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PubMed2003

Anorexia nervosa: the cost of long-term disability.

This study was performed to estimate the cost of long-term disability in people who have anorexia nervosa (AN) that live in the province of British Columbia (BC), Canada. Canada provides universal socialized health and welfare services, and each of the 10 provinces is responsible for its own funding. As the provincial government of BC does not categorize its disability payments by the cause of the disability, a survey was used to determine the rate of disability from AN. A sensitivity analysis was performed to assess the influence of variations on the yearly cost of disability in BC: the number of patients with AN was varied between 1.0 and 2.0% of the female and 0.05 and 0.1% of the male population; the percentage of patients with AN receiving disability payments was determined by the survey to be 35%; the cost of these payments was varied between the lowest and highest benefits a single person can receive from the BC provincial government; and finally, to allow for possible sampling bias and a possible lower prevalence of AN, the lower limit of the sensitivity analysis was derived by dividing the lowest estimate above by seven. The sensitivity analysis revealed that the total estimated cost of long-term disability in BC could be as low as $2.5 million (Canadian) or as high as $101.7 million per year, which is a cost of up to 30 times the total yearly cost of all tertiary care services for the treatment of eating disorders in BC. In view of this finding, an increase in funding is warranted for primary, secondary and tertiary prevention programs for AN in BC.

Adolescent↗

PubMed2005

Treatment alternatives for chronic hepatitis B virus infection: a cost-effectiveness analysis.

BACKGROUND: Treatment options for chronic hepatitis B virus (HBV) infection have disparate risks and benefits. Interferon has clinically significant side effects, and lamivudine is associated with viral resistance. In contrast, adefovir is safe and has lower viral resistance but is more expensive. The most cost-effective approach is uncertain. OBJECTIVE: To determine whether and under what circumstances the improved efficacy of adefovir offsets its increased cost compared with lamivudine or interferon. DESIGN: Cost-utility analysis stratified by hepatitis B e antigen (HBeAg) status. DATA SOURCES: Systematic review of MEDLINE from 1970 to 2005. TARGET POPULATION: Patients with chronic HBV infection, elevated aminotransferase levels, and no cirrhosis. TIME HORIZON: Lifetime. PERSPECTIVE: Third-party payer. INTERVENTIONS: 1) No HBV treatment ("do nothing" strategy), 2) interferon monotherapy, 3) lamivudine monotherapy, 4) adefovir monotherapy, or 5) lamivudine with crossover to adefovir upon resistance ("adefovir salvage" strategy). OUTCOME MEASURE: Incremental cost per quality-adjusted life-year (QALY) gained. RESULTS OF BASE-CASE ANALYSIS: The "do nothing" strategy was least effective yet least expensive. Compared with the "do nothing" strategy, using interferon cost an incremental 6337 dollars to gain 1 additional QALY. Compared with interferon, the adefovir salvage strategy cost an incremental 8446 dollars per QALY gained. Both the lamivudine and adefovir monotherapy strategies were more expensive yet less effective than the alternative strategies and were therefore dominated. RESULTS OF SENSITIVITY ANALYSIS: In sensitivity analysis, interferon was most cost-effective in health care systems with tight budgetary constraints and a high prevalence of HBeAg-negative patients. LIMITATIONS: These results apply only to patients with chronic HBV infection, elevated aminotransferase levels, and no clinical or histologic evidence of cirrhosis. They do not apply to alternative populations. CONCLUSIONS: Neither lamivudine nor adefovir monotherapy is cost-effective in chronic HBV infection. However, a hybrid salvage strategy reserving adefovir only for lamivudine-associated viral resistance may be highly cost-effective across most health care settings. Interferon therapy may still be preferred in health care systems with limited resources, especially in those serving populations with a high prevalence of HBeAg-negative HBV.

Adenine↗

PubMed2005

Cost-effectiveness of pathogen inactivation for platelet transfusions in the Netherlands.

The objective of this study is to estimate cost-effectiveness of pathogen inactivation for platelet transfusions in the Netherlands. We used decision tree analysis to evaluate the cost-effectiveness of the addition of pathogen inactivation of pooled platelets to standard procedures for platelet transfusion safety (such as, donor recruitment and screening). Data on transfusions were derived from the University Medical Centre Groningen (the Netherlands) for 1997. Characteristics of platelet recipients (patient group, age, gender and survival) and data/assumptions on viral and bacterial risks were linked to direct and indirect costs/benefits of pathogen inactivation. Post-transfusion survival was simulated with a Markov model. Standard methods for cost-effectiveness were used. Cost-effectiveness was expressed in net costs per life-year gained (LYG) and estimated in baseline- and sensitivity analysis. Sensitivity was analysed with respect to various assumptions including sepsis risk, reduction of the discard rate and discounting. Stochastic analysis to derive 90% simulation intervals (SIs) was performed on sepsis risk. Net costs per LYG for pathogen inactivation were estimated 554,000 euro in the baseline-weighted average over the three patient groups (90% SI: 354,000-1092,500 euro). Sensitivity analysis revealed that cost-effectiveness was insensitive to viral risks and indirect costing, but highly sensitive to the assumed excess transfusions required and discounting of LYG. Given relatively high net costs per LYG that are internationally accepted for blood transfusion safety interventions, our estimated cost-effectiveness figures for pathogen inactivation may reflect acceptable cost-effectiveness in this specific area. Two main assumptions of our model were that the pathogen inactivation was 100% effective in preventing transmission of the pathogens considered and was not associated with major and/or costly adverse reactions. Validation of several crucial parameters is required, in particular the Dutch risk for acquiring and dying of transfusion-related sepsis.

Adolescent↗

PubMed1992

Sensitivity of lod scores to changes in diagnostic status.

This paper investigates effects on lod scores when one individual in a data set changes diagnostic or recombinant status. First we examine the situation in which a single offspring in a nuclear family changes status. The nuclear-family situation, in addition to being of interest in its own right, also has general theoretical importance, since nuclear families are "transparent"; that is, one can track genetic events more precisely in nuclear families than in complex pedigrees. We demonstrate that in nuclear families log10 [(1-theta)/theta] gives an upper limit on the impact that a single offspring's change in status can have on the lod score at that recombination fraction (theta). These limits hold for a fully penetrant dominant condition and fully informative marker, in either phase-known or phase-unknown matings. Moreover, log10 [(1-theta)/theta] (where theta denotes the value of theta at which Zmax occurs) gives an upper limit on the impact of a single offspring's status change on the maximum lod score (Zmax). In extended pedigrees, in contrast to nuclear families, no comparable limit can be set on the impact of a single individual on the lod score. Complex pedigrees are subject to both stabilizing and destabilizing influences, and these are described. Finally, we describe a "sensitivity analysis," in which, after all linkage analysis is completed, every informative individual in the data set is changed, one at a time, to see the effect which each separate change has on the lod scores. The procedure includes identifying "critical individuals," i.e., those who would have the greatest impact on the lod scores, should their diagnostic status in fact change. To illustrate use of the sensitivity analysis, we apply it to the large bipolar pedigree reported by Egeland et al. and Kelsoe et al. We show that the changes in lod scores observed there, on the order of 1.1-1.2 per person, are not unusual. We recommend that investigators include a sensitivity analysis as a standard part of reporting the results of a linkage analysis.

Female↗

PubMed2001

Structural asymmetry as a dermatoscopic indicator of malignant melanoma--a latent class analysis of sensitivity and classification errors.

Asymmetry of pigmented skin lesions is an important indicator of possible malignant melanoma and contributes substantially to the diagnosis of melanoma in the dermatoscopic ABCD rule for melanocytic lesions and other algorithms. However, it may be observer dependent. Dermatoscopic asymmetry cannot be assessed objectively and no golden standard of asymmetry diagnosis exists. The aim of this study was to assess the sensitivity of axis (a-) symmetry using latent class analysis. We analysed ratings from four experts in dermatoscopy of 232 pigmented lesions by latent class analysis (LCA). Possible ratings were 'no asymmetry', 'asymmetry in one axis' and 'asymmetry in two axes'. A subset of melanocytic lesions (blue naevi excluded) was analysed. Based on LCA, the asymmetry of the singular lesion was determined. The sensitivity of 'no asymmetry' was 40-77%, 40-70% for one-axis asymmetry, and 77-92% for two-axes asymmetry. Overestimation of asymmetry was more common than underestimation. Melanomas were significantly more asymmetric than pigmented naevi, atypical naevi and papillomas, but not basal cell cancers. Analysis of the melanocytic subset gave similar results. The median asymmetry of malignant melanomas (1.67, interquartile range 1.81-1.99) was higher than for melanocytic naevi. In conclusion, asymmetry and symmetry are important criteria for diagnosing or excluding malignant melanoma using the dermatoscopic ABCD rule, risk stratification and other diagnostic rules. Using LCA, we minimized observer dependence in the assessment of axis (a-) symmetry. LCA, besides conceptualizing the diagnostic process, enables the assignment of lesions to their true diagnostic class.

Basal Cell Carcinoma↗

PubMed2006

Evaluating linguistic equivalence of patient-reported outcomes in a cancer clinical trial.

BACKGROUND: In order to make meaningful cross-cultural or cross-linguistic comparisons of health-related quality of life (HRQL) or to pool international research data, it is essential to create unbiased measures that can detect clinically important differences. When HRQL scores differ between cultural/linguistic groups, it is important to determine whether this reflects real group differences, or is the result of systematic measurement variability. PURPOSE: To investigate the linguistic measurement equivalence of a cancer-specific HRQL questionnaire, and to conduct a sensitivity analysis of treatment differences in HRQL in a clinical trial. METHODS: Patients with newly diagnosed chronic myelogenous leukemia (n = 1049) completed serial HRQL assessments in an international Phase III trial. Two types of differential item functioning (uniform and non-uniform) were evaluated using item response theory and classical test theory approaches. A sensitivity analysis was conducted to compare HRQL between treatment arms using items without evidence of differential functioning. RESULTS: Among 27 items, nine (33%) did not exhibit any evidence of differential functioning in both linguistic comparisons (English versus French, English versus German). Although 18 items functioned differently, there was no evidence of systematic bias. In a sensitivity analysis, adjustment for differential functioning affected the magnitude, but not the direction or interpretation of clinical trial treatment arm differences. LIMITATIONS: Sufficient sample sizes were available for only three of the eight language groups. Identification of differential functioning in two-thirds of the items suggests that current psychometric methods may be too sensitive. CONCLUSIONS: Enhanced methodologies are needed to differentiate trivial from substantive differential item functioning. Systematic variability in HRQL across different groups can be evaluated for its effect upon clinical trial results; a practice recommended when data are pooled across cultural or linguistic groups to make conclusions about treatment effects.

Clinical Trials, Phase III as Topic↗

PubMed2004

Cost utility of photodynamic therapy for predominantly classic neovascular age related macular degeneration.

BACKGROUND/AIM: Age related macular degeneration (AMD) is the leading cause of severe vision impairment and blindness in older people throughout the developed world and currently affects around 420 000 UK citizens. Choroidal neovascularisation (CNV) is treatable with photodynamic therapy (PDT) but is expensive at over pound 1200 per treatment. The aim of this study was to assess the cost utility of PDT for better eye, predominantly classic, subfoveal choroidal neovascular lesions secondary to AMD. METHODS: Cost utility analysis (CUA) was conducted to estimate the cost effectiveness of PDT for scenarios involving reasonable (6/12) and poor (6/60) visual acuity. The models incorporated data from the Treatment of Age-related Macular Degeneration with PDT (TAP) Study and patient based utilities. The incremental CUA was based on decision analytical models, comparing treatment to a placebo comparator. Extensive one way sensitivity analysis of parameters was conducted to determine the robustness of the model. A discount rate of 6% was used for costs and quality adjusted life years (QALY). RESULTS: Model 1: in people with reasonable initial visual acuity, the cost utility of treating applicable neovascular AMD lesions was pound 31 607 per QALY saved, with a sensitivity analysis range from pound 25 285 to pound 37 928. Model 2: in people with poor initial visual acuity, the cost utility was pound 63 214 per QALY saved, with a sensitivity analysis range from pound 54 183 to pound 75 856. CONCLUSIONS: PDT treatment is the only available treatment for some forms of neovascular ("wet") AMD. Under these assumptions, PDT can be considered moderately cost effective for those with reasonable visual acuity but less cost effective for those with initial poor visual acuity. These findings have implications for ophthalmic practice and healthcare planning.

Aged↗

PubMed1994

Recombinant human erythropoietin vs transfusions in the treatment of anemia of prematurity. A cost-benefit analysis.

OBJECTIVE: To evaluate the costs relative to the benefits of using recombinant human erythropoietin (rHuEPO) therapy as an alternative to red blood cell (RBC) transfusions in infants with anemia of prematurity. DESIGN: A cost-benefit analysis of rHuEPO therapy was performed based on its use in very-low-birth-weight premature infants. SETTING AND PATIENTS: Data were drawn from published studies or were provided by the University of Iowa Hospitals and Clinics, Iowa City. MAIN OUTCOME MEASURES: Costs and benefits were analyzed as a comparison of incurred costs to averted costs. Incurred and averted costs of rHuEPO therapy and RBC transfusions included direct product costs and estimates of costs of adverse events. The analysis was viewed in terms of net savings. Sensitivity analysis was performed. RESULTS: The base case analysis yielded a net loss of $299.48 per infant. A 54% reduction in the direct product costs of rHuEPO therapy yielded a break-even point. No other variations in the sensitivity analysis resulted in a net savings. CONCLUSION: Using assumptions based on the current state of clinical research, it appears that routine use of rHuEPO with supplemental RBC transfusions would not generate any cost savings as an alternative to RBC transfusions alone. As further evidence is compiled on the efficacy of rHuEPO therapy in very-low-birth-weight premature infants, the true costs may be better established.

Anemia, Neonatal↗

PubMed2000

A study of biomechanical parameters in gait analysis and sensitive cronaxie of diabetic neuropathic patients.

OBJECTIVE: The present investigation aims at studying the sensitive cronaxie in neuropathic and non-neuropathic diabetic patients as a measure of sensorial deficit. We seek to describe the gait using dynamic and temporal parameters. We have compared the results of the neuropathic patients to the results of a non-diabetic group. We have looked for relationships between peak plantar pressure and sensitive cronaxie in selected plantar areas. DESIGN AND METHODS: The experimental procedures were divided in: (a) determination of the sensitive cronaxie in four selected plantar areas, (b) determination and description of peak plantar pressure, ground reaction force variables and single and double stance time. We analyzed and compared the results of the sensitive cronaxie and the biomechanical parameters obtained by three experimental groups: diabetic, neuropathic and non-diabetic subjects. RESULTS: The pathological response of the sensitive cronaxie worsened progressively for neuropathic and diabetic patients, respectively. Longer double and single stance times, lower minimum vertical force and lower growth rates were seen in the neuropathic patients when compared to diabetic and non-diabetic subjects. CONCLUSIONS: These results indicate an alteration in the neuropathic patient movement structure. We have speculated that compensatory musculoskeletal mechanisms have been developed by neuropathic patients to compensate for their sensorial deficit. Future research is necessary to verify the relationship between neurophysiological and dynamic variables, since this relationship seems to be a good parameter for the interpretation and comprehension of the peripheral neuropathy. RelevancePeripheral neuropathy is one of the most insidious chronic complications of diabetes. It has been observed that dynamic changes in gait are usually associated with the peripheral neuropathy somatosensory deficits. Biomechanical studies have highlighted that dynamic gait evaluation can identify functional alterations, besides the analysis of sensitive cronaxie as a measure of sensorial deficits. They are also useful as a complimentary routine in the clinic treatment of diabetes and its further long-term complications.

Adult↗

PubMedDate not supplied

[Cost effectiveness study on the use of somatostatin for reduction of acute pancreatitis after ERCP].

OBJECTIVES: Recent studies show that intravenous injection of somatostatin before endoscopic retrograde cholangiopancreatography (ERCP) is associated with a significant reduction in the rate of post-ERCP acute pancreatitis. The lack of data in our environment led us to study the possible economic benefits of somatostatin administration, obtained through the reduction of costs due to post-ERCP acute pancreatitis. MATERIAL AND METHODS: Theoretical study of the direct costs of post-ERCP acute pancreatitis using Markov's tree decisions. The costs of the group pre-treated with intravenous administration of 3 mg of somatostatin were compared with those of the control group. Post-ERCP rates of pancreatitis of 10% were accepted in the control group and rates of 3% were accepted in the somatostatin group. The costs of the different types of pancreatitis were as follows: costs with and without complications and with surgical intervention were based on the diagnosis related group-weights applied by the Ministry of Health in the Contract-program of the Health Service of Navarre for 1999. A sensitivity analysis was carried out to determine the rate of post-ERCP pancreatitis from which an economic benefit would be obtained in the group pre-treated with somatostatin. RESULTS: Mean theoretical cost per procedure was 121,640 pesetas for the control group and 105,539 for the group pre-treated with somatostatin. Saving per patient was 13.26% (16,101 pesetas). The sensitivity analysis revealed that in the control group premedication produced an economic benefit starting from a pancreatitis rate of 4.2%. CONCLUSIONS: Independently of the clinical benefit signifying the reduction of post-ERCP pancreatitis, somatostatin administration led to a saving of 16,101 pesetas per patient. Accepting that the pancreatitis rate in the treated group was proportionately reduced, the sensitivity analysis showed that premedication produced an economic benefit starting from a pancreatitis rate of 4.2% in the control group.

Acute Disease↗

PubMed2001

Cost-benefit analysis of social work services in the emergency department: a conceptual model.

OBJECTIVE: To describe an economic model for formal cost-benefit analysis of emergency department (ED)-based social services. METHODS: The varied monetary costs and benefits associated with ED-based social work services were projected for three hypothetical levels of ED volume (30,000, 60,000, and 90,000 patients/year). Primary benefits included the prevention of return ED visits, the prevention of "social" hospital admissions, and the protection of doctor and nurse time. The primary cost was salary support for full-time social work staffing. Sensitivity analysis was performed to account for varying estimates. RESULTS: For a small-volume ED, total benefits to offset costs ranged from $43,869 to $81,504, yielding a net cost of $99,936 up to $137,571 for full-time social work coverage. For a moderate-size ED, total benefits ranged from $87,660 to $162,930, yielding a net cost of only $18,510 on the high end of the sensitivity analysis, and $87,668 on the low end. For a large-volume ED, total benefits ranged from $131,529 to $247,434, yielding a net cost of $49,911 on the low end of the sensitivity analysis, but a net benefit of $65,994 on the high end. CONCLUSIONS: Dedicated social work staffing of EDs may yield net economic benefits, especially in large urban centers. Moderate-size EDs may almost "break even" in economic terms, and small EDs may realize a net cost, but in either case, the cost of social services can be significantly offset by decreased utilization of hospital and ED services, and by more efficient use of medical staff time.

Cost-Benefit Analysis↗

PubMed2006

Circular dichroism thermal lens microscope for sensitive chiral analysis on microchip.

A novel chiral detector, a circular-dichroism thermal lens microscope (CD-TLM), was developed to realize sensitive and selective detection of small volume chiral samples on a microchip. To realize chiral recognition on TLM, an excitation beam was phase-modulated at a frequency of 1.2 kHz, and left-circularly polarized light (LCPL) and right-circularly polarized light (RCPL) were generated. Then, the differential light absorption between LCPL and RCPL, which is the CD effect, was detected as thermal lens signal intensity and phase. As a standard sample, optically active tris(ethylenediamine)cobalt(III) [Co-(en)3]3+I3- aqueous solutions were used for performance evaluations. First, we verified the basic principle for selective chiral analysis by comparing the signals in intensity-modulation and phase-modulation modes of the excitation beam. Also, we found that the g-factor, which is significant for determining enantiomeric excess, agreed well with the value obtained by the CD spectrometer. The limit of detection (LOD) for enantiopure [Co-(en)3]3+I3- was 6.3 x 10(-5) M (1.9 x 10(-7) abs) for (-)-Co(en)3(3+), and the sensitivity in absorbance units was more than 250 times higher than that in a CD spectrophotometer. Finally, we demonstrated enantiomeric excess determination on a microchip. The LOD was 1.7% (8.5 x 10(-7) abs) for (-)-Co(en)3(3+) and at least one order superior to the LOD of a CD spectrometer. The applicability of CD-TLM for sensitive chiral analysis on a microchip was verified, and CD-TLM is expected to be promising for microchip-based chiral synthesis and analysis systems.

Journal Article↗

PubMed1996

Fluconazole versus oral polyenes in the prophylaxis of immunocompromised patients: a cost-minimization analysis.

This study compares 100 mg daily fluconazole with oral polyenes four times daily in the prophylaxis of fungal infections in immunocompromised patients, to determine a cost-minimization strategy. Data was gathered through a literature survey and clinical interviews conducted in nine different UK hospitals. This was used to construct a decision tree, modelling the drug choices available to a clinician at various stages of a patient's treatment, and assigning probabilities to the different corresponding outcomes. UK cost data were fed into this model to determine the expected cost per patient of the different prophylaxis strategies. Two different patient groups were considered: chemotherapy-only patients, and bone-marrow-transplant (BMT) patients who have higher risks of fungal infection. Probabilities derived from the literature suggest that a cost-minimization strategy to manage both chemotherapy patients and BMT patients is to administer oral fluconazole, both as prophylaxis and as first line treatment, against superficial fungal infection. Probabilities gathered from clinical interviews yield similar results, suggesting that the cost-minimization strategy with chemotherapy-only patients is to administer oral polyenes as prophylaxis, and oral fluconazole in case of superficial fungal infection, while for BMT patients it is a combination of fluconazole and oral polyenes as prophylaxis, with oral fluconazole for the treatment of superficial fungal infections. Using the probabilities from the literature, the lowest cost strategies produce an expected cost of pounds 567.20 for chemotherapy-only patients, and an expected cost of pounds 804.87 for BMT patients for a course of treatment lasting from seven to 28 days. The clinical interview probabilities produce expected costs of pounds 826.48 and pounds 1529.43, respectively. Sensitivity analysis was then conducted, and it was found that in the majority of cases, using the literature probabilities, the cost-minimizing strategy remained prophylaxis with oral fluconazole. The sensitivity analysis for chemotherapy-only patients using the interview probabilities tended to favour oral polyenes as the cost-minimization strategy, whereas for BMT patients the sensitivity analysis favoured a combination of fluconazole and oral polyenes in the majority of cases. The key economic advantage of prophylaxis with fluconazole or a combination of fluconazole with oral polyenes in the prophylaxis of fungal infection in immunocompromised patients, results from the reduction of the expected cost of subsequent fungal infection among those who are most at risk.

Antifungal Agents↗

PubMed2005

Evaluation of the cost-effectiveness of sirolimus versus cyclosporin for immunosuppression after renal transplantation in the United Kingdom.

OBJECTIVE: The purpose of this study was to evaluate the cost-effectiveness of sirolimus compared with cyclosporin for the postsurgical management of renal transplant recipients, from the perspective of the UK National Health Service and the Personal Social Service. METHODS: A discrete event stochastic simulation model was developed to evaluate both cost-effectiveness and cost utility over 10 and 20 years after transplant using historical data on 937 renal transplant recipients from the University Hospital of Wales in Cardiff, United Kingdom. The simulation was designed to forecast the incidence of acute rejection events, graft failure, retransplant, frequency of hemodialysis (HD) and peritoneal dialysis (PD), and death. Cox proportional hazard models were derived from historical transplant data, in which 1-, 2-, and 3-year post-transplant serum creatinine levels were used as the key drivers for predicting graft success and survival. Costs were reported as year-2003 UK pounds sterling (1 UK pound = US $1.76). Probabilistic sensitivity analysis was conducted and results reported with particular attention to 2 threshold values, 30,000/QALY and 20,000/QALY RESULTS: Over a 10-year time horizon, treatment with sirolimus was projected to produce a gain of 0.60 discounted year of functioning graft with a cost savings of 276 UK pounds per patient. Over a 20-year time horizon these benefits increased to 1.59 discounted years of functioning graft and a cost savings of 7405 UK pounds per patient. Using sensitivity analysis of the 10-year model, the only factors found to cause the probability of exceeding a 30,000 ceiling to be >5% were the proportion of subjects maintaining continuous graft function and the use of low-dose cyclosporin. With the 20-year model, sirolimus maintained cost-effectiveness across most scenarios in sensitivity analysis. CONCLUSIONS: In this model analysis, sirolimus was cost-effective compared with cyclosporin for 10 to 20 years after renal transplantation in the United Kingdom, from the perspective of the UK National Health Service and Personal Social Service.

Adult↗

PubMed2002

Development of an economic model to assess the cost effectiveness of asthma management strategies.

BACKGROUND AND OBJECTIVE: Asthma is a chronic-episodic disease characterised by acute, symptomatic episodes of varying severity. We developed a Markov model that can be used to estimate the cost effectiveness of alternative asthma treatments. Because of the costs they incur, asthma exacerbations ('attacks') requiring intervention by a healthcare professional were a central consideration in the development of the model. METHODS: Treatment success was assessed as asthma control, a composite measure based on goals defined in world-wide asthma management guidelines and in terms of quality-adjusted life-years (QALYs). The data from which the transition probabilities were derived came from patients with asthma who received either salmeterol/fluticasone propionate combination (SFC) 50/100microg or fluticasone propionate (FP) 100microg, administered twice daily via an inhaler, in a 12-week, randomised, double-blind, clinical trial. Costs were estimated from resource profiles defined for each of the model states. A key aspect of the model was the use of probabilistic sensitivity analysis techniques to examine the uncertainty in the cost-effectiveness results. Distributions were fitted to transition probabilities and to cost input parameters and values were sampled at random from these distributions using a second order Monte Carlo simulation technique. This produced a distribution for incremental cost effectiveness that was employed to construct 95% uncertainty intervals and to construct cost effectiveness acceptability curves. RESULTS: In this analysis, the model was run over a 12-week period using transition probabilities derived from the trial data. The results showed that treatment with SFC resulted in a higher proportion of successfully controlled weeks per patient than treatment with FP (66 vs 47%), and higher mean weekly direct asthma management costs (pound sterling 15.77 vs pound sterling 11.83; 2000 values). The average incremental cost per successfully controlled week with SFC was pound sterling 20.83. Probabilistic sensitivity analysis showed that the 95% uncertainty intervals for the incremental cost-effectiveness ratio was - pound sterling 64.94 to pound sterling 112.66. In approximately 25% of cases, SFC was dominant (more effective and less costly), but in the remaining cases, it was both more effective and more costly. It was shown that if decision makers are willing to pay approximately pound sterling 45 for an additional successfully controlled week, SFC will be the more cost-effective strategy in this patient population for 80% of the time. CONCLUSIONS: This is one of the first decision-analytic models of asthma to incorporate probabilistic sensitivity analysis techniques to explore uncertainty. The model's flexible yet standardised framework permits the cost effectiveness of alternative asthma management strategies in different healthcare settings to be established.

Adolescent↗

PubMed2000

Cisapride treatment for gastro-oesophageal reflux in children.

BACKGROUND: Gastro-oesophageal reflux (GOR) is an extremely common and usually self limiting condition in infants. When treatment is required, Cisapride, a pro-kinetic agent, has been commonly prescribed for the symptomatic management of GOR. There have been recent reports of possibly serious adverse events e.g. an increased QTc interval, cardiac arrhythmias, and death, associated with the use of Cisapride. OBJECTIVES: To determine the effectiveness of Cisapride for symptoms of GOR in children compared with placebo or any other non-surgical treatments. SEARCH STRATEGY: Searches were conducted of the Cochrane Central Trials Register and the specialised Trials register of the Cochrane Upper Gastrointestinal and Pancreatic Diseases Group, MEDLINE and Embase. Reference lists of relevant review articles and identified trials were scrutinised and forward citation searches were performed in the Science Citation Index on all trials identified. SELECTION CRITERIA: Randomised controlled trials that compared oral Cisapride therapy with placebo or with other non-surgical treatments for children with a diagnosis of GOR were included. Only studies in which Cisapride was administered orally for a minimum of one week and which documented at least one of the primary outcomes were included. DATA COLLECTION AND ANALYSIS: The primary outcomes were defined as a change in symptoms at the end of treatment, presence of adverse events, occurrence of clinical complications, and weight gain. The secondary outcomes included physiological measures of GOR or histological evidence of oesophagitis. We dichotomised symptoms into 'same or worse' vs 'improved' and calculated summary odds ratios. Continuous measures of GOR (e.g. reflux index) were summarised as a weighted mean difference. All outcomes were analysed using a random effects method. Sensitivity analyses were also performed. MAIN RESULTS: Searches identified eight trials which met the inclusion criteria. Seven trials (a total of 236 participants) compared Cisapride with placebo. The odds ratio for 'same or worse' vs 'improved symptoms' at the end of treatment was 0.34 (95%CI 0.10, 1.19), thus showing no statistically significant difference between the two interventions. There was significant heterogeneity between the studies and the funnel plot suggested substantial publication bias. In the sensitivity analysis, the definition of outcomes was changed to 'any symptoms' vs 'no symptoms'. This resulted in the exclusion of three trials (one of them the largest, best quality trial). The resulting pooled odds ratio showed a significant effect of Cisapride (OR 0.19, 95%CI 0.08, 0.44). There were fewer adverse events with placebo than with Cisapride, but the difference was not statistically significant (OR 1.80, 95%CI 0.87, 3.70) and the result was based on small numbers. Cisapride compared with placebo produced a statistically significant reduction in the reflux index (weighted mean difference -6.49, 95%CI -10.13, -2.85), but as reflux index and clinical symptoms are poorly correlated, the clinical importance of this finding is uncertain. Other measures of oesophageal pH monitoring did not reach significance. One included study compared Cisapride with Gaviscon (or Gaviscon and Carobel). The odds ratio for 'same or worse' vs 'improvement' in the Cisapride group compared with Gaviscon was 3.26 (95%CI 0.93, 11.38). REVIEWER'S CONCLUSIONS: We found no clear evidence that Cisapride reduces symptoms of GOR. The results suggested substantial publication bias favouring studies showing a positive effect of Cisapride. Due to reports of serious adverse events, the company will stop marketing the drug as of July 14th, 2000 and therefore a larger study to provide more conclusive evidence of the effect of Cisapride is no longer possible.

Alginates↗

PubMed2002

Fast, high-sensitivity, multipesticide analysis of complex mixtures with supersonic gas chromatography-mass spectrometry.

We developed a new instrumental approach, termed Supersonic GC-MS, which achieves fast, sensitive, confirmatory and quantitative analysis of a broad range of pesticides in complex agricultural matrices. Our Supersonic GC-MS system is a modification of a bench-top Agilent 6890 GC+5972 MSD with a supersonic molecular beam (SMB) interface and fly-through EI ion source. One of the main advantages of Supersonic GC-MS is an enhanced molecular ion (M+) in the resulting mass spectra. For example, the M+ was observed in all 88 pesticides that we studied using the Supersonic GC-MS whereas only 36 of 63 (57%) pesticides that we investigated in standard GC-MS exhibited a M+. We also found that the degree of matrix interference is exponentially reduced with the fragment mass by about 20-fold per 100 amu increasing mass. The enhancement of the M+ combined with the reduction in matrix background noise permit rapid full scan analysis of a potentially unlimited number of pesticides, unlike selected ion monitoring or MS-MS in which specific conditions are required in segments for targeted pesticides. Furthermore, unlike the case with chemical ionization, EI-SMB-MS spectra still give accurate identification of compounds using common mass spectral libraries. In practice,we found thatlibraries favor mass spectra in which the M+ appears, thus Supersonic GC-MS produced better spectra for compound identification than standard GC-MS. To achieve even lower identification limits, the M+ plus a second major ion (still using full scan data) gives higher signal-to-chemical noise ratios than the traditional 3-ion approach. The replacement of two low-mass ions with the M+ (supersonic two-ions method) results in a significant reduction of matrix interference by a factor of up to 90. Another main advantage of Supersonic GC-MS is its exceptional suitability for fast GC-MS with high carrier gas flow-rate. Fast Supersonic GC-MS was able to analyze thermally labile pesticides, such as carbamates, that are difficult or impossible to analyze in standard GC-MS. Large volume injection using a ChromatoProbe was also demonstrated, in the 6 min analysis of pesticides at 20 ng/g in a spice matrix.

Gas Chromatography-Mass Spectrometry↗

PubMed1980

Methods and approaches to determine "optimal" quality for clinical chemical data.

Although clinical reasoning and decision-making may be very complex, there are methods to perform both piecemeal and more complete optimizations with regard to the use of clinical chemical data and for assessing quality specification. Some methods and approaches are described and illustrated with examples: (i) rules for propagation of errors in simple algebraic/statistical transformations; (ii) systems and sensitivity analysis using biochemical/pathophysiological simulation models; (iii) systems and sensitivity analysis of simulated clinical classification and decision processes. It is concluded that the possible gain of useful information by improving analytical and pre-analytical quality should be related to the often more important aspects of test selection test and test combination, period and frequency of observation, and the use of correct conceptual models for transformation of data.

Chemistry Techniques, Analytical↗