Can an evidence-based guideline reduce unnecessary imaging of road trauma patients with cervical spine injury in the emergency department?

The aim of this study was to determine if an unvalidated imaging guideline can reduce the use of imaging in patients with cervical spine trauma. A non-randomized clinical trial using historical controls was conducted in the emergency department from October 2001 to September 2002. Following an education programme, which introduced the imaging guideline to clinicians, the use of guideline and imaging were measured. The guideline was also converted to decision-support software for use in the emergency department. Three hundred and fifty-three patients satisfied inclusion criteria during the study period and these were compared with 403 historical control subjects. No significant difference was found between the two groups for age, sex or fracture prevalence. A significant increase was observed during the study period in the proportion of patients who were managed without the use of any cervical spine imaging (21.25 vs 31.2%; P=0.03; 95% confidence interval, 3-13). There were no delayed diagnoses of cervical spine injury among those not imaged. It is feasible to disseminate and implement an evidence-based imaging guideline for patients with cervical spine trauma. The use of a computerized decision-support system can facilitate this and is associated with a safe reduction in the proportion of patients imaged.

Barriers to success for an evidence-based guideline for chronic obstructive pulmonary disease.

OBJECTIVES: To evaluate 1) barriers to clinical guideline use and 2) the relationship between guideline use and inpatient outcomes in chronic obstructive pulmonary disease (COPD). METHODS: 1) Four focus groups of specific health professions (n = 30), from three metropolitan hospitals, and interview of 99 medical officers (MOs), linked to 349 admissions, both guided by behavioural modelling theory; 2) association between guideline use and patient outcomes (length of hospital stay > or = 14 days, and readmission within 28 or 90 days) was evaluated in a cohort of 405 COPD patients. RESULTS: 1) In focus groups, nurses and allied health professionals emphasized facilitation issues including paperwork duplication and time limitations as barriers, but considered improved patient care outcomes as the major guideline use determinant. There were similar findings in junior MOs (nonconsultants) by both focus group and interview, with the addition of a need for a sense of ownership. Senior MOs (consultants) greatly emphasized sense of ownership. Barriers to guideline use varied between types of units. Behavioural modelling explained 49% of the variation in intention to use the guideline for MOs. For nonconsultants, habit and intention were significantly associated with extent of guideline use. 2) Patient outcomes: guideline use was not associated with length of stay or readmission. CONCLUSIONS: 1) Guideline implementation should address issues relevant to different health professions, units and seniority of profession. 2) Guideline use was not associated with reductions in readmission or length of stay.

Do the findings of case series studies vary significantly according to methodological characteristics?

OBJECTIVES: To review the use of case series in National Institute for Clinical Excellence (NICE) Health Technology Assessment (HTA) reports, to review systematically the methodological literature for papers relating to the validity of aspects of case series design, and to investigate characteristics and findings of case series using examples from the UK's Health Technology Assessment programme. DATA SOURCES: Electronic databases. NICE website. Reports produced as part of the UK's HTA programme. REVIEW METHODS: NICE HTAs that used information from case series studies were obtained from the NICE website and a range of quality criteria applied. Searches of electronic databases, handsearched journals and the bibliographies of papers were made in order to find studies that assessed aspects of case series design, analysis or quality in relation to study validity. Hypotheses relating to the design of case series studies were developed and empirically investigated using four case examples from existing reports produced as part of the UK's HTA programme (functional endoscopic sinus surgery for nasal polyps, spinal cord stimulation for chronic back pain, percutaneous transluminal coronary angioplasty and coronary artery bypass grafting for chronic angina). Analysis was undertaken comparing studies within each review. RESULTS: There was no consensus on which case series to include in HTAs, how to use them or how to assess their quality, despite them being used in 30% of NICE HTAs. No previous studies empirically investigating methodological characteristics of case series were found. However, it is possible that the search strategy failed to find relevant studies. Poor reporting of case series characteristics severely constrained analysis and there were insufficient data to investigate all the hypotheses. Findings were not consistent across the different topics and were subject to considerable uncertainty. All the examples in our analysis were surgical interventions, which are prone to additional confounding factors due to difficulties of standardisation compared with drug treatment. Our findings may not be generalisable outside the interventions studied. The case series reports included generally exhibited poor reporting of methodological characteristics. This constrained our analysis. The use of several methods of analysis has led to apparently discrepant results. Given the number of analysis performed, the usual level of significance (p = 0.05) should be viewed with caution. The most important limitation of this study is the small number of cases on which the findings are based. The results are therefore tentative and should be viewed with caution. CONCLUSIONS: Case series are incorporated in a significant proportion of health technology assessments. Quality criteria have been used to appraise the quality of case series and decide on their inclusion in reviews of studies using this design. In this small series of case studies drawn from HTAs carried out for the NHS HTA programme, little evidence was found to support the use of many of the factors included in quality assessment tools. Importantly, no relationship was found between study size and outcome across the four examples studied. Isolated examples of a potentially important relationship between other methodological factors and outcome were shown, such as blinding of outcome measurement, but these were not shown consistently across the small number of examples studied. This study is based on a very small sample of studies and should therefore be considered as exploratory. Further investigation of the relationship between methodological features and outcome is justified given the frequency of use of case series in health technology assessments. Further research into the methodological features of case series and their outcome is justified in a wider sample of technologies and larger sets of case series. Value of information analyses including case series could be explored. Further exploration of the differences between case series and randomised controlled trial results, preferably using registry or comprehensive case series data, would be valuable.

Effectiveness and cost-effectiveness of imatinib for first-line treatment of chronic myeloid leukaemia in chronic phase: a systematic review and economic analysis.

OBJECTIVES: To evaluate the effectiveness of imatinib as first-line treatment for chronic myeloid leukaemia (CML) compared with interferon-alpha (IFN-alpha), hydroxyurea and bone marrow transplantation (BMT), and the cost-effectiveness of imatinib compared with IFN-alpha and hydroxyurea. DATA SOURCES: Electronic databases. REVIEW METHODS: Selected studies and full-text articles were screened and rigorously selected. Survival was the key outcome measure. Surrogate outcome measures included haematological (blood) response and cytogenetic (bone marrow) response (CR). As no published cost-effectiveness studies were found that compared imatinib and IFN-alpha, an independent Markov model was constructed and this was compared with models submitted to the National Institute for Clinical Excellence by the manufacturer of imatinib. RESULTS: Intention-to-treat analysis showed that imatinib was associated with complete CR at 12 months follow-up of 68% compared with 20% for the IFN-alpha plus Ara-C group. The estimated proportion of people taking imatinib who had not progressed to accelerated or blast phases at 12 months was 98.5%, and 93.1% for IFN-alpha plus Ara-C. Overall survival was not statistically significantly different. Withdrawal due to side-effects was 2% for imatinib and 5.6% for IFN-alpha plus Ara-C. Cross-over due to intolerance was 0.7% and 22.8% for imatinib and for IFN-alpha plus Ara-C, respectively. Quality of life was better in the imatinib group than the IFN-alpha group when assessed at 1, 3 and 6 months. Median survival across the four IFN-alpha versus hydroxyurea studies was 66 and 56.2 months, respectively. Median complete CR was 6% for IFN-alpha and 0 for hydroxyurea. Median withdrawal due to side-effects was 24% and 4% for IFN-alpha and hydroxyurea, respectively. Four out of the five studies comparing BMT and IFN-alpha showed a long-term survival advantage for BMT over IFN-alpha, but a short-term disadvantage. In four of the five studies comparing BMT and IFN-alpha, median survival had not yet been reached in the BMT groups in 6--10 years. Median survival in the IFN-alpha arms ranged from 5.2 to 7 years. The BMT group gained a survival advantage over IFN-alpha at 3--5.5 years. In the BMT group death due to transplant-related complications ranged from 36 to 45%. The incremental cost-effectiveness ratio (ICER) of imatinib compared with IFN-alpha from the independent model was GBP26,180 per quality-adjusted-life-years (QALY) gained and was relatively robust. Imatinib was less cost-effective than hydroxyurea with an ICER of GBP86,934. CONCLUSIONS: Imatinib appears to be more effective than current standard drug treatments in terms of cytogenetic response and progression-free survival, with fewer side-effects. However, there is uncertainty concerning longer term outcomes, the development of resistance to imatinib, the duration of response and the place of imatinib relative to BMT. New issues are continually arising, such as optimal management pathways and combination therapies. Recommendations for research include: long-term follow-up data from the first- and second-line imatinib trials; investigation into specific subgroups, e.g. high-risk patients, the elderly, children or those eligible for BMT; long-term comparisons of imatinib with BMT performed in early stages of CML; the use of imatinib in combination with other therapies, and further detailed economic studies. Investigation of the impact of CML and imatinib on quality of life is also important.

Systematic review of endoscopic sinus surgery for nasal polyps.

OBJECTIVES: To provide a systematic review of the clinical effectiveness of endoscopic sinus surgery (ESS) for the removal of nasal polyps. DATA SOURCES: Searches of electronic databases, websites and reference lists were made to identify relevant studies. REVIEW METHODS: An extensive search was performed to identify all articles where FESS is used for the excision of nasal polyps. Two reviewers independently screened articles for inclusion according to predefined criteria. Comparative studies were included if they were primary research, focused on FESS for the removal of nasal polyps, reported patient relevant outcomes and were published in English. In addition, case series studies were included if they met the above criteria and enrolled more than 50 patients with polyps. Data were then extracted by one reviewer and checked by a second. A structured form was used to assess the internal and external validity of included studies. Comparative data were reported where available. Excluded case series and case reports were grouped and described. A group of nine ear, nose and throat (ENT) experts were selected, then using the literature and their own experience, they generated a list of priority research questions. Existing economic evaluations were sought and described. RESULTS: Of the 33 studies included, the randomised controlled trials and controlled trials reported overall symptomatic improvement that ranged from 78 to 88% for FESS compared with 43 to 84% for similar techniques (including polypectomy, Caldwell-Luc and intranasal ethmoidectomy). Disease recurrence was 8% for FESS compared with 14% for Caldwell-Luc and polyp recurrence was 28% for endoscopic ethmoidectomy compared with 35% for polypectomy. Revision surgery was reported in one study only and was the same for FESS and Caldwell-Luc procedures. Percentage of overall complications was reported in only one comparative study and was 1.4% for FESS compared with 0.8% for conventional procedures. The case series studies reported overall symptomatic improvement for patients with nasal polyps ranging from 37 to 99% (median 89%). For the mixed patient groups (with and without polypoid disease) overall symptomatic improvement ranged from 40 to 98% (median 88%). Total complications in the case series studies ranged from 22.4 to 0.3% (median 6%). CONCLUSIONS: The majority of studies report that symptoms improve following FESS with relatively few complications; however, only a small proportion of evidence is comparative. Results from non-comparative studies do not inform the choices that need to be made by ENT surgeons and commissioners. Health economics data are also lacking and therefore cannot inform these decisions. FESS may offer some advantages in effectiveness over comparative techniques, but there is enormous variation in the range of results reported and there are severe methodological limitations. There is a clear need for quality-controlled trials in order to answer questions regarding the effectiveness of FESS. A number of priority research questions from a selection of ENT surgeons within the UK are identified and presented.

Localization of a gene (MCUL1) for multiple cutaneous leiomyomata and uterine fibroids to chromosome 1q42.3-q43.

Dominant transmission of multiple uterine and cutaneous smooth-muscle tumors is seen in the disorder multiple leiomyomatosis (ML). We undertook a genomewide screen of 11 families segregating ML and found evidence for linkage to chromosome 1q42.3-q43 (maximum multipoint LOD score 5.40). Haplotype construction and analysis of recombinations permitted the minimal interval containing the locus, which we have designated "MCUL1," to be refined to an approximately 14-cM region flanked by markers D1S517 and D1S2842. Allelic-loss studies of tumors indicated that MCUL1 may act as a tumor suppressor. Identification of MCUL1 should have wide interest, since this gene may harbor low-penetrance variants predisposing to the common form of uterine fibroids and/or may undergo somatic mutation in sporadic leiomyomata.

Developing a one-stop clinic for leg ulcer patients.

Leg ulceration may be caused by a variety of different factors and specialist assessment is required. Patients with complex leg ulcers in Nottingham are assessed at a one-stop dermatology/vascular clinic. Nurses undertake assessments, provide education and support and liaise with the community nursing services.

Papulonecrotic tuberculide and stenosis of the abdominal aorta.

Papulonecrotic tuberculide (PNT) is a rare form of skin tuberculosis affecting predominantly young adults, with a history of immunity to Mycobacterium tuberculosis. We report a case of a young Caucasian female with PNT who was also documented to have a stenotic segment in the abdominal aorta. The difficulty in clarifying and treating the primary disease and the association between a tuberculous infection and Takayasu's arteritis are discussed.

Childhood vulval pemphigoid: a clinical and immunopathological study of five patients.

We describe five girls with vulval pemphigoid: two had bullous pemphigoid confined to the vulva and three had cicatricial pemphigoid. They demonstrate a spectrum of severity from localized disease to extensive vulval scarring necessitating long-term immunosuppressive therapy and surgical correction. The age at onset of their disease ranged between 6 and 13 years. All presented with vulval discomfort and erosions. Three had oral lesions, two perianal and one eye and cutaneous involvement. Two girls with only vulval lesions and one with vulval and oral lesions responded well to topical steroids. In two, systemic treatment with prednisolone and dapsone or azathioprine was required. The diagnosis was made on the basis of histology and immunofluorescence (IF). All had positive direct IF with IgG and C3. Indirect IF demonstrated circulating IgG binding to the basement membrane zone in four, with dermal or epidermal binding on salt-split skin substrate. Immunoblotting revealed antibodies to the BP230 and BP180 antigens. Immunoelectron microscopy in the child with dermal binding IgG and BP180 and BP230 on immunoblotting showed labelling at the lamina densa-lamina lucida interface adjacent to hemidesmosomes.

The under-reporting of skin disease in association with squamous cell carcinoma of the vulva.

Histology sections from 61 cases of squamous cell carcinoma (SCC) of the vulva presenting after 1988 were reviewed for evidence of associated epithelial abnormality. Of the 50 patients with epithelium adjacent to the tumour, 24 had histological evidence of lichen sclerosus (LS), 20 of severe vulvar intraepithelial neoplasia (VIN 3), 22 of human papilloma virus (HPV) infection and three of lichen planus (LP). The clinical records and the original histology report were also subsequently reviewed and with the exception of VIN 3, these disorders were poorly reported by both clinicians and pathologists. Lichen sclerosus was diagnosed clinically in only two of the 36 hospital records available for inspection. Old terminology was used to describe some patients with epithelial disease (erythroleucoplakia in one patient with LS, leucoplakia in two patients with LS and one with LP). This study demonstrates the need to adopt standard nomenclature and increase the awareness of epithelial disease associated with SCC of the vulva among clinicians and pathologists.

Survival of 1476 patients initially resuscitated from out of hospital cardiac arrest.

OBJECTIVES: To determine the short and long term outcome of patients admitted to hospital after initially successful resuscitation from cardiac arrest out of hospital. DESIGN: Review of ambulance and hospital records. Follow up of mortality by "flagging" with the registrar general. Cox proportional hazards analysis of predictors of mortality in patients discharged alive from hospital. SETTING: Scottish Ambulance Service and acute hospitals throughout Scotland. SUBJECTS: 1476 patients admitted to a hospital ward, of whom 680 (46%) were discharged alive. MAIN OUTCOME MEASURES: Survival to hospital discharge, neurological status at discharge, time to death, and cause of death after discharge. RESULTS: The median duration of hospital stay was 10 days (interquartile range 8-15) in patients discharged alive and 1 (1-4) day in those dying in hospital. Neurological status at discharge in survivors was normal or mildly impaired in 605 (89%), moderately impaired in 58 (8.5%), and severely impaired in 13 (2%); one patient was comatose. Direct discharge to home occurred in 622 (91%) cases. The 680 discharged survivors were followed up for a median of 25 (range 0-68) months. There were 176 deaths, of which 81 were sudden cardiac deaths, 55 were non-sudden cardiac deaths, and 40 were due to other causes. The product limit estimate of 4 year survival after discharge was 68%. The independent predictors of mortality on follow up were increased age, treatment for heart failure, and cardiac arrest not due to definite myocardial infarction. CONCLUSION: About 40% of initial survivors of resuscitation out of hospital are discharged home without major neurological disability. Patients at high risk of subsequent cardiac death can be identified and may benefit from further cardiological evaluation.

Occupational contact sensitization to the stabilized chlorinated paraffin fraction in neat cutting oil.

Twelve men developed contact sensitization to a neat cutting oil to which they were occupationally exposed in the same factory. Serial patch testing ultimately showed strong positive reactions to the chlorinated paraffin fraction of the oil in all 12 patients, whereas negative results were obtained in all 25 controls. Patch testing to pure chlorinated paraffin, on the other hand, gave negative results. Unexplained positive patch test reactions to epoxy resin from the standard series were elicited in half of the cases, suggesting that an epoxy stabilizer within the chlorinated paraffin fraction was the most likely sensitizer responsible for the outbreak of dermatitis. Because of insufficient manufacturer cooperation, we were not able to specifically identify the sensitizer. A number of deficiencies in the work practice, which accounted for the relatively large size of the sensitized group, were identified.