Post 2

Links are given to online full text resources, all other materials can be obtained via the Fade Library, just mail your request to library.services@fade.nhs.uk

---

Latest Technology Assessments and Appraisals

---

The causes and effects of socio-demographic exclusions from clinical trials (Bartlett) 168 pages, Volume 9, number 38

Study finds that the issue of exclusion from trials of women, older people and ethnic minorities has been relatively neglected in the UK research community and suggests the need for multi-disciplinary assessment of realistic options for trialists to address this.

---

Is hydrotherapy cost effective? A randomised controlled trial of combined hydrotherapy programmes compared with physiotherapy land techniques in children with juvenile idiopathic arthritis (Epps) 76 pages, Volume 9, number 39

This research demonstrates a beneficial effect from both combined hydrotherapy and land-based physiotherapy treatment and land-based physiotherapy treatment alone in juvenile idiopathic arthritis without any exacerbation of disease, but until further research is undertaken it is not possible to determine if the initiation and costs of building new hydrotherapy pools is justifiable or cost-effective in the long term.

---

The British Rheumatoid Outcome Study Group (BROSG) randomised controlled trial to compare the effectiveness and cost-effectiveness of aggressive versus symptomatic therapy in established rheumatoid arthritis (Symmons) 94 pages, Volume 9, number 34

This trial showed no additional benefit of aggressive treatment in patients with stable established rheumatoid arthritis (RA). Approximately one-third of current clinic attenders with stable RA could be managed in a shared care setting with an annual review by a rheumatologist and regular contact with a rheumatologist nurse.

---

Conceptual framework and systematic review of the effects of participants' and professionals' preferences in randomised controlled trials (King) 186 pages, Volume 9, number 35

This comprehensive study advances our understanding of how people's preferences affect randomised controlled trials, suggesting that the greatest impact is usually on recruitment of patients and how better information may help improve the external validation of trials.

---

The clinical effectiveness and cost-effectiveness of implantable cardioverter defibrillators: a systematic review (Bryant) 150 pages, Volume 9, number 36

---

A trial of problem-solving by community mental health nurses for anxiety, depression and life difficulties among general practice patients. The CPN_GP study (Kendrick) 104 pages, Volume 9, number 37

The study found that specialist mental health nurse support is no better than support from GPs for most patients with anxiety, depression and reactions to life difficulties, although there may be other roles in primary care that community mental health nurses could play effectively.

---

Appraisal Consultaion Document: Alendronate, etidronate, risedronate, raloxifene and strontium ranelate for the primary prevention of osteoporotic fragility fractures in postmenopausal women

---

Appraisal Consultation Document: Alendronate, etidronate, risedronate, raloxifene, strontium ranelate and teriparatide for the secondary prevention of osteoporotic fragility fractures in postmenopausal women

---

Final Appraisal Determination on etanercept and infliximab for psoriatic arthritis

After considering the feedback from consultation, the Appraisal Committee has prepared a Final Appraisal Determination (FAD) on etanercept and infliximab for psoriatic arthritis and submitted it to the Institute. The FAD makes the following recommendations:

Etanercept, within its licensed indications, is recommended for the treatment of an adult with severe active psoriatic arthritis only when the following criteria are met:

The person has peripheral arthritis with three or more tender joints and three or more swollen joints

The psoriatic arthritis has not responded to adequate trials of at least two standard DMARDs administered either individually or in combination

Etanercept treatment should be discontinued in patients whose psoriatic arthritis has not shown an adequate response when assessed using the Psoriatic Arthritis Response Criteria (PsARC) at 12 weeks.

Infliximab, within its licensed indications, is recommended for the treatment of an adult with severe active psoriatic arthritis if, under the circumstances outlined above, treatment with an anti-TNF agent is considered appropriate and the person is intolerant to etanercept.

Infliximab treatment should be discontinued in patients whose psoriatic arthritis has not responded adequately at 12 weeks.

The use of either etanercept or infliximab should be initiated and supervised by specialist physicians experienced in the diagnosis and treatment of psoriatic arthritis.

---

Latest Guidelines

---

Final Appraisal Determination on efalizumab and etanercept for psoriasis

After considering the feedback from consultation, the Appraisal Committee has prepared a Final Appraisal Determination (FAD) on efalizumab and etanercept for psoriasis and submitted it to the Institute. The FAD makes the following recommendations:

Etanercept, within its licensed indications, administered at a dose not exceeding 25mg twice weekly is recommended for the treatment of adults with plaque psoriasis only when the following criteria are met:

The disease is severe, as defined by a total Psoriasis Area Severity Index (PASI) of ten or more and a Dermatology Life Quality Index (DLQI) of more than ten

The psoriasis has failed to respond to standard systemic therapies including ciclosporin, methotrexate and PUVA; or the person is intolerant to, or has a contraindication to, these treatments

Etanercept treatment should be discontinued in patients whose psoriasis has not responded adequately at 12 weeks and further treatment cycles are not recommended in these patients

Efalizumab, within its licensed indications, is recommended for the treatment of adults with plaque psoriasis under the circumstances detailed previously, only if their psoriasis has failed to respond to etanercept or they are shown to be intolerant of, or have contraindications to, treatment with etanercept.

Further treatment with efalizumab is not recommended unless their psoriasis has responded adequately at 12 weeks

The use of etanercept and efalizumab for psoriasis should be initiated and supervised only by specialist physicians experienced in the diagnosis and treatment of psoriasis

---

Depression in children and young people: identification and management in primary, community and secondary care

NICE and the National Collaborating Centre for Mental Health have published a guideline for the NHS in England and Wales on identifying and managing depression in children and young people.

The full version of this guideline will be available shortly.

---

Guidance for the use of methadone for them treatment of opioid dependence in primary care

Opioid dependence is common in the UK and methadone is an effective treatment.

---

SIGN Draft Guidelines. Assessment, diagnosis and clinical interventions for children and young people with autism spectrum disorders.

For consultation.

---

Pressure ulcers: The management of pressure ulcers in primary and secondary care

The quick reference guide below summarises the recommendations made in:

Pressure ulcer prevention: pressure ulcer risk assessment and prevention, including the use of pressure-relieving devices (beds, mattresses and overlays) for the prevention of pressure ulcers in primary and secondary care. NICE Clinical Guideline No. 7.

The management of pressure ulcers in primary and secondary care*.

Because of the overlap between these guidelines, particularly in the areas of risk assessment and the use of pressure relieving devices, NICE’s new quick reference guide combines the major elements of all the pressure ulcer guidelines in a single algorithm to provide one clear source of information on pressure ulcer management and prevention. Accordingly, NICE’s existing guideline Pressure ulcer prevention has been withdrawn.

---

Management of atopic eczema in children from birth up to the age of 10 years

NICE has issued a draft scope for the management of atopic eczema in children from birth up to the age of 10 years. The consultation period runs from 3 - 28 October 2005.

---

Latest Reports

---

Practical lessons for dealing with inequalities in health impact assessment

This publication is a companion to Addressing inequalities through health impact assessment (Taylor et al., 2003a), which described what a focus on inequalities could achieve, offered case study examples, and outlined promising practice. This bulletin discusses recent publications and presents a further two case studies that attempt to address health inequalities through the use of HIA.

---

Incentives for reform in the NHS: An assessment of current incentives in the south-east London health economy

Following the Governments vision for the NHS, and incentives to drive change in the NHS as detailed in the NHS Plan, the King’s Fund has published a report which considers whether the current system of incentives is ‘fit for purpose’. Or, on the contrary, do they work against each other, making it harder for local organisations to meet all the targets and objectives they have been set? To answer this question the research has examined one health economy – south-east London – as a case study.

The key questions that the research in south-east London investigated were:

How do national policies impact at a local level?

How far are tensions in the current policy framework, as outlined above, perceived to be important in the field by those responsible for implementation?

what solutions are being pursued locally?

The research examined four areas.

Competition and collaboration - Can competition encouraged by the financial regime, new payment systems and foundation status and collaboration between trusts co-exist?

Managing demand for care - Do policies designed to create better access generate extra demand in the system and increase the pressure on services?

Transfer of services from hospitals to primary or community settings - Do current incentives enable PCTs to do this?

The role of the district general hospital (DGH) - Does the financial pressure on services and stronger market-style incentives challenge the sustainability of weaker organisations, especially smaller DGHs?

The project used three methods: a literature review, interviews and quantitative analysis.

The interviews were conducted with chief executives, chairs and finance directors from each trust in the South East London Strategic Health Authority.

---

Evidence from Journals

---

Review: short term psychotherapy is an effective treatment for psychiatric disorders
Pilling
Evid Based Ment Health.2005; 8: 84

---

Review: pharmacotherapy provides minimal improvements in the neuropsychiatric symptoms...
Mulsant
Evid Based Ment Health.2005; 8: 83

---

Review: hypericum extracts are safer and lead to fewer adverse effects than older...
Valerio
Evid Based Ment Health.2005; 8: 71

---

Review: cognitive behaviour therapy is beneficial in children with anxiety disorders
Manassis
Evid Based Ment Health.2005; 8: 77

---

Prophylactic mirtazapine may help to prevent post-stroke depression in people with...
Ween
Evid Based Ment Health.2005; 8: 74

---

Metyrapone is an effective adjuvant treatment for major depression
Young
Evid Based Ment Health.2005; 8: 72

---

Lithium may reduce gambling severity in pathological gamblers with bipolar disorder
Rogers and Goodwin
Evid Based Ment Health.2005; 8: 80

---

Glycine and D-serine improve the negative symptoms of schizophrenia
Stip and Trudeau
Evid Based Ment Health.2005; 8: 82

---

Cognitive behavioural therapy has short term but not long term benefits in people...
Perlis
Evid Based Ment Health.2005; 8: 75

---

Improving quality of primary care reduces depression and improves quality of life...
Kates
Evid Based Ment Health.2005; 8: 76

---

Adding a nurse-based intervention programme to usual care improves manic symptoms...
Sachs
Evid Based Ment Health.2005; 8: 81

---

Adding mixed amphetamine salts to divalproex sodium improves ADHD symptoms in children...
Wozniak
Evid Based Ment Health.2005; 8: 78

---

Review: depression may increase mortality in coronary heart disease
Maggi
Evid Based Ment Health.2005; 8: 66

---

Review: after myocardial infarction, depression and poor prognosis are associated
Lane and Carroll
Evid Based Ment Health.2005; 8: 67

---

People diagnosed with schizophrenia retain the diagnosis long term
Kessing
Evid Based Ment Health.2005; 8: 68

---

Valproate reduces alcohol consumption in people with comorbid alcohol dependency...
Le Fauve
Evid Based Ment Health.2005; 8: 79

---

Intoxicant use increased among Norwegian adolescents between 1992 and 2002, and...
Maharajh
Evid Based Ment Health.2005; 8: 88

---

The Screening Tool for Autism in Two Year Olds can identify children at risk of...
Zwaigenbaum
Evid Based Ment Health.2005; 8: 69

---

Middelheim Frontality Score may be useful for differentiating between Alzheimer’s...
Hatanpaa and Blass
Evid Based Ment Health.2005; 8: 70

---

Review: migrants are at increased risk of developing schizophrenia
Compton
Evid Based Ment Health.2005; 8: 85

---

Low intelligence increases risk of suicide
Cerel and Knox
Evid Based Ment Health.2005; 8: 86

---

Cannabis use increases the risk of young people developing psychotic symptoms, particularly...
Addington
Evid Based Ment Health.2005; 8: 87

---

Liker H., Hungin P., Wiklund I. Managing gastroesophageal reflux disease in primary care: the patient perspective. J Am Board Fam Pract. 2005 Sep-Oct;18(5):393-400

Gastroesophageal reflux disease (GERD) is a chronic disease that affects up to 20% of the population of Western countries and accounts for around 5% of a primary-care physician’s workload. A better understanding of how GERD affects many aspects of patients’ lives may aid the management of patients in primary care. We conducted a systematic review of the effect of GERD on health-related quality of life (HRQL) in the primary-care setting and in the community. Validated questionnaires have shown that GERD patients consulting in primary care experience substantial reductions in both physical and psychosocial aspects of HRQL, as well as work productivity. Impairments in HRQL are seen whether or not reflux esophagitis or Barrett’s esophagus is present on endoscopy, and are comparable with or worse than those seen in patients with other chronic diseases such as heart disease, diabetes, and cancer. Surveys in primary care and in the community highlight disrupted sleep, reduced concentration at work, and interference with physical activities such as exercise, housework, and gardening. Psychosocial aspects of patient well-being are also impaired, including enjoyment of social gatherings, intimacy, sex, and many individuals with GERD remain worried about the underlying cause of their symptoms. In conclusion, many aspects of HRQL are impaired in GERD patients. The primary-care physician is uniquely placed to assess and address the impact of GERD on patients’ lives.

---

Tylee A., Gandhi P. The importance of somatic symptoms in depression in primary care. Prim Care Companion J Clin Psychiatry. 2005;7(4):167-76

Objective: Patients with depression present with psychological and somatic symptoms, including general aches and pains. In primary care, somatic symptoms often dominate. A review of the literature was conducted to ascertain the importance of somatic symptoms in depression in primary care. Data sources and extraction: MEDLINE, EMBASE, and PsychLIT/PsychINFO databases (1985–January 2004) were searched for the terms depression, depressive, depressed AND physical, somatic, unexplained symptoms, complaints, problems; somatised, somatized symptoms; somatisation, somatization, somatoform, psychosomatic; pain; recognition, underrecognition; diagnosis, underdiagnosis; acknowledgment, underacknowledgment; treatment, undertreatment AND primary care, ambulatory care; primary physician; office; general practice; attribution, reattribution; and normalising, normalizing. Only English-language publications and abstracts were considered. Study selection: More than 80 papers related to somatic symptoms in depression were identified using the content of their titles and abstracts. Data synthesis: Approximately two thirds of patients with depression in primary care present with somatic symptoms. These patients are difficult to diagnose, feel an increased burden of disease, rely heavily on health care services, and are harder to treat. Patient and physician factors that prevent discussion of psychological symptoms during consultations must be overcome. Conclusions: Educational initiatives that raise awareness of somatic symptoms in depression and help patients to reattribute these symptoms should help to improve the recognition of depression in primary care.

---

van Hout H.P., Nijpels G., van Marwijk H.W., Jansen A.P., van 't Veer P.J., Tybout W., Stalman W.A. Design and pilot results of a single blind randomized controlled trial of systematic demand-led home visits by nurses to frail elderly persons in primary care. BMC Geriatr. 2005 Sep 8;5(1):11

Background The objective of this article is to describe the design of an evaluation of the cost-effectiveness of systematic home visits by nurses to frail elderly primary care patients. Pilot objectives were: 1. To determine the feasibility of postal multidimensional frailty screening instruments; 2. to identify the need for home visits to elderly. Methods Main study: The main study concerns a randomized controlled in primary care practices (PCP) with 18 months follow-up and blinded PCPs. Frail persons aged 75 years or older and living at home but neither terminally ill nor demented from 33 PCPs were eligible. Trained community nurses (1) visit patients at home and assess the care needs with the Resident Assessment Instrument-Home Care, a multidimensional computerized geriatric assessment instrument, enabling direct identification of problem areas; (2) determine the care priorities together with the patient; (3) design and execute interventions according to protocols; (4) and visit patients at least five times during a year in order to execute and monitor the care-plan. Controls receive usual care. Outcome measures are Quality of life, and Quality Adjusted Life Years; time to nursing home admission; mortality; hospital admissions; health care utilization. Pilot 1: Three brief postal multidimensional screening measures to identify frail health among elderly persons were tested on percentage complete item response (selected after a literature search): 1) Vulnerable Elders Screen, 2) Strawbridge's frailty screen, and 3) COOP-WONCA charts. Pilot 2: Three nurses visited elderly frail patients as identified by PCPs in a health center of 5400 patients and used an assessment protocol to identify psychosocial and medical problems. The needs and experiences of all participants were gathered by semi-structured interviews. Discussion The design holds several unique elements such as early identification of frail persons combined with case-management by nurses. From two pilots we learned that of three potential postal frailty measures, the COOP-WONCA charts were completed best by elderly and that preventive home visits by nurses were positively evaluated to have potential for quality of care improvement.

---

Warfarin was not more effective than aspirin and increased adverse events in symptomatic...
Eikelboom
Evid Based Med.2005; 10: 136

---

Screening for abdominal aortic aneurysm (AAA) reduced AAA mortality in Danish men...
Michaels
Evid Based Med.2005; 10: 142

---

Review: sparse high quality evidence supports surgery for obesity
Kennel
Evid Based Med.2005; 10: 141

---

Review: several pharmacological therapies promote modest weight loss
Kennel
Evid Based Med.2005; 10: 140

---

Review: bright light therapy and dawn simulation reduce symptom severity in seasonal...
Simon
Evid Based Med.2005; 10: 146

---

Low dose aspirin lowered stroke risk but not risks of MI or cardiovascular deaths...
Eikelboom
Evid Based Med.2005; 10: 137

---

Intensified blood pressure (BP) control was not better than conventional BP control in non-diabetic chronic renal disease
Ruggenenti P
Evidence-Based Medicine 2005; 10: 138

---

Cognitive therapy reduced relapses and number of days in bipolar episodes in DSM-IV...
Persons and Gruber
Evid Based Med.2005; 10: 145

---

Clinician advice, an interactive computer program, and motivational counselling...
Lancaster
Evid Based Med.2005; 10: 144

---

A smoking cessation programme plus inhaled ipratropium improved survival in asymptomatic...
Schorling
Evid Based Med.2005; 10: 143

---

Pharmacist led, primary care based disease management reduced risk factors and improved...
Smith and Smith
Evid Based Med.2005; 10: 154

---

Overall mortality was 2.2% in children after a first unprovoked afebrile seizure
Kirshner
Evid Based Med.2005; 10: 152

---

Gleason score predicted mortality rate to 20 years for untreated early prostate...
Barry
Evid Based Med.2005; 10: 151

---

Statistical approaches to uncertainty: p values and confidence intervals unpacked
DOLL and CARNEY
Evid Based Med.2005; 10: 133-134

In a previous Statistics Note, we defined terms such as experimental event risk (EER), control event risk (CER), absolute risk reduction (ARR), and number needed to treat (NNT).1 Estimates such as ARR and NNT alone, however, do not describe the uncertainty around the results. P values and CIs provide additional information to help us determine whether the results are both clinically and statistically significant (table 1).

---

Evidently...
LEHMAN
Evid Based Med.2005; 10: 135

---

BNP and amino terminal proBNP assays did not differ for detecting congestive heart...
Doust
Evid Based Med.2005; 10: 148

---

A decrease of 2 points on the Mini-Mental State Examination was the best determinant...
Fields
Evid Based Med.2005; 10: 149

---

Subclinical hypothyroidism increased the risk of placental abruption and poor neonatal...
Foster
Evid Based Med.2005; 10: 153

---

ED use of magnesium sulphate improved rate control in atrial fibrillation with rapid...
Lang
Evid Based Med.2005; 10: 139

---

Buccal oxycodone reduced pain more than placebo in children with acute undifferentiated...
Attia
Evid Based Med.2005; 10: 147

---

Review: B type natriuretic peptide consistently predicts death and cardiovascular...
Deswal
Evid Based Med.2005; 10: 150

---

A clinical prediction model predicted absence of significant fibrosis in chronic...
Reichen
Evid Based Med.2005; 10: 155

---

Trials

---

Phase III trial of Canvaxin for patients with stage III melanoma discontinued

According to BioSpace, a Phase III clinical trial of Canvaxin in patients with Stage III melanoma has been stopped, following the recommendation of the independent Data and Safety Monitoring Board (DSMB). The board recently completed its planned, third, interim analysis of the data from this study and concluded that the data are unlikely to provide significant evidence of an overall survival benefit for patients with Stage III melanoma treated with Canvaxin vs. placebo.

---

Hitting the Headlines - Evidence Behind the Press Stories

---

'Stem cells can help repair the liver'

Damaged livers have been repaired using bone marrow stem cells from patients' own blood reported the Daily Mail (6 October 2005)(1). The newspaper article accurately reported on a news item in New Scientist about five patients who had received the treatment. Approval for further research to refine the technique is being sought.

Damaged livers have been repaired using bone marrow stem cells extracted from the patients' own blood reported the Daily Mail on 6 October 2005(1).The treatment involved injecting the stem cells into the blood vessels leading to the liver of the patient. The stem cells then appeared to regenerate tissue in the liver.

The newspaper article was based on a study reported in the news section of the New Scientist (2). The researcher stated that three out of the five patients that received the treatment experienced significant improvements in liver function and general health within two months. The remaining two patients without health improvements experienced no ill effects as a result of the treatment.

The newspaper article accurately outlined the report in New Scientist. There were however insufficient details in the New Scientist report for an assessment of the quality of the research to be carried out. The newspaper article appropriately stated that the treatment needs to be proven to work. Approval for a follow-up trial is being sought by the researchers.

Systematic reviews

Information staff at CRD searched for systematic reviews relevant to this topic. Systematic reviews are valuable sources of evidence as they locate, appraise and synthesize all available evidence on a particular topic.

---

'Statin drugs could cut heart attacks by third'

Wider use of statins could cut heart attacks or stroke by a third, reported three newspapers (27 September 2005). The reports are based on a well conducted study which found that statin therapy could benefit people at risk of heart attack or stroke even if their cholesterol level is not high.

Three newspapers (1-3) reported that cholesterol lowering drugs called statins can reduce the risk of a heart attack or stroke by at least a third. The newspapers also reported that use of statins did not increase the risk of cancer.

The newspaper articles are based on the findings of a prospective meta-analysis which combined results from over 90,000 participants from 14 randomised controlled trials (4). The study found that statins reduced the incidence of all-cause mortality by around 12% per mmol/L cholesterol reduction. Reductions were also found for major coronary events, stroke, and for coronary revascularisation. Statin therapy was not found to increase the incidence of cancer overall, or at any particular site.

The reports are broadly accurate. However, the figure which both papers emphasise of a reduction of one-third is based on the authors' estimates of lowered LDL cholesterol of 1.5mmol/L, in a compliant setting, sustained for five years. This was a well conducted prospective meta-analysis.

---

National Library for Health - Focus On

Value is a really difficult thing to define. There are some great quotes about value, like the famous Oscar Wilde definition of a cynic as a man who knows the price of everything and the value of nothing. Across the water in the USA, HL Mencken quipped that the chief value of money lies in the fact that one lives in a world in which it is overestimated.

Neither of which is particularly useful in exploring what value means in healthcare. There is a narrow definition, that of a cost per quality adjusted life year (QALY). Informally we tend to accept in the UK that anything with a cost per QALY of £30,000 or less is good value, and if it is more than that it is poor value.

That's fine as far as it goes. The trouble is that calculating a cost per QALY is not always the easiest thing in the world. First you need a cost, and then you need a QALY. Given that in some circumstances there can be considerable uncertainty, then opportunities for disagreement are probable - they occur when cost is high and quality of life low, with uncertainty in both.

---

On Value

---

Document of the Week from the National Library for Health

---

Early clinical experience has a positive effect on medical education

The British Medical Journal reports on a systematic review on the affect of early experience in clinical and community settings on medical education, and finds that it makes the learning process easier, and benefits all involved, patients, teachers and students.

---

What's New from the National Library for Health

---

Palliative and Supportive Care Specialist Library Now Available