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[A medico-economic evaluation of second line chemotherapy in metastatic breast cancer: comparison between docetaxel, paclitaxel, and vinorelbine].

Despite health public problems arised by metastatic breast cancer, specific studies remain rare, and especially when concerning second line chemotherapy. Today, these studies seem essential to allow the clinician, facing the choice between different treatments, to make the best decision. Two recent treatments, docetaxel and paclitaxel, administered every 3 weeks, were compared to the referenced treatment: vinorelbine administered every week. The study aims at evaluating these 3 therapeutic options on second line treatment of metastatic breast cancer. For each of these 3 strategies, our end points were: (1) the duration of progression free survival; (2) the quality adjusted on progression free survival; (3) the cost including the intrinsic cost of chemotherapy as well as the cost of treatment-related and disease-related complications, due to toxicity. Savings obtained with the treatment by delaying relapse were subtracted from expenditure. We used a Markov model to describe the patient's evolution after the administration of the compared treatments. The evaluation concerns the period from the beginning of second line chemotherapy to death. Only direct medical costs were taken into account. Non medical costs and indirect costs were excluded. For each clinical state, resources utilisation was estimated by a retrospective multicentric analysis of 153 medical records of metastatic breast cancer, treated on second line. Resources valuation of hospital costs were based on a national survey on the cost of medical services per DRGs. Quality of life was estimated by a group of nurses in oncology, using the feeling thermometer and standard gamble technics. Incremental cost utility ratios were calculated. Docetaxel reduces the time spent in progression, decreases the number of complications due to progressive disease and thereby provides better quality of life. It provides a benefit of 57 disease- and discomfort-free days, compared to vinorelbine and 22 days compared to paclitaxel. Docetaxel may be thought of as a self-financing strategy as a result of savings in hospital admissions, providing net saving of French Francs (FF) 6,800 in 1993 prices, compared with expenditure associated with vinorelbine treatment and FF 700 compared with the equivalent figures for paclitaxel. A sensitivity analysis confirms the robustness of those results.

Aged↗

Methods for studying protein synthesis and degradation in liver and skeletal muscle.

Different methods used for measuring protein turnover in liver and skeletal muscle are described, with special emphasis on technical and practical aspects and the advantages and limitations of different techniques. In the first part of the review, the concept of precursor specific radioactivity and its importance for accurate determination of protein synthesis rate is discussed. In the second part, different in vivo techniques for protein turnover measurements are reviewed, including continuous administration of tracer amino acid, flooding dose technique, indirect measurement of protein synthesis, and estimation of protein degradation in vivo. In the third part of the report, in vitro techniques are described, including measurement of protein turnover in incubated liver slices, perfused liver, isolated hepatocytes, incubated isolated muscles or muscle biopsies, and perfused rat hemicorpus. In vivo techniques are preferred when accurate absolute values of protein turnover rates are desired. In vitro techniques offer the advantage of standardized conditions, maintaining strict control of substrate and hormone concentrations, and eliminating complicating interactions with other tissues. For several in vitro techniques, a good correlation has been demonstrated between relative changes in protein turnover in vitro and in vivo in different conditions.

Animals↗

Radiographic methods in the evaluation of periodontal therapy.

Radiographic methods are commonly utilized to assess periodontal bone changes in clinical trials. Radiographs are unique as a data source in that they provide a permanent visual record of the bone support and allow for linear, area, and volume measurements of periodontal lesions. The major limiting factors in the use of radiographic outcomes measures are geometric distortion and radiographic processing errors. The use of standardized methods and computer algorithms has reduced the effect of these errors on data from radiographs. Radiographic analysis in clinical trials is largely done in digital format by indirect digitizing film with a video camera. Direct digital detectors are now available for intra-oral use. The use of a direct detector eliminates the need for film processing and allows for dose reduction. The detectors currently available are limited in size and resolution. Subtraction radiography allows for area and volume estimates of bone gain or loss. The subtraction methods are highly precise, but are also technically exacting and labor intensive. The clinical trial hypothesis, size, length, and accuracy required should be the final consideration in choosing a radiographic method.

Alveolar Bone Loss↗

Endoscope-induced colitis: description, probable cause by glutaraldehyde, and prevention.

Six cases of acute, self-limited colitis that occurred after screening flexible sigmoidoscopy were deduced to be iatrogenic, probably caused by glutaraldehyde residues in the endoscopes after disinfection in an automatic disinfecting machine. The concentration of these residues was indirectly estimated by conductivity measurements of electrolyte concentration in the rinse-water tank of the disinfecting machine during and after five cycles and also in fluid remaining on the surface of the endoscopes and in the endoscope channels. After five cycles, residues in both the rinse water and fluid in the endoscope channels contained the equivalent of 0.2% glutaraldehyde. This was the result of a combination of technical and human errors. It can be prevented by changing the rinse water after each cycle, using forced air to dry the instruments, and washing the endoscopes before use. Users of the automatic disinfecting machine should be aware of the potential accumulation of toxic levels of residues that remain in endoscopes after disinfection.

Acute Disease↗

Occupational change, employer change, internal migration, and earnings.

"In this paper I use microdata from the [U.S.] Panel Study of Income Dynamics to measure the financial returns to intercounty and interstate migration for individuals in a temporal framework accounting for gains that accrue over time.... To account for the indirect effects of migration on earnings, explanatory variables are created by interacting migration status with: (1) occupational change, (2) employer change and (3) changes in both occupation and employer. These interaction terms are then included in the earnings functions. Earnings are estimated for three years subsequent to the migration decision to account for the financial returns to migration accruing over time. Results indicate that, when estimating earnings, the use of a simple migration dummy variable will mask the indirect effects of migration on earnings."

Americas↗

Some mathematical and technical issues in the measurement and interpretation of open-circuit indirect calorimetry in small animals.

Indirect calorimetry is increasingly used to investigate why compounds or genetic manipulations affect body weight or composition in small animals. This review introduces the principles of indirect (primarily open-circuit) calorimetry and explains some common misunderstandings. It is not widely understood that in open-circuit systems in which carbon dioxide (CO2) is not removed from the air leaving the respiratory chamber, measurement of airflow out of the chamber and its oxygen (O2) content paradoxically allows a more reliable estimate of energy expenditure (EE) than of O2 consumption. If the CO2 content of the exiting air is also measured, both O2 consumption and CO2 production, and hence respiratory quotient (RQ), can be calculated. Respiratory quotient coupled with nitrogen excretion allows the calculation of the relative combustion of the macronutrients only if measurements are over a period where interconversions of macronutrients that alter their pool sizes can be ignored. Changes in rates of O2 consumption and CO2 production are not instantly reflected in changes in the concentrations of O2 and CO2 in the air leaving the respiratory chamber. Consequently, unless air-flow is high and chamber size is small, or rates of change of O2 and CO2 concentrations are included in the calculations, maxima and minima are underestimated and will appear later than their real times. It is widely appreciated that bigger animals with more body tissue will expend more energy than smaller animals. A major issue is how to compare animals correcting for such differences in body size. Comparison of the EE or O2 consumption per gram body weight of lean and obese animals is misleading because tissues vary in their energy requirements or in how they influence EE in other ways. Moreover, the contribution of fat to EE is lower than that of lean tissue. Use of metabolic mass for normalisation, based on interspecific scaling exponents (0.75 or 0.66), is similarly flawed. It is best to use analysis of covariance to determine the relationship of EE to body mass or fat-free mass within each group, and then test whether this relationship differs between groups.

Animals↗

Enzyme linked immunosorbent assay for potency testing of vaccines containing Clostridium perfringens type D epsilon-toxoid.

For ethical, economic and technical reasons in vivo assays need to be replaced in routine laboratory procedures. Based on a method which is already accepted by the British authorities, an indirect ELISA has been developed and evaluated for Clostridium perfringens type D-containing vaccines. Individual and pooled sera of vaccinated rabbits were tested at a single dilution level, the results transferred into IU/ml, and compared with the conventional toxin neutralization test in mice. The ELISA was found to give reproducible estimates of antitoxin levels and showed good correlation with the conventional in vivo test in mice.

Animals↗

Nitrocellulose-enzyme-linked immunosorbent assay (NC-ELISA) - a sensitive technique for the rapid visual detection of both viral antigens and antibodies.

A modification of the enzyme-linked immunosorbent assay (ELISA) is described for sensitive and rapid direct visual detection of antigens of four adenoviruses (Ad) and anti-Ad antibodies using nitrocellulose (NC) membrane discs as high-capacity solid phase. The NC-ELISA was performed in microtitre plates containing NC-discs. Small amounts of crude supernatants from Ad-infected cells as antigen were bound to the discs. Additional binding capacity was blocked with an excess of bovine serum albumin. The subsequent reaction of virus antigen with specific rabbit antibody was visualized using alkaline phosphatase-conjugated anti-rabbit IgG and histochemical substrates. The sensitivity of the NC-ELISA for the detection of Ad-antigens was found to be 8-10-fold higher than a conventional ELISA using polystyrene solid phase supports. The sensitivity levels were estimated to be similar comparing NC-ELISA and tissue culture assay results. The quantitative determination of anti-Ad antibodies by NC-ELISA showed 8-fold higher sensitivity compared to microneutralization test. The NC-ELISA could detect purified immunoglobulin at a level of 1 ng using a direct test procedure and 10 ng using the indirect method. The detection limits are good compared to other highly sensitive assays. The use of crude antigen combined with high sensitivity and easy technical performance makes the NC-ELISA useful as a tool for rapid viral diagnosis.

Adenoviridae Infections↗

Estimation of left ventricular systolic function by nonvolumetric echocardiographic analysis in subjects with poor left ventricular visualization: a pilot study.

BACKGROUND: Accurate assessment of left ventricular (LV) systolic function is an essential requirement in clinical cardiology. Several echocardiographic methods provide quantitative analysis of LV volumes and ejection fraction (EF) based on the precise tracing of endocardial borders. Often, however, technically limited studies prohibit such direct analysis, and alternative techniques must be applied. HYPOTHESIS: Nonvolumetric echocardiographic methods which do not require endocardial edge definition and tracing may accurately provide quantitative LV systolic function data. METHODS: A pilot study was conducted to validate and compare two recently described indirect echocardiographic methods of LV systolic function analysis, with LVEF by radionuclear cardiac angiography (RNCA). Thirty-two consecutive patients undergoing RNCA for clinical indications also underwent echocardiography within 24 h, with LV analysis performed by the techniques of (1) atrioventricular plane displacement (AVPD) and (2) mitral valve leaflet coaptation point to interventricular septum distance at end-systole (MVC-IVS). RESULTS: Thirteen patients had an echocardiogram with poor two-dimensional visualization of LV endocardial borders. One patient could not be evaluated by the MVC-IVS method and two others by the AVPD method because of technical limitations. Chi-square analysis to compare how each method could discriminate between an RNCA LVEF of < or > or = 50% demonstrated high correlations for the AVPD method (r = 0.6530, p < 0.0005) and the MVC-IVS method (r = -0.7029, p < 0.0001). Sensitivity, specificity, positive and negative predictive values, and test accuracy for the AVPD and MVC-IVS methods were 85 and 80%, 88 and 94%, 85 and 92%, 82 and 83%, and 83 and 87%, respectively. CONCLUSION: This pilot study demonstrates that both alternative echocardiographic methods may be useful in the assessment of LV systolic performance, even in the setting of poor LV endocardial border visualization. A larger study is warranted to apply and contrast these methods in different patient subsets.

Adult↗

Indoor biofuel air pollution and respiratory health: the role of confounding factors among women in highland Guatemala.

BACKGROUND: A number of studies have reported associations between indoor biofuel air pollution in developing countries and chronic obstructive lung disease (COLD) in adults and acute lower respiratory infection (ALRI) in children. Most of these studies have used indirect measures of exposure and generally dealt inadequately with confounding. More reliable, quantified information about this presumed effect is an important pre-requisite for prevention, not least because of the technical, economic and cultural barriers to achieving substantial exposure reductions in the world's poorest households, where ambient pollution levels are typically between ten and a hundred times higher than recommended standards. This study was carried out as part of a programme of research designed to inform the development of intervention studies capable of providing quantified estimates of health benefits. METHODS: The association between respiratory symptoms and the use of open fires and chimney woodstoves ('planchas'), and the distribution of confounding factors, were examined in a cross-sectional study of 340 women aged 15-45 years, living in a poor rural area in the western highlands of Guatemala. RESULTS: The prevalence of reported cough and phlegm was significantly higher for three of six symptom measures among women using open fires. Although this finding is consistent with a number of other studies, none has systematically examined the extent to which strong associations with confounding variables in these settings limit the ability of observational studies to define the effect of indoor air pollution adequately. Very strong associations (P < 0.0001) were found between the type of fire and a number of household and socioeconomic factors including the arrangement of rooms, floor type, and possession of a radio and television. The spouse's economic activity type was also significantly associated (P < 0.05). Thus, while 82% of open fire users had dirt floors and only 18% cement or tile floors, the situation was reversed for plancha users, only 16% of whom had dirt floors. CONCLUSIONS: Confounding presents a substantial problem for observational studies of indoor air pollution and health, although there is a reasonable case for believing that the observed association is causal. Intervention studies are required for stronger evidence of this association, and more importantly, to determine the size of health benefit achievable through feasible exposure reductions.

Adolescent↗

The measurement of energy expenditure.

Proper nutrition support depends upon the clinician's ability to estimate the patient's energy expenditure. The accuracy of estimation is inversely proportional to the severity of the patient's illness. This fact has spurred academic and industry groups to pursue the measurement of energy expenditure. Harris and Benedict used indirect calorimetry to develop their now-famous equation nearly 100 years ago. The concept of indirect calorimetry is simple; if you know the concentration of inspired gases and expired gases, along with the flow, you can determine the amount of a gas consumed or produced. The complexity and expense of indirect calorimeters suggest that this simple concept is technically challenging. Because we desire to know the energy expenditure of the most critically ill patients, indirect calorimetry is further confounded by the presence of oxygen and mechanical ventilation. This paper will discuss the myriad of variables and obstacles that complicate the measurement of energy expenditure and will suggest methods to avoid or overcome them.

Journal Article↗

The role of sustainable agriculture and renewable-resource management in reducing greenhouse-gas emissions and increasing sinks in China and India.

This paper contains an analysis of the technical options in agriculture for reducing greenhouse-gas emissions and increasing sinks, arising from three distinct mechanisms: (i) increasing carbon sinks in soil organic matter and above-ground biomass; (ii) avoiding carbon emissions from farms by reducing direct and indirect energy use; and (iii) increasing renewable-energy production from biomass that either substitutes for consumption of fossil fuels or replaces inefficient burning of fuelwood or crop residues, and so avoids carbon emissions, together with use of biogas digesters and improved cookstoves. We then review best-practice sustainable agriculture and renewable-resource-management projects and initiatives in China and India, and analyse the annual net sinks being created by these projects, and the potential market value of the carbon sequestered. We conclude with a summary of the policy and institutional conditions and reforms required for adoption of best sustainability practice in the agricultural sector to achieve the desired reductions in emissions and increases in sinks. A review of 40 sustainable agriculture and renewable-resource-management projects in China and India under the three mechanisms estimated a carbon mitigation potential of 64.8 MtC yr(-1) from 5.5 Mha. The potential income for carbon mitigation is $324 million at $5 per tonne of carbon. The potential exists to increase this by orders of magnitude, and so contribute significantly to greenhouse-gas abatement. Most agricultural mitigation options also provide several ancillary benefits. However, there are many technical, financial, policy, legal and institutional barriers to overcome.

Agriculture↗

The theoretical bases of indirect calorimetry: a review.

Indirect calorimetry is the method by which the type and rate of substrate utilization, and energy metabolism are estimated in vivo starting from gas exchange measurements. This technique provides unique information, is noninvasive, and can be advantageously combined with other experimental methods to investigate numerous aspects of nutrient assimilation, thermogenesis, the energetics of physical exercise, and the pathogenesis of metabolic diseases. Since its use as a research tool in metabolism is growing, the theoretical bases of indirect calorimetry are here reviewed in a detailed and orderly fashion. Special cases, such as the occurrence of net lipid synthesis or gluconeogenesis, are formally considered with derivation of explicit stoichiometric equations. The limitations of indirect calorimetry, both theoretical and technical, are discussed in the context of circumstances of clinical interest in metabolism.

Adenosine Triphosphate↗

A cost analysis comparing xeroradiography to film technics for intraoral radiography.

In the United States during 1978 $730 million was spent on dental radiographic services. Currently there are three alternatives for the processing of intraoral radiographs: manual wet-tanks, automatic film units, or xeroradiography. It was the intent of this study to determine which processing system is the most economical. Cost estimates were based on a usage rate of 750 patient images per month and included a calculation of the average cost per radiograph over a five-year period. Capital costs included initial processing equipment and site preparation. Operational costs included labor, supplies, utilities, darkroom rental, and breakdown costs. Clinical time trials were employed to measure examination times. Maintenance logs were employed to assess labor costs. Indirect costs of training were estimated. Results indicated that xeroradiography was the most cost effective ($0.81 per image) compared to either automatic film processing ($1.14 per image) or manual processing ($1.35 per image). Variations in projected costs indicated that if a dental practice performs primarily complete-mouth surveys, exposes less than 120 radiographs per month, and pays less than +6.50 per hour in wages, then manual (wet-tank) processing is the most economical method for producing intraoral radiographs.

Costs and Cost Analysis↗

[The measurement of blood volume--state-of-the-art].

The term blood volume (BV) measurement can be understood as the exact volumetric definition of both components of blood, the red cell volume (RCV) and the plasma volume (PV) using tracer dilution methods. The tracer used to measure the RCV must be bound to the erythrocytes and for the PV to plasma proteins, in order to label the distribution space of each carrier (i.e. erythrocytes and albumin molecules). To differentiate this there are indirect methods to estimate the BV, such as measurement of the diastolic pressure or transoesophageal echocardiography, which will not be discussed here. Alterations in the RCV and PV cannot be routinely measured, or at most only roughly estimated by means of the haematocrit (Hc) or haemoglobin (Hb) concentration which can lead to serious errors when large changes have occurred. At present measurements of the RCV and PV are not carried out in routine clinical practice. The introduction of nonradioactive tracers with a faster elimination now renders possible a relatively exact measurement of both volumes under certain clinical situations, albeit with a high technical outlay. The RCV is measured using the tracer sodium fluorescein (SoF) and the PV with the dye indocyanine green (ICG). The RCV measurement seems to be suitable for certain clinical situations, such as characterization of the preoperative condition of a patient or quantification of surgical blood loss after an operation, because it is less invasive and has a high precision. However, the results of the RCV measurement can only be delivered after 1 h which makes it more suitable for clinically stable situations. In contrast the PV estimation is based on the measurement of the ICG concentration in the arterial bloodstream after a bolus injection of the dye in the central veins and is used more in intensive care because of the invasivity. The results can be obtained 5 min after injection of the dye and therefore even rapid changes in the PV can be monitored.

Blood Volume Determination↗

Level and pattern of mortality in the Kuwaiti population, 1980.

"Vital registration data together with 1980 census data [are] used for assessing the mortality level among the Kuwaiti male and female population in 1980. Under the eclectic approach adopted in this paper, mortality estimates for different sections of age-spans are derived through various indirect techniques. For early childhood mortality estimates, the method developed by Brass...has been employed, whereas, for old age, mortality estimates are derived through Coale's method.... The results show that, as in the developed societies, Kuwaiti females have lower mortality compared with Kuwaiti males."

Adult↗

Infant mortality levels in Africa: does method of estimation matter?

"Using data from 13 Demographic and Health Surveys in Africa, this paper compares estimates of infant mortality directly calculated from data with those indirectly calculated using the Trussell (1975) and Feeney (1980) techniques. The results indicate that, on average, the directly calculated infant mortality rates were significantly lower than those estimated from indirect methods. Data errors alone can not plausibly explain such differences. Such series could in fact show increases or decreases in infant mortality rates that would result mainly from differences in methods of calculation." (SUMMARY IN ITA AND FRE)

Africa↗