Clinical effectiveness and cost-effectiveness of continuous subcutaneous insulin infusion for diabetes: systematic review and economic evaluation.

BACKGROUND: The National Institute for Health and Clinical Excellence (NICE) was reviewing its previous guidance on continuous subcutaneous insulin infusion (CSII). The review provided an assessment of evidence which had been published since the previous NICE appraisal (TA 151) in 2007. OBJECTIVES: To examine the clinical effectiveness and cost-effectiveness of using CSII to treat diabetes. To update the previous assessment report by reviewing evidence that has emerged since the last appraisal, and to take account of developments in alternative therapies, in particular the long-acting analogue insulins, which cause fewer problems with hypoglycaemia. DATA SOURCES: A systematic review of the literature and an economic evaluation were carried out. The bibliographic databases used were MEDLINE and EMBASE, 2002 to June 2007. The Cochrane Library (all sections), the Science Citation Index (for meeting abstracts only) and the website of the 2007 American Diabetes Association were also searched. REVIEW METHODS: The primary focus for type 1 diabetes mellitus (T1DM) was the comparison of CSII with multiple daily injection (MDI), based on the newer insulin analogues, but trials of neutral protamine Hagedorn (NPH)-based MDI that had been published since the last assessment were identified and described in brief. For type 2 diabetes mellitus (T2DM), all trials of MDI versus CSII were included, whether the long-acting insulin was analogue or not, because there was no evidence that analogue-based MDI was better than NPH-based MDI. Trials that were shorter than 12 weeks were excluded. Information on the patients' perspectives was obtained from four sources: the submission from the pump users group--Insulin Pump Therapy (INPUT); interviews with parents of young children who were members of INPUT; some recent studies; and from a summary of findings from the previous assessment report. Economic modelling used the Center for Outcomes Research (CORE) model, through an arrangement with the NICE and the pump manufacturers, whose submission also used the CORE model. RESULTS: The 74 studies used for analysis included eight randomised controlled trials (RCTs) of CSII versus analogue-based MDI in either T1DM or T2DM, eight new (since the last NICE appraisal) RCTs of CSII versus NPH-based MDI in T1DM, 48 observational studies of CSII, six studies of CSII in pregnancy, and four systematic reviews. The following benefits of CSII were highlighted: better control of blood glucose levels, as reflected by glycated haemoglobin (HbA1c) levels, with the size of improvement depending on the level before starting CSII; reduction in swings in blood glucose levels, and in problems due to the dawn phenomenon; fewer problems with hypoglycaemic episodes; reduction in insulin dose per day, thereby partly off-setting the cost of CSII; improved quality of life, including a reduction in the chronic fear of severe hypoglycaemia; more flexibility of lifestyle--no need to eat at fixed intervals, more freedom of lifestyle and easier participation in social and physical activity; and benefits for the patients' family. The submission from INPUT emphasised the quality of life gains from CSII, as well as improved control and fewer hypoglycaemic episodes. Also, there was a marked discrepancy between the improvement in social quality of life reported by successful pump users, and the lack of convincing health-related quality of life gains reported in the trials. With regard to economic evaluation, the main cost of CSII is for consumables, such as tubing and cannulas, and is about 1800-2000 pounds per year. The cost of the pump, assuming 4-year life, adds another 430-720 pounds per annum. The extra cost compared with analogue-based MDI averages 1700 pounds. Most studies, assuming a reduction in HbA1c level of 1.2%, found CSII to be cost-effective. LIMITATIONS: The most important weakness of the evidence was the very small number of randomised trials of CSII against the most modern forms of MDI, using analogue insulins. CONCLUSIONS: Based on the totality of evidence, using observational studies to supplement the limited data from randomised trials against best MDI, CSII provides some advantages over MDI in T1DM for both children and adults. However, there was no evidence that CSII is better than analogue-based MDI in T2DM or in pregnancy. Further trials with larger numbers and longer durations comparing CSII and optimised MDI in adults, adolescents and children are needed. In addition, there should be a trial of CSII versus MDI with similar provision of structured education in both arms. A trial is also needed for pregnant women with pre-existing diabetes, to investigate using CSII to the best effect.

Systematic review of the effectiveness of preventing and treating Staphylococcus aureus carriage in reducing peritoneal catheter-related infections.

OBJECTIVES: To determine the clinical effectiveness and cost-effectiveness of (1) alternative strategies for the prevention of Staphylococcus aureus carriage in patients on peritoneal dialysis (PD) and (2) alternative strategies for the eradication of S. aureus carriage in patients on PD. DATA SOURCES: Major electronic databases were searched up to December 2005 (MEDLINE Extra up to 6 January 2006). REVIEW METHODS: Electronic searches were undertaken to identify published and unpublished reports of randomised controlled trials and systematic reviews evaluating the effectiveness of preventing and treating S. aureus carriage on peritoneal catheter-related infections. The quality of the included studies was assessed and data synthesised. Where data were not sufficient for formal meta-analysis, a qualitative narrative review looking for consistency between studies was performed. RESULTS: Twenty-two relevant trials were found. These fell into several groups: the first split is between prophylactic trials, aiming to prevent carriage, and trials which aimed to eradicate carriage in those who already had it; the second split is between antiseptics and antibiotics; and the third split is between those that included patients having the catheter inserted before dialysis started and people already on dialysis. Many of the trials were small or short-term. The quality was often not good by today's standards. The body of evidence suggested a reduction in exit-site infections, but this did not seem to lead to a significant reduction in peritonitis, although to some extent this reflected insufficient power in the studies and a low incidence of peritonitis in them. The costs of interventions to prevent or treat S. aureus carriage are relatively modest. For example, the annual cost of antibiotic treatment of S. aureus carriage per identified carrier of S. aureus was estimated at 179 pounds (73 pounds screening and 106 pounds cost of antibiotic). However, without better data on the effectiveness of the interventions, it is not clear whether such costs are offset by the cost of treating infections and averting changes from peritoneal dialysis to haemodialysis. Although treatment is not expensive, the lack of convincing evidence of clinical effectiveness made cost-effectiveness analysis unrewarding at present. However, consideration was given to the factors needed in a hypothetical model describing patient pathways from methods to prevent S. aureus carriage, its detection and treatment and the detection and treatment of the consequences of S. aureus (e.g. catheter infections and peritonitis). Had data been available, the model would have compared the cost-effectiveness of alternative interventions from the perspective of the UK NHS, but as such it helped identify what future research would be needed to fill the gaps. CONCLUSIONS: The importance of peritonitis is not in doubt. It is the main cause of people having to switch from peritoneal dialysis to haemodialysis, which then leads to reduced quality of life for patients and increased costs to the NHS. Unfortunately, the present evidence base for the prevention of peritonitis is disappointing; it suggests that the interventions reduce exit-site infections, but not peritonitis, although this may be due to trials being in too small numbers for too short periods. Trials are needed with larger numbers of patients for longer durations.

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.

Syndrome specificity and behavioural disorders in young adults with intellectual disability: cultural differences in family impact.

BACKGROUND: This study examined whether behaviour problems and adaptive behaviour of low functioning young adults, and well-being of their families, varied by diagnostic syndrome [intellectual disability (ID) only, cerebral palsy, Down syndrome, autism], as well as by cultural group. METHODS: Behaviour disorders in young adults with moderate to severe ID were assessed from information provided by 282 caregivers during in-home interviews. The sample consisted of 150 Anglo participants, and 132 Latino, primarily Spanish-speaking, participants drawn from Southern California. RESULTS: Behaviour disorders and maternal well-being showed the same pattern across disability syndromes. Autism was associated with the highest scores in multiple behaviour problem areas as well as maternal reports of lower well-being. Down syndrome was associated with the lowest behaviour problem scores and the highest maternal well-being. When behaviour problems were controlled for, diagnostic groups accounted for no additional variance in maternal stress or depression. The pattern of behaviour problems and well-being did not differ by sample (Anglo vs. Latino), although level on well-being measures did. Latina mothers reported significantly higher depression symptoms and lower morale, but also higher positive impact from their child than did Anglo mothers. CONCLUSIONS: Caregivers of young adults with autism report more maladaptive behaviour problems and lower personal well-being, or stress, relative to other diagnostic groups, regardless of cultural group. However, cultural differences exist in caregiver reports of depression, morale, and positive perceptions. Implications for service provision aimed at families of children with challenging behaviour problems are discussed in the context of culture.

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.

Consultant supported intermediate care--a model for remote and island hospitals.

INTRODUCTION: Providing local consultant-delivered hospital services in remote and island communities in the United Kingdom is increasingly problematic due to difficulties with recruitment and retention of staff, statutory restrictions to hours worked by health professionals and the expectation each clinician must manage an externally defined volume of cases to maintain clinical standards. This article describes a before-and-after evaluation of a novel method of providing consultant support for acute internal medicine to an island grouping off the Scottish coast. Under the scheme, local GPs provided acute medical care of inpatients. A consultant general physician was appointed in a district general hospital on the mainland, approximately 100 miles from the island group, to provide a lead clinician role for inpatient services at the island hospital, visiting the island on a twice-monthly basis, undertaking educational sessions and developing local guidelines and care pathways for the management of individual medical conditions. In addition, two junior doctors were appointed to the island hospital to support inpatient care. METHODS: A prospective recording system for case mix was established with agreed evidence-based protocols, developed as integrated care pathways (ICP), for indicator conditions. General case mix was determined during two 6-month periods, June-November 2001 and June-November 2002, before and after implementation of the new arrangements. Performance against an ICP for management of suspected cardiac chest pain was evaluated in detail, examining the process of management, clinical outcome and economics. Data from the clinical literature were used to estimate the potential health gains from observed changes in clinical practice. RESULTS: Total admissions rose by 25% in the second time period, with particular increases noted for cardiovascular, cerebrovascular disease, and cancer. Total air ambulance transfers between the islands and the mainland within these time periods increased by 31%, from 88 to 115 transfers. Recording specific details from the history and frequency of appropriate blood investigations increased and initial steps in management changed considerably after introduction of the ICP. The number of transfers to the mainland teaching hospital increased from 3/37 (8%) in 2001 to 15/56 (27%) in 2002. Based on an estimated 100 patients per year, of whom 15 would receive thrombolysis, total additional patient costs would be 64,000 pounds sterling. The annual cost of the additional resource input into the medical service was 148,000 pounds sterling. Approximately 16 adverse events would be avoided at a combined cost of 212,000 pounds sterling (148,000 pounds sterling direct costs of intervention + 64,000 pounds sterling additional treatment costs) or 13,250 pounds sterling per event avoided. This is a conservative estimate of benefit as all the direct costs of the intervention have been included. CONCLUSIONS: This study shows that appropriate standards of care can be delivered in the setting described. Costs of care increased, but the level of service provided increased concomitantly, and the health benefits were achieved at costs that compare favourably with other interventions recommended by health technology assessment groups. An estimate of notional costs involved in alternative models for the delivery of hospital medical services in a remote area suggests that costs would be similar for a three-consultant service, the present model, and a triage and transfer system. In the future, the models chosen by remote and island communities and healthcare providers are therefore likely to be determined by viability, sustainability and public acceptability rather than cost. Our study indicates that consultant supported intermediate care is a viable model.

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.

Behaviour/mental health problems in young adults with intellectual disability: the impact on families.

BACKGROUND: The present authors studied the impact of dual diagnosis [i.e. intellectual disability (ID) and mental disorder] in young adults on their mothers' perceived levels of stress and decisions about placement. METHODS: The mothers of 103 young adults with severe ID were interviewed using a 2-3-h in-depth protocol of measures designed to assess their child's adaptive functioning, maladaptive behaviour, mental health problems and negative impact on the family, as well as their own thoughts on out-of-home placement. The Scales of Independent Behavior--Revised Problem Behavior Scale assessed problem behaviours and the Reiss Screen assessed mental disorder. RESULTS: These measures were highly correlated (r = 0.64), but tapped some different domains of maladaptive behaviour and proved to be most predictive when employed together. Behaviour and/or mental health (B/MH) problems significantly predicted the mothers' perceived negative impact of the young adult on the family, even after controlling for other young adult characteristics. These problems also predicted the family's steps toward seeking out-of-home placement, as did better young adult health and the mother's higher educational attainment; stress did not predict additional variance in placement once these variables were accounted for. CONCLUSIONS: The discussion focuses on the implications for service provision to families of young adults with B/MH problems.

Rater agreement and utility of the mutagen-induced chromosome damage assay.

Chromosomal damage in peripheral blood lymphocytes induced by short-term in vitro exposure to the cytotoxic antibiotic bleomycin was first described in 1983 and proposed as a phenotypic assay for chromosome instability. This assay was subsequently described as potentially useful in assessing an individual's risk to environmental carcinogens in 1989. Since 1995 numerous published studies have used this assay to assess risk for cancer in the aerodigestive tract, particularly lung cancer, in various ethnic populations. Odds ratios up to 8.5 have been reported for individuals deemed "mutagen sensitive" (defined as > or = 1 chromatid break per metaphase averaged in 50 metaphases analyzed). While this phenotypic assay is appealing for lung cancer risk assessment it has not been reproduced by other investigators. Because of our interest in lung cancer biology, epidemiology, and genetics, we sought to independently assess the rater agreement of this assay. We found that 1) the assay is laborious to conduct (8 hours of labor) and relatively expensive (> $100), yet reducing the number of metaphases from 50 to 20 produced a reliable, less expensive, and less laborious test; and 2) the rater agreement of individual metaphase readings is poor, but agreement for a summary measure is high.

Clinical and cost-effectiveness of donepezil, rivastigmine and galantamine for Alzheimer's disease: a rapid and systematic review.

BACKGROUND: Alzheimer's disease is the most common cause of dementia and is characterised by an insidious onset and slow deterioration. The estimated prevalence of Alzheimer's disease for a standard health authority (500,000 people) is about 3330. Current service involves a wide range of agencies, and drug therapy for some patients. OBJECTIVES: To provide a rapid and systematic review of the clinical effectiveness and cost-effectiveness of donepezil, rivastigmine and galantamine in the symptomatic treatment of people suffering from Alzheimer's disease. METHODS: A systematic review of the literature was undertaken. METHODS - DATA SOURCES: Searches were made of electronic databases, including MEDLINE, EMBASE, The Cochrane Library, Database of Abstracts of Reviews of Effectiveness, NHS Economic Evaluation Database, National Research Register, Science Citation Index, BIOSIS, EconLit, MRC Trials database, Early Warning System, Current Controlled Trials, TOXLINE, Index of Scientific and Technical Proceedings, and Getting Easier Access to Reviews. All sources were searched over the period covered by the databases up to March/July 2000. Bibliographies of related papers were assessed for relevant studies and experts were contacted for advice and peer review, and to identify additional published and unpublished references. Manufacturer submissions to the National Institute for Clinical Excellence (NICE) were reviewed. METHODS - STUDY SELECTION: Studies were included if they fulfilled the following criteria: (1) INTERVENTION: donepezil, rivastigmine or galantamine used to treat Alzheimer's disease. (2) PARTICIPANTS: people diagnosed with Alzheimer's disease who meet the criteria for treatment with donepezil, rivastigmine and galantamine. (3) OUTCOMES: measures assessing changes in cognition, function, behaviour and mood, quality of life (including studies assessing carer well-being and carer-input), and time to institutionalisation. (4) DESIGN: systematic reviews of randomised controlled trials (RCTs) and RCTs comparing donepezil, rivastigmine or galantamine with placebo or each other or non-drug comparators were included in the review of effectiveness. Economic studies of donepezil, rivastigmine or galantamine used to treat Alzheimer's disease that included a comparator (or placebo) and both the costs and consequence (outcomes) of treatment were included in the review of cost-effectiveness. Studies in non-English language, and abstracts and conference poster presentations of systematic reviews, RCTs and economic evaluations were excluded. Two reviewers identified studies by independently screening study titles and abstracts, and then by examining the full text of selected studies to decide inclusion. METHODS - DATA EXTRACTION AND QUALITY ASSESSMENT: Data extraction and quality assessment were undertaken by one reviewer and checked by a second reviewer, with any disagreements resolved through discussion. The quality of RCTs was assessed using the Jadad scale and the quality of systematic reviews was assessed using criteria developed by the NHS Centre for Reviews and Dissemination. The quality of economic evaluation studies was assessed by their internal validity (i.e. the methods used) using a standard checklist, and external validity (i.e. the generalisability of the economic study to the population of interest) using a series of relevant questions. METHODS - DATA SYNTHESIS: The clinical effectiveness and cost-effectiveness of donepezil, rivastigmine and galantamine were synthesised through a narrative review with full tabulation of results of all included studies. In the economic evaluation, the reviewers assessed whether adjustments could be made to existing models to reflect the current situation in England and Wales. RESULTS - CLINICAL EFFECTIVENESS: (1) Donepezil--three systematic reviews and five RCTs (plus four studies from industry (unpublished data, submitted as commercial in confidence)) were found. Results suggest that donepezil is beneficial when assessed using global and cognitive outcome measures. (2) Rivastigmine--three systematic reviews and five RCTs (plus two studies from industry (unpublished data, submitted as commercial in confidence)) were found. Results suggest that rivastigmine is beneficial in terms of global outcome measures. (3) Galantamine--one systematic review and three RCTs (plus three studies from industry (unpublished data, submitted as commercial in confidence)) were found. Results suggest that galantamine is beneficial in terms of global, cognitive and functional scales. RESULTS - SUMMARY OF BENEFITS: It is difficult to quantify benefits from the evidence available in the literature. Statistically significant improvements in tests such as ADAS-cog (Alzheimer's Disease Assessment Scale cognitive subscale) may not be reflected in changes in daily life. (ABSTRACT TRUNCATED)

Child hunger in Canada: results of the 1994 National Longitudinal Survey of Children and Youth.

BACKGROUND: In Canada, hunger is believed to be rare. This study examined the prevalence of hunger among Canadian children and the characteristics of, and coping strategies used by, families with children experiencing hunger. METHODS: The data originated from the first wave of data collection for the National Longitudinal Survey of Children and Youth, conducted in 1994, which included 13,439 randomly selected Canadian families with children aged 11 years or less. The respondents were asked about the child's experience of hunger and consequent use of coping strategies. Sociodemographic and other risk factors for families experiencing hunger, use of food assistance programs and other coping strategies were analyzed by means of multiple logistic regression analysis. RESULTS: Hunger was experienced by 1.2% (206) of the families in the survey, representing 57,000 Canadian families. Single-parent families, families relying on social assistance and off-reserve Aboriginal families were overrepresented among those experiencing hunger. Hunger coexisted with the mother's poor health and activity limitation and poor child health. Parents offset the needs of their children by depriving themselves of food. INTERPRETATION: Physicians may wish to use these demographic characteristics to identify and assist families with children potentially at risk for hunger.

Racial variation in wanting and obtaining mental health services among women veterans in a primary care clinic.

Epidemiologic studies suggest that African-American women may be less likely to obtain mental health services. Racial differences were explored in wanting and obtaining mental health services among women in an equal access primary care clinic setting after adjusting for demographics, mental disorder symptoms, and a history of sexual trauma. Participating in the study were women veterans at a primary care clinic at the Durham Veterans Affairs Medical Center. Consecutive women patients (n = 526) between the ages of 20 and 49 years were screened for a desire to obtain mental health services. Patients were given the Primary Care Evaluation of Mental Disorders questionnaire (PRIME-MD) and a sexual trauma questionnaire. Mental health service utilization was monitored for 12 months. The median age of the women was 35.8 years; 54.4% of them were African-American. African-American women expressed a greater desire for mental health services than whites, yet mental health resources at the clinic were similarly used by both racial groups. African-American women may want more mental health services; however, given an equal access system, there were no racial differences in mental health use.

Circumventing multiple testing: a multilocus Monte Carlo approach to testing for association.

Advances in marker technology have made a dense marker map a reality. If each marker is considered separately, and separate tests for association with a disease gene are performed, then multiple testing becomes an issue. A common solution uses a Bonferroni correction to account for multiple tests performed. However, with dense marker maps, neighboring markers are tightly linked and may have associated alleles; thus tests at nearby marker loci may not be independent. When alleles at different marker loci are associated, the Bonferroni correction may lead to a conservative test, and hence a power loss. As an alternative, for tests of association that use family data, we propose a Monte Carlo procedure that provides a global assessment of significance. We examine the case of tightly linked markers with varying amounts of association between them. Using computer simulations, we study a family-based test for association (the transmission/disequilibrium test), and compare its power when either the Bonferroni or Monte Carlo procedure is used to determine significance. Our results show that when the alleles at different marker loci are not associated, using either procedure results in tests with similar power. However, when alleles at linked markers are associated, the test using the Monte Carlo procedure is more powerful than the test using the Bonferroni procedure. This proposed Monte Carlo procedure can be applied whenever it is suspected that markers examined have high amounts of association, or as a general approach to ensure appropriate significance levels and optimal power.

Children's feeding programs in Atlantic Canada: reducing or reproducing inequities?

This study analyzed, through case studies of day-to-day observations and interviews with recipients and operators, the operations of nine children's feeding programs in Nova Scotia, New Brunswick, and Newfoundland. We found that children's feeding programs result in the stigmatization of participants and families, despite an ideology of equality. Most programs adopt a family substitution role in the lives of children they serve and function in a way that excludes parental participation. Programs also transmit a hidden curriculum to children that teaches them how to behave and how a 'proper' family functions. We found that the professionalization of food and nutrition, a desire for an expanded client base, and dependency creation through the provision of other material goods, permit programs to exert increasing institutional control over recipients, a process we, following Illich, call the dragnet. While these programs may be meeting some nutritional needs in a few poverty-stricken children, they ultimately reproduce, rather than reduce, inequities.

The reliability of a self-reported measure of disease, impairment, and function in persons with spinal cord dysfunction.

OBJECTIVE: To develop a self-report instrument that would provide information about the different levels of the disablement process, and that (1) was suitable for persons with spinal cord disease (SCD), (2) could be completed quickly, (3) could be mailed, (4) had acceptable reliability, and (5) would be clinically useful. STUDY DESIGN: Test-retest using a convenience sample. METHODS: Review of the literature and an expert panel were used to develop the instrument. It was mailed to 49,458 individuals in June 1995 and a second mailing was done in August 1995. A subset of 725 individuals who responded to both mailings was used to examine the instrument's test-retest reliability. RESULTS: The instrument has a 4th grade reading level and has questions on causal disease, disease severity, impairment, activities of daily living (including a self-reported version of the Functional Independence Measure, the SRFM), and resource utilization. Individual item test-retest reliability was high for a mailed questionnaire; all kappa coefficients were near or above .60 and most were over .70. Intraclass correlation coefficient for the SRFM was .90 and internal consistency (Chronbach's alpha) was .96. CONCLUSION: This instrument provides a new, rapid way to obtain information relative to the differing levels of the disablement process.

Understanding racial variation in the use of carotid endarterectomy: the role of aversion to surgery.

Previous studies indicate that African-American patients undergo carotid endarterectomy at one fourth the rate of white patients. This study was undertaken to determine if differences in aversion to carotid endarterectomy might account for some of the racial difference in utilization of this procedure. A sample of 185 African-American and white patients was selected from a cohort of patients hospitalized for stroke or transient ischemic attack at four Veterans Affairs medical centers. Of these patients, 115 (62%) were able to be contacted by telephone and 95 (83%) agreed to be interviewed. The interview included assessments of functional status, patient preferences for their current health status, and risk aversion to a hypothetical carotid endarterectomy. Patients from both racial groups were similar in age, marital status, level of education, and comorbid medical illnesses. All respondents were male. Functional status for both groups was high and not statistically different. There were no significant racial differences in patients' perceptions of their current health state. However, African-American patients expressed more aversion to the hypothetical surgery than whites. The median excess risk of death accepted to avoid surgery was 20% for African Americans versus 2.5% for whites. These results indicate that racial differences in the utilization of carotid endarterectomy may be due in part to differences in patients' levels of aversion to this surgery.

Technology assessment of nonsurgical closure of patent ductus arteriosus: an evaluation of the clinical effectiveness and costs of a new medical device.

OBJECTIVE: To assess the clinical efficacy and cost impact of a new medical device for the nonsurgical closure of patent ductus arteriosus (PDA). METHODS: This was a before-after study comparing the most recent 20 surgical procedures with the first 20 nonsurgical procedures for PDA using a new medical device. Clinical outcome, hospital stay, device cost, and physician fees were compared. RESULTS: Surgical closure was effective in all 20 patients, with an average cost of $4667. In a similar patient group, nonsurgical closure was achieved in 18 of 20 patients (90%), with an estimated average cost per successful procedure of $4690. A clinically insignificant PDA leak persisted beyond 12 months in four nonsurgically managed patients. CONCLUSION: Nonsurgical closure of PDA can be recommended as an effective new medical technique that is not associated with a measurable increase in direct costs and that provides significant indirect and intangible cost advantages.