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PubMed1994

Quantitative analysis of planar technetium-99m Sestamibi myocardial perfusion images. Clinical application of a modified method for the subtracton of tissue crosstalk.

Application of the Thallium-201 quantitative analysis method to Tc-99m Sestamibi planar myocardial perfusion images results in oversubtraction of tissue crosstalk, defined as 'activity within the myocardial image, which originated outside the heart'. A modified algorithm, specific for Tc-99m Sestamibi, was applied in 60 patients and the results of quantitative analysis to estimate the risk of coronary artery disease were compared with coronary angiographic findings and with visual analysis. New crosstalk planes were generated based on the results in 20 male healthy volunteers. The results in our study group indicate a higher diagnostic accuracy when circumferential profiles are generated on the basis of maximal counts compared to mean counts. Quantitative analysis was able to predict the presence or absence of CAD as accurately as visual analysis. Odds ratios were 1.07 and 1.32 respectively (P < 0.001) for both quantitative maximal uptake and visual uptake analysis. Sensitivity of visual analysis alone was 89%, increasing to 96% with combined visual/quantitative analysis. Specificity of visual analysis decreased from 79% to 64% with combined analysis. Although only minor differences are seen, the maximal count uptake profiles were found to have additional diagnostic value compared to visual analysis alone.

Adult↗
PubMedDate not supplied

The magnitude of dementia occurrence in the world.

In this study, the worldwide occurrence of dementia in 2000 and during the period 1950-2050 was estimated. The calculations were based on worldwide demographics of the elderly and age-specific prevalence and incidence values of dementia, estimated from a meta-analysis. In a sensitivity analysis, different prevalence sources were used. The worldwide number of persons with dementia in 2000 was estimated at about 25 million persons. Almost half of the demented persons (46%) lived in Asia, 30% in Europe, and 12% in North America. Fifty-two percent lived in less developed regions. About 6.1% of the population 65 years of age and older suffered from dementia (about 0.5% of the worldwide population) and 59% were female. The number of new cases of dementia in 2000 was estimated to be 4.6 million. The forecast indicated a considerable increase in the number of demented elderly from 25 million in the year 2000 to 63 million in 2030 (41 million in less developed regions) and to 114 million in 2050 (84 million in less developed regions). In conclusion, the majority of demented elders live in less developed regions, and this proportion will increase considerably in the future.

Adult↗
PubMedDate not supplied

Methodologic principles of cost analyses in the nursing, medical, and health services literature, 1990-1996.

BACKGROUND: Cost analyses are needed to inform resource decisions. Oftentimes, however cost-benefit analysis (CBA), cost-effectiveness analysis (CEA), cost-minimization analysis (CMA), and cost-utility analysis (CUA) are performed using untested techniques and adhering to a variety of questionable principles. OBJECTIVES: To analyze, compare, and present a set of useful principles for the main types and methods of cost analyses through a synthesis of current information in the published literature. METHODS: The area of interest included all reports of cost research published as full articles in professional journals from January 1990 to August 1996 in the nursing, medical, and health services fields. In all, 88 sampled articles met the criteria for inclusion. A four-page data collection guide with 28 items grouped as demographics, cost-analysis types, methods, and principles was designed for the review. Incremental testing for interrater reliability using the kappa statistic for two raters was performed. Sampling, process-oriented, construct, and correlational validity were assessed. RESULTS: The 88 articles included 4 from nursing, 59 from medical, and 25 from health services journals. Of these articles, 45 (51%) reported CBA, 36 (41%) CEA, 2 CMA, 4 CUA, and 1 both CBA and CEA. Three nursing studies were authored only by nurses. Three fourths of the medical and four fifths of the health services publications had interdisciplinary authorship. Existing databases were the primary source of data in 61 (69%) publications. Adherence to six main methodologic principles was apparent in 19 (22%) articles. None of the nursing studies adhered to all six principles, whereas 16% of the health services and 25% of the medical studies did. CONCLUSIONS: Funded cost analyses of nursing interventions that adhere to the six known methodologic principles are needed to inform policy-level health care decisions. Because of the complexity of cost analysis methodology, including sensitivity analysis, future interdisciplinary efforts using existing databases may prove most effective. The six methodologic principles presented in this article can be useful for future nursing education and cost-analysis research designed to control cost and increase the quality of health care.

Costs and Cost Analysis↗
PubMed2002

Comprehensive survey of the relationship between serum concentration and therapeutic effect of amitriptyline in depression.

The relationship between serum concentration (C(s)) of amitriptyline and its therapeutic effect in depression has been investigated frequently over the last 3 decades; however, the results were controversial and no consensus was reached. Therefore, we have performed a comprehensive survey and meta-analysis of the subject. All relevant literature was included, and the design of studies on the serum concentration-therapeutic effect relationship (SCTER) of amitriptyline was evaluated. Pooled original data from SCTER studies with adequate design were analysed by various statistical methods: regression analysis of therapeutic effect and C(s); comparison of the mean therapeutic effect in various ranges of C(s); dichotomisation of outcome and analysis according to sensitivity of receiver operation curves; frequency of responders and nonresponders in ranges determined by points of sensitivity; analysis of the distribution of C(s) in responders and nonresponders; logistic regression of responders and nonresponders with C(s) and other independent variables; calculation of effect size (g) and mean effect size (g(m)). Forty-five SCTER studies of amitriptyline were identified, and 27 studies met the minimum criteria of adequate study design. Inadequate study design predicted the finding of no SCTER. Analysis of the pooled data from studies with adequate design confirmed a therapeutic window of the sum of C(s) of amitriptyline and its active metabolite nortriptyline of about 80 to 200 microg/L. A moderate and significant positive g(m) (0.538, 95% confidence interval 0.167 to 0.909) was calculated for treatment with C(s) within the therapeutic window in comparison with treatment with C(s) outside the therapeutic window (19 studies with adequate design and original data available, n = 583). In conclusion, the evidence for a biphasic SCTER of amitriptyline in depression is considerably improved, and the results may help to find a consensus in the future. However, the clinical benefit of therapeutic drug monitoring of amitriptyline can only be demonstrated in a controlled and randomised study. Furthermore, the results provide further evidence that antidepressants at optimum C(s) are superior to placebo in the treatment of depression.

Amitriptyline↗
PubMed2004

Pharmacoeconomic analysis of amphotericin B lipid complex versus liposomal amphotericin B in the treatment of fungal infections.

BACKGROUND: Potential differences in toxicity, potency and acquisition price among the liposomal amphotericin B formulations makes it unclear which agent is less costly when total resource consumption and treatment-associated costs are considered. DESIGN: A retrospective cost-minimisation analysis in 51 patients was performed to compare the cost of amphotericin B lipid complex (ABLC) and liposomal amphotericin B (L-AMB) from the hospital perspective. Costs ($US, 2001 values) were divided into level I (acquisition price only), level II (costs of all associated treatment, i.e. adverse events, failures, etc.) and level III (total fungal-related hospitalisation) costs. RESULTS: No significant differences in patient demographics or length of therapy were apparent among those receiving ABLC or L-AMB. The clinical success rate in this population was similar between ABLC and L-AMB (53% vs 60%, p = 0.68), thus justifying the use of a cost-minimisation analysis. Among patients with baseline elevations in serum creatinine, 47% receiving ABLC and 10% receiving L-AMB experienced further increases in serum creatinine (p = 0.025). No differences in total treatment costs (level I, II, or III) were evident between patients receiving ABLC or L-AMB. When adjusted for duration of therapy, however, costs were significantly lower for ABLC than for L-AMB (level I: ABLC $US340 versus L-AMB $US435, p = 0.002; level II: ABLC $US361 versus L-AMB $US454, p = 0.027). The costs attributable to the prevention or treatment of adverse events were not different between the two treatments, and the economic outcome in this analysis was highly sensitive to the acquisition price and dosage of the lipid antifungal formulation. Two-way sensitivity analysis revealed that as long as the milligram price of L-AMB was greater than 135% of the milligram price of ABLC, ABLC remained the less costly formulation. CONCLUSION: In this patient population, total hospitalisation costs were not different between lipid antifungal formulations. However, after controlling for duration of therapy, ABLC was less costly than L-AMB, when considering acquisition costs of the lipid antifungal agent and costs associated with concomitant antifungal therapy and the treatment of adverse events or lipid failures, indicating that the acquisition price of these agents should be predictive of their cost differences.

APACHE↗
PubMed2003

Systematic review of the clinical effectiveness and cost-effectiveness of tension-free vaginal tape for treatment of urinary stress incontinence.

OBJECTIVES: To evaluate the effectiveness and cost-effectiveness of tension-free vaginal tape (TVT) in comparison with the standard surgical interventions currently used. DATA SOURCES: Literature searches were carried out on electronic databases and websites for data covering the period 1966--2002. Other sources included references lists of relevant articles; selected experts in the field; abstracts of a limited number of conference proceedings titles; and the Internet. REVIEW METHODS: A systematic review of studies including comparisons of TVT with any of the comparators was conducted. Alternative treatments considered were abdominal retropubic colposuspension (including both open and laparoscopic colposuspension), traditional suburethral sling procedures and injectable agents (periurethral bulking agents). The identified studies were critically appraised and their results summarised. A Markov model comparing TVT with the comparators was developed using the results of the review of effectiveness and data on resource use and costs from previously conducted studies. The Markov model was used to estimate costs and quality-adjusted life-years for up to 10 years following surgery and it incorporated a probabilistic analysis and also sensitivity analysis around key assumptions of the model. RESULTS: Based on limited data from direct comparisons with TVT and from systematic reviews, laparoscopic colposuspension and traditional slings have broadly similar cure rates to TVT and open colposuspension, whereas injectable agents appear to have lower cure rates. TVT is less invasive than colposuspension and traditional sling procedures, and is also usually performed under regional or local anaesthesia. The principal operative complication is bladder perforation. There are currently no randomised controlled trial (RCT) data beyond 2 years post-surgery, and long-term effects are therefore currently not known reliably. TVT was more likely to be considered cost-effective compared with the other surgical procedures. Increasing the absolute probability of cure following TVT reduced the likelihood that TVT would be considered cost-effective. CONCLUSIONS: The long-term performance of TVT in terms of both continence and unanticipated adverse effects is not known reliably at the moment. Despite relatively few robust comparative data, it appears that in the short to medium term TVT's effectiveness approaches that of alternative procedures currently available, and is of lower cost. As TVT is a less invasive procedure, it is possible that some women who would currently be managed non-surgically will be considered eligible for TVT. Increased adoption of TVT will require additional surgeons proficient in the technique. It is likely that some of the higher rates of complications, e.g. bladder perforation, reported for TVT are associated with a 'learning curve'. Appropriate training will therefore be needed for surgeons new to the operation, in respect of both the technical aspects of the procedure and the choice of women suitable for the operation. Further research suggestions include unbiased assessments of longer term performance from follow-up of controlled trials or population-based registries; more data from methodologically sound RCTs using standard outcome measures; a surveillance system to detect longer term complications, if any, associated with the use of tape; and rigorous evaluation before extending the use of TVT to women who are currently managed non-surgically.

Colposcopy↗
PubMed1992

On-site occupational health nursing services: estimating the net savings: Part II.

1. A primary management use of this quantitative assessment model is to estimate the overall net cost savings from operating an entire on-site occupational health nursing program. 2. Another management use of this model is to estimate the net cost savings contributed by individual occupational health nursing services included in the on-site program. 3. The exclusive focus of the model on the net cost savings arising from the direct substitution of on-site for off-site occupational health nursing services can be extended with the application of a break even analysis. 4. A sensitivity analysis can be applied to factors of the model to help overcome the effects of substantial uncertainty concerning their estimates.

Cost Savings↗
PubMed1994

Safety and cost-effectiveness of solvent-detergent-treated plasma. In search of a zero-risk blood supply.

OBJECTIVE: To determine the public health and economic implications of solvent-detergent-treated frozen plasma (SD FP). While this processing technique nearly eliminates the risk of transmitting lipid-enveloped viruses (hepatitis B and C and human immunodeficiency virus), it has associated costs and, because it requires pooling many plasma units, may increase risks of nonenveloped virus transmission. DESIGN: A previously published Markov decision analysis model was modified to assess transfusion-related outcomes in hypothetical cohorts of plasma recipients. In-hospital mortality and other characteristics were determined in 61 patients receiving plasma transfusions at a medium-sized tertiary care center to provide data for the model. Other parameters were obtained from the medical literature. MAIN OUTCOME MEASURES: Expected SD FP costs, benefits, and cost-effectiveness, assessed as cost per quality-adjusted life-year saved. RESULTS: Compared with untreated plasma, a unit of SD FP produces a net benefit of 35 minutes in quality-adjusted life expectancy at a cost of about $19. Extrapolated to the 2.2 million plasma units transfused annually in the United States, SD FP would save 147 quality-adjusted life-years at a cost of $42.5 million. The marginal cost-effectiveness, $289,300 per quality-adjusted life-year saved in the baseline analysis, was most sensitive to estimates of SD treatment cost and the clinical setting of plasma use. In sensitivity analysis, the net benefit of SD FP was negated by the existence of even a minute risk of nonenveloped virus infection. CONCLUSIONS: From a public health perspective, the relatively high costs and small benefits of reducing enveloped virus infection risks with SD FP (and the additional risks of noneveloped virus transmission) do not appear to justify widespread implementation of this new technology.

Blood Component Transfusion↗
PubMed2001

High-sensitivity array analysis of gene expression for the early detection of disseminated breast tumor cells in peripheral blood.

Early detection is an effective means of reducing cancer mortality. Here, we describe a highly sensitive high-throughput screen that can identify panels of markers for the early detection of solid tumor cells disseminated in peripheral blood. The method is a two-step combination of differential display and high-sensitivity cDNA arrays. In a primary screen, differential display identified 170 candidate marker genes differentially expressed between breast tumor cells and normal breast epithelial cells. In a secondary screen, high-sensitivity arrays assessed expression levels of these genes in 48 blood samples, 22 from healthy volunteers and 26 from breast cancer patients. Cluster analysis identified a group of 12 genes that were elevated in the blood of cancer patients. Permutation analysis of individual genes defined five core genes (P < or = 0.05, permax test). As a group, the 12 genes generally distinguished accurately between healthy volunteers and patients with breast cancer. Mean expression levels of the 12 genes were elevated in 77% (10 of 13) untreated invasive cancer patients, whereas cluster analysis correctly classified volunteers and patients (P = 0.0022, Fisher's exact test). Quantitative real-time PCR confirmed array results and indicated that the sensitivity of the assay (1:2 x 10(8) transcripts) was sufficient to detect disseminated solid tumor cells in blood. Expression-based blood assays developed with the screening approach described here have the potential to detect and classify solid tumor cells originating from virtually any primary site in the body.

Breast Neoplasms↗
PubMed2004

Heritability and linkage analysis of sensitivity to cisplatin-induced cytotoxicity.

Little is known about the genetic determinants explaining variation in sensitivity to chemotherapeutic cytotoxicity. We characterized the degree of cisplatin sensitivity, using lymphoblastoid cell lines derived from 10 Centre d'Etude du Polymorphisme Humain pedigrees. We estimated the heritability for susceptibility to cisplatin-induced cytotoxicity to be approximately 0.47; therefore, sensitivity to the cytotoxic effects of cisplatin is under appreciable genetic influence. Linkage analysis was performed, and the strongest signal (lod score, 2.16; empirical P = 0.0005) was found on chromosome 1 at 44 cM. Susceptibility to cisplatin-induced cytotoxicity is likely due to multiple loci, with low locus-specific heritability contributing to the trait. These data show the power of using large pedigrees that have been extensively genotyped for evaluating the genetic contribution to sensitivity to cell growth inhibition by anticancer agents.

Antineoplastic Agents↗
PubMed2003

Quantifying and reporting uncertainty from systematic errors.

Optimal use of epidemiologic findings in decision making requires more information than standard analyses provide. It requires calculating and reporting the total uncertainty in the results, which in turn requires methods for quantifying the uncertainty introduced by systematic error. Quantified uncertainty can improve policy and clinical decisions, better direct further research, and aid public understanding, and thus enhance the contributions of epidemiology. The error quantification approach proposed here is based on estimating a probability distribution for a bias-corrected effect measure based on externally-derived distributions of bias levels. Using Monte Carlo simulation, corrections for multiple biases are combined by identifying the steps through which true causal effects become data, and (in reverse order) correcting for the errors introduced by each step. The bias-correction calculations are the same as those used in sensitivity analysis, but the resulting distribution of possible true values is more than a sensitivity analysis; it is a more complete reporting of the actual study results. The approach is illustrated with an application to a recent study that resulted in the drug, phenylpropanolamine, being removed from the market.

Appetite Depressants↗
PubMed2002

Cost effectiveness of telemedicine for the delivery of outpatient pulmonary care to a rural population.

The objective of this study was to determine the cost effectiveness of outpatient pulmonary subspecialty consultations via telemedicine. A decision-analytic model was used to compare the cost effectiveness of providing outpatient telemedicine pulmonary consultations with alternative treatment methods. Model options included: (1) telemedicine, (2) routine care (patients travel from a remote site to the hub site to receive care), and (3) on-site care (patients receive care at the remote site). Cost and effectiveness data from the Milwaukee and Iron Mountain Veterans Affairs Medical Centers (VAMC) telepulmonary program were collected for a period of 1 year. The cost-effectiveness analysis was conducted from a societal perspective. Average and incremental cost-effectiveness ratios were calculated together with sensitivity analysis. Telemedicine was found to be more cost effective ($335 per patient/year) compared to routine care ($585 per patient/year) and on-site care ($1,166 per patient/year). Sensitivity analysis revealed that cost effectiveness of telemedicine was sensitive to changes in the values for the number of patients, probability of successful telemedicine consultation, telemedicine equipment cost, utility of telemedicine, and percentage effort assigned to the on-site pulmonary physician. Telemedicine is a cost-effective alternative for the delivery of outpatient pulmonary care for rural populations with limited access to subspecialty services. Cost effectiveness of telemedicine is related to three major factors: cost sharing, i.e., adequate patient volume and sharing of telemedicine infrastructure amongst various clinical users; effectiveness of telemedicine in terms of patient utility and successful clinical consultations; and indirect cost savings accrued by decreasing cost of patients' lost productivity.

Ambulatory Care↗
PubMed1977

[A flow-through method for the O2-sensitive, enzymatic analysis of glucose (author's transl)].

A flow-through glucose-analyser is described based on an oxygen-sensitive enzymatic system. Leak-current-proof welded PTFE-membranes contribute considerably to an easy maintenance of the O2-sensors. Soluble or immobilized glucose oxidase may be used in automatic analysers. As a primary instrument of analysis, the oxygen pO2-electrode lends itself to the measurement of other enzymatic reactions that involve oxygen.

Autoanalysis↗
PubMedDate not supplied

An analysis of the effect of selection bias on the association of hormone replacement therapy and breast cancer risk.

A sensitivity analysis was conducted to determine the impact on measures of effect of a suspected differential participation response rate between hormone replacement therapy (HRT) users and nonusers, among controls recruited to a population-based case-control study of breast cancer. The age-specific prevalence of current HRT use among controls was compared to data from the 1996 Canadian National Population Health Survey (NPHS). Control women identified as current HRT users were randomly re-sampled to replicate the prevalence of HRT use reported by the NPHS. Unconditional logistic regression was conducted to estimate odds ratios (OR) and 95 percent confidence intervals (CI) for the use of HRT and breast cancer risk before and after re-sampling. Multivariate adjusted ORs for breast cancer and estrogen-only and estrogen-progestin formulations were 0.76 (0.53-1.10) and 0.94 (95% CI: 0.64 - 1.38), respectively, using the original case-control controls and 0.99 (0.77-1.27) and 1.57 (95% CI: 1.02 - 2.40), respectively, following re-sampling of the controls. This sensitivity analysis illustrates the extent to which differential participation rates between HRT users and nonusers may affect estimates of measures of effect.

Aged↗
PubMed2024

Effect of inflammatory cytokines and plasma metabolome on OSA: a bidirectional two- sample Mendelian randomization study and mediation analysis.

BACKGROUND: Obstructive sleep apnea (OSA) is a common sleep disorder. Inflammatory factors and plasma metabolites are important in assessing its progression. However, the causal relationship between them and OSA remains unclear, hampering early clinical diagnosis and treatment decisions. METHODS: We conducted a large-scale study using data from the FinnGen database, with 43,901 cases and 366,484 controls for our discovery MR analysis. We employed 91 plasma proteins from 11 cohorts (totaling 14,824 participants of European descent) as instrumental variables (IVs). Additionally, we conducted a GWAS involving 13,818 cases and 463,035 controls to replicate the MR analysis. We primarily used the IVW method, supplemented by MR Egger, weighted median, simple mode, and weighted mode methods. Meta-analysis was used to synthesize MR findings, followed by tests for heterogeneity, pleiotropy, and sensitivity analysis (LOO). Reverse MR analysis was also performed to explore causal relationships. RESULTS: The meta-analysis showed a correlation between elevated Eotaxin levels and an increased risk of OSA (OR=1.050, 95% CI: 1.008-1.096; p < 0.05). Furthermore, we found that the increased risk of OSA could be attributed to reduced levels of X-11849 and X-24978 (decreases of 7.1% and 8.4%, respectively). Sensitivity analysis results supported the reliability of these findings. CONCLUSIONS: In this study, we uncovered a novel biomarker and identified two previously unknown metabolites strongly linked to OSA. These findings underscore the potential significance of inflammatory factors and metabolites in the genetic underpinnings of OSA development and prognosis.

Female↗
PubMed1994

Effectiveness of training health professionals to provide smoking cessation interventions: systematic review of randomised controlled trials.

OBJECTIVE: To assess the effectiveness of interventions that train healthcare professionals in methods for improving the quality of care delivered to patients who smoke. DESIGN: Systematic literature review. SETTING: Primary care medical and dental practices in the United States and Canada. Patients were recruited opportunistically. SUBJECTS: 878 healthcare professionals and 11,228 patients who smoked and were identified in eight randomised controlled trials. In each of these trials healthcare professionals received formal training in smoking cessation, and their performance was compared with that of a control group. MAIN MEASURES: Point prevalence rates of abstinence from smoking at six or 12 months in patients who were smokers at baseline. Rates of performance of tasks of smoking cessation by healthcare professionals, including offering counselling, setting dates to stop smoking, giving follow up appointments, distributing self help materials, and recommending nicotine gum. METHODS: Trials were identified by multiple methods. Data were abstracted according to predetermined criteria by two observers. When possible, meta-analysis was performed using a fixed effects model and the results were subjected to sensitivity analysis. RESULTS: Healthcare professionals who had received training were significantly more likely to perform tasks of smoking cessation than untrained controls. There was a modest increase in the odds of stopping smoking for smokers attending health professionals who had received training compared with patients attending control practitioners (odds ratio 1.35 (95% confidence interval 1.09 to 1.68)). This result was not robust to sensitivity analysis. The effects of training were increased if prompts and reminders were used. There was no definite benefit found for more intensive forms of counselling compared with minimal contact strategies. CONCLUSIONS: Training health professionals to provide smoking cessation interventions had a measurable impact on professional performance. A modest, but non-robust, effect on patient outcome was also found, suggesting that training alone is unlikely to be an effective strategy for improving quality of care, unless organisational and other factors are also considered.

Behavior Therapy↗