Use Of Schedule Research Articles

Small cell lung cancer in the elderly: Byrne A, Carney DN. Department of Medical Oncology, Mater Misericordiae Hospital, Eccles St, Dublin 7. Semin Oncol 1994;21:Suppl 6:43–48

Mortality rates for patients with lung cancer remain high, despite advances both in our understanding of lung cancer biology and in survival statistics for other types of cancer. Important strategies for improving the figures for lung cancer are identification of subgroups at highest risk for the disease and targeting high-intensity therapy to patients with the greatest chance for cure. In this context, special attention must be given to the elderly population, which accounts for approximately 60% of all cancer cases. Recognizing that close to 13% of the population of the United States can be considered elderly and that this figure is expected to more than double over the next 40 years, the elderly cohort clearly has a significant impact on cancer statistics in general. While approximately 26% of lung cancer patients are potentially curable, the 74% majority has only a remote chance of being cured of their disease. More active therapeutic modalities, with a meaningful effect on survival and quality of life but with more acceptable toxicity than intensive therapy designed for patients with a good chance of cure, are clearly needed for these patients. Several studies have demonstrated that use of oral active agents such as etoposide, alone or in combination with other agents, produce an overall response rate and median survival time similar to those of the more intensive schedules. Once further studies clarify the optimum schedule for use of oral etoposide, it is hoped that its use in combination with other therapeutic agents and/or with radiation therapy will improve the overall response and survival rates among patients at high risk or with poor prognostic factors, such as the elderly.

Non-surgical management of early breast cancer in the United Kingdom: Radiotherapy fractionation practices

A national survey of British radiotherapy schedules used in women with early breast cancer was undertaken to document variation in treatment practices and to consider its clinical significance. Although the variation is considerable, the analysis suggests that the majority of schedules in use are very similar in terms of treatment intensity when allowance is made for fraction size and overall time. Half the respondents used one of three dosage schedules, which probably differ very little in terms of late normal-tissue effects and tumour control from a conventional schedule giving 50 Gy in daily 2 Gy fractions. Eighty-two per cent of respondents were using schedules that are equivalent to a dose of between 45 Gy and 50 Gy in 2 Gy fractions. The study suggests that the protocols in use by a minority of respondents may be unduly conservative or aggressive, and it leads to the proposal that oncologists should set up trials comparing commonly used schedules as a matter of urgency.

Mortal Managers and Long-Term Goals: An Impossibility Result

This article examines decision myopia under effort and risk neutrality. An infinite, non-overlapping sequence of mortal managers is selected and their performance evaluated. Contracts admit premature termination. Plant condition depends on maintenance, which induces an interstage linkage in production. When ability and action are imprecisely known by employers, no contract achieves the first-best outcome. Furthermore, if the manager discounts less than the owners, inefficiency is partially due to moral hazard, which resembles myopia. Optimal contracts infer ability and motivate behavior via manipulation of wage schedules and tenure guidelines.

Treatment Schedules for Research A Model for Physiotherapy

Summary Recognition of the lack of appropriate methods of standardising physiotherapy for clinical trials led to the development of inclusive treatment schedules for use in research. The aim of the schedules is to provide a range of techniques which reflect current clinical practice so that the physiotherapists can use their clinical judgement in the treatment situation, yet be able to record what has been done. Development of the schedules is based on the literature about the technique to be used, and peer agreement of suitable experienced physiotherapists. Information is provided about the development of two schedules for a clinical trial of physiotherapy for hemiplegic shoulder pain, using the Bobath approach and cryotherapy. It is suggested that this concept could be used in other studies evaluating physiotherapy treatment and management.

Unemployment and the Composition of Labour Slack: An International Comparison

AbstractThe present statistical apparatus allows us to construct a single indicator of the degree of non‐utilisation of labour resources that mitigates the shortcomings of the traditional unemployment rate. This paper defines a method to measure aggregate labour slack, and applies it to post‐1973 data for four countries: Canada, the Netherlands, Sweden and the U.S.A. The estimates take into account non‐utilised labour resources due to unemployment, to changes in the number of hours actually worked and to changes in registered labour force participation. Since changes in and the manipulation of working time schedules on the one hand, and of labour supply on the other, have become more frequent over the last few decades, it is highly relevant to investigate international and intertemporal differences in the non‐utilisation of labour resources by means of a ratio that accounts for these changes. Unemployment is ill‐suited for this purpose, and therefore a labour slack estimate is constructed, which takes working time developments and changes in labour force participation into consideration. The estimate is cyclically more sensitive and more internationally comparable than the traditional unemployment rate.

Nonhematologic toxicities of selected chemotherapeutic agents used in the treatment of adult leukemia

p ROGRESS has been made in the treatment of acute non-lymphocytic leukemia (ANLL), acute lymphocytic leukemia (ALL), and blastic phase of chronic myelogenous leukemia (CMLBC). However, until long-term survival improves, manipulation of drug dose, schedules, and combinations can be expected. With these manipulations, the incidence and severity of nonhematologic toxicities will vary. Because these toxicities can result in dosage alterations or delays in treatment, the prevention, early detection, and objective measurement of these toxicities are essential. There are four chemotherapeutic agents commonly used in the treatment of ANLL, ALL, and CML-BC. These drugs, cytosine arabinoside, mitoxantrone, amsacrine, and daunorubicin, have various gastrointestinal, ophthalmologic, dermatologic, pulmonary, cardiologic, and neurologic toxicities. This article outlines the toxicities of these drugs, used singly and in combination, and describes assessment and intervention strategies for the toxic effects. Because bone marrow hypoplasia is a goal of therapy for these malignancies, myelosuppression will not be addressed.

Pharmacokinetics and anti-emetic efficacy of BRL43694, a new selective 5HT-3 antagonist.

Twenty patients receiving a variety of emetogenic cytotoxics (including cisplatin in 5) were given a single i.v. infusion of 40 micrograms kg-1 of BRL43694 (as the hydrochloride salt) in successive groups of 3-4 patients between 0-6 hours after chemotherapy. Eleven patients were completely protected from vomiting; 9 had mild to moderate nausea and vomiting, but none severe enough to require alternative anti-emetic 'rescue'. In 4 of the patients in whom BRL43694 was delayed until 4-6 h after chemotherapy, vomiting had already begun; in each case immediate termination of vomiting occurred when BRL43694 was infused. No adverse effects attributable to the anti-emetic were observed. Mean pharmacokinetic parameters in 14 patients in whom plasma assay data are available were: Maximum observed concentration = 30.7 ng ml-1; terminal phase half-life = 8.96 h; total body clearance = 0.376 (1 h-1) kg-1; apparent volume of distribution = 2.85 l kg-1. This study shows BRL43694 to be an effective and well tolerated anti-emetic. Further studies aimed at defining an optimal dose and schedule for use against the most emetogenic cytotoxics are in progress.

Duration of effectiveness of pertussis vaccine: evidence from a 10 year community study.

A 10 year study of whooping cough in a discrete general practice community was performed to assess longitudinally the efficacy of pertussis vaccine from one to seven years after immunisation. Of the 436 cases of whooping cough over 10 years, 326 occurred in children aged 1-7 years. The rate of immunisation was known for each cohort of children born during each year, and the attack rate of whooping cough was thus calculated for those immunised and unimmunized. The attack rates were highest in those cohorts exposed to the epidemics of 1977-9, 1981-3, and 1985-7. The efficacy of the vaccine was calculated as a percentage as (attack rate in unimmunized group--attack rate in immunised group) x 100/attack rate in unimmunized group. It fell from 100% in the first year to 46% in the seventh, being 84% in the fourth and only 52% in the fifth. Thus the pertussis vaccine or its schedule of use does not seem to provide sufficient herd immunity to prevent outbreaks of whooping cough. Matters might be improved if vaccination against pertussis were included in the preschool immunisation programme.

Observing Pupils and Teachers In Classrooms (OPTIC): a behavioural observation schedule for use in schools

Abstract A new behavioural observation schedule for use in classrooms (OPTIC) is described. Its development and its purpose are detailed and its psychometric credentials are examined in terms of its reliability, validity and sensitivity. Suggestions are made as to its possible uses.

Phase I and pharmacologic study of 72-hour infused 5-fluorouracil in man.

The relationships between the administered dose, clearance, and the toxicity spectrum of 5-fluorouracil (5-FU) administered as 72-hour constant infusion have been studied in 21 patients with advanced cancer. This was done as a pilot study for possible future combination using 5-FU as a radiosensitizer. Individual patients tolerated up to 65 mg/kg/24 hours, but serious toxicity appeared once as low as 35 mg/kg. Limiting toxicity proved to be "mixed" with upper intestinal symptoms (nausea and vomiting), stomatitis, and central nervous system signs all occurring in various patients. Central nervous system effects (both cerebellar and vomiting) proved as troublesome as stomatitis. There was only a general link between the administered dose and the subsequent toxicity grade, but a reasonably quantitative relationship emerged when the serum 5-Fu levels obtained and the degree of patient toxicity were compared. The clearance of 5-FU was confirmed to be nonlinear over the entire dose range studied (25-65 mg/kg/24 hours), consistent with a two-compartment model of drug metabolism. One compartment appears to be systemic (extra-hepatic) metabolism (probably anabolic removal) which is saturated at just below 15 mg/kg/day. Doses above that level lead to drug accumulation. No steady state was reached, contrary to previous reports. At the higher infusion rates, clearance progressively approaches that predicted by the assumption that the second compartment is splanchnic blood flow and catabolism. While 5-FU can be administered as a 72-hour infusion as one possible schedule for use as a single agent or for combined modality studies, CNS effects are quite troublesome in comparison to longer infusions to toxicity.

Inhibition of phorbol ester--induced human epidermal ornithine decarboxylase activity by oral compounds: a possible role in human chemoprevention studies.

Extensive animal data have suggested that, in some systems, the induction of ornithine decarboxylase (ODC) is an essential, although not sufficient, aspect of tumor promotion and that compounds that inhibit ODC can inhibit tumor formation. Using fasting human volunteers, we report that human epidermal and dermal ODC are consistently induced by the tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA) in a manner similar to that seen in mouse skin. There is a marked intersubject variation in TPA-induced epidermal ODC activity levels. Orally administered compounds significantly inhibited TPA-caused human epidermal ODC induction. These data may be useful in the further development of drugs, doses, and dose schedules for use in human cancer chemoprevention studies.

An Interview Schedule for Use in the Behavioural Assessment of Children's Problems

A crucial aspect of behavioural assessment and intervention is the initial interview with the client. Although the interview is the most frequently employed method of assessment, very few published behavioural interview schedules are available to clinicians. The authors present an interview schedule for the behavioural assessment of children's problems. Hopefully, such devices will improve the reliability and validity of problem identification and facilitate effective case management.

Choice and amount of reinforcement in rats

Rats were exposed to concurrent-chains schedules in which the terminal links were equal, fixed-interval (FI) schedules terminating in one or a varying number of food pellets. In most rats, choice proportions for the larger reinforcer increased with increases in reinforcer amount (e.g., from one to five food pellets). When log response ratios were plotted against log reinforcer amount ratios, the results indicated that the effects of reinforcer amount depended on the length of fixed-interval terminal links, by showing that rats undermatched their response ratios to reinforcer amount ratios with the shorter terminal links (FI 5 s, Experiment 1), whereas they overmatched with the longer terminal links (FI 20 s, Experiment 2). These results demonstrated that the manipulation of FI terminal-link schedules affected the sensitivity of choice to reinforcer amount, and are consistent with the previous findings that choice proportions for the larger of two reinforcers (one vs three food pellets) increased with increases in the length of FI terminal-link schedules.

Pharmacokinetic approach to the selection of dose schedules for medroxyprogesterone acetate in clinical oncology.

The pharmacokinetic and bioavailability properties of medroxyprogesterone acetate (MPA) after single PO and IM doses in man were used as a basis to predict, on a theoretical pharmacokinetic basis, the blood level profile of the drug during repeated dose administration with various dosage schedules. Because of the unusually long-lasting depot effect of IM MPA, a different build-up process of blood levels is expected during repeated IM or PO administration, and this should be taken into account when dose schedules for use in clinical oncology are selected. As regards the IM route, dose schedules based on 4 weeks' treatment with daily injections of 500-1,000 mg followed by a maintenance therapy with 1,000 mg/week are suggested, since they permit rapid achievement and maintenance of relatively high plasma levels. A similar plasma level profile can be obtained with oral MPA provided that daily doses twice as large as the IM doses are given during the first month of treatment and continued during the maintenance period. The serum levels observed in 25 patients with advanced breast cancer treated with MPA given IM or PO according to various dose schedules and recent literature data are very close to the serum level profiles predicted on a theoretical pharmacokinetic basis.

An Observation Schedule for Use with Children Who Have Severe Learning Difficulties

Classroom observation instruments exist in abundance. American authors, writing from an American perspective, have spoken of 120 systems as an underestimation. Galton (1979) surveyed 41 native British systems currently in use. Evans and Wragg (1971) did adapt Flanders' system to investigate laguage in an ESN(s) school, but, as Beveridge (1976) points out, there have been relatively few naturalistic studies of the classroom behaviour of children with severe learning difficulties. We were certainly unable to find an observational schedule for use with such children and therefore developed our own instrument to allow us to observe a range of pupil behaviours.

Modification of the Pleasant and Unpleasant Events Schedules for use with the elderly.

Modification of the Pleasant and Unpleasant Events Schedules for use with the elderly.

Attentive Audience Delivery of TV Advertising Schedules

Television program ratings are used extensively by media planners in developing advertising schedules for use in marketing strategies. The authors describe a study of TV program exposure and attention that produced two equations for predicting attentive audience delivery of TV advertising schedules from program ratings and may thus facilitate media planning.

RESPONDING UNDER SEQUENCE SCHEDULES OF ELECTRIC SHOCK PRESENTATION

Lever pressing by squirrel monkeys was examined under second-order schedules of electric shock presentation in which different discriminative stimuli were associated with consecutive components (sequence schedules). Components were always two-minute fixed-interval schedules, and three different overall schedules were studied. Under an overall eight-minute fixed-interval schedule, the first component completion after at least eight minutes had elapsed produced electric shock. The number of components actually completed ranged from one to four; thus, different discriminative stimuli were occasionally associated with electric shock presentation. Under an overall "yoked" variable-ratio schedule, electric shock was presented after completion of a variable number of components; the required number and the distribution of components were matched to those obtained under the overall eight-minute fixed-interval schedule. Under an overall fixed-ratio schedule, electric shock was presented after completion of four components (chained schedule). Under all three sequence schedules, responding in early components was characterized by a pause followed by a single response after the end of the two-minute interval; responding in later components was characterized by a shorter pause followed by positively accelerated responding. Manipulation of overall schedules of shock presentation in these complex behavioral situations produced changes in responding comparable to those ordinarily obtained after similar manipulation of dependencies under both single and second-order schedules of food presentation. These experiments extend the range of conditions and levels of complexity under which responding can be maintained by presentation of electric shock.

Peripheral neuropathies associated with chronic renal failure.

A variety of peripheral nerve disorders may be associated with chronic renal failure. The polyneuropathy due to uremic toxins is a distal, motor and sensory polyneuropathy in which there is segmental demyelination, axonal degeneration, and segmental remyelination. The nature of the uremic toxin and the underly mechanism of these changes is unknown. The incidence in patients with "end-stage" renal disease has fallen in recent years, severe cases now being rare, perhaps due to refinements in chronic hemodialysis, transplantation, and other therapies. However, while chronic hemodialysis stabilizes uremic neuropathy, manipulation of hemodialysis schedules may not alter its course, according to current assessment. Successful renal transplantation improves both the clinical and electrophysiological signs, even in severe uremic neuropathy.

Comparison of Procedures for Promoting Reading Proficiency of Two Children with Behavioral and Learning Disorders

This study investigated the effects of two discrete teaching strategies for developing proficiency in oral reading. The use of teacher praise contingent upon pupil correct responses was compared with teacher modeling of words erred. The results clearly indicate that, for two learning/behavior disordered youngsters approaching a proficiency level in oral reading, manipulation of reinforcement schedules was demonstrated to be the more effective approach.