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Biomedical subjects

N Waugh

Publications and source records attributed to N Waugh.

At least 19 recordsLinked to original sources

Trends in incidence and histological subtypes of lung cancer, Kingston and St Andrew, Jamaica, 1968-1997.

Several scientific publications have reported a progressive shift in the distribution of the histologic subtypes of lung carcinoma in the latter decades of the 20th century, with adenocarcinoma now surpassing squamous cell carcinoma as the most commonly diagnosed morphologic pattern. A 30-year review (1968-1997) of lung cancer cases registered in the Jamaica cancer registry shows a similar trend among males in Kingston and St Andrew with a progressive increase in the documented cases of adenocarcinoma relative to squamous cell carcinoma. Similar changes were not observed in females.

Adenocarcinoma↗

The clinical effectiveness and cost-effectiveness of computed tomography screening for lung cancer: systematic reviews.

OBJECTIVES: The aim of this review is to examine the clinical and cost-effectiveness of screening for lung cancer using computed tomography (CT) to assist policy making and to clarify research needs. DATA SOURCES: Electronic databases and Internet resources. REVIEW METHODS: A systematic review was undertaken and selected studies were assessed using the checklists and methods described in NHS Centre for Reviews and Dissemination (CRD) Report 4. Separate narrative summaries were performed for clinical effectiveness and cost-effectiveness. Cost-effectiveness analysis resulting in a cost per quality-adjusted life-year was not feasible, therefore the main elements of such an appraisal were summarised and the key issues relating to the existing evidence base were discussed. RESULTS: Twelve studies of CT screening for lung cancer were identified, including two randomised controlled trials (RCTs) and ten studies of screening without comparator groups. The quality of reporting of these studies was variable, but the overall quality was adequate. The two RCTs were of short duration (1 year) and therefore there was currently no evidence that screening improves survival or reduces mortality. The proportion of people with abnormal CT findings varied widely between studies (5-51%). The prevalence of lung cancer detected was between 0.4% and 3.2% (number need to screen to detect one lung cancer = 31-249). Incidence rates of lung cancer were lower (0.1-1% per year). Detection of stage I and resectable tumours was high, 100% in some studies. Adverse events, as a result of investigation or surgery, or the screening process per se were poorly reported. Incidental findings of other abnormalities requiring medical follow-up were reported to be as high as 49%. Six full economic evaluations of population CT screening programmes for lung cancer were included in the review. The magnitude of cost-effectiveness ratios reported varied widely. None was set in the UK and generalisation was complicated by wide variation in the data used in different countries and a paucity of UK data for comparison. All six made the fundamental assumption that screening with CT for lung cancer reduced mortality. At the current time, there is no evidence to support that assumption. In the absence of evidence of health gains from screening for lung cancer, in terms of either quantity or quality of life, and faced with a range of uncertainties, from the frequency of abnormal screening findings within a population to the natural history of screening detected lung cancers, it is not feasible at the current time to develop accurately and meaningfully an economic argument for CT screening for lung cancer in the UK. For subgroups, in particular certain occupational groups, there is evidence of increased risk of lung cancer, but the role of screening has not been demonstrated by the current studies. CONCLUSIONS: The accepted National Screening Committee criteria are not currently met, with no RCTs, no evidence to support clinical effectiveness and no evidence of cost-effectiveness. RCTs are needed to examine the effect of CT screening on mortality, either with whole-population screening or for particular subgroups; to determine the rate of positive screening and detected lung cancers. Research is also needed to understand better the natural history and epidemiology of screening-detected lung cancers, particularly small, well-differentiated adenocarcinomas; as well as the impacts on quality of life. Increased collection is needed of UK health service data regarding resource use and safety data for lung cancer management and services. Research is also needed into the feasibility and logistics of tracing people who have in the past worked in industry where there was exposure to lung carcinogens.

Adult↗

Systematic review of the effectiveness and cost-effectiveness of HealOzone for the treatment of occlusal pit/fissure caries and root caries.

OBJECTIVES: To assess the effectiveness and cost-effectiveness of HealOzone (CurOzone USA Inc., Ontario, Canada) for the management of pit and fissure caries, and root caries. The complete HealOzone procedure involves the direct application of ozone gas to the caries lesion on the tooth surface, the use of a remineralising solution immediately after application of ozone and the supply of a 'patient kit', which consists of toothpaste, oral rinse and oral spray all containing fluoride. DATA SOURCES: Electronic databases up to May 2004 (except Conference Papers Index, which were searched up to May 2002). REVIEW METHODS: A systematic review of the effectiveness of HealOzone for the management of tooth decay was carried out. A systematic review of existing economic evaluations of ozone for dental caries was also planned but no suitable studies were identified. The economic evaluation included in the industry submission was critically appraised and summarised. A Markov model was constructed to explore possible cost-effectiveness aspects of HealOzone in addition to current management of dental caries. RESULTS: Five full-text reports and five studies published as abstracts met the inclusion criteria. The five full-text reports consisted of two randomised controlled trials (RCTs) assessing the use of HealOzone for the management of primary root caries and two doctoral theses of three unpublished randomised trials assessing the use of HealOzone for the management of occlusal caries. Of the abstracts, four assessed the effects of HealOzone for the management of occlusal caries and one the effects of HealOzone for the management of root caries. Overall, the quality of the studies was modest, with many important methodological aspects not reported (e.g. concealment of allocation, blinding procedures, compliance of patients with home treatment). In particular, there were some concerns about the choice of statistical analyses. In most of the full-text studies analyses were undertaken at lesion level, ignoring the clustering of lesions within patients. The nature of the methodological concerns was sufficient to raise doubts about the validity of the included studies' findings. A quantitative synthesis of results was deemed inappropriate. On the whole, there is not enough evidence from published RCTs on which to judge the effectiveness of ozone for the management of both occlusal and root caries. The perspective adopted for the study was that of the NHS and Personal Social Services. The analysis, carried out over a 5-year period, indicated that treatment using current management plus HealOzone cost more than current management alone for non-cavitated pit and fissure caries (40.49 pounds versus 24.78 pounds), but cost less for non-cavitated root caries ( 14.63 pounds versus 21.45 pounds). Given the limitations of the calculations these figures should be regarded as illustrative, not definitive. It was not possible to measure health benefits in terms of quality-adjusted life-years, due to uncertainties around the evidence of clinical effectiveness, and to the fact that the adverse events avoided are transient (e.g. pain from injection of local anaesthetic, fear of the drill). One-way sensitivity analysis was applied to the model. However, owing to the limitations of the economic analysis, this should be regarded as merely speculative. For non-cavitated pit and fissure caries, the HealOzone option was always more expensive than current management when the probability of cure using the HealOzone option was 70% or lower. For non-cavitated root caries the costs of the HealOzone comparator were lower than those of current management only when cure rates from HealOzone were at least 80%. The costs of current management were higher than those of the HealOzone option when the cure rate for current management was 40% or lower. One-way sensitivity analysis was also performed using similar NHS Statement of Dental Remuneration codes to those that are used in the industry submission. This did not alter the results for non-cavitated pit fissure caries as the discounted net present value of current management remained lower than that of the HealOzone comparator ( 22.65 pounds versus 33.39 pounds). CONCLUSIONS: Any treatment that preserves teeth and avoids fillings is welcome. However, the current evidence base for HealOzone is insufficient to conclude that it is a cost-effective addition to the management and treatment of occlusal and root caries. To make a decision on whether HealOzone is a cost-effective alternative to current preventive methods for the management of dental caries, further research into its clinical effectiveness is required. Independent RCTs of the effectiveness and cost-effectiveness of HealOzone for the management of occlusal caries and root caries need to be properly conducted with adequate design, outcome measures and methods for statistical analyses.

Adolescent↗

The effectiveness and cost-effectiveness of computed tomography screening for coronary artery disease: systematic review.

OBJECTIVES: To assess the clinical and cost-effectiveness of computed tomography (CT) screening for asymptomatic coronary artery disease; also to establish whether coronary artery calcification (CAC) predicts coronary events and adds anything to risk factor scores, and whether measuring CAC changes treatment. DATA SOURCES: Main electronic databases were searched up to 2005, with a MEDLINE update in February 2006. METHODS: A systematic review of screening studies and economic evaluations was carried out. Studies were included in the review if screening for coronary heart disease was the principal theme of the study, and if data were provided that allowed comparison of CT screening with current practice, which was taken to be risk factor scoring. Mismatches between CAC scores and risk factor scoring were of particular interest. A review of the case for screening against the criteria used by the National Screening Committee (NSC) for assessing screening programmes was also undertaken. RESULTS: No randomised control trials (RCTs) were found that assessed the value of CT screening in reducing cardiac events. Seven studies were identified that assessed the association between CAC scores on CT and cardiac outcomes in asymptomatic people and included 30,599 people. Six used electron-beam CT. The relative risk of a cardiac event was 4.4 if CAC was present, compared to there being no CAC. As CAC score increased, so did the risk of cardiac events. The correlation between CAC and cardiac risk was consistent across studies. There was evidence that CAC scores varied among people with the same Framingham risk factor scores, and that within the same Framingham bands, people with higher CAC scores had significantly higher cardiac event rates. This applied mainly when the CAC scores exceeded 300. There was little difference in event rates among the groups with no CAC, and scores of 1-100 and 101-300. In one study, CAC score was a better predictor of cardiac events than the Framingham risk scores. No studies were found that showed whether the addition of CAC scores to standard risk factor assessment would improve outcomes. There were reports from two observational studies that lowering of low-density lipoprotein cholesterol to about 3 mmol/l; or below with statin treatment modestly reduced CAC scores, but this was not confirmed in two RCTs. In three studies examining whether knowledge of CAC scores would affect compliance with lifestyle measures, perception of risk was affected, but it did not improve smoking cessation rates, although it did increase anxiety. There were a few economic studies of CT screening for heart disease, which provided useful data on costs of scans, other investigations and treatment, but relied on a number of assumptions, and were unable to provide definitive answers. One modelling study estimated that adding CT screening to risk factor scoring, and only giving statins to those with CAC score over 100, would save money, based on a cost per CT screen of US$400 and statin costs of US$1000 per annum per patient. However, the arrival of generic statins has reduced the price dramatically, and these savings no longer apply. CONCLUSIONS: CT examination of the coronary arteries can detect calcification indicative of arterial disease in asymptomatic people, many of whom would be at low risk when assessed by traditional risk factors. The higher the CAC score, the higher the risk. Treatment with statins can reduce that risk. However, CT screening would miss many of the most dangerous patches of arterial disease, because they are not yet calcified, and so there would be false-negative results: normal CT followed by a heart attack. There would also be false-positive results in that many calcified arteries will have normal blood flow and will not be affected by clinically apparent thrombosis: abnormal CT not followed by a heart attack. For CT screening to be cost-effective, it has to add value over risk factor scoring, by producing sufficient additional information to change treatment and hence cardiac outcomes, at an affordable cost per quality-adjusted life-year. There was insufficient evidence to support this. Most of the NSC criteria were either not met or only partially met. It would be useful to have more data on the distributions of risk scores and CAC scores in asymptomatic people, and the level of concordance between risk factor and CAC scores, the risk of cardiac events per annum according to CAC score and risk factor scores, information on the acceptability of CT screening, after information about the radiation dose, and an RCT of adding CT screening to current risk factor-based practice.

Coronary Artery Disease↗

Clinical effectiveness and cost-effectiveness of immediate angioplasty for acute myocardial infarction: systematic review and economic evaluation.

OBJECTIVES: To review the clinical evidence comparing immediate angioplasty with thrombolysis, and to consider whether it would be cost-effective. DATA SOURCES: Electronic databases. Experts in the field. REVIEW METHODS: For clinical effectiveness, a comprehensive review of randomised control trials (RCTs) was used for efficacy, and a selection of observational studies such as case series or audit data used for effectiveness in routine practice. RCTs of thrombolysis were used to assess the relative value of prehospital and hospital thrombolysis. Observational studies were used to assess the representativeness of patients in the RCTs, and to determine whether different groups have different capacity to benefit. Clinical effectiveness was synthesised through a narrative review with full tabulation of results of all included studies and a meta-analysis to provide a precise estimate of absolute clinical benefit. Consideration was given to the effect of the growing use of stents. The economic modelling adopted an NHS perspective to develop a decision-analytical model of cost-effectiveness focusing on opportunity costs over the short term (6 months). RESULTS: The results were consistent in showing an advantage of immediate angioplasty over hospital thrombolysis. The updated meta-analysis showed that mortality is reduced by about one-third, from 7.6% to 4.9% in the first 6 months, and by about the same in studies of up to 24 months. Reinfarction is reduced by over half, from 7.6% to 3.1%. Stroke is reduced by about two-thirds, from 2.3% with thrombolysis to 0.7% with percutaneous coronary intervention (PCI), with the difference being due to haemorrhagic stroke. The need for coronary artery bypass graft is reduced by about one-third, from 13.2% to 8.4%. Caution is needed in interpreting some of the older trials, as changes such as an increase in stenting and the use of the glycoprotein IIb/IIa inhibitors may improve the results of PCI. There is little evidence comparing prehospital thrombolysis with immediate PCI. Research on thrombolysis followed by PCI, known as 'facilitated PCI', is underway, but results are not yet available. Trials may be done in select centres and results may not be as good in lower volume centres, or out of normal working hours. In addition, much of the marginal mortality benefit of PCI over hospital thrombolysis may be lost if door-to-balloon time were more than an hour longer than door-to-needle time. Conversely, within the initial 6 hours, the later patients present, the greater the relative advantage of PCI. Results suggest that PCI is more cost-effective than thrombolysis, providing additional benefits in health status at some extra cost. In the longer term, the cost difference is expected to be reduced because of higher recurrence and reintervention rates among those who had thrombolysis. CONCLUSIONS: If both interventions were routinely available, the economic analysis favours PCI, given the assumptions of the model. However, very few units in England could offer a routine immediate PCI service at present, and there would be considerable resource implications of setting up such services. Without a detailed survey of existing provision, it is not possible to quantify the implications, but they include both capital and revenue: an increase in catheter laboratory provision and running costs. The greatest problem would be staffing, and that would take some years to resolve. A gradual incrementalist approach based on clinical networks, with transfer to centres able to offer PCI, may be used. In rural areas, one option may be to promote an increase in prehospital thrombolysis, with PCI for thrombolysis failures. There is a need for data on the long-term consequences of treatment, the quality of life of patients after treatment, and the effects of PCI following thrombolysis failure.

Angioplasty↗

Clinical and cost-effectiveness of autologous chondrocyte implantation for cartilage defects in knee joints: systematic review and economic evaluation.

OBJECTIVE: To support a review of the guidance issued by the National Institute for Health and Clinical Excellence (NICE) in December 2000 by examining the current clinical and cost-effectiveness evidence on autologous cartilage transplantation. DATA SOURCES: Electronic databases. REVIEW METHODS: Evidence on clinical effectiveness was obtained from randomised trials, supplemented by data from selected observational studies for longer term results, and for the natural history of chondral lesions. Because of a lack of long-term results on outcomes such as later osteoarthritis and knee replacement, only illustrative modelling was done, using a range of assumptions that seemed reasonable, but were not evidence based. RESULTS: Four randomised controlled trials were included, as well as observational data from case series. The trials studied a total of 266 patients and the observational studies up to 101 patients. Two studies compared autologous chondrocyte implantation (ACI) with mosaicplasty, the third compared ACI with microfracture, and the fourth compared matrix-guided ACI (MACI) with microfracture. Follow-up was 1 year in one study, and up to 3 years in the remaining three studies. The first trial of ACI versus mosaicplasty found that ACI gave better results than mosaicplasty at 1 year. Overall, 88% had excellent or good results with ACI versus 69% with mosaicplasty. About half of the biopsies after ACI showed hyaline cartilage. The second trial of ACI versus mosaicplasty found little difference in clinical outcomes at 2 years. Disappointingly, biopsies from the ACI group showed fibrocartilage rather than hyaline cartilage. The trial of ACI versus microfracture also found only small differences in outcomes at 2 years. Finally, the trial of MACI versus microfracture contained insufficient long-term results at present, but the study does show the feasibility of doing ACI by the MACI technique. It also suggested that after ACI, it takes 2 years for full-thickness cartilage to be produced. Reliable costs per quality-adjusted life-year (QALY) could not be calculated owing to the absence of necessary data. Simple short-term modelling suggests that the quality of life gain from ACI versus microfracture would have to be between 70 and 100% greater over 2 years for it to be more cost-effective within the 20,000--30,000 pounds sterling per QALY cost-effectiveness thresholds. However, if the quality of life gains could be maintained for a decade, increments relative to microfracture would only have to be 10--20% greater to justify additional treatment costs within the cost-effectiveness band indicated above. Follow-up from the trials so far has only been up to 2 years, with longer term outcomes being uncertain. CONCLUSIONS: There is insufficient evidence at present to say that ACI is cost-effective compared with microfracture or mosaicplasty. Longer term outcomes are required. Economic modelling using some assumptions about long-term outcomes that seem reasonable suggests that ACI would be cost-effective because it is more likely to produce hyaline cartilage, which is more likely to be durable and to prevent osteoarthritis in the longer term (e.g. 20 years). Further research is needed into earlier methods of predicting long-term results. Basic science research is also needed into factors that influence stem cells to become chondrocytes and to produce high-quality cartilage, as it may be possible to have more patients developing hyaline cartilage after microfracture. Study is also needed into cost-effective methods of rehabilitation and the effect of early mobilisation on cartilage growth.

Cartilage, Articular↗

Inhaled insulin in diabetes mellitus.

BACKGROUND: Insulin therapy often relies on multiple daily injections of insulin. However this is a considerable burden to many people with diabetes and adherence to such an insulin regimen can be difficult to maintain, hence compromising optimal glycaemic control. Also, short acting injected insulin is absorbed more slowly than insulin released by the normal pancreas in response to a meal. Inhaled insulin has the potential to reduce the number of injections to perhaps one long-acting insulin per day, and provide a closer match to the natural state, by more rapid absorption from the lung. OBJECTIVES: To compare the efficacy, adverse effects and patient acceptability of inhaled versus injected insulin. SEARCH STRATEGY: A sensitive search strategy for randomised controlled or cross-over trials was combined with key terms for inhaled insulins. Databases searched were: The Cochrane Library, MEDLINE, PubMed, EMBASE, Science Citation Index, BIOSIS, Web of Science Proceedings, National Research Register UK, Current Controlled Trials, ClinicalTrials.gov, Conference Papers Index, LexisNexis, and web sites of the ADA and EASD were searched for recent meeting abstracts. Reference lists and journals were handsearched. There were no language restrictions on searching. Manufacturers of inhaled insulin were also contacted. Date of last search October 2002. SELECTION CRITERIA: Only randomised controlled trials with parallel groups or controlled cross-over trials, including type 1 or type 2 diabetic patients of any age treated with insulin, were considered eligible. The minimum trial duration considered was 10 weeks, as this is the time taken for glycated haemoglobin to reliably reflect changes in glycaemic control. DATA COLLECTION AND ANALYSIS: Trial selection and evaluation of study quality was performed independently by two reviewers. The quality of reporting of each trial was assessed according to a modification of the criteria outlined in Centre for Reviews and Dissemination (CRD) Report 4, Spitzer; and Jadad. MAIN RESULTS: Six randomised controlled trials were found and the overall number of participants was 1191. Three trials included patients with type 1 diabetes and three with type 2 diabetes. Three trials had a duration of 24 weeks, and three of 12 weeks. All were open label. There was insufficient information to determine the study quality. Results for HbA1c were similar for all trials, in that all showed comparable glycaemic control for inhaled insulin compared to an entirely subcutaneous regimen. All trials that reported patient satisfaction and quality of life showed that these were significantly greater in the inhaled insulin group. Overall there was no difference in total hypoglycaemic episodes between the groups, but one trial showed a statistically significant increase in severe hypoglycaemic episodes for the inhaled insulin group. No adverse pulmonary effects were observed in any of the studies, but longer follow-up will be required to be sure that there are no adverse side-effects. Cavets include: few studies published in full (so quality could not be assessed), and only two studies used the same basal regimen in both the inhaled and injected groups. REVIEWERS' CONCLUSIONS: Inhaled insulin taken before meals, in conjunction with an injected basal insulin, has been shown to maintain glycaemic control comparable to that of patients taking multiple daily injections. The key benefit appears to be that patient satisfaction and quality of life are significantly improved, presumably due to the reduced number of daily injections required. However, the patient satisfaction data is based on five trials, of which only two have been published in full; also the three trials containing quality of life data are all only published in abstract form at present. In addition, longer term pulmonary safety data are still needed. Also, the lower bioavailability, and hence higher doses of inhaled insulin required, may make it less cost-effective than injected insulin.

Administration, Inhalation↗

Pegylated interferon alpha-2a and -2b in combination with ribavirin in the treatment of chronic hepatitis C: a systematic review and economic evaluation.

OBJECTIVES: To assess the clinical-effectiveness and cost-effectiveness of pegylated interferon-alpha combined with ribavirin in the treatment of chronic hepatitis C. DATA SOURCES: Electronic databases, reference lists of retrieved reports, and the industry submissions to the National Institute for Clinical Excellence. REVIEW METHODS: Sources were rigorously searched and studies were selected that met the inclusion criteria of being randomised controlled trials (RCTs) involving comparisons between pegylated interferon-alpha plus ribavirin and non-pegylated interferon plus ribavirin (two trials) or pegylated interferon alone and non-pegylated interferon alone (four trials). The primary outcome in all trials was sustained virological response (SVR) at follow-up. The trials were generally of good quality, although reporting of methodological details could have been more thorough in places. A cost-effectiveness model followed a hypothetical cohort of 1000 individuals with chronic hepatitis C over a 30-year period. RESULTS: In the two trials that tested pegylated interferon plus ribavirin against non-pegylated interferon plus ribavirin the combined percentage of sustained virological response was 55%. The relative risk (RR) for remaining infected was reduced by 17% for pegylated interferon plus ribavirin compared with non-pegylated interferon plus ribavirin. Response to therapy varied according to viral genotype. Patients with genotype 1 had the lowest levels of sustained virological response and patients with genotype 2 or 3 had the highest. In the four trials that evaluated pegylated interferon monotherapy against non-pegylated interferon the combined sustained virological response rates were 31% for pegylated interferon and 14% for non-pegylated interferon. The RR for remaining infected with hepatitis C was reduced by 20% with the use of pegylated interferon. Patients with genotype 1 had the lowest levels of sustained virological response. There were also variations in sustained virological response according to other prognostic variables such as baseline viral load. Regimens involving pegylated interferon appear to be fairly well tolerated. Adverse events were been reported, but they did not differ substantially from levels of adverse events in regimens involving non-pegylated interferon. The incremental discounted cost per QALY for comparing no active treatment to 48 weeks of dual therapy with pegylated interferon and ribavirin (PEG + RBV) was 6045 pounds sterling. When moving from 48 weeks of dual therapy with non-pegylated interferon and ribavirin (IFN + RBV) to 48 weeks of dual therapy with PEG + RBV the figure was 12,123 pounds sterling. Subgroup analyses for dual PEG + RBV therapy demonstrated that the most favourable incremental discounted cost per QALY estimates were for patients infected with genotypes 2 and 3, and with low baseline viral load (3921 pounds sterling) compared with no active treatment. Results of one-way sensitivity analyses showed that the estimates varied according to differences in SVRs, drug costs and discount rates. In general estimates remained under 30,000 pounds sterling per QALY. The incremental discounted cost per QALY when moving from no active treatment to 48 weeks of monotherapy with pegylated interferon was 6484 pounds sterling. When moving from 48 weeks of monotherapy with IFN to 48 weeks of monotherapy with PEG the figure was 8404 pounds sterling. As with dual therapy, the lowest incremental cost per QALY was for patients with genotypes 2 and 3 and low baseline viral load, in the range 2641-4194 pounds sterling. The highest estimates were for patients with genotype 1 and high baseline viral load, around 30,000 pounds sterling. CONCLUSIONS: Well-designed RCTs show that patients treated with pegylated interferon, both as dual therapy and as monotherapy, experience higher sustained viral response rates than those treated with non-pegylated interferon. Patients with genotypes 2 and 3 experience the highest response, with rates in excess of 80%. Patients with the harder to treat genotype 1 nevertheless benefit, with up to 46% of patients experiencing an SVR in one of the trials. Pegylated interferon also appears to be relatively cost-effective in both monotherapy and dual therapy, with cost per QALY estimates remaining generally under 30,000 pounds sterling. The most favourable estimates were for patients with genotypes 2 and 3. Pegylated interferon is a relatively new intervention in the treatment of hepatitis C and therefore there are areas where further research is needed. These include: efficacies of therapy with PEG-alpha-2a vs PEG-alpha-2b; retreatment of previous non-responders using pegylated interferon; efficacy of treatments and long-term outcomes in patients who have other co-morbidities; prospective tests of rules governing stopping treatment; treating patients with acute hepatitis C; problems that may occur in a minority of patients with hepatitis C, such as cryoglobulinaemia and vasculitis; additional psychological effects on quality of life due to hepatitis C and also on the treatment of children and adolescents with hepatitis C.

Antiviral Agents↗

Clinical and cost-effectiveness of continuous subcutaneous insulin infusion for diabetes.

OBJECTIVES: To assess the clinical and cost-effectiveness of continuous subcutaneous insulin infusion (CSII) compared with multiple daily injections (MDI) in the delivery of intensive insulin therapy for the treatment of diabetes mellitus. DATA SOURCES: Electronic databases, references of retrieved articles and manufacturer submissions. Experts in the field were consulted. REVIEW METHODS: For the systematic review of clinical and cost-effectiveness, studies were assessed for inclusion according to predefined criteria by two reviewers. Data extraction and quality assessment were undertaken by one reviewer and checked by a second reviewer. Data on clinical effectiveness were synthesised through a narrative review with full tabulation of all eligible studies, with meta-analysis performed where appropriate. RESULTS: Twenty studies comparing CSII with MDI were identified. Quality was generally poor. In adults with Type 1 diabetes, glycated haemoglobin improved by 0.61% (95% CI -1.29 to 0.07) in longer term studies, although this improvement was smaller when a study using bovine ultralente was excluded. A reduction in insulin dose with CSII of about 12 units per day (-11.90, 95% CI -18.16 to 5.63) was found in short-term studies, with smaller differences in longer term studies. Body weight and cholesterol levels were similar between treatments. Hypoglycaemic events did not differ significantly between CSII and MDI in most trials, but some found fewer events with CSII and one found more hypoglycaemia and hypoglycaemic coma with CSII. There was no consistency between the studies in patient preference, but progress has been made both with insulin pumps and injector pens since the publication of many of the older studies. No difference in glycated haemoglobin between CSII and MDI was found in pregnancy; one study found less insulin was required by patients with CSII, but two other studies found no significant difference. One study of adolescents found lower glycated haemoglobin and insulin dose with CSII whereas a second study found no significant difference. In CSII analogue insulin was associated with lower glycated haemoglobin levels than soluble insulin. No economic evaluations comparing CSII with MDI were identified. The estimated additional cost of CSII compared to MDI varies from GBP1091 per annum to GBP1680 per annum, according to the make of the insulin pump and the estimated life of the device. These estimates include the costs for the insulin pump, the consumables associated with delivery of CSII, and an allowance for the initial education required when patients switch from MDI to CSII. The largest component of the annual cost for CSII is the cost of consumable items (e.g. infusion sets). CONCLUSIONS: When compared with optimised MDI, CSII results in a modest but worthwhile improvement in glycated haemoglobin in adults with Type 1 diabetes. It has not been possible to establish the longer term benefits of such a difference in glycated haemoglobin, although there is an expectation that it would be reflected in a reduction in long-term complications. More immediate primary benefits from CSII may be associated with an impact on the incidence of hypoglycaemic events and the dawn phenomenon, and greater flexibility of lifestyle. However, there is limited evidence on this, and information presented to offer context on quality-of-life is based on testimonies from those patients who have had a positive experience of CSII. The estimated cost to the NHS per year for CSII would be around GBP3.5 million in England and Wales if 1% of people with Type 1 diabetes used CSII, GBP10.5 million for 3%, and GBP17.5 million for 5%. Further research should focus on wider benefits of CSII, such as flexibility of lifestyle and quality of life, and on the psychological impact of wearing a device for 24 hours every day. Research into the use of CSII in children of different ages is also needed.

Cost-Benefit Analysis↗

Specialist nurses in diabetes mellitus.

BACKGROUND: The patient with diabetes has many different learning needs relating to diet, monitoring, and treatments. In many health care systems specialist nurses provide much of these needs, usually aiming to empower patients to self-manage their diabetes. The present review aims to assess the effects of the involvement of specialist nurse care on outcomes for people with diabetes, compared to usual care in hospital clinics or primary care with no input from specialist nurses. OBJECTIVES: To assess the effects of diabetes specialist nurses / nurse case manager in diabetes on the metabolic control of patients with type 1 and type 2 diabetes mellitus. SEARCH STRATEGY: We carried out a comprehensive search of databases including the Cochrane Library, MEDLINE and EMBASE to identify trials. Bibliographies of relevant papers were searched, and hand searching of relevant publications was undertaken to identify additional trials (Date of last search November 2002). SELECTION CRITERIA: Randomised controlled trials and controlled clinical trials of the effects of a specialist nurse practitioner on short and long term diabetic outcomes were included in the review. DATA COLLECTION AND ANALYSIS: Three investigators performed data extraction and quality scoring independently; any discrepancies were resolved by consensus. MAIN RESULTS: Six trials including 1382 participants followed for six to 12 months were included. Two trials were in adolescents. Due to substantial heterogeneity between trials a meta-analysis was not performed. Glycated haemoglobin (HbA1c) in the intervention groups was not found to be significantly different from the control groups over a 12 month follow up period. One study demonstrated a significant reduction in HbA1c in the presence of the diabetes specialist nurse/nurse case manager at 6 months. Significant differences in episodes of hypoglycaemia and hyperglycaemia between intervention and control groups were found in one trial. Where reported, emergency admissions and quality of life were not found to be significantly different between groups. No information was found regarding BMI, mortality, long term diabetic complications, adverse effects, or costs. REVIEWER'S CONCLUSIONS: The presence of a diabetes specialist nurse / nurse case manager may improve patients' diabetic control over short time periods, but from currently available trials the effects over longer periods of time are not evident. There were no significant differences overall in hypoglycaemic episodes, hyperglycaemic incidents, or hospital admissions. Quality of life was not shown to be affected by input from a diabetes specialist nurse/nurse case manager.

Case Management↗

Inhaled insulin in diabetes mellitus.

BACKGROUND: Insulin therapy often relies on multiple daily injections of insulin. However this is a considerable burden to many people with diabetes and adherence to such an insulin regimen can be difficult to maintain, hence compromising optimal glycaemic control. Also, short acting injected insulin is absorbed more slowly than insulin released by the normal pancreas in response to a meal. Inhaled insulin has the potential to reduce the number of injections to perhaps one long-acting insulin per day, and provide a closer match to the natural state, by more rapid absorption from the lung. OBJECTIVES: To compare the efficacy, adverse effects and patient acceptability of inhaled versus injected insulin. SEARCH STRATEGY: A sensitive search strategy for randomised controlled or cross-over trials was combined with key terms for inhaled insulins. Databases searched were: The Cochrane Library, MEDLINE, PubMed, EMBASE, Science Citation Index, BIOSIS, Web of Science Proceedings, National Research Register UK, Current Controlled Trials, ClinicalTrials.gov, Conference Papers Index, LexisNexis, and web sites of the ADA and EASD were searched for recent meeting abstracts. Reference lists and journals were handsearched. There were no language restrictions on searching. Manufacturers of inhaled insulin were also contacted. Date of last search October 2002. SELECTION CRITERIA: Only randomised controlled trials with parallel groups or controlled cross-over trials, including type 1 or type 2 diabetic patients of any age treated with insulin, were considered eligible. The minimum trial duration considered was 10 weeks, as this is the time taken for glycated haemoglobin to reliably reflect changes in glycaemic control. DATA COLLECTION AND ANALYSIS: Trial selection and evaluation of study quality was performed independently by two reviewers. The quality of reporting of each trial was assessed according to a modification of the criteria outlined in Centre for Reviews and Dissemination (CRD) Report 4, Spitzer; and Jadad. MAIN RESULTS: Six randomised controlled trials were found and the overall number of participants was 1191. Three trials included patients with type 1 diabetes and three with type 2 diabetes. Three trials had a duration of 24 weeks, and three of 12 weeks. All were open label. There was insufficient information to determine the study quality. Results for HbA1c were similar for all trials, in that all showed comparable glycaemic control for inhaled insulin compared to an entirely subcutaneous regimen. All trials that reported patient satisfaction and quality of life showed that these were significantly greater in the inhaled insulin group. Overall there was no difference in total hypoglycaemic episodes between the groups, but one trial showed a statistically significant increase in severe hypoglycaemic episodes for the inhaled insulin group. No adverse pulmonary effects were observed in any of the studies, but longer follow-up will be required to be sure that there are no adverse side-effects. Cavets include: few studies published in full (so quality could not be assessed), and only two studies used the same basal regimen in both the inhaled and injected groups. REVIEWER'S CONCLUSIONS: Inhaled insulin taken before meals, in conjunction with an injected basal insulin, has been shown to maintain glycaemic control comparable to that of patients taking multiple daily injections. The key benefit appears to be that patient satisfaction and quality of life are significantly improved, presumably due to the reduced number of daily injections required. However, the patient satisfaction data is based on five trials, of which only two have been published in full; also the three trials containing quality of life data are all only published in abstract form at present. In addition, longer term pulmonary safety data are still needed. Also, the lower bioavailability, and hence higher doses of inhaled insulin required, may make it less cost-effective than injected insulin.

Administration, Inhalation↗

Routine hospital admission versus out-patient or home care in children at diagnosis of type 1 diabetes mellitus.

BACKGROUND: In many places, children newly diagnosed with type 1 diabetes mellitus are admitted to hospital for metabolic stabilisation and training, even if they are not acutely ill. Out-patient or home based management of these children could avoid the stress associated with a hospital stay, could provide a more natural learning environment for the child and its family, and might reduce costs for both the health care system and the families. OBJECTIVES: To assess the effects of routine hospital admission compared to out-patient or home-based management in children newly diagnosed with type 1 diabetes who are not acutely ill, on metabolic control, wellbeing and self-efficacy of the patient and his/her family. SEARCH STRATEGY: We searched the Cochrane Library (including the Cochrane Controlled Trials Register), Medline, Embase, Cinahl, and the British Nursing Index. Additionally, we searched reference lists of relevant studies identified and contacted one of the trialists about further studies. Date of latest search: February 2003. SELECTION CRITERIA: Comparative studies of initial hospitalisation compared to home-based and/or out-patient management in children with newly diagnosed type 1 diabetes. DATA COLLECTION AND ANALYSIS: Studies were independently selected by two reviewers. Data extraction and quality assessment of trials were done independently by two reviewers. Any differences in opinion were resolved by discussion. Authors of included studies were contacted for missing information. Results were summarised descriptively, using tables and text. MAIN RESULTS: Six studies were included in the review, including a total of 237 children in the out-patient/home group. Two studies were randomised controlled trials, three were retrospective cohort studies, and one was a prospective cohort study. Except for one randomised controlled trial that included children in the intervention group who were initially hospitalised for a brief period, studies were of low quality. The one high quality trial identified suggested that home-based management of children with newly diagnosed type 1 diabetes may lead to slightly improved long term metabolic control (at two and three years follow-up). No differences between comparison groups were found in any of the psychosocial and behavioural variables assessed or in rates of acute diabetic complications within two years. Parental costs were found to be decreased, while health system costs were increased, leaving total social costs virtually unchanged. None of the other studies assessing metabolic control found a difference between the comparison groups. There seemed to be no differences in hospitalisations or acute diabetic complications between the out-patient/home groups and the hospital groups. Results with respect to psychosocial and behavioural variables were inconclusive, with only one study finding significant results on some selected subscales of tests used. In another study, the out-patient/home group did significantly better on the assessments of treatment adherence, familial relationship and sociability, but upon further analysis this only seemed to apply to selected socioeconomic subgroups, with no clear explanations offered. REVIEWER'S CONCLUSIONS: Due to the generally low quality or limited applicability of the studies identified, the results of this review are inconclusive. On the whole, the data seem to suggest that out-patient/home management of type 1 diabetes in children at diagnosis does not lead to any disadvantages in terms of metabolic control, acute diabetic complications and hospitalisations, psychosocial variables and behaviour, or total costs. Primary research, ideally a high quality randomised controlled trial, is required.

Adolescent↗

Are analogue insulins better than soluble in continuous subcutaneous insulin infusion? Results of a meta-analysis.

AIMS: The properties of rapid-acting insulin analogues are thought to be particularly appropriate for use in continuous subcutaneous insulin infusion (CSII) or insulin pump therapy. We conducted a systematic review and meta-analysis of trials comparing rapid-acting insulin analogues with soluble insulin in CSII. METHODS: The following databases were searched (last search June 2002): MEDLINE 1985-2002; Embase 1980-2002; PubMed internet version, records added June 2001 to June 2002; Science Citation Index 1990-2002; BIOSIS 1999-2002; Web of Science Proceedings 1990-2002; and the Cochrane Library, including DARE and the HTA databases. Randomized controlled trials and crossover studies with at least 10 weeks on each treatment were included. Data extraction and quality assessment were undertaken by one reviewer and checked by a second. A meta-analysis was undertaken using a random effects model. RESULTS: A significant improvement of 0.26% (95% confidence interval -0.47, -0.06%) in glycated haemoglobin was demonstrated with lispro. Some studies reported fewer hypoglycaemic episodes with analogue insulin but this varied according to the definitions used. No differences in insulin dosage or weight were seen. Two studies reported patient preference, with analogues preferred in both. The extra cost per annum ranges from pound 72 (at 40 units per day) to pound 150 (at 84 units per day). CONCLUSIONS: Insulin analogues result in a modest but significant reduction in HbA1c compared with soluble insulin when used in CSII, and are preferred by patients.

Cross-Over Studies↗

The clinical and cost-effectiveness of patient education models for diabetes: a systematic review and economic evaluation.

OBJECTIVES: To assess the clinical effectiveness and cost-effectiveness of educational interventions for patients with diabetes, compared with usual care or other educational interventions. DATA SOURCES: Electronic databases, reference lists and experts were all consulted in this study. Sponsor submissions to the National Institute of Clinical Excellence were also reviewed. REVIEW METHODS: Electronic databases were searched, references of all retrieved articles were checked for relevant studies, and experts were contacted for advice and peer review and to identify additional published and unpublished references. Randomised clinical trials (RCTs) and controlled clinical trials (CCTs) were included if they fulfilled pre-specified criteria, among which was follow-up from inception for 12 months or longer. Data were synthesised through a narrative review because the diversity of studies prevented a meta-analysis. RESULTS: Twenty-four studies (18 RCTs and six CCTs) that compared education with either a control group or with another educational intervention were included. The quality of reporting and methodology was generally found to be poor by today's standards. As part of treatment intensification, education in Type 1 diabetes (four studies) resulted in significant and long-lasting improvements in metabolic control and reductions in complications. In Type 2 diabetes (16 studies) a diversity of educational programmes did not yield consistent results on measures of metabolic control. Inconsistent results on metabolic control were also found in studies of diabetes of either type (four studies), with studies of lower quality producing significant effects. Few studies evaluated quality of life. Economic evaluations comparing education with usual care or other educational interventions were not identified. CONCLUSIONS: Education as part of intensification of treatment produces improvement in diabetic control in Type 1 diabetes. Mixed results in Type 2 diabetes mean that no clear characterisation is possible as to what features of education may be beneficial. Cost analysis and information from sponsor submissions indicated that where costs associated with patient education were in the region of 500-600 pounds sterling per patients, the benefits over time would have to be very modest to offer an attractive cost-effectiveness profile. Further research should focus on RCTs with clear designs based on explicit hypotheses and with a range of outcomes evaluated after long follow-up intervals.

Cost-Benefit Analysis↗

The effectiveness of diagnostic tests for the assessment of shoulder pain due to soft tissue disorders: a systematic review.

OBJECTIVES: To evaluate the evidence for the effectiveness and cost-effectiveness of the newer diagnostic imaging tests as an addition to clinical examination and patient history for the diagnosis of soft tissue shoulder disorders. DATA SOURCES: Literature was identified from several sources including general medical databases. REVIEW METHODS: Studies were identified that evaluated clinical examination, ultrasound, magnetic resonance imaging (MRI), or magnetic resonance arthrography (MRA) in patients suspected of having soft tissue shoulder disorders. Outcomes assessed were clinical impingement syndrome or rotator cuff tear (full, partial or any). Only cohort studies were included. The methodological quality of included test accuracy studies was assessed using a formal quality assessment tool for diagnostic studies and the extraction of study findings was conducted in duplicate using a pre-designed and piloted data extraction form to avoid any errors. For each test, sensitivity, specificity and positive and negative likelihood ratios with 95% confidence intervals were calculated for each study. Where possible pooled estimates of sensitivity, specificity and likelihood ratios were calculated using random effects methods. Potential sources of heterogeneity were investigated by conducting subgroup analyses. RESULTS: In the included studies, the prevalence of rotator cuff disorders was generally high, partial verification of patients was common and in many cases patients who were selected retrospectively because they had undergone the reference test. Sample sizes were generally very small. Reference tests were often inappropriate with many studies using arthrography alone, despite problems with its sensitivity. For clinical assessment, 10 cohort studies were found that examined either the accuracy of individual tests or clinical examination as a whole: individual tests were either good at ruling out rotator cuff tears when negative (high sensitivity) or at ruling in such disorders when positive (high specificity), but small sample sizes meant that there was no conclusive evidence. Ultrasound was investigated in 38 cohort studies and found to be most accurate when used for the detection of full-thickness tears; sensitivity was lower for detection of partial-thickness tears. For MRI, 29 cohort studies were included. For full-thickness tears, overall pooled sensitivities and specificities were fairly high and the studies were not statistically heterogeneous; however for the detection of partial-thickness rotator cuff tears, the pooled sensitivity estimate was much lower. The results from six MRA studies suggested that it may be very accurate for detection of full-thickness rotator cuff tears, although its performance for the detection of partial-thickness tears was less consistent. Direct evidence for the performance of one test compared with another is very limited. CONCLUSIONS: The results suggest that clinical examination by specialists can rule out the presence of a rotator cuff tear, and that either MRI or ultrasound could equally be used for detection of full-thickness rotator cuff tears, although ultrasound may be better at picking up partial tears. Ultrasound also may be more cost-effective in a specialist hospital setting for identification of full-thickness tears. Further research suggestions include the need for large, well-designed, prospective studies of the diagnosis of shoulder pain, in particular a follow-up study of patients with shoulder pain in primary care and a prospective cohort study of clinical examination, ultrasound and MRI, alone and/or in combination.

Arthrography↗

The value of digital imaging in diabetic retinopathy.

OBJECTIVES: To assess the performance of digital imaging, compared with other modalities, in screening for and monitoring the development of diabetic retinopathy. DESIGN: All imaging was acquired at a hospital assessment clinic. Subsequently, study optometrists examined the patients in their own premises. A subset of patients also had fluorescein angiography performed every 6 months. SETTING: Research clinic at the hospital eye clinic and optometrists' own premises. PARTICIPANTS: Study comprised 103 patients who had type 1 diabetes mellitus, 481 had type 2 diabetes mellitus and two had secondary diabetes mellitus; 157 (26.8%) had some form of retinopathy ('any') and 58 (9.9%) had referable retinopathy. INTERVENTIONS: A repeat assessment was carried out of all patients 1 year after their initial assessment. Patients who had more severe forms of retinopathy were monitored more frequently for evidence of progression. MAIN OUTCOME MEASURES: Detection of retinopathy, progression of retinopathy and determination of when treatment is required. RESULTS: Manual grading of 35-mm colour slides produced the highest sensitivity and specificity figures, with optometrist examination recording most false negatives. Manual and automated analysis of digital images had intermediate sensitivity. Both manual grading of 35-mm colour slides and digital images gave sensitivities of over 90% with few false positives. Digital imaging produced 50% fewer ungradable images than colour slides. This part of the study was limited as patients with the more severe levels of retinopathy opted for treatment. There was an increase in the number of microaneurysms in those patients who developed from mild to moderate. There was no difference between the turnover rate of either new or regressed microaneurysms for patients with mild or with sight-threatening retinopathy. It was not possible in this study to ascertain whether digital imaging systems determine when treatment is warranted. CONCLUSIONS: In the context of a national screening programme for referable retinopathy, digital imaging is an effective method. In addition, technical failure rates are lower with digital imaging than conventional photography. Digital imaging is also a more sensitive technique than slit-lamp examination by optometrists. Automated grading can improve efficiency by correctly identifying just under half the population as having no retinopathy. Recommendations for future research include: investigating whether the nasal field is required for grading; a large screening programme is required to ascertain if automated grading can safely perform as a first-level grader; if colour improves the performance of grading digital images; investigating methods to ensure effective uptake in a diabetic retinopathy screening programme.

Diabetes Mellitus, Type 1↗

Literature searching for clinical and cost-effectiveness studies used in health technology assessment reports carried out for the National Institute for Clinical Excellence appraisal system.

OBJECTIVE: To contribute to making searching for Technology Assessment Reports (TARs) more cost-effective by suggesting an optimum literature retrieval strategy. DATA SOURCES: A sample of 20 recent TARs. REVIEW METHODS: All sources used to search for clinical and cost-effectiveness studies were recorded. In addition, all studies that were included in the clinical and cost-effectiveness sections of the TARs were identified, and their characteristics recorded, including author, journal, year, study design, study size and quality score. Each was also classified by publication type, and then checked to see whether it was indexed in the following databases: MEDLINE, EMBASE, and then either the Cochrane Controlled Trials Register (CCTR) for clinical effectiveness studies or the NHS Economic Evaluation Database (NHS EED) for the cost-effectiveness studies. Any study not found in at least one of these databases was checked to see whether it was indexed in the Science Citation Index (SCI) and BIOSIS, and the American Society of Clinical Oncology (ASCO) Online if a cancer review. Any studies still not found were checked to see whether they were in a number of additional databases. RESULTS: The median number of sources searched per TAR was 20, and the range was from 13 to 33 sources. Six sources (CCTR, DARE, EMBASE, MEDLINE, NHS EED and sponsor/industry submissions to National Institute for Clinical Excellence) were used in all reviews. After searching the MEDLINE, EMBASE and NHS EED databases, 87.3% of the clinical effectiveness studies and 94.8% of the cost-effectiveness studies were found, rising to 98.2% when SCI, BIOSIS and ASCO Online and 97.9% when SCI and ASCO Online, respectively, were added. The median number of sources searched for the 14 TARs that included an economic model was 9.0 per TAR. A sensitive search filter for identifying non-randomised controlled trials (RCT), constructed for MEDLINE and using the search terms from the bibliographic records in the included studies, retrieved only 85% of the known sample. Therefore, it is recommended that when searching for non-RCT studies a search is done for the intervention alone, and records are then scanned manually for those that look relevant. CONCLUSIONS: Searching additional databases beyond the Cochrane Library (which includes CCTR, NHS EED and the HTA database), MEDLINE, EMBASE and SCI, plus BIOSIS limited to meeting abstracts only, was seldom found to be effective in retrieving additional studies for inclusion in the clinical and cost-effectiveness sections of TARs (apart from reviews of cancer therapies, where a search of the ASCO database is recommended). A more selective approach to database searching would suffice in most cases and would save resources, thereby making the TAR process more efficient. However, searching non-database sources (including submissions from manufacturers, recent meeting abstracts, contact with experts and checking reference lists) does appear to be a productive way of identifying further studies.

Abstracting and Indexing↗

Gynaecologic cancer incidence, Kingston and St Andrew, Jamaica, 1973-1997, and gynaecologic cancer mortality, Jamaica, 1999.

The incidence of gynaecologic cancers in women from Kingston and St Andrew for the period 1973-1997 were reviewed by analyzing data previously published by the Jamaica Cancer Registry. Gynaecologic cancer-related mortality statistics for the entire island for 1999 were compiled from data obtained from the Registrar General's Department (RGD) and the Statistical Institute of Jamaica (STATIN). Data were compared to gynaecologic cancer statistics for women from the United States of America for 1973-1997. A total of 2862 gynaecologic cancers were registered for the years 1973-1997, which represents 26.8% of all female cancers from Kingston and St Andrew. Cervical cancer accounted for 62% of these gynaecologic cancers. The 268 cancer-related deaths (168 due to cervical cancer) registered in Jamaican women for 1999 represent approximately 15% of all female cancer-related deaths. The present incidence (27.9 per 100,000) and mortality rate (15.8 per 100,000) of cervical cancer are much higher than that documented for American women--both African Americans and Caucasians--and signify the limited success, to date, of efforts to decrease the incidence and mortality of cervical cancer by the implementation of cervical cancer screening programmes. For the time period reviewed, an increase was noted in the incidence of cancer of the corpus uteri while decreases were recorded for the incidence of choriocarcinoma, ovarian cancer and cancers arising from the vulva, vagina and fallopian tube.

Age Factors↗