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PubMed1998

Valuing temporary and chronic health states associated with breast screening.

The aim of this study was to derive quality of life values for the four key breast screening outcomes (true negative, false positive, true positive and false negative), including the quality of life effects of the screening and treatment processes. In doing so, methodological issues in health status measurement were explored, in particular the valuation of temporary health states. The true negative and false positive descriptions were temporary health states, lasting for short term durations (12 months) and the true positive and false negative outcomes were chronic health states lasting for long term durations (rest of life). Descriptions of breast screening outcomes were valued using the time trade-off technique and the visual analogue scale. Paired comparisons between TTO values for states with the same duration found a difference between the true negative and the false positive time trade-off values but no difference for true positive and false negative descriptions. The TTO values for the false positive were low. The study highlights several important methodological issues such as the use of the two stage procedure for valuing temporary health states, the impact of duration on values, the impact of anchor points, and the importance of qualitative analysis of respondents values. Further empirical testing of all these issues is recommended.

Adult↗
PubMed1999

Towards a psychological model of midlife crisis.

Midlife crisis in men is seen as a process of intensive and subjectively difficult transition of the self dealing with a reinterpretation of time perspective, the confrontation with death as a future personal event, the re-evaluation of life values and goals, and planning the second half of life. Midlife crisis arises on the relationships between the changing sociopsychological situation and internal predispositions. This study was conducted in Poland, using a sample of 144 men (aged 35-45 years). Measures were the Midlife Crisis Questionnaire, the Time Orientation Scale, the Adjective Check List, the modified version of the Ways of Coping Checklist, and the Value crisis Questionnaire. The findings indicated that the midlife crisis consists of three relatively independent dimensions, extracted by factor analysis, namely, (i) intensity of symptoms focused on changes in the self-concept, (ii) psychological maturity, and (iii) acceptance of time passing and death. Necessary and sufficient conditions of the crisis appeared to be (1) value crisis, understood as difficulties in hierarchization, integration, and realization of values, (2) emotion-focused coping versus problem-focused coping, (3) past versus future time orientation and lack of goals for the future, (4) sense of time pressure, (5) some conscientiousness, introversion, and openness to experience.

Adaptation, Psychological↗
PubMed1991

Assessment of quality of life.

Assessment of quality of life has emerged in recent years as an important part of the overall evaluation of drug therapy and health care in general. Measurement techniques for this difficult assessment range from simple unqualified questions on patient well-being to complex statistical analyses of a wide range of lifestyle and activity variables. The factors that influence quality of life during chronic drug therapy differ in the treatment of symptomatic (e.g., heart failure) vs asymptomatic (e.g., hypertension) disease, and include drug side effects, relief of symptoms, improved prognosis, return to work, physical activity and the need for further hospital treatments. The manifestation of quality of life varies for different people leading to lack of agreement on the precise definition. The absence of standardization of methods of measurement also contributes to this and leads to lack of comparability of studies and unreasonable claims by some drug manufacturers. Further complicating issues in multicenter trials across countries include language problems and interethnic differences in "sickness" behavior. The recently introduced quality-adjusted life year (QALY) index, designed to take account of both the quality and duration of life in assessing the outcome of treatments, may avoid some of these problems. By classifying illness states (the Rosser index) on the basis of disability and distress, and comparing outcomes in terms of improved prognosis, QALYs have already been used for cost/benefit analyses of a number of new and expensive therapies. Like other methods, QALYs have problems related to variability in individual appreciation of life values. To date, a perfect method of quality of life assessment remains elusive.

Disability Evaluation↗
PubMed1991

Sites of first-pass bioactivation (hydrolysis) of orally administered zofenopril calcium in dogs.

The relative contribution of the gut, liver, and lungs as sites of first-pass bioactivation (hydrolysis) of the orally administered ester prodrug, zofenopril calcium (SQ 26,991), to the active angiotensin converting enzyme (ACE) inhibitor, SQ 26,333, was determined. With a five-way study design, two dogs each received a single 1.6-mg/kg dose of zofenopril [as its soluble potassium salt (SQ 26,900)] via the following routes of administration: intraarterial, intravenous, intraportal, and oral. Each dog also received an equimolar oral dose of zofenopril calcium (1.5 mg/kg). Concentrations of zofenopril in plasma were quantitated with a GC/MSD assay. Extraction ratios (E) for zofenopril by the gut, liver, and lungs were calculated based on the ratios of the area under the curve (AUC) values of zofenopril in arterial plasma after administration by the various routes. As individual eliminating organs, the gut and liver each had a high intrinsic capability to hydrolyze zofenopril; E values ranged from 45 to 89%. The lungs were found to have low, but measurable, hydrolytic activity with estimated E values that ranged from 5 to 26%. Overall, about 95% of the orally administered dose of zofenopril calcium was hydrolyzed during the first pass. Because the prodrug is sequentially exposed to the gut, liver, and lungs, the contribution of the gut to the overall first-pass hydrolysis (ca. 87%) was estimated to be significantly greater than that of the liver (less than 10%) or lungs (less than 2%). Zofenopril was rapidly eliminated after parenteral administration; mean residence time values were 2 min and the elimination half-life values (intraarterial route only) were 9 min.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗
PubMedDate not supplied

Ketamine psychedelic therapy (KPT): a review of the results of ten years of research.

Ketamine is a prescription drug used for general anesthesia. In subanesthetic doses, it induces profound psychedelic experiences and hallucinations. The subanesthetic effect of ketamine was the hypothesized therapeutic mechanism in the authors' use of ketamine-assisted psychotherapy for alcoholism. The results of a controlled clinical trial demonstrated a considerable increase in efficacy of the authors' standard alcoholism treatment when supplemented by ketamine psychedelic therapy (KPT). Total abstinence for more than one year was observed in 73 out of 111 (65.8%) alcoholic patients in the KPT group, compared to 24% (24 out of 100 patients) of the conventional treatment control group (p < 0.01). The authors' studies of the underlying psychological mechanisms of KPT have indicated that ketamine-assisted psychedelic therapy of alcoholic patients induces a harmonization of the Minnesota Multiphasic Personality Inventory (MMPI) personality profile, positive transformation of nonverbalized (mostly unconscious) self-concept and emotional attitudes to various aspects of self and other people, positive changes in life values and purposes, important insights into the meaning of life and an increase in the level of spiritual development. Most importantly, these psychological changes were shown to favor a sober lifestyle. The data from biochemical investigations showed that pharmacological action of KPT affects both monoaminergic and opioidergic neurotransmitter metabolism, i.e., those neurochemical systems which are involved in the pathogenesis of alcohol dependence. The data from EEG computer-assisted analysis demonstrated that ketamine increases theta activity in cerebrocortical regions of alcoholic patients. This is evidence of the reinforcement of limbic cortex interaction during KPT session.

Adult↗
PubMedDate not supplied

Clinical pharmacokinetics of co-trimazine.

The clinical pharmacokinetics of co-trimazine (trimethoprim plus sulphadiazine) are reviewed and compared with those of co-trimoxazole (trimethoprim plus sulphamethoxazole). Both combination drugs have similar serum half-life values in persons with normal renal function (half-life of 8 to 12 hours), but the sulphamethoxazole metabolites are retained more than trimethoprim in reduced renal function. Sulphadiazine is less metabolised and the total sulphonamide load of therapeutic doses of co-trimazine is therefore less than for co-trimoxazole. Both co-trimazine and co-trimoxazole have high bioavailability. A suspension of co-trimazine gives serum concentrations comparable with those of tablets. The extravascular penetration of the co-trimazine components is reflected by the total area under the lymph concentration curve in comparison with serum. This measure shows a penetration into peripheral human lymph of 68% for sulphadiazine and 59% for trimethoprim. The proportions eliminated in urine are about 55% for sulphadiazine, 30% for its acetylated metabolite and 75% for trimethoprim. In comparison, for co-trimoxazole, the proportion of sulphamethoxazole eliminated in urine is 15%, that of the acetylated derivative 47%, and that of trimethoprim is also 75%. Urine concentrations of both combinations have similar bioactivity against urinary pathogens after 500 mg of co-trimazine and 960 mg of co-trimoxazole.

Aging↗
PubMed1989

Pharmacokinetics of cyanamide in dog and rat.

A pharmacokinetic study of cyanamide, an inhibitor of aldehyde dehydrogenase (E.C. 1.2.1.3) has been made in the beagle dog and Sprague-Dawley rat. Cyanamide plasma levels were determined by a sensitive high performance liquid chromatographic assay, specific for cyanamide. In the dog, i.v. administration of cyanamide at 1, 2 and 4 mg kg-1, produced a dose-dependent pharmacokinetic behaviour. Statistically significant changes were observed in plasma clearance values (12.6 to 19.7 mL kg-1 min-1), half life values (39 to 61 min) and mean residence times (50 to 79 min). Peak plasma concentrations, after oral administration of 4 mg kg-1 were achieved at 30 min and oral bioavailability was about 65%. In the rat after i.v. or oral administration, cyanamide (2 mg kg-1) had a half life of 30 min, a total plasma clearance of 117 mL kg-1 min-1 and a mean residence time of 26 min. Oral bioavailability was about 69%.

Administration, Oral↗
PubMedDate not supplied

Acute massive chloral hydrate intoxication treated with hemodialysis: a clinical pharmacokinetic analysis.

A 38-year-old female became comatose and exhibited signs of cardiac toxicity 2 hours after ingestion of approximately 38 Gm chloral hydrate. Hemodialysis was initiated 21 hours after ingestion, using twin coils in series, and was continued for 4.5 hours. Trichloroethanol, the active metabolite of chloral hydrate, was measured in plasma and dialysate. Two hours after ingestion, the plasma level was 330 micrograms/ml (average therapeutic level is 12 micrograms/ml or less). The predialysis level was 216 micrograms/ml and after dialysis declined to 141 micrograms/ml. The pre- and post-plasma half-life values were 35 hours, while on dialysis the half-life was only 6 hours. The average dialysis clearance was 120 ml/minute, and the amount of chloral hydrate removed by dialysis was 5.79 Gm. By the end of dialysis, the patient could respond to verbal commands and was ambulatory 36 hours later. In conclusion, hemodialysis can be a clinically important method of treating chloral hydrate overdose.

Adult↗
PubMed1994

Family values system of Polish single youth in the 1980s.

"We have presented the selected results of [a] family attitude (to marriage and procreation) survey, viewed against the Polish single youth's value system.... The empirical data...consists of 4,316 questionnaires answered by youth, aged 18-34, who were single in 1986. We focussed on selected elements of a hypothetical model of the future family: pattern of marital values and pattern of procreational values. Moreover, we identified the Polish youth's system of family values, taking into account the motivation for entering marriage, marital life values and evaluation of marital success."

Adolescent↗
PubMed1984

A comparison of chromium-51 and iron-59 for estimating erythrocyte survival in the cat.

Erythrocyte survival studies were conducted on eight, normal, healthy, 1-year-old male specific-pathogen-free cats using both chromium-51 and iron-59 simultaneously. The chromium-51 procedure gave a half-life value of 11.1 +/- 0.9 days. This was considerably lower than would be expected on the basis of the experimentally determined iron-59 erythrocyte survival time of 51.2 +/- 14.9 days. The results of this study indicated that there was considerable loss of the chromium-51 label in the cat other than that from senescence alone. An analysis of the chromium-51 disappearance curve indicated that there were two exponential disappearance rates for the chromium-51 label and, in the absence of cell death, approximately 67% of the label was lost with a rate constant of 0.02 per day and 33% was lost with a rate constant of 0.1 per day. An equation is presented which models the loss of chromium-51 label which could be used to calculate erythrocyte survival from a chromium-51 disappearance curve. Blood volume measurements, hemograms, bone marrow differential results, and iron kinetic values also were determined and the results presented. While a reasonable approximation of the erythrocyte life span could be made by correcting the chromium-51 values for losses other than senescence, the iron-59 procedure would be the preferred method in cats.

Animals↗
PubMed1990

Pharmacokinetics of recombinant human erythropoietin in chronic haemodialysis patients.

Single dose intravenous and subcutaneous pharmacokinetics of recombinant human erythropoietin (rhEPO) has been determined in 6 chronic haemodialysis patients. Four patients, all on maintenance therapy with rhEPO, were consecutively treated both intravenously and subcutaneously with injections of rhEPO in a dose of 50 U/kg. Two previously untreated patients received 150 U/kg of rhEPO intravenously and subcutaneously. After intravenous injection of 50 U/kg of rhEPO a mean serum half-life value of 5.4 +/- 0.9 hr was found. The corresponding half-life after injection of 150 U/kg was 7.6 hr. The peak concentration of serum EPO after subcutaneous injection was 12.5-20 times lower than the corresponding intravenous Cmax. After administration of 150 U/kg subcutaneously the absorption of EPO was monitored to completion at 120 hr. The complete bioavailability of subcutaneous rhEPO after injection of 150 U/kg was 31.7%. Whether this low and protracted subcutaneous absorption of rhEPO is accounted for by either impeded absorption or partial skin degradation of rhEPO is not known.

Adult↗
PubMed1992

Environmental concentrations and aquatic toxicity data on diflubenzuron (dimilin).

The insecticide diflubenzuron (DFB) is commonly used in various mid-Atlantic states for suppression of gypsy moths in hardwood forests. DFB is potentially toxic to nontarget biota because it can enter aquatic systems through aerial application or runoff after precipitation events. Based on this concern, the objectives of this study were to: (1) compile, review, and synthesize literature on the fate, persistence, and environmental concentrations of DFB in both freshwater and saltwater environments; (2) compile, review, and synthesize acute and chronic aquatic toxicity data on DFB effects on freshwater and saltwater organisms; (3) assess possible risk to aquatic biota associated with the use of this insecticide in one specific area (Maryland); and (4) recommend future research based on the data gaps identified from this study. DFB has low solubility in water and exists as a technical grade (TG) and wettable powder (WP) formulation. The toxicity of both formulations is similar at concentrations less than 10 micrograms/l. Organic matter is a major factor influencing the adsorption and degradation of DFB in freshwater, saltwater, and sediment. The half-life of this insecticide in freshwater is approximately 3 days at a pH of 10 and temperature of 36 degrees C. At lower pH conditions of 6 and at the same temperature, DFB is more persistent since half-life values of approximately 9 days have been reported. The half-life of DFB in soil is less than 14 days when the particle size was approximately 2 microns. The half-life is generally greater in cool, dry soil than in hot, wet soil. Aquatic vegetation acts as a sink for DFB by gradually adsorbing the chemical and releasing it over a period of time. Freshwater organisms demonstrated a wide range of sensitivity to DFB. Sensitivity was dependent on body composition (i.e., exo- vs. endoskeleton), trophic level, and life stage. During acute exposures, aquatic invertebrates were more than 25,000 times as sensitive to DFB than fishes. The most acutely sensitive species tested was the Amphipod, Hyallela azteca (96-h LC50 = 1.84 micrograms/l). A mature Plecopteran, Skwala sp., was the most resistant invertebrate species tested in acute tests (96-h LC50 greater than 100,000 micrograms/l). In chronic tests, DFB concentrations of 1 microgram/l or greater were reported to eliminate populations of various Plecopteran (stoneflies) and Ephemeropteran (mayflies) species after 1 month of exposure. A 30-day LC50 of 0.1 micrograms/l DFB was also reported for the Tricopteran, Clistorinia magnifica.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1980

Bacterial kill rates of amoxycillin and ampicillin at exponentially diminishing concentrations simulating in vivo conditions.

The responses of bacteria exposed to amoxycillin and ampicillin were studied at continuously decreasing levels with half-life values similar to those which could occur in vivo. For Escherichia coli, the kill-rates were higher with amoxycillin than with ampicillin. The bactericidal response was exponential. With an antibiotic half-life of one hour, the amoxycillin first order inactivation rate was 3.544 h-1 and the viable cell half-life was 0.196 h; the respective values for ampicillin were 2.341 h-1 and 0.296 h. With an antibiotic half-life of five hours, the inactivation rate was 0.704 h-1 corresponding to a viable cell half-life of 0.985 h for amoxycillin compared to 0.358 h-1 and 1.937 h respectively for ampicillin. Comparison of viable counts and photometric monitoring showed that the former is the preferable method for recording the bacterial response to these beta-lactam antibiotics. During the phase of exponential kill, a plateau occurred in the optical density values. This was due in part to an increased biomass per cell. During the recovery phase, the number of viable cells started to increase several hours sooner than did the rise in optical density. For Staphylococcus aureus,the rates of kill were similar with both agents. Amoxycillin had a long bacteriostatic phase which was not seen with ampicillin. This led to a longer lasting antibacterial effect and reduction to a lower total count with amoxycillin. With staphylococci, the viable counts and the photometric responses were parallel.

Amoxicillin↗
PubMed1980

Determining gentamicin dosage in infants and children with renal failure.

Gentamicin half-life values based on pharmacologic calculations were determined in 23 infants and children with diminished renal function. The half-life times correlated significantly with serum creatinine concentrations in patients who had steady-state creatinine levels (Y = 0.379 + 3.841 X, R = 0.951, P less than 0.001). This relationship provides a basis for formulating gentamicin dosage in pediatric patients with renal failure. The half-life of gentamicin is estimated by multiplying the serum creatinine concentration by four; three-quarters of the loading dose is administered every two half-lives. When renal function is unstable and changing daily, gentamicin half-life cannot be reliably predicted from the serum creatinine value.

Bacterial Infections↗
PubMed1993

Life-sustaining technologies: value issues.

This article examines life-extending technologies such as resuscitation, mechanical ventilation, antibiotics, dialysis, and artificial nutrition and hydration. It considers these technologies in terms of the value issues of (1) equity of access, (2) equity of allocation, (3) cost-effectiveness and appropriateness of use, (4) legal concerns, and (5) determination and control of the application of technology. How we resolve these issues tests our character as individuals and as a society--it plays a key role in determining who shall live and what kind of society we shall become.

Age Factors↗
PubMed2003

Long-term flux of Chernobyl-derived 137Cs from soil to French rivers: a study on sediment and biological indicators.

Sediment and aquatic plants were collected annually since the early 1990s in the main French rivers, upstream of nuclear power plants. These time series were used in order to assess the parameters of a compartmental model describing the Chernobyl-derived (137)Cs flux from soil to rivers. In order to reduce the dispersal of (137)Cs measured activities in sediment samples due to the granulometric heterogeneity, a correction method was set up using sediment test-fractions artificially enriched with specific diameter particles. The method was based on (137)Cs affinity for fine particles, especially clays, and thus clay and fine silt contents of each sample was analysed. Corrected sediment data showed (1) that the method efficiently reduced the variability; and (2) that (137)Cs activities in French rivers decreased with a half-life of 4 to 6 years since 1987 (after correction by radioactive decay). A similar half-life value was obtained for aquatic plants pointing out that this half-life is related to the gradual decay of the flux from soil to rivers, not to the indicator itself. Comparing our results with similar ones published by other authors, it appeared possible that this kinetic varies with the time period over which the study is conducted, the longer the period the lower is the kinetic.

Bryopsida↗
PubMedDate not supplied

Repeated bone lead levels in Queensland, Australia--previously a high lead environment.

Bone lead levels (finger and tibia) were measured, both in vivo and in vitro, with an x-ray fluorescence technique. In vivo finger-bone lead levels of 105 volunteers were estimated and subsequently re-estimated after a 5-y period. In many instances, elevated levels in some of these individuals probably resulted from lead ingested during childhood (i.e., more than 60 y ago). A decline in finger-bone lead from the initial value was accompanied by a mean finger-bone lead half-life of 6.2 y (n = 25); many individual's half-life values were less than 3.0 y. Perhaps one reason for these low values is the special propensity of finger bone to resorption during the involutional period, at which time there are high levels of circulating parathormone.

Adult↗
PubMed1997

Economic analysis of adjuvant interferon alfa-2b in high-risk melanoma based on projections from Eastern Cooperative Oncology Group 1684.

PURPOSE: Interferon alfa-2b (IFN) in a randomized clinical trial (E1684) prolonged relapse-free and total survival in high-risk resected melanoma. However, the costs and toxicities of IFN are barriers to its widespread use. This study was undertaken to analyze the projected costs and long-term benefits of IFN by combining prospectively collected data on IFN actual dosage, time of recurrence, and survival with secondary data on long-term melanoma recurrence risks to project the cost-effectiveness of adjuvant IFN compared with observation. PATIENTS AND METHODS: Two hypothetical cohorts of 50-year-old melanoma patients whose mean IFN dosage and clinical results were directly taken from E1684 were included in the study. Melanoma recurrence risks beyond 5 years were derived from international databases. Melanoma recurrence care costs and quality-of-life adjustments, when considered, were based on expert consensus. End points were incremental costs, life-years gained, and cost per life-year gained with and without quality-of-life adjustments. RESULTS: The IFN cohort was projected to have an increased (undiscounted) survival of 0.52 years at 7 years and 1.90 years over a lifetime. The projected incremental cost (in 1996 United States dollars) per life-year gained in the IFN cohort ranged from $13,700 after 35 years to $32,600 at 7 years, the median follow-up of E1684. Using assigned quality-of-life values for IFN and recurrence, the lifetime cost per quality adjusted life-year increased to $15,200. Even if treatment costs for recurrence were excluded, the lifetime incremental cost per life-year gained was $21,600. CONCLUSION: The cost and toxicity of IFN must be balanced against its projected benefits in high-risk melanoma. The derived cost-effectiveness and cost-utility ratios for IFN were comparable to other cancer interventions for which cost-effectiveness analysis has been performed.

Cost-Benefit Analysis↗