatives of the pharmaceutical industry were contacted. SELECTION CRITERIA: Parallel group randomised controlled trials comparing selective serotonin reuptake inhibitors with tricyclic or heterocyclic antidepressants in people with depression. DATA COLLECTION AND ANALYSIS: Two reviewers independently extracted data and a third reviewer checked any cases of disagreement. MAIN RESULTS: We included 136 trials. The selective serotonin reuptake inhibitors showed less participants dropping out compared to the tricyclic/heterocyclic group (odds ratio 1.21, 95% confidence interval 1.12 to 1.30). A statistically significant difference was found in total drop-outs between the selective serotonin reuptake inhibitors and the old tricyclics as well as the newer tricyclics. When the selective serotonin reuptake inhibitors were compared to the heterocyclic antidepressants, there was a non significant difference favouring the selective serotonin reuptake inhibitors. The poor tolerability profile of the old tricyclics was explained by differences in drop-outs for side-effects, but not for inefficacy. AUTHORS' CONCLUSIONS: Whilst selective serotonin reuptake inhibitors do appear to show an advantage over tricyclic drugs in terms of total drop-outs, this advantage is relatively modest. This has implications for pharmaco-economic models, some of which may have overestimated the difference of drop-out rates between selective serotonin reuptake inhibitors and tricyclic antidepressants. These results are based on short-term randomised controlled trials, and may not generalise into clinical practice.

What do we know about how to do audit and feedback? Pitfalls in applying evidence from a systematic review.

BACKGROUND: Improving the quality of health care requires a range of evidence-based activities. Audit and feedback is commonly used as a quality improvement tool in the UK National Health Service [NHS]. We set out to assess whether current guidance and systematic review evidence can sufficiently inform practical decisions about how to use audit and feedback to improve quality of care. METHODS: We selected an important chronic disease encountered in primary care: diabetes mellitus. We identified recommendations from National Institute for Clinical Excellence (NICE) guidance on conducting audit and generated questions which would be relevant to any attempt to operationalise audit and feedback in a healthcare service setting. We explored the extent to which a systematic review of audit and feedback could provide practical guidance about whether audit and feedback should be used to improve quality of diabetes care and, if so, how audit and feedback could be optimised. RESULTS: National guidance suggests the importance of securing the right organisational conditions and processes. Review evidence suggests that audit and feedback can be effective in changing healthcare professional practice. However, the available evidence says relatively little about the detail of how to use audit and feedback most efficiently. CONCLUSION: Audit and feedback will continue to be an unreliable approach to quality improvement until we learn how and when it works best. Conceptualising audit and feedback within a theoretical framework offers a way forward.

Effectiveness and efficiency of guideline dissemination and implementation strategies.

OBJECTIVES: To undertake a systematic review of the effectiveness and costs of different guideline development, dissemination and implementation strategies. To estimate the resource implications of these strategies. To develop a framework for deciding when it is efficient to develop and introduce clinical guidelines. DATA SOURCES: MEDLINE, Healthstar, Cochrane Controlled Trial Register, EMBASE, SIGLE and the specialised register of the Cochrane Effective Practice and Organisation of Care (EPOC) group. REVIEW METHODS: Single estimates of dichotomous process variables were derived for each study comparison based upon the primary end-point or the median measure across several reported end-points. Separate analyses were undertaken for comparisons of different types of intervention. The study also explored whether the effects of multifaceted interventions increased with the number of intervention components. Studies reporting economic data were also critically appraised. A survey to estimate the feasibility and likely resource requirements of guideline dissemination and implementation strategies in UK settings was carried out with key informants from primary and secondary care. RESULTS: In total, 235 studies reporting 309 comparisons met the inclusion criteria; of these 73% of comparisons evaluated multifaceted interventions, although the maximum number of replications of a specific multifaceted intervention was 11 comparisons. Overall, the majority of comparisons reporting dichotomous process data observed improvements in care; however, there was considerable variation in the observed effects both within and across interventions. Commonly evaluated single interventions were reminders, dissemination of educational materials, and audit and feedback. There were 23 comparisons of multifaceted interventions involving educational outreach. The majority of interventions observed modest to moderate improvements in care. No relationship was found between the number of component interventions and the effects of multifaceted interventions. Only 29.4% of comparisons reported any economic data. The majority of studies only reported costs of treatment; only 25 studies reported data on the costs of guideline development or guideline dissemination and implementation. The majority of studies used process measures for their primary end-point, despite the fact that only three guidelines were explicitly evidence based (and may not have been efficient). Respondents to the key informant survey rarely identified existing budgets to support guideline dissemination and implementation strategies. In general, the respondents thought that only dissemination of educational materials and short (lunchtime) educational meetings were generally feasible within current resources. CONCLUSIONS: There is an imperfect evidence base to support decisions about which guideline dissemination and implementation strategies are likely to be efficient under different circumstances. Decision makers need to use considerable judgement about how best to use the limited resources they have for clinical governance and related activities to maximise population benefits. They need to consider the potential clinical areas for clinical effectiveness activities, the likely benefits and costs required to introduce guidelines and the likely benefits and costs as a result of any changes in provider behaviour. Further research is required to: develop and validate a coherent theoretical framework of health professional and organisational behaviour and behaviour change to inform better the choice of interventions in research and service settings, and to estimate the efficiency of dissemination and implementation strategies in the presence of different barriers and effect modifiers.

Developing outcome measures for ambulatory care--an application to asthma and diabetes.

Increasing emphasis is now being placed on the assessment of patient outcomes, both in evaluating medical interventions and in quality assurance initiatives. Clinicians, purchasers, managers and researchers need outcome measures that are valid, reliable and responsive. This paper describes the theory and practice underlying the development of outcome measures for two chronic conditions, asthma and diabetes, for application in ambulatory settings. Existing generic and condition-specific health status and health-related quality-of-life measures were administered to almost 1300 patients. The psychometric properties of these measures were examined to identify those that were of adequate validity and reliability in these population groups. Step-wise regression procedures were then used to identify a core set of scales that best predicted patients' general health perceptions, which could be used in measuring general health outcomes for each of these groups. These core sets consist of up to 40 items, spanning physical function, energy and vitality, emotional well-being and condition-specific aspects of health such as symptom control. Further analysis is being carried out to assess the responsiveness to change of these core item sets.

Factors influencing sleeping metabolic rate in infants.

Seven West African infants were studied prospectively from birth to 1 year to investigate factors affecting sleeping metabolic rate (SMR), particularly acute infection. There was no rise in SMR associated with acute infection, after adjustment for the effects of changes in body weight and body temperature. In the case of two illnesses, malaria and 'fever', there were falls in adjusted SMR. It is suggested that these falls can be accounted for by the effects of altered energy intake. Other effects on SMR were in close agreement with previous work.

Influences on prescribing in non-fundholding general practices.

BACKGROUND: The experience from general practice fundholding suggests that financial incentives may influence prescribing; guidelines and hospital prescribing are two other suggested influences. AIM: A study was undertaken to establish general practitioners' attitudes to a financial prescribing incentive scheme, the presence and use of guidelines, and the influence of prescribing initiated within secondary care. METHOD: A postal questionnaire survey of non-fundholding general practices in the former Northern Region was conducted. RESULTS: Practices' thinking and subsequent decisions about the incentive prescribing scheme were most often influenced by discussions within the practice (45%). Those practices that achieved their savings under the incentive scheme were less likely than those not achieving savings to feel that the target was not achievable, the time scale was unacceptable, and that the philosophy behind the scheme was unacceptable. Forty-five per cent of practices received advice from neither a medical nor a pharmaceutical adviser; 27% of practices received advice from both, 12% from a medical adviser only and 16% from a pharmaceutical adviser only. Of the practices that tried to make their target savings, 91% intended to increase generic prescribing; fewer than one-third of practices mentioned any other measure. Prescribing guidelines were reported by a minority of practices, although reported rates of use were high when these were present. Clinical guidelines for three conditions, asthma, diabetes and hypertension, were present in more than 50% of practices; 25% of practices had no clinical guidelines. Hospital prescribing was reported as 'always' or 'usually' influencing prescribing for diabetes by 57% of respondents, ischaemic heart disease by 55%, peptic ulceration by 49%, asthma by 42% and hypertension by 39%. CONCLUSIONS: General practitioner prescribing is influenced by a complex web of factors, with no single factor pre-eminent. To understand this area further, there is a need to take each of these areas and ascertain the match between doctors' perceptions and actual practice.

SSRIs versus other antidepressants for depressive disorder.

OBJECTIVES: To examine the relative efficacy of selective serotonin reuptake inhibitors (SSRIs) compared to other antidepressants. SEARCH STRATEGY: The search strategy included a search of (a) Electronic bibliographic databases (MEDLINE, EMBASE); (b) reference lists of related reviews (c) reference lists of all located studies (d) contact with the manufacturer and (e) the Cochrane Group register of controlled trials SELECTION CRITERIA: Randomised controlled trials comparing selective serotonin reuptake inhibitors with other kinds of antidepressants in the treatment of patients with depressive disorders. The outcome measures assessed included measures of the severity of depression. DATA COLLECTION AND ANALYSIS: Data were collected from each study the main outcome measurefrom each study. These included: mean Hamilton depression rating scale, mean Montgomery & Asberg depression rating scale, Clinical Global Impression rating scale. An analysis of standardised mean difference of these scales was performed using Review Manager 3. 1 software. The presence of heterogeneity of treatment effect was assessed MAIN RESULTS: Ninety-eight trials contributed data to the analysis of the relative efficacy of SSRIs and related drugs with comparator antidepressants (Figure 3 & Appendix 3). Analysis of efficacy was based upon 5044 patients treated with an SSRI or related drug, and 4510 treated with an alternative antidepressant. The standardised effect size for SSRIs and related drugs together versus alternative antidepressants using a fixed effects model was 0. 035 (95% CI -0.006 to 0.076; Q = 149.25, df = 97, p < 0.001). REVIEWER'S CONCLUSIONS: There are no clinically significant differences in effectiveness between selective serotonin reuptake inhibitors and tricyclic antidepressants. Treatment decisions need to be based on considerations of relative patient acceptability, toxicity and cost.

Selective serotonin reuptake inhibitors versus tricyclic and heterocyclic antidepressants: comparison of drug adherence.

BACKGROUND: Selective serotonin reuptake inhibitors are thought to have better discontinuation rates (i.e. less people dropping out) than tricyclic and heterocyclic antidepressant drugs. It is important to quantify the drop-out rates of different antidepressant drugs in order to have a better understanding of the relative tolerability of these drugs. OBJECTIVES: To assess the comparative tolerability of selective serotonin reuptake inhibitors and tricyclic/heterocyclic antidepressant drugs. SEARCH STRATEGY: We searched the Cochrane Collaboration Depression, Anxiety and Neurosis Controlled Trials Registers (1997 to 1999), MEDLINE (1966 to 1999), EMBASE (1974 to 1999) We also searched specialist journals, the reference lists of relevant papers and previous systematic reviews, conference abstracts and government documents. Representatives of the pharmaceutical industry were contacted. SELECTION CRITERIA: Parallel group randomised controlled trials comparing selective serotonin reuptake inhibitors with tricyclic or heterocyclic antidepressants in people with depression. DATA COLLECTION AND ANALYSIS: Two reviewers independently extracted data and a third reviewer checked any cases of disagreement. MAIN RESULTS: We included 136 trials. The selective serotonin reuptake inhibitors showed less participants dropping out compared to the tricyclic/heterocyclic group (odds ratio 1.21, 95% confidence interval 1.12 to 1.30). A statistically significant difference was found in total drop-outs between the selective serotonin reuptake inhibitors and the old tricyclics as well as the newer tricyclics. When the selective serotonin reuptake inhibitors were compared to the heterocyclic antidepressants, there was a non significant difference favouring the selective serotonin reuptake inhibitors. The poor tolerability profile of the old tricyclics was explained by differences in drop-outs for side-effects, but not for inefficacy. REVIEWER'S CONCLUSIONS: Whilst selective serotonin reuptake inhibitors do appear to show an advantage over tricyclic drugs in terms of total drop-outs, this advantage is relatively modest. This has implications for pharmaco-economic models, some of which may have overestimated the difference of drop-out rates between selective serotonin reuptake inhibitors and tricyclic antdepressants. These results are based on short-term randomised controlled trials, and may not generalise into clinical practice.

A natural survey of audit activity across the primary-secondary care interface.

OBJECTIVE: To document the nature of audit activity at the primary-secondary care interface; to explore participants' experiences of undertaking such interface audit; to identify factors associated with these experiences; and to gather views on future interface audit activities. DESIGN: A three phase national survey by postal questionnaire with a cascade sampling approach. SETTING: England and Wales. RESULTS: Response rates were: 65% to the first questionnaire; 34% to the second questionnaire; and 45% to the third questionnaire. 56% of the audits covered some element of management of patients or disease; only 33% of the audits were within a single topic area. Most audits had more than one trigger: for 61% the trigger was a perceived problem; for 58% it was of mutual interest. Only 18% of audits were initiated collaboratively; doctors were the most frequent initiators (72%), and most audits (63%) involved collaborative groups convened specifically for the audit. 58% of groups had between three and eight members, 23% had 12 or more. Doctors were the most frequent group members. There was differential involvement of group members in various group tasks; the setting of guidelines was highly dominated by doctors. Of reportedly complete audits, only two fifths had implemented change and only a quarter had evaluated this change. There was widespread feeling of successful group work, with evidence of benefit in terms of the two sectors of care being able to consider issues of mutual concern. Levels of understanding of the group task and of participation were positively related to the duration of meetings. Joint initiation of audits facilitated greater understanding of the group task. Larger group sizes allowed primary and secondary carers to discuss issues of common concern; however, larger groups were more likely to experience disagreements. Having previously worked with group members increased trust and good working relations. The main lessons learnt from the experience included the importance of setting clear objectives and good communications between primary and secondary carers. Factors identified as important for future audit activity at the primary-secondary care interface included commitment, enthusiasm, time, and money. CONCLUSIONS: Audit at the primary-secondary care interface is taking place on a wide scale and has been an enjoyable experience for most of the respondents in this study. IMPLICATIONS: Despite being a positive experience most audits stopped short of implementing change. Care must be taken to complete the audit cycle if audit at the primary-secondary care interface is to move beyond the roles of education and professional development and to fulfil its potential in improving the quality of care.

Development of a symptom based outcome measure for asthma.

Measuring symptom specific health outcome is complex, but the methodologies now exist to develop measures with the appropriate properties. As one element of a major programme to develop multidomain health outcome measures for chronic disease, a symptom based measure for asthma care has been developed for use in general practice and outpatient departments. This article outlines the development process, which used a framework recently described in the theoretical literature to show the constraints that scientific criteria place on the development of outcome measures and the means of overcoming such limiting factors. Although substantial effort is required to undertake a rigorous process of development, useful tools are the result. Two five item, symptom based outcome measures for adult asthma are described.

Impact of CONSORT extension for cluster randomised trials on quality of reporting and study methodology: review of random sample of 300 trials, 2000-8.

OBJECTIVE: To assess the impact of the 2004 extension of the CONSORT guidelines on the reporting and methodological quality of cluster randomised trials. DESIGN: Methodological review of 300 randomly sampled cluster randomised trials. Two reviewers independently abstracted 14 criteria related to quality of reporting and four methodological criteria specific to cluster randomised trials. We compared manuscripts published before CONSORT (2000-4) with those published after CONSORT (2005-8). We also investigated differences by journal impact factor, type of journal, and trial setting. DATA SOURCES: A validated Medline search strategy. Eligibility criteria for selecting studies Cluster randomised trials published in English language journals, 2000-8. RESULTS: There were significant improvements in five of 14 reporting criteria: identification as cluster randomised; justification for cluster randomisation; reporting whether outcome assessments were blind; reporting the number of clusters randomised; and reporting the number of clusters lost to follow-up. No significant improvements were found in adherence to methodological criteria. Trials conducted in clinical rather than non-clinical settings and studies published in medical journals with higher impact factor or general medical journals were more likely to adhere to recommended reporting and methodological criteria overall, but there was no evidence that improvements after publication of the CONSORT extension for cluster trials were more likely in trials conducted in clinical settings nor in trials published in either general medical journals or in higher impact factor journals. CONCLUSION: The quality of reporting of cluster randomised trials improved in only a few aspects since the publication of the extension of CONSORT for cluster randomised trials, and no improvements at all were observed in essential methodological features. Overall, the adherence to reporting and methodological guidelines for cluster randomised trials remains suboptimal, and further efforts are needed to improve both reporting and methodology.

Qualitative methods in a randomised controlled trial: the role of an integrated qualitative process evaluation in providing evidence to discontinue the intervention in one arm of a trial of a decision support tool.

OBJECTIVE: To understand participants' experiences and understandings of the interventions in the trial of a computerised decision support tool in patients with atrial fibrillation being considered for anti-coagulation treatment. DESIGN: Qualitative process evaluation carried out alongside the trial: non-participant observation and semistructured interviews. PARTICIPANTS: 30 participants aged >60 years taking part in the trial of a computerised decision support tool. RESULTS: Qualitative evidence provided the rationale to undertake a decision to discontinue one arm of the trial on the basis that the intervention in that arm, a standard gamble values elicitation exercise was causing confusion and was unlikely to produce valid data on participant values. CONCLUSIONS: Qualitative methods used alongside a trial allow an understanding of the process and progress of a trial, and provide evidence to intervene in the trial if necessary, including evidence for the rationale to discontinue an intervention arm of the trial.

Can general practitioners assess diabetic control? Can anybody do any better?

A prospective study assessing the ability of various health professionals to estimate the control of diabetic patients from the accepted measures made for diabetes care was carried out. Patients were stratified into four categories according to the estimated HbA1c, and 45-60% were accurately assigned by the professionals. Patients were also divided into two broader groups according to their need to have changes in treatment made. None of the professionals could assign patients with Type 1 diabetes into these two groups with an accuracy of greater than 71%. With Type 2 diabetic patients accuracy improved up to 98% and there was little difference between the professionals. The current HbA1c was accurately predicted into two broad groups by the previous HbA1c alone in 89% of cases of Type 2 diabetes. These findings have implications for the routine care of diabetic patients and the education of health care professionals.

Can we understand partnerships in general practice? A pilot study.

BACKGROUND: Partnerships have been investigated in different professions, but other than identifying problems, little work has been carried out on general practice. OBJECTIVE: The aim of this present study was to develop methods for studying partnerships in general practice. METHOD: A tripartite methodological approach was used, with questionnaires adapted from other instruments in use in other professions, followed by an individual interview with each partner, and non-participant observation at a partnership meeting. Results for one case-study partnership are given. RESULTS: There were no major differences between the partners on all dimensions measured; the minor differences indicated by the results of the questionnaires were corroborated by the partner interviews and observations. CONCLUSIONS: We conclude that the use of such techniques could provide support to partnerships going through significant periods of change.

Identification of factors affecting infant growth in developing countries.

The anthropometric progress of seven infants was followed throughout their first year of life. Weight, length, mid upper arm circumference, triceps and subscapular skinfold thicknesses were measured on a mean (SD) of 30 (6) occasions with weight alone being measured on a further 6 (2) occasions. The effects of infection and energy intake were identified and illustrated using both standard deviation (SD) score graphs for individual subjects, and more traditionally, regression analysis for the group. Diarrhoea and vomiting, pneumonia, and diarrhoea alone each resulted in significant reductions in growth velocity of 30 g/day. Multimeasurement SD score graphs showed the effects of all illnesses, and permitted simultaneous comparison of anthropometric measurements.

Management of older patients with hypertension in primary care: improvement on the rule of halves.

OBJECTIVES: the benefits of treatment of hypertension in older people are well-established but implementation of this knowledge may be sub-optimal. We have determined recent primary care management of older people with hypertension. METHODS: we examined health records (n = 6986) of a 1 in 7 sample of patients aged 65-80 years from a random sample of practices (n = 51) in the former Northern Region of the UK, stratified by health authority, for the previous 6 years. We recorded documented risk factors, diagnosis of hypertension, three most recent blood pressure readings, current drug therapy and previous blood pressure lowering therapy, and presence of coexistent pathology. RESULTS: blood pressure was defined as hypertensive (> or = 160/> or = 90 mmHg; one or both values above these limits), normotensive or undetermined using a validated algorithm. In 30% of patients, blood pressure status was undetermined. Thirty-five percent of subjects were found to be hypertensive. Of these, 70% were receiving antihypertensive treatment but only 30% of treated patients had controlled (< 150 and 90 mmHg) and 13% well controlled (< 140 and 85 mmHg) blood pressure. In all, 14% of older hypertensive patients were detected, treated and had their hypertension controlled. There were significant differences between practices in the proportion of hypertensive patients treated (P < 0.001) and in the proportion of hypertensive patients whose blood pressure was controlled (P < 0.01). CONCLUSIONS: treatment of hypertension in older people in primary care has improved in terms of detection and treatment but in only one-third of patients is high blood pressure controlled. There remain important opportunities for prevention of stroke and myocardial infarction in this age group through achieving improved blood pressure control.

Work-load and outcomes of diabetes care in general practice.

The effect of starting a general practice diabetes clinic on practice work-load and intermediate outcome measures was studied retrospectively using patient records. The 35 diabetic patients included had been diagnosed greater than 4 years before the diabetes clinic started and were followed for 6 years in the clinic, together with a group of age- and sex-matched controls. There was a significant rise in the consultation rates of the diabetic patients, due to an increase in diabetes-related consultations, from 3.9 consultations yr-1 to 6.7 consultations yr-1 (p less than 0.001). There was a fall in HbA1c level of 0.22 (99% CI 0.13, 0.32) %Hb yr-1 over the 6 years and in body mass index of 0.37 (99% CI 0.22, 0.52) kg m-2 yr-1, suggesting an improvement in diabetes management.