The Needs Assessment for Advanced Cancer Patients (NA-ACP): a measure of the perceived needs of patients with advanced, incurable cancer. a study of validity, reliability and acceptability.

AIMS: To describe the psychometric evaluation of a measure designed to assess the perceived needs of patients with advanced, incurable cancer. METHOD: A questionnaire known as the Needs Assessment for Advanced Cancer Patients (NA-ACP) was developed based on a review of available literature and professional opinion. A sample of 246 patients (consent rate = 59%) completed the NA-ACP, 28 patients completed the acceptability questions, while 41 completed a retest copy of the NA-ACP. The construct validity of the questionnaire was examined via principal components analysis, while reliability was evaluated in terms of the internal consistency of domains and test-retest scores. RESULTS: The principal components analysis revealed seven domains assessing patients' psychological/emotional, medical information/communication, social, symptom, daily living, spiritual and financial needs. The test-retest reliability estimates were within accepted levels, as were all but one of the internal consistency scores. The NA-ACP was highly acceptable for this patient group. CONCLUSION: The NA-ACP is one of the first multi-dimensional instruments specifically designed to assess the needs of patients with advanced, incurable cancer. The present study provides evidence of the NA-ACP's validity, reliability, and acceptability. The NA-ACP has potential applications both as a research tool and within clinical settings.

Nonpeptide alpha(v)beta(3) antagonists. 1. Transformation of a potent, integrin-selective alpha(IIb)beta(3) antagonist into a potent alpha(v)beta(3) antagonist.

Modification of the potent fibrinogen receptor (alpha(IIb)beta(3)) antagonist 1 generated compounds with high affinity for the vitronectin receptor alpha(v)beta(3). Sequential modification of the basic N-terminus of 1 led to the identification of the 5,6,7, 8-tetrahydro[1,8]naphthyridine moiety (THN) as a lipophilic, moderately basic N-terminus that provides molecules with excellent potency and selectivity for the integrin receptor alpha(v)beta(3). The THN-containing analogue 5 is a potent inhibitor of bone resorption in vitro and in vivo. In addition, the identification of a novel, nonpeptide radioligand with high affinity to alpha(v)beta(3) is also reported.

Nonpeptide glycoprotein IIB/IIIA inhibitors. 19. A new design paradigm employing linearly minimized, centrally constrained, exosite inhibitors.

A new series of potent, linearly-minimized, orally active, selective GPIIb/IIIa inhibitors is identified. Thus 15 (L-750,034) achieves interaction via a constrained, non-turned conformation that maintains the proper distance between its charged termini and full sulfonamide exosite interaction. The diminutive stature and the proposed linear conformation of L-750,034 define a new paradigm for the conceptualization of RGD mimics.

Factors relating to cervical screening in New South Wales, Australia.

The aims of this paper were to describe the geographical variation in Pap smear screening rates, standardised for age and adjusted for rates of hysterectomies and to assess the sociodemographic and health care factors associated with the variation. The data used in the study were the percentage of women who had had Pap smears between the years 1990 and 1992 based on the records of the Australian Health Insurance Commission (HIC). The best predictors of screening extracted from the model were the Index of Economic Resources and the proportion of women within each region who were born in non-English speaking countries.

Adaptation and validation of the SF-36 Health Survey for use in Australia.

This article reports on the process undertaken to adapt the U.S. version of the SF-36 to an Australian setting. In addition, the results of psychometric testing, using the International Quality of Life Assessment (IQOLA) Project process and standards, is also reported. The adaptation process involved a number of steps including: a series of forward and backward translations; ratings of the difficulty of translating the SF-36 and the quality of the resulting translation. To assess the psychometric properties of the Australian form, a random sample of people residing in the Hunter region of New South Wales, Australia, were invited to complete the SF-36 with 855 respondents consenting to complete the measure. Principal components analyses supported the assumption of two factors underlying the measure with the percentage of variance explained by these factors ranging from between 0.66 and 0.77. Demonstrable internal consistency (both item and scale) and test-retest reliability were also found.

An examination of self- and telephone-administered modes of administration for the Australian SF-36.

The impact of administration mode on health-related quality of life measurement instruments has received little attention, especially for the SF-36. General community members were randomly selected to complete the Australian version of the SF-36 Health Survey using either telephone or mail modes. Modes were compared across a number of indices: data collection costs; consent rates and non-consent bias; data quality (completeness of data and internal consistency reliability); and response effects. Data collection costs were lower for the telephone mode. A significantly higher consent rate was achieved with the telephone mode. Those who were younger were more likely to refuse to participate when the mail mode was adopted, while older people were more likely not to consent to the telephone mode. The rate of missing responses was higher for the mail mode, while significant differences were found between modes in internal consistency reliability estimates. Health ratings were more favorable for the telephone administration. The results are discussed in light of the advantages and disadvantages of each administration mode.

An exploration of screening practices for prostate cancer and the associated community expenditure.

OBJECTIVES: To determine: (i) the prevalence, reasons for, and demographic and psychosocial predictors of prostate cancer screening among a randomly selected sample of men; and (ii) to estimate the community expenditure involved in the screening of asymptomatic men. SUBJECTS AND METHODS: A random sample of men aged 40-79 years was selected from the State Electoral Register of New South Wales, Australia, and asked to complete a computer-assisted telephone interview. The questions determined their demographic characteristics, their subjective health rating compared with others of the same age (5-point scale), the prevalence and reasons for any screening for prostate cancer ('ever screened' and 'screened within the last 12 months'), whether they had undergone a digital rectal examination (DRE), a blood test for prostate-specific antigen (PSA) or transrectal ultrasonography (TRUS), and the prevalence of urinary symptoms. Those who had been screened were then asked to nominate the single most important factor in the decision to undergo prostate cancer screening. To estimate community expenditure, the costs for prostate cancer screening were estimated by applying Medicare schedule charges to the screening and subsequent diagnostic tests performed. Two scenarios were developed to estimate costs: the first used guidelines which do not recommend the use of routine screening for all asymptomatic men, and the second was based on guidelines where the routine use of PSA or TRUS as part of a periodic health examination is not recommended, but the use of DRE in asymptomatic men aged 50-70 years is. RESULTS: Of the 551 eligible participants, 86% completed the interview; 44% of participants reported that they had 'ever' been screened, whilst 23% had been screened in the year before the study. Among those who had been screened, the reason reported most often for screening, apart from symptoms and family history, was the doctor's recommendation after a medical assessment of their prostate cancer risk status. Screening status was predicted both by the age of the man and his symptom score. As a result, the community expenditure in New South Wales for screening among asymptomatic men was estimated to be A$6.4 million and A$5.2 million for the first and second scenarios, respectively. CONCLUSIONS: The results of this study suggest that, despite the recommendations of primary bodies that asymptomatic men not be screened for prostate cancer, screening is occurring at a high level and with significant costs to the healthcare system.

A preliminary exploration of the interactional skills of trainee surgeons.

BACKGROUND: The interactional skills of 21 surgical trainees were studied in the areas of breaking bad news to patients and preparing patients for potentially threatening medical procedures. When compared to the established guidelines for dealing with these issues, the trainees performed poorly. METHODS: Trainees were videotaped using clinical histories delivered by simulated patients in simulated consulting rooms. All videos were scored on standard rating scales where the criteria for rating the specific interactional skills were adopted from existing guidelines. RESULTS: The proportion of trainees who could meet the guidelines when breaking bad news was low. The proportion of trainees who met the guidelines were: closing the the consultation (0%), provided patient information about prognosis (43%) and treatment (38%) and when they gave support (10%). There were also low numbers of trainees who could meet the guidelines when they prepared patients for potentially threatening procedures. Ten per cent of trainees followed the guidelines when providing information, 25% could establish treatment goals, 35% could give a prognosis and 0% could deal appropriately with psychosocial issues or close the consultation appropriately. CONCLUSIONS: It is concluded that there is a need for further formal training in interactional skills as part of surgical training.

Structural requirements and cell-type specificity for ligand activation of peroxisome proliferator-activated receptors.

The mammalian peroxisome proliferator-activated receptor (PPAR) family consists of three different subtypes, PPARalpha, hNUC1/PPARdelta and PPARgamma. Selective agonists have been identified for PPARalpha and PPARgamma but not for hNUC1, and consequently little is known about the genes that are controlled by this receptor. Using ligand-dependent transcription assays in COS-7 cells, we screened a variety of PPAR activating agents to identify a selective activator of hNUC1. We found that the potent peroxisome proliferator, Wy-14643, and the PPARgamma-selective thiazolidinedione, BRL 49653, were poor activators of hNUC1 (EC50s of > 100 microM). Short chain fatty acids (FAs) appeared more selective for PPARalpha than for hNUC1, whereas the very long chain FA, erucic acid (C22:1) was more selective for hNUC1. Using erucic acid as a probe, we conducted a topological similarity search of the Merck Chemical Collection and identified a fatty acid-like compound, L-631,033 4-(2-acetyl-6-hydroxyundecyl) cinnamic acid, that was a selective activator of hNUC1 (EC50 of 2 microM), but was much less selective for PPARalpha or PPARgamma (EC50s of > 100 microM). Structure-function analysis of PPAR activation by L-631,033 structural analogues showed that receptor selectivity depends on the position of the carboxyl group relative to the phenyl ring on the molecule. Transfection experiments in several cell types: an osteoblastic cell line (MB 1.8), a mouse liver cell line (ML-457), rat aortic smooth muscle cells (RSMCs) and COS-7 cells revealed differences in the activation profile of specific ligands. The most notable differences were observed in RSMCs, where transactivation by L-631,033 and Wy-14643, but not by BRL 49653, was markedly reduced, and in MB 1.8 cells, where oleic acid failed to activate PPARs. These findings identify certain structural features in PPAR-activating agents that modulate PPAR activation, and suggest that as with other nuclear receptors, activation is cell-type specific.

Nonpeptide glycoprotein IIb/IIIa inhibitors. 8. Antiplatelet activity and oral antithrombotic efficacy of L-734,217.

The antiplatelet activity of L-734,217, a nonpeptide platelet GPIIb/IIIa antagonist, was evaluated in the rat, guinea pig and dog. IC50 for inhibition of in vitro platelet aggregation for these species (agonists: adenosine diphosphate, collagen) were rat, 838,000 and > 1,100,000 nM; guinea pig, 124 and 156 nM; dog, 42 and 50 nM. In an in vivo rat/in vitro dog platelet aggregation assay, effective antiaggregatory plasma concentrations of L-734,217 were achieved after 8.0 to 16.0 mg/kg p.o. vs. 0.3 to 1.0 mg/kg i.v. to rats. Delays in platelet-dependent hemostatic plug formation in severed mesenteric arteries were observed after 2.0 to 5.0 mg/kg p.o. vs. 0.1 to 0.2 mg/kg i.v. to guinea pigs. Dose-dependent inhibitions of ex vivo platelet aggregation after 0.3 to 3.0 mg/kg p.o. and 0.03 to 0.3 mg/kg i.v. L-734,217 to conscious dogs yielded estimates of 8 to 16% oral bioavailability. The antiplatelet activity of 3.0 mg/kg p.o. L-734,217 in dogs was unaffected by dosage form or food. In a conscious dog model of left circumflex coronary artery electrolytic lesion, 3.0 mg/kg p.o. L-734,217 q4 to 8 hr reduced thrombus mass, prevented occlusive coronary artery thrombosis and reduced or prevented myocardial infarction and ventricular ectopy. In anesthetized dogs, a dissociation between inhibition of ex vivo platelet aggregation and template bleeding time prolongation was observed with i.v. L-734,217. The results of the coadministration of heparin, aspirin and L-734,217 to anesthetized dogs suggested a synergistic effect on template bleeding time with no effect on plasma L-734,217 concentrations. These findings indicate L-734,217 to be an important lead structure for the development of therapeutically useful oral antiplatelet agents.

Increased focus on the teaching of interactional skills to medical practitioners.

The interaction which occurs between the doctor and patient has been described as the cornerstone of medial care. Research has shown that interactional skills can have a substantial impact on patient outcomes in a number of areas. However, as practitioners do not necessarily acquire such skills through clinical practice, the introduction of formal training programmes for both under and postgraduate medical practitioners should be more closely examined. This paper outlines a number of issues which need to be considered in the formal instruction of medical practitioners in interactional skills. These issues include the teaching of skills within a clinical context that will reflect actual medical practice, the use of all medical disciplines to teach the skills and the inclusion of formal assessment strategies based on the same rigorous criteria as other components of the medical curriculum.

Non-peptide fibrinogen receptor antagonists. 7. Design and synthesis of a potent, orally active fibrinogen receptor antagonist.

The design, synthesis, and pharmacological evaluation of L-734,217, a potent, low-molecular weight, orally active fibrinogen receptor antagonist, is reported. A strategy for producing low-molecular weight inhibitors from the peptide c-[(Ac)CRGDC] A, previously reported from these laboratories, is outlined. This strategy combines a retrodesign analysis of the conformationally defined cyclic peptide A with stereochemical information present in the arginine-glycine-aspartic acid (RGD) tripeptide sequence, culminating with the discovery of L-734,217. L-734,217 inhibited the aggregation of human, dog, and chimpanzee platelets at concentrations below 100 nM and was found to be > 15000-fold less effective at inhibiting the attachment of human umbilical vein endothelial cells to fibrinogen, fibronectin, and vitronectin than it was at inhibiting the aggregation of platelets. L-734,217 showed significant ex vivo antiplatelet activity following oral administration in dogs and chimpanzees at doses of 1.0 and 2.0 mg/kg, respectively, and has been selected as a clinical candidate for development as an antithrombotic agent.

The development of a new methodology to assess perceived needs among indigenous Australians.

The present study examined a new methodology to assess the perceived needs of Indigenous Australians in two urban communities. This methodology, utilizing graphics, allowed for the classification of general areas of need into four domains namely, health, education and employment, housing as well as social issues and community facilities. In addition participants were able to prioritize their identified needs both within the four domains as well as across domains. Overall, a number of similarities of perceived needs were noted between the communities. The results are discussed in terms of the lack of information on Indigenous Australian peoples' perceptions of their needs and the use of the new methodology to allow a wider examination of perceived needs.

The prevalence of drug use in urban aboriginal communities.

The use of both licit and illicit drugs has been identified as a major health issue for Australian Aborigines. However, data on the proportion of people who use such drugs is scant. This cross-sectional survey of a randomly selected sample of urban Aboriginal people provides information on the use of the drugs alcohol, tobacco, marijuana, cocaine, heroin as well as petrol sniffing. Overall, a significantly smaller proportion of Aboriginal people were found to be current alcohol drinkers compared to non-Aboriginal Australians. A larger proportion of these drinkers were, however, found to be drinking at levels that were hazardous to their health. A significantly greater proportion of people from the Aboriginal sample were also found to be smokers compared to their non-Aboriginal counterparts. An examination of the use of the illicit substances revealed that a greater proportion reported they had ever used marijuana, compared to the other substances. The findings are discussed in terms of their implications for the health of Aboriginal people.

Training medical practitioners in information transfer skills: the new challenge.

Traditionally, undergraduate medical education has concentrated on teaching students how to gather information or take medical histories from their patients. However, research increasingly indicates that there is a need for medical practitioners to improve their skills in information transfer in a way which will increase the probability that patients are active collaborators in their treatment. Consequently, Newcastle Medical School has sought to develop training packages for medical students in information transfer skills. This paper describes the resulting training programme with particular emphasis on the areas selected for training, the methods by which students are taught, the necessary interactional skills and the assessment procedures which are applied.