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At least 433 records · Page 24Linked to original sources

PubMed2006

The magnitude of an iatrogenic disorder: a systematic review of the incidence of venous thromboembolism for general medical inpatients.

Venous thromboembolism (VTE) is recognized as a potential serious complication of hospitalization, and anticoagulant prophylaxis is widely recommended for medical inpatients. The purpose of this review was to systematically inspect the literature to determine the incidence of VTE without anticoagulant prophylaxis for hospitalized general medical patients. A systematic review was performed using MEDLINE and Cochrane Collaboration searches of the English-language literature. References of the retrieved articles were reviewed for additional studies, and pharmaceutical companies were contacted directly to identify unpublished studies. Studies were eligible if they reported the incidence of symptomatic or asymptomatic VTE in hospitalized general medical patients and included a group which did not receive prophylaxis. Eight trials were identified. Study design, quality, and results were heterogeneous. The incidence of symptomatic VTE without prophylaxis was examined in three trials; the incidence was 2.3% in the only randomized trial, and was 0.8% and 6.2% in two observational studies. The incidence of asymptomatic VTE ranged from 3.7% to 26.0% (median 12.8%). Risk factors identified were older age, prior VTE, and obesity. Though there is little high quality evidence, the best estimate of the incidence of hospital-acquired VTE for general medical patients is approximately 2% for patients at moderate to high risk and <1% for patients at low risk. Further studies are needed to more precisely define a low risk group for whom anticoagulant prophylaxis is unnecessary.

Anticoagulants↗

PubMed2006

Knee versus thigh length graduated compression stockings for prevention of deep venous thrombosis: a systematic review.

OBJECTIVE: Graduated compression stockings are a valuable means of thrombo-prophylaxis but it is unclear whether knee-length (KL) or thigh length (TL) stockings are more effective. The aim of this review was to systematically analyse randomised controlled trials that have evaluated stocking length and efficacy of thromboprophylaxis. METHOD: A systematic review of the literature was undertaken. Clinical trials on hospitalised populations and passengers on long haul flights were selected according to specific criteria and analysed to generate summated data. RESULTS: 14 randomized control trials were analysed. Thirty six of 1568 (2.3%) participants randomised to KL stockings developed a deep venous thrombosis, compared with 79 of 1696 (5%) in the TL control/thigh length group. Substantial heterogeneity was observed amongst trials. KL stockings had a significant effect to reduce the incidence of DVT in long haul flight passengers, odds ration 0.08 (95%CI 0.03-0.22). In hospitalised patients KL stockings did not appear to be far worse than TL stockings, odds ratio 1.01 (95%CI 0.35-2.90). For combined passengers and patients, there was a benefit in favour of KL stockings, weighted odds ratio 0.45 (95% CI 0.30-0.68). CONCLUSION: KL graduated stockings can be as effective as TL stockings for the prevention of DVT, whilst offering advantages in terms of patient compliance and cost.

Aircraft↗

PubMed2004

Systematic review and economic evaluation of a long-acting insulin analogue, insulin glargine.

OBJECTIVES: To evaluate the use of insulin glargine in its licensed basal-bolus indication in terms of both clinical and cost-effectiveness. DATA SOURCES: Electronic databases. REVIEW METHODS: A systematic review of the literature, involving a range of databases, was performed to identify all papers relating to insulin glargine. RESULTS: Nineteen studies met the inclusion criteria but full reports were available for only six. For type 1 diabetes patients, insulin glargine appears to be more effective than neutral protamine Hagedorn (NPH) in reducing fasting blood glucose (FBG) but not in reducing glycosylated haemoglobin (HbA1c) and there is some evidence that both insulins are as effective as each other in both FBG and HbA1c control. For type 2 patients for whom oral antidiabetic agents provide inadequate glycaemic control, there is no evidence that insulin glargine is more effective than NPH in reducing either FBG or HbA1c and some evidence that both insulins are as effective as each other in both FBG and HbA1c control. Evidence for control of hypoglycaemia is equivocal. In studies where insulin glargine is demonstrated to be superior to NPH in controlling nocturnal hypoglycaemia, this may be only apparent when compared with once-daily NPH and not twice-daily NPH. Further, this superiority of glargine over NPH in the control of nocturnal hypoglycaemia may relate to one formulation of insulin glargine (HOE901[80]) and not another (HOE901[30]). There is no conclusive evidence that insulin glargine is superior to NPH in controlling symptomatic hypoglycaemia and severe hypoglycaemia. Insufficient data are available to conclude whether insulin glargine is different from each of the commonly used NPH dosing regimens: once daily and more than once daily. Given the lack of a published evidence base for the cost-effectiveness of insulin glargine, the economic review concentrates on a review of the industry submission and an amended model. Three economic models are provided in the submission, two relating to type 1 diabetes and one relating to type 2 diabetes. All three models compare the cost--utility of insulin glargine against NPH insulin. In general, the structures of the models are poor and in all three models, mistakes relating to assumptions and calculations have been made. The assessment team believe that the cost per QALY estimates generated by the Aventis model may be an underestimate for several reasons. The cost-effectiveness of insulin glargine in both type 1 and type 2 diabetes is highly sensitive to the amount of utility associated with reducing the fear of hypoglycaemia. CONCLUSIONS: The evidence suggests that, compared with NPH insulin, insulin glargine is effective in reducing the number of nocturnal hypoglycaemic episodes, especially when compared with once-daily NPH. There appears to be no improvement in long-term glycaemic control and therefore insulin glargine is unlikely to reduce the incidence of the long-term microvascular and cardiovascular complications of diabetes. Further research into insulin glargine is needed that addresses the quality of life issues associated with fear of hypoglycaemia and also the economic impact of balance of HbA1c control and incidence of hypoglycaemia achieved in practice. Studies examining the economic evidence on insulin glargine should be published.

Adult↗

PubMed2005

Systematic review: strategies for using exercise therapy to improve outcomes in chronic low back pain.

BACKGROUND: Exercise therapy encompasses a heterogeneous group of interventions. There continues to be uncertainty about the most effective exercise approach in chronic low back pain. PURPOSE: To identify particular exercise intervention characteristics that decrease pain and improve function in adults with nonspecific chronic low back pain. DATA SOURCES: MEDLINE, EMBASE, PsychInfo, CINAHL, and Cochrane Library databases to October 2004 and citation searches and bibliographic reviews of previous systematic reviews. STUDY SELECTION: Randomized, controlled trials evaluating exercise therapy in populations with chronic (>12 weeks duration) low back pain. DATA EXTRACTION: Two reviewers independently extracted data on exercise intervention characteristics: program design (individually designed or standard program), delivery type (independent home exercises, group, or individual supervision), dose or intensity (hours of intervention time), and inclusion of additional conservative interventions. DATA SYNTHESIS: 43 trials of 72 exercise treatment and 31 comparison groups were included. Bayesian multivariable random-effects meta-regression found improved pain scores for individually designed programs (5.4 points [95% credible interval (CrI), 1.3 to 9.5 points]), supervised home exercise (6.1 points [CrI, -0.2 to 12.4 points]), group (4.8 points [CrI, 0.2 to 9.4 points]), and individually supervised programs (5.9 points [CrI, 2.1 to 9.8 points]) compared with home exercises only. High-dose exercise programs fared better than low-dose exercise programs (1.8 points [CrI, -2.1 to 5.5 points]). Interventions that included additional conservative care were better (5.1 points [CrI, 1.8 to 8.4 points]). A model including these most effective intervention characteristics would be expected to demonstrate important improvement in pain (18.1 points [CrI, 11.1 to 25.0 points] compared with no treatment and 13.0 points [CrI, 6.0 to 19.9 points] compared with other conservative treatment) and small improvement in function (5.5 points [CrI, 0.5 to 10.5 points] compared with no treatment and 2.7 points [CrI, -1.7 to 7.1 points] compared with other conservative treatment). Stretching and strengthening demonstrated the largest improvement over comparisons. LIMITATIONS: Limitations of the literature, including low-quality studies with heterogeneous outcome measures and inconsistent and poor reporting; publication bias. CONCLUSIONS: Exercise therapy that consists of individually designed programs, including stretching or strengthening, and is delivered with supervision may improve pain and function in chronic nonspecific low back pain. Strategies should be used to encourage adherence. Future studies should test this multivariable model and further assess specific patient-level characteristics and exercise types.

Adult↗

PubMed2006

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↗

PubMed2006

Computerised cognitive behaviour therapy for depression and anxiety update: a systematic review and economic evaluation.

OBJECTIVES: To evaluate computerised cognitive behaviour therapy (CCBT) for the treatment of anxiety, depression, phobias, panic and obsessive-compulsive behaviour (OCD). The software packages to be considered include Beating the Blues (BtB), Overcoming Depression: a five areas approach, FearFighter (FF), Cope and BT Steps. Other packages or programmes incorporating CCBT were also considered. DATA SOURCES: Electronic databases from 1966 to March 2004. Evidence submitted by sponsors for CCBT products. REVIEW METHODS: A systematic review was a review of the literature and the evidence submitted by sponsors for each of the products. A series of cost-effectiveness models was developed and run by the project team for the five CCBT products across the three mental health conditions. RESULTS: Twenty studies were identified in the clinical effectiveness review. The analysis of these results showed some evidence that CCBT is as effective as therapist-led cognitive behaviour therapy (TCBT) for the treatment of depression/anxiety and phobia/panic and is more effective than treatment as usual (TAU) in the treatment of depression/anxiety. CCBT also appears to reduce therapist time compared with TCBT. When reviewing cost-effectiveness studies, only one published economic evaluation of CCBT was found. This was an economic evaluation of the depression software BtB alongside a randomised controlled trial (RCT), which found that BtB was cost-effective against TAU in terms of cost per quality-adjusted life-year (QALY) (less than 2000 pounds), however it contained weaknesses that were then addressed in the cost-effectiveness model developed for the study. The results of the model for the depression software packages in terms of incremental cost per QALY compared with TAU and the chance of being cost-effective at 30,000 pounds per QALY were for BtB 1801 pounds and 86.8%, for Cope 7139 pounds and 62.6% and for Overcoming Depression 5391 pounds and 54.4%. The strength of the BtB software being that it has been evaluated in the context of an RCT with a control group. The subgroup analysis found no differences across the severity groupings. For phobia/panic software, the model showed an incremental cost per QALY of FF over relaxation was 2380 pounds. Its position compared with TCBT is less clear. When modelling OCD packages, using the practice-level licence cost meant that BT Steps was dominated by TCBT, which had significantly better outcomes and was cheaper. However, the cheaper PCT licence resulted in the incremental cost-effectiveness of BT Steps over relaxation being 15,581 pounds and TCBT over BT Steps being 22,484 pounds. CONCLUSIONS: The study findings are subject to substantial uncertainties around the organisational level for purchasing these products and the likely throughput. This is in addition to concerns with the quality of evidence on response to therapy, longer term outcomes and quality of life. The position of CCBT within a stepped care programme needs to be identified, as well as its relationship to other efforts to increase access to CBT and psychological therapies. Research is needed to compare CCBT with other therapies that reduce therapist time, in particular bibliotherapy and to explore the use of CCBT via the Internet. Independent research is needed, particularly RCTs, that examine areas such as patient preference and therapist involvement within primary care.

Anxiety Disorders↗

PubMed2005

The effectiveness and cost-effectiveness of pimecrolimus and tacrolimus for atopic eczema: a systematic review and economic evaluation.

OBJECTIVES: To consider the effectiveness and cost-effectiveness of pimecrolimus for mild to moderate atopic eczema and tacrolimus for moderate to severe atopic eczema compared with current standard treatment in adults and children. DATA SOURCES: Electronic databases. Experts and the manufacturers of these agents were also approached for information. REVIEW METHODS: The systematic review was carried out using standard methodological guidelines and a stringent quality assessment strategy. A state transition (Markov) model was developed to estimate cost--utility of tacrolimus and pimecrolimus separately, compared with current standard practice with topical corticosteroids, (a) as first-line treatment and (b) as second-line treatment. Pimecrolimus was also compared to emollients only. RESULTS: The pimecrolimus trial reports were of varying quality; however when compared with a placebo (emollient), pimecrolimus was found to be more effective and to provide quality of life improvements. There is very little evidence available about pimecrolimus compared with topical corticosteroids. Compared with a placebo (emollient), both 0.03% and 0.1% tacrolimus were found to be more effective. Compared with a mild corticosteroid, 0.03% tacrolimus is more effective in children as measured by a 90% or better improvement in the Physician's Global Evaluation (PGE). Compared with potent topical corticosteroids, no significant difference in effectiveness is seen with 0.1% tacrolimus as measured by a 75% or greater improvement in the PGE. Minor application site adverse effects are common with tacrolimus. However, this did not lead to increased rates of withdrawal from treatment in trial populations. The PenTag economic model demonstrates a large degree of uncertainty, which was explored in both deterministic and stochastic analyses. This is the case for the cost-effectiveness of pimecrolimus and tacrolimus in first- or second-line use compared with topical steroids. In all cases immunosuppressant regimes were estimated to be more costly than alternatives and differences in benefits to be small and subject to considerable uncertainty. CONCLUSIONS: There is limited evidence from a small number of randomised controlled trials (RCTs) that pimecrolimus is more effective than placebo treatment in controlling mild to moderate atopic eczema. Although greater than for pimecrolimus, the evidence base for tacrolimus in moderate to severe atopic eczema is also limited. At both 0.1% and 0.03% potencies, tacrolimus appears to be more effective than the placebo treatment and mild topical corticosteroids. However, these are not the most clinically relevant comparators. Compared with potent topical corticosteroids, no significant difference was shown. Short-term adverse effects with both immunosuppressants are relatively common, but appear to be mild. Experience of long-term use of the agents is lacking so the risk of rare but serious adverse effects remains unknown. No conclusions can be confidently drawn about the cost-effectiveness of pimecrolimus or tacrolimus compared with active topical corticosteroid comparators. Areas for further research should focus on the effectiveness and safety of the treatments through good-quality RCTs and further economic analysis.

Adrenal Cortex Hormones↗

PubMed2006

The clinical and cost-effectiveness of oxaliplatin and capecitabine for the adjuvant treatment of colon cancer: systematic review and economic evaluation.

OBJECTIVES: To assess the clinical and cost-effectiveness of oxaliplatin in combination with 5-fluorouracil/leucovorin (5-FU/LV), and capecitabine monotherapy (within their licensed indications), as adjuvant therapies in the treatment of patients with Stage III (Dukes' C) colon cancer after complete surgical resection of the primary tumour, as compared with adjuvant chemotherapy with an established fluorouracil-containing regimen. DATA SOURCES: Ten electronic bibliographic databases were searched from inception to January 2005. Searches were supplemented by hand searching relevant articles, sponsor and other submissions of evidence to the National Institute of Health and Clinical Excellence and conference proceedings. REVIEW METHODS: A systematic review and meta-analysis (where appropriate) of clinical efficacy evidence and a cost-effectiveness review and economic modelling were carried out. Marginal costs, life years gained and cost-effectiveness acceptability curves were estimated. Probabilistic sensitivity analysis was used to generate information on the likelihood that each of the interventions was optimal. RESULTS: Three randomised active-controlled trials, of varying methodological quality, were included in the review. The MOSAIC trial and NSABP C-07 study considered the addition of oxaliplatin to adjuvant treatment (albeit administered in different 5-FU/LV regimens) and the X-ACT study compared oral capecitabine with bolus 5-FU/LV alone. A review of the available evidence indicated that in patients with Stage III colon cancer, oxaliplatin in combination with an infusional de Gramont schedule of 5-FU/LV (FOLFOX4) was more effective in preventing and delaying disease recurrence than infusional 5-FU/LV alone (de Gramont regimen). Serious adverse events and treatment discontinuations due to toxicity were more evident with oxaliplatin-based regimens (FOLFOX4 and FLOX regimen) than infusional or bolus 5-FU/LV alone (de Gramont and Roswell Park regimen). Oral capecitabine was at least equivalent in disease-free survival to the bolus Mayo Clinic 5-FU/LV regimen for patients with resected Stage III colon cancer. Although, the safety and tolerability profile of capecitabine was superior to that of the Mayo Clinic 5-FU/LV regimen, it has not been evaluated in comparison with other less toxic 5-FU/LV regimens currently in common use in the UK. Based on the assumptions and survival analysis methods used, the cost-effectiveness analysis using economic modelling estimated that capecitabine was a dominating strategy and resulted in a cost-saving of approximately pound 3320 per patient in comparison with the Mayo Clinic 5-FU/LV regimen, while also providing an additional 0.98 quality-adjusted life-years (QALYs) over a 50-year model time horizon. Oxaliplatin in combination with 5-FU/LV (FOLFOX4 regimen) is estimated to cost an additional pound 2970 per QALY gained when compared with the de Gramont 5-FU/LV regimen and demonstrated superior survival outcomes with marginal costs. The uncertainty analysis suggests that both interventions have a high probability of being cost-effective at a threshold of both pound 20,000 and pound 30,000. An indirect comparison of the FOLFOX4 and Mayo Clinic 5-FU/LV regimens suggests that the use of FOLFOX4 in place of the Mayo Clinic 5-FU/LV regimen would cost an additional pound 5777 per QALY gained. An incremental cost-effectiveness ratio (ICER) is estimated to be approximately pound 13,000 per QALY gained from treatment with FOLFOX4 compared with capecitabine. However, if the Mayo Clinic and the de Gramont 5-FU/LV regimens are assumed to be equivalent in terms of effectiveness, the ICER of FOLFOX4 in comparison with capecitabine may be greater than pound 30,000 per QALY. CONCLUSIONS: The evidence suggests that both capecitabine and FOLFOX4 are clinically effective and cost-effective in comparison with 5-FU/LV regimens (Mayo Clinic and de Gramont schedules). Further research is suggested into the effectiveness, tolerability, patient acceptability and costs of different oxaliplatin/fluoropyrimidine schedules in the adjuvant setting; the effects of treatment duration on efficacy; adverse events; resource data collection strategies and reporting of summary statistics; subgroups benefiting most from adjuvant chemotherapy; and methods for estimating mean survival.

Antimetabolites, Antineoplastic↗

PubMed2005

Newborn screening for congenital heart defects: a systematic review and cost-effectiveness analysis.

OBJECTIVES: To provide evidence to inform policy decisions about the most appropriate newborn screening strategy for congenital heart defects, identifying priorities for future research that might reduce important uncertainties in the evidence base for such decisions. DATA SOURCES: Electronic databases. Groups of parents and health professionals. REVIEW METHODS: A systematic review of the published medical literature concerning outcomes for children with congenital heart defects was carried out. A decision analytic model was developed to assess the cost-effectiveness of alternative screening strategies for congenital heart defects relevant to the UK. A further study was then carried out using a self-administered anonymous questionnaire to explore the perspectives of parents and health professionals towards the quality of life of children with congenital heart defects. The findings from a structured review of the medical literature regarding parental experiences were linked with those from a focus group of parents of children with congenital heart defects. RESULTS: Current newborn screening policy comprises a clinical examination at birth and 6 weeks, with specific cardiac investigations for specified high-risk children. Routine data are lacking, but under half of affected babies, not previously identified antenatally or because of symptoms, are identified by current newborn screening. There is evidence that screen-positive infants do not receive timely management. Pulse oximetry and echocardiography, in addition to clinical examination, are alternative newborn screening strategies but their cost-effectiveness has not been adequately evaluated in a UK setting. In a population of 100,000 live-born infants, the model predicts 121 infants with life-threatening congenital heart defects undiagnosed at screening, of whom 82 (68%) and 83 (69%) are detected by pulse oximetry and screening echocardiography, respectively, but only 39 (32%) by clinical examination alone. Of these, 71, 71 and 34, respectively, receive a timely diagnosis. The model predicts 46 (0.5%) false-positive screening diagnoses per 100,000 infants with clinical examination, 1168 (1.3%) with pulse oximetry and 4857 (5.4%) with screening echocardiography. The latter includes infants with clinically non-significant defects. Total programme costs are predicted of pound 300,000 for clinical examination, pound 480,000 for pulse oximetry and pound 3.54 million for screening echocardiography. The additional cost per additional timely diagnosis of life-threatening congenital heart defects ranges from pound 4900 for pulse oximetry to pound 4.5 million for screening echocardiography. Including clinically significant congenital heart defects gives an additional cost per additional diagnosis of pound 1500 for pulse oximetry and pound 36,000 for screening echocardiography. Key determinants for cost-effectiveness are detection rates for pulse oximetry and screening echocardiography. Parents and health professionals place similar values on the quality of life outcomes of children with congenital heart defects and both are more averse to neurological than to cardiac disability. Adverse psychosocial effects for parents are focused around poor management and/or false test results. CONCLUSIONS: Early detection through newborn screening potentially can improve the outcome of congenital heart defects; however the current programme performs poorly, and lacks monitoring of quality assurance, performance management and longer term outcomes. Pulse oximetry is a promising alternative newborn screening strategy but further evaluation is needed to obtain more precise estimates of test performance and to inform optimal timing, diagnostic and management strategies. Although screening echocardiography is associated with the highest detection rate, it is the most costly strategy and has a 5% false-positive rate. Improving antenatal detection of congenital heart defects increases the cost per timely postnatal diagnosis afforded by any newborn screening strategy but does not alter the relative effects of the strategies. An improvement of timely management of screen positive infants is essential. Further research is required to refine the detection rate and other aspects of pulse oximetry, to evaluate antenatal screening strategies more directly, and to investigate the psychosocial effects of newborn screening for congenital heart defects.

Adolescent↗

PubMed2007

Pemetrexed disodium for the treatment of malignant pleural mesothelioma: a systematic review and economic evaluation.

OBJECTIVES: To assess the clinical effectiveness and cost-effectiveness of pemetrexed disodium in combination with cisplatin for the treatment of unresectable pleural mesothelioma in chemotherapy-naive patients. DATA SOURCES: Electronic databases were searched up to May 2005. REVIEW METHODS: The systematic review was conducted following accepted guidelines. An assessment of the economic submission received from the manufacturer of pemetrexed was also carried out. This comprised two sections, each employing an economic model. One of these models was then reformulated in order to carry out a separate exploration of economic performance. RESULTS: One randomised controlled trial comparing pemetrexed and cisplatin with cisplatin alone, and involving a total study population of 448 patients, met the inclusion criteria. Pemetrexed in combination with cisplatin in this trial showed a 2.8-month gain in median survival compared with cisplatin alone in an intention-to-treat (ITT) population (12.1 and 9.3 months, respectively, p = 0.020, hazard ratio of 0.77). During the trial, increased reporting of severe toxicity in the pemetrexed arm led to a change in the protocol to add folic acid and vitamin B12 supplementation to therapy. For fully supplemented patients (n = 331) the hazard ratio for median survival in favour of pemetrexed plus cisplatin was also comparable (0.75), but of borderline significance between treatment arms (p = 0.051). The trial inclusion criteria restricted recruitment to those with a Karnofsky performance status of 70 or greater (equivalent to ECOG/WHO 0 or 1 scales more widely used in the UK). Quality of life scores using the Lung Cancer Symptom Scale demonstrated significantly greater improvement for pain and dyspnoea for patients in the combination group compared with those in the cisplatin group. In the ITT population, the incidence of serious toxicities with pemetrexed plus cisplatin was higher compared with cisplatin alone. However, the grade 3/4 toxicities of the combination arm, particularly leucopenia, neutropenia and diarrhoea, were found to be greatly improved by the addition of vitamin B12 and folic acid. The existing published economic literature was very limited. The economic evaluation conducted by the study (and that submitted by the manufacturer) suggested that pemetrexed is unlikely to be considered cost-effective at conventionally accepted thresholds in the UK for all patients, mainly because of the high cost of pemetrexed itself compared with cisplatin. These findings were better for some patient subgroups, e.g. especially for fully supplemented (FS) patients with good performance status (0/1) and advanced disease (AD). These findings seem robust. The estimated cost-effectiveness results were for the FS population, incremental cost-effectiveness ratio (ICER) per quality-adjusted life-year (QALY) gained = pound59,600; for the FS with AD population, ICER per QALY = pound47,600; for the FS with performance status 0/1 population, ICER per QALY = pound49,800; and for the FS with performance status 0/1 and AD population, ICER per QALY = pound36,700. CONCLUSIONS: The new therapy examined in this document demonstrates an extension of life expectancy and palliation, as measured by time to progression of disease and other end-points. However, the absolute benefit obtained is small, and it needs to be weighed against the benefits of effective palliative care services. The limited benefit was also at the expense of considerable toxicity to patients. The economic evaluation conducted in this study and that of the manufacturers suggest that pemetrexed is not cost-effective at conventional thresholds for all patients. Cost-effectiveness seems better for some patient subgroups, e.g. especially for patients with good performance status and with advanced diseases, where it is estimated the ICER per QALY would be pound36,700. Given the relatively small number of patients with mesothelioma, albeit increasing, the overall budget impact of pemetrexed would be unlikely to be more than pound5 million per year at present costs. Much more research is needed into the optimum chemotherapy for patients with mesothelioma and a clear definition of what constitutes best supportive care.

Antineoplastic Agents↗

PubMed2005

Clinical effectiveness and cost-effectiveness of drotrecogin alfa (activated) (Xigris) for the treatment of severe sepsis in adults: a systematic review and economic evaluation.

OBJECTIVES: To assess the clinical and cost-effectiveness of drotrecogin alfa (activated) for the treatment of adults with severe sepsis in a UK context. DATA SOURCES: Electronic databases. Data from the commercial use of the drug up to April 2002. Data from the manufacturer submission to the National Institute for Clinical Excellence (NICE). REVIEW METHODS: A systematic review of the literature and an economic evaluation were undertaken. Data were synthesised through a narrative review with full tabulation of results from included studies. RESULTS: The evidence on the effectiveness of drotrecogin alfa (activated) for the treatment of severe sepsis came primarily from one large pivotal randomised controlled trial, the PROWESS study. This study demonstrated a statistically significant absolute reduction in 28-day mortality of 6.5%. Longer term survival benefit was maintained to 90 days. By 9 months, the trend towards increased median survival was non-significant, although the survival curves did not cross. Results presented by the number of organ dysfunctions were not statistically significant, but when mortality rates for those with two or more organ failures were combined, the relative risk of death was significantly lower in those treated with drotrecogin alfa (activated) compared with placebo. However, this report highlights a number of considerations relevant to the subgroup analyses reported for the PROWESS study. Published cost-effectiveness studies of treatment with drotrecogin alfa (activated) have applied a range of methods to the estimation of benefits, estimating an incremental gain per treated patient of between 0.38 and 0.68 life-years (for patients with severe sepsis). For patients with severe sepsis and multiple organ dysfunction, the manufacturer (Eli Lilly) estimated an incremental gain of 1.115 life-years per treated patient, compared to 1.351 life-years per treated patient estimated by the Southampton Health Technology Assessments Centre (SHTAC). These latter UK analyses are based on a patient group that is more severely affected by disease, where effectiveness is greater and the baseline risk of all-cause mortality is much higher (SHTAC analysis), these factors are associated with the noted difference in effect. The three published cost-effectiveness studies report cost for US and Canadian patient groups; for those patients with severe sepsis they report the additional cost per patient treated in a range around 10,000-16,000 dollars. The manufacturer's submission reports analysis for the UK, based on 28-day survival data in patients with severe sepsis and multiple organ dysfunction (the European licence indication), with the additional mean cost per treated patient estimated to be 5106 pounds. The analysis undertaken by SHTAC, for a UK group of patients with severe sepsis and multiple organ dysfunction, estimates an additional mean cost per patient treated of 6661 pounds. The manufacturer's submission to NICE presents cost-effectiveness estimates for drotrecogin alfa (activated) in the UK, in patients with severe sepsis and multiple organ dysfunction, at 6637 pounds per quality-adjusted life-year (QALY) based on 28-day effectiveness data, and 10,937 pounds per QALY based on longer term follow-up data. SHTAC developed an independent cost-effectiveness model and estimated a base-case cost per QALY of 8228 pounds in patients with severe sepsis and multiple organ failure (based on 28-day survival data). Simulation results indicate that where the NHS is willing to pay 20,000 pounds per QALY, drotrecogin alfa (activated) is a cost-effective use of resources in 98.7% of cases. Published economic evaluations report various sensitivity analyses, with results sensitive to changes in the measure of treatment effect, but otherwise studies reported that results were robust to variations in most assumptions used in the cost-effectiveness analysis. CONCLUSIONS: Drotrecogin alfa (activated) plus best supportive care appears clinically and cost-effective compared with best supportive care alone, in a UK cohort of severe sepsis patients, and in the subgroup of more severely affected patients with severe sepsis and multiple organ failure. The introduction of drotrecogin alfa (activated) will involve a substantial additional cost to the NHS. The treatment-eligible population in England and Wales may comprise up to 16,570 patients, with an estimated annual drug acquisition cost of over 80 million pounds, excluding VAT. Further research is required on the longer term impact of drotrecogin alfa (activated) on both mortality and morbidity in UK patients with severe sepsis, on the clinical and cost-effectiveness of drotrecogin alfa (activated) in children (under 18 years) with severe sepsis, and on the effect of the timing of dosage and duration of treatment on outcomes in severe sepsis.

Adolescent↗

PubMed2002

An evaluation of systematic reviews of palliative care services.

This review aimed to identify and appraise all systematic reviews of palliative care services, to examine their findings in relation to methods used, and to explore whether further methods such as meta-analysis and meta-regression may be worthwhile. Ten databases were searched and augmented by hand searching specific journals, contacting authors, and examining the reference lists of all papers retrieved. Five systematic reviews met the inclusion criteria, and the update electronic search identified a further systematic review which found similar studies. A total of 39 studies were identified by the five systematic reviews. Of the 39 studies, 15 were RCTS, and 12 of those were North American. In comparison, the majority of U.K. studies were retrospective. Each review concluded similarly that there was a lack of good quality evidence on which to base conclusions. The more recent reviews were more rigorous, but none used a quantitative analysis. Despite the difficulties in combining heterogeneous interventions and outcomes in meta-analysis or meta-regression, such techniques may be valuable. More high quality evidence is needed to compare the relative merits of the differences in models of palliative care services, so that countries can learn from other appropriate systems of care at end of life.

Humans↗

PubMed2000

Systematic review and meta-analysis in anatomic pathology.

Systematic reviews and meta-analyses are techniques of data retrieval and analysis which complement traditional narrative reviews. They are widely used in clinical medicine and are finding an increasing role in anatomical pathology. Performing high quality systematic review and meta-analysis requires the accumulation of large numbers of cases from well planned and executed studies and is facilitated if data is presented in a standardized manner. Techniques which allow data from individual patients included in a variety of different studies are now being developed indicating that in future research papers may require a more detailed description of results than in the past. This need may be met by posting anonymised data on the Internet. Systematic reviews and meta-analyses are never complete since data are continually contributed and analyses constantly updated. As with any research paper, the results of these techniques require careful evaluation and the role of the expert reviewer is enlarged by these methodologies.

Humans↗

PubMedDate not supplied

Duration of short-term indwelling catheters--a systematic review of the evidence.

OBJECTIVE: A systematic review on the effect of duration of catheterization on urinary retention. MATERIALS AND METHODS: Published and unpublished randomized and nonrandomized control trials from January 1966 to July 2004 comparing the effects of duration of catheterization on patient outcomes were systematically reviewed. Relative risks (RR) for dichotomous data and a weighted mean difference for continuous data were calculated with 95% confidence intervals (CI). Where synthesis was inappropriate, a narrative overview was undertaken. RESULTS: Eight trials were included. Two trials on patients following urethrotomy demonstrated no statistically significant difference in the number of patients developing restenosis, epididymitis, or urethral pain at any follow-up periods. Two trials comparing removal of the indwelling urethral catheter within 24-48 hours to usual surgical criteria after transurethral surgery demonstrated no statistically significant difference in the number of patients requiring recatheterization. However, significant reduction in the length of hospitalization was reported after removal of the indwelling urethral catheter within 24-48 hours. An increased risk of urinary tract infection was found when the catheter was removed after 48 hours. Catheter removal on day 1 compared to day 3 after vaginal or retropubic surgery demonstrated no statistically significant difference in urinary retention or urinary tract infection. CONCLUSIONS: No significant differences in patient outcome were found, but the timing of catheter removal is a balance between avoiding infection by early removal and circumventing voiding dysfunction by later removal. Shorter catheterizations appear to reduce mean length of hospital stay.

Catheters, Indwelling↗

PubMed2001

Factors of the innovation, organization, environment, and individual that predict the influence five systematic reviews had on public health decisions.

OBJECTIVE: To determine the extent to which systematic reviews of public health interventions influenced public health decisions and which factors were associated with influencing these decisions. METHODS: This cross-sectional follow-up survey evaluated the use of five systematic reviews in public health decision making. Independent variables included characteristics of the innovation, organization, environment, and individual. Primary data were collected using a telephone survey and a self-administered organizational demographics questionnaire. Public health decision makers in all 41 public health units in Ontario were invited to participate in the study. Multiple linear regression analyses on the five program decisions were conducted. RESULTS: The systematic reviews were perceived as having the greatest amount of influence on decisions related to program justification and program planning, and the least influence on program evaluation decisions. The greater the perception that one's organization valued the use of research evidence for decision making and that ongoing training in the critical appraisal of research literature was provided, the greater the perception of the influence the systematic review had on public health decisions. CONCLUSIONS: Organizational characteristics are important predictors of the use of systematic reviews in public health decision making. Future dissemination strategies need to promote the value of using systematic reviews for program decision making as well as promote ongoing training in critical appraisal among intended users in Ontario.

Cross-Sectional Studies↗

PubMed2005

Non-somatic effects of patient aggression on nurses: a systematic review.

AIM: This paper describes a systematic review of the predominant non-somatic effects of patient assault on nurses. Background. Patient aggression towards nurses is a longstanding problem in most nursing domains. Although reports on the consequences of physical aggression are more numerous, the non-physical effects create much suffering. METHOD: A systematic review of literature from 1983 to May 2003 was conducted using the Medline, CINAHL, PsychINFO and PSYINDEX databases. Articles from international journals in English or German and reporting at least three non-somatic responses to patient aggression were included. FINDINGS: The electronic search produced 6616 articles. After application of the inclusion and exclusion criteria, 25 texts from eight countries and four domains of nursing remained. Twenty-eight main effects were found, and these were categorized using a system suggested by Lanza and including bio-physiological, emotional, cognitive, and social dimensions. The predominant responses were anger, fear or anxiety, post-traumatic stress disorder symptoms, guilt, self-blame, and shame. These main effects occurred across most countries and nursing domains. CONCLUSION: Despite differing countries, cultures, research designs and settings, nurses' responses to patient aggression are similar. Standardized questionnaires could help improve estimations of the real prevalence of non-somatic effects. Given the suffering caused by non-somatic effects, research should be aimed at preventing patient aggression and at developing better ways to prepare nurses to cope with this problem.

Aggression↗

PubMed2006

Systematic reviews of surgical interventions.

All physicians are familiar with the type of general review articles found in many medical journals. Systematic reviews are different. They apply a strict, scientific methodology to the reviewing process to produce a review that is comprehensive, reliable, and as free from bias as possible. As a result, systematic reviews occupy the highest position in the "levels of evidence" tables associated with the practice of evidence-based health care. Systematic reviews relevant to surgery are no less relevant than systematic reviews in other areas of health care. They should be a prerequisite of any new research, a key component in decision making, and an opportunity for all surgical practitioners to get involved in the conduct and interpretation of research.

Bias↗

PubMed2006

Nursing diagnoses, interventions and outcomes - application and impact on nursing practice: systematic review.

AIM: This paper reports a systematic review on the outcomes of nursing diagnostics. Specifically, it examines effects on documentation of assessment quality; frequency, accuracy and completeness of nursing diagnoses; and on coherence between nursing diagnoses, interventions and outcomes. BACKGROUND: Escalating healthcare costs demand the measurement of nursing's contribution to care. Use of standardized terminologies facilitates this measurement. Although several studies have evaluated nursing diagnosis documentation and their relationship with interventions and outcomes, a systematic review has not been carried out. METHOD: A Medline, CINAHL, and Cochrane Database search (1982-2004) was conducted and enhanced by the addition of primary source and conference proceeding articles. Inclusion criteria were established and applied. Thirty-six articles were selected and subjected to thematic content analysis; each study was then assessed, and a level of evidence and grades of recommendations assigned. FINDINGS: Nursing diagnosis use improved the quality of documented patient assessments (n = 14 studies), identification of commonly occurring diagnoses within similar settings (n = 10), and coherence among nursing diagnoses, interventions, and outcomes (n = 8). Four studies employed a continuing education intervention and found statistically significant improvements in the documentation of diagnoses, interventions and outcomes. However, limitations in diagnostic accuracy, reporting of signs/symptoms, and aetiology were also reported (14 studies). One meta-analysis of eight trials including 1497 patients showed no evidence that standardized electronic documentation of nursing diagnosis and related interventions led to better nursing outcomes. CONCLUSION: Despite variable results, the trend indicated that nursing diagnostics improved assessment documentation, the quality of interventions reported, and outcomes attained. The study reveals deficits in reporting of signs/symptoms and aetiology. Consequently, staff educational measures to enhance diagnostic accuracy are recommended. The relationships among diagnoses, interventions and outcomes require further evaluation. Studies are needed to determine the relationship between the quality of documentation and practice.

Humans↗