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Biomedical subjects

M T King

Publications and source records attributed to M T King.

At least 19 recordsLinked to original sources
PubMed2002

Adapting portfolio theory for the evaluation of multiple investments in health with a multiplicative extension for treatment synergies.

Portfolio theory is central to the analysis of risk in many areas of economics but is seldom used appropriately in health economics. This contribution examines the use of portfolio theory in the context of cost-effectiveness analysis (CEA). A number of modifications are needed to apply portfolio analysis to the economic evaluation of health care interventions. First, the method of reporting the results of a CEA, and consequently some of the underlying assumptions, needs to be modified. Second, portfolio theory needs to be expressed in terms of effects on individuals aggregated to a population. Finally, one needs to allow for the possibility of synergy between the various health interventions. This paper derives a general formula for a portfolio of health care interventions that allows for synergies between interventions where the population effects are aggregated from individual effects. A number of special cases are also derived to highlight the nature of the formulation of the modified portfolio theory. We conclude that, while modified portfolio theory adds a theoretical foundation to health care evaluations, it may not be operational until estimates of the correlation between interventions are available, and the question of uncertainty is resolved in health care evaluation. Also, while a synergy may be present at the individual level, when aggregated over a large population it may not be significant given the standard assumption of constant returns to scale.

Journal Article↗
PubMed2000

A clinical model for quality of life assessment in cancer patients receiving chemotherapy.

BACKGROUND: The pattern of symptoms experienced by cancer patients during chemotherapy is very complex. Consequently, quality of life (QOL) assessment has to be carefully planned to capture clinically relevant changes. PATIENTS AND METHODS: A clinical model of changes in symptoms experienced by symptomatic metastatic patients during several courses of chemotherapy has been developed. The model differentiates cancer-related symptoms, acute side-effects, chronic side-effects and symptoms not related to cancer. The model was used to predict changes in each of these four symptom groups. Three time points were selected (post-cycle 2, pre-cycle 3, post-cycle 5) and an appropriate window around each time point was set. The model predictions were tested empirically with 56 patients with advanced ovarian cancer who completed the EORTC QLQ-C30 plus disease specific items during a six-cycle course of chemotherapy. RESULTS: The changes observed in the sample were in accordance with the changes predicted by the clinical model. Results from patients who did not complete the questionnaire within the specified time windows tended to dilute the findings from the group who did. CONCLUSIONS: A clinical model is useful in the planning of QOL assessments in order to capture clinically relevant effects. Such models also facilitate the interpretation of QOL studies, particularly when cyclic short-term effects and chronic side-effects are overlaid on disease symptoms, as is the case with chemotherapy for cancer.

Antineoplastic Agents↗
PubMed2000

Quality of life three months and one year after first treatment for early stage breast cancer: influence of treatment and patient characteristics.

This paper reports the quality of life (QoL) of a large cohort of Australian women three and twelve months after surgery for early stage breast cancer (ESBC), and shows that the impact of disease and treatment on QoL differed by age, education and marital status. Eighty-three percent of eligible patients were recruited; 86% had breast conserving surgery and 14% mastectomy. Response rates were 93% (n = 305) at three months and 88% (n = 291) at one year. Quality of life was measured with the EORTC core questionnaire (QLQ-C30) and an ESBC-specific questionnaire. Multilevel analysis was used to estimate the effects and interactions of time, treatment and patient characteristics. Most symptoms declined between three months and one year, but arm and menopausal symptoms persisted. Emotional, social and role functioning improved over time, and fear of disease recurrence diminished. Younger women faired worse than older women on a broad range of QoL dimensions. Single women and those with less education faired worse on a number of dimensions. The negative impact of mastectomy on body image was greatest among married women, particularly young married women. These sociodemographic distinctions are relevant when discussing treatment options with women facing a diagnosis of ESBC.

Adult↗
PubMed2000

Patterns over time in quality of life, coping and psychological adjustment in late stage melanoma patients: an application of multilevel models.

BACKGROUND: Quality of life (QOL) assessment is an important component within cancer research. There is often variability in QOL scores both between patients and across time. Understanding this variability in terms of personal characteristics and psychosocial factors would be useful but is often obstructed by the types of analyses that are applied to longitudinal data sets. Improved understanding can be gained with the application of multi-level or hierarchical models that allow for greater flexibility for modelling individual patterns of change over time. METHODS AND PATIENTS: Questionnaires were sent to a cohort of stage IV melanoma patients seen at the Sydney Melanoma Unit between 1991 and 1996, approximately every 3 months for up to 2 years. The data reported here are from a sub-sample of 44 patients who each completed between 3 and 8 questionnaires. Three aspects of QOL were measured (effort to cope, mood and physical well-being), each with a single LASA line. Multilevel techniques were used to model the patterns of QOL over time. Covariates were added to explain variation between patients in their average QOL and change in QOL over time. RESULTS: The scores of each of the three QOL measures showed marked fluctuations over time. However, there was little systematic change during the study in either effort to cope (p = 0.32) or mood (p = 0.06). In contrast, the physical well-being scores of some patients improved while others deteriorated (p < 0.001). On average, physical well-being deteriorated (p < 0.001). Variability between patients accounted for 60% (effort to cope), 45% (mood) and 44% (physical well-being) of the total variance of each scale. A range of psycho-social factors including active and avoidant coping styles and psychological adjustment accounted for significant amounts of the variability between patients in each QOL measure. CONCLUSION: Individual coping and psychological adjustment are related to individual changes in QOL and to differences among patients' QOL. The study illustrates the use of multi-level techniques to further our understanding of differences between patients in their QOL and how it changes over time.

Adaptation, Psychological↗
PubMed2000

Early stage breast cancer: costs and quality of life one year after treatment by mastectomy or conservative surgery and radiation therapy.

This paper reports a descriptive study of the costs and quality of life (QoL) outcome of treatments for early stage breast cancer in a cohort of Australian women, one year after initial surgical treatment. Mastectomy without breast reconstruction is compared to breast conserving surgery and radiotherapy (breast conservation). Of the 397 women eligible for the study, costing data were collected for 81% and quality of life data for 73%. The cost differences between treatment groups were mainly accounted for by adjuvant therapies, the more expensive being radiotherapy. When compared to women treated by mastectomy, those treated by breast conservation reported better body image but worse physical function. The negative impact of breast cancer and its treatment was greater for younger women, across a number of dimensions of quality of life (regardless of treatment type). While this study shows that breast conservation is more expensive than mastectomy, the QoL results reinforce the importance of patient participation in treatment decisions.

Journal Article↗
PubMed2000

Home or hospital? An evaluation of the costs, preferences, and outcomes of domiciliary chemotherapy.

This study compares the costs and outcomes of domiciliary and hospital-based chemotherapy, using a prospective randomized cross-over design. Eighty-seven eligible patients were recruited from oncology services at two metropolitan hospitals in Sydney, Australia. Forty patients completed study evaluation requirements, having two months of chemotherapy in each location (home and hospital). The domiciliary service was staffed by hospital-based oncology nurses. Marginal costs of domiciliary treatment over hospital treatment were estimated from the health service perspective. Home-based care was more expensive, largely due to extra nurse time. About half of the eligible patients (n = 87) and 73 percent of the evaluated patients (n = 40) preferred domiciliary care. Most evaluated patients and their informal carers were satisfied with the medical care provided, regardless of location. Patient needs were well met in either location, and no differences were found in quality of life. At current throughput rates, providing chemotherapy in the home was more expensive than providing it in hospital. However, if the demand for chemotherapy were to exceed ward capacity by up to 50 percent, moving chemotherapy into the home could provide a less costly strategy for the expansion of a chemotherapy service without compromising patient outcomes.

Cross-Over Studies↗
PubMed1997

Substrate signaling by insulin: a ketone bodies ratio mimics insulin action in heart.

The administration of saturating doses of insulin to the glucose perfused, working rat heart acutely increased activity of the glucose transporter 4, GLUT 4, in the plasma membrane (equilibrating extracellular glucose and intracellular [glucose]), activated glycogen synthase (stimulating the rate of glycogen synthesis), and increased mitochondrial acetyl CoA production by the pyruvate dehydrogenase multienzyme complex. Unexpectedly, insulin increased cardiac hydraulic work but decreased net glycolytic flux and O2 consumption, improving net cardiac efficiency by 28%. These improvements in physiologic performance and metabolic efficiency resulted from reduction of the mitochondrial free [NAD+]/[NADH] and oxidation of mitochondrial [coenzyme Q]/[coenzyme QH2], increasing the energy of the proton gradient between cytosolic and mitochondrial phases and leading to a doubling of the cytosolic free [sigmaATP]/[sigmaADP][sigmaPi]. The acute metabolic effects of insulin were qualitatively duplicated by addition of a ratio of 4 mM D-beta-hydroxybutyrate and 1 mM acetoacetate, and the increase in the efficiency was the same as with addition of insulin. Addition of both insulin and ketones to the glucose perfusate increased the efficiency of cardiac hydraulic work by 35%. The ability of a physiologic ratio of ketone bodies to correct most of the metabolic defects of acute insulin deficiency suggests therapeutic roles for these natural substrates during periods of impaired cardiac performance and in insulin-resistant states.

3-Hydroxybutyric Acid↗
PubMed1996

The beta/alpha peak height ratio of ATP. A measure of free [Mg2+] using 31P NMR.

From 31P NMR measurements made in vitro at 38 degrees C, I = 0.25, pH 5. 75-8.5, and calculated free [Mg2+] from 0 to 5 mM, we show that, within the physiological range of cytosolic free [Mg2+] from 0.25 to 1.5 mM, the chemical shift difference between the alpha- and beta-ATP resonances, deltaalphabeta, changes by only 0.6 ppm. Consequently, we developed new formalisms from known acid and Mg2+ dissociation constants by which the observed chemical shift of Pi, deltaPi, and the peak height ratio of the beta- and alpha-ATP resonances, hbeta/alpha, could be related to free [Mg2+] by simultaneous solution of: [equation: see text] We found that hbeta/alpha changed 2.5-fold as free [Mg2+] varied from 0.25 to 1.5 mM, providing a more sensitive and accurate measure of free cytosolic [Mg2+]. In working rat heart perfused with glucose, free [Mg2+] was 1.0 +/- 0.1 from hbeta/alpha and 1.2 +/- 0.03 from measured [citrate]/[isocitrate] but 0.51 +/- 0.1 from deltaalphabeta. Addition of ketone bodies to the perfusate decreased free [Mg2+] estimated from hbeta/alpha to 0.61 +/- 0.02 and 0.74 +/- 0.11 by [citrate]/[isocitrate] but the estimate from deltaalphabeta was unchanged at 0.46 +/- 0.04 mM. Such differences in estimated free [Mg2+] alter the apparent Keq of the creatine kinase reaction and hence the estimated cytosolic free [SigmaADP].

Adenosine Triphosphate↗
PubMed1996

Emerging issues in sleep-disordered breathing.

Community studies of problems with breathing during sleep suggest that sleep-disordered breathing is a better general term than sleep apnoea. Male sex, increasing age and increasing neck size are the main factors differentiating people with from those without sleep-disordered breathing. The contribution of sleep-disordered breathing to morbidity has not been established. Future research should address the possible cardiovascular associations of sleep-disordered breathing, its impact on sleepiness in the community, and the cost-effectiveness of treatment.

Australia↗
PubMed1996

The interpretation of scores from the EORTC quality of life questionnaire QLQ-C30.

While quality of life (QOL) assessment is becoming more common, interpreting the results remains problematic. This paper demonstrates an approach to developing clinically-based interpretations for QOL outcomes, using the QLQ-C30 as an example. The results from 14 published QLQ-C30 studies which group patients by performance status, weight loss, toxicity, extent or severity of disease are collated. Groups with lower clinical status generally have worse QOL. The largest differences are between performance status groups, and the smallest differences are between groups of patients with local disease and those with metastases. The physical and role scores have the largest ranges of means across patient groups, and show the largest differences between clinical groups, while the cognitive and emotional scores have the smallest ranges of means and differences. Sicker groups have larger score standard deviations than healthier groups. Relatively large and small means and differences, and corresponding effect sizes, are presented. Collectively, the results provide a sense of the relative sizes of means and of differences, and of the types of clinical groups which give rise to them, thereby providing clinically-based benchmarks by which to interpret QLQ-C30 results.

Activities of Daily Living↗
PubMed1996

A comparison of two quality-of-life questionnaires for cancer clinical trials: the functional living index--cancer (FLIC) and the quality of life questionnaire core module (QLQ-C30).

Choosing a measure instrument for a study raises the question of whether instruments designed for the same purpose produce the same results. We investigated this question for two instruments designed to measure subjective quality of life (QOL) in cancer clinical trials: the Functional Living Index-Cancer (FLIC) and the Quality of Life Questionnaire Core module (QLQ-C30). These were administered concurrently to 98 cancer patients. Four patient groups were defined: (1) well, no chemotherapy (n = 23); (2) adjuvant chemotherapy (n = 24); (3) stable disease, active chemotherapy (n = 24); (4) progressive disease (n = 27). Both instruments have global, role, social, emotional, pain, and nausea scales; QLQ-C30 also assesses physical function, cognitive function, and fatigue, while FLIC assesses hardship. Correlation analysis indicated convergent validity for the global, role, emotional, pain and nausea dimensions, but not the social dimension. Both instruments indicated that groups 1 and 2 had better QOL than group 4 in at least one dimension. However, different dimension-specific results meant that qualitatively different conclusions would have been drawn if either instrument had been used singly: FLIC indicated that group 1 had better role function that group 4 and suffered less hardship and that group 1 suffered less nausea than group 3, while the QLQ-C30 data indicated that group 2 had better physical function than group 4. The only consistent result was for pain: both instruments indicated group 4 had more pain than either groups 1 or 2. Thus the choice of QOL instrument for use in a particular trial will affect both the results and conclusions. It is important, therefore, to consider carefully which instrument is most likely to detect important differences relevant to the patients' lives in that setting.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1995

Insulin, ketone bodies, and mitochondrial energy transduction.

Addition of insulin or a physiological ratio of ketone bodies to buffer with 10 mM glucose increased efficiency (hydraulic work/energy from O2 consumed) of working rat heart by 25%, and the two in combination increased efficiency by 36%. These additions increased the content of acetyl CoA by 9- to 18-fold, increased the contents of metabolites of the first third of the tricarboxylic acid (TCA) cycle 2- to 5-fold, and decreased succinate, oxaloacetate, and aspartate 2- to 3-fold. Succinyl CoA, fumarate, and malate were essentially unchanged. The changes in content of TCA metabolites resulted from a reduction of the free mitochondrial NAD couple by 2- to 10-fold and oxidation of the mitochondrial coenzyme Q couple by 2- to 4-fold. Cytosolic pH, measured using 31P-NMR spectra, was invariant at about 7.0. The total intracellular bicarbonate indicated an increase in mitochondrial pH from 7.1 with glucose to 7.2, 7.5 and 7.4 with insulin, ketones, and the combination, respectively. The decrease in Eh7 of the mitochondrial NAD couple, Eh7NAD+/NADH, from -280 to -300 mV and the increase in Eh7 of the coenzyme Q couple, Eh7Q/QH2, from -4 to +12 mV was equivalent to an increase from -53 kJ to -60 kJ/2 mol e in the reaction catalyzed by the mitochondrial NADH dehydrogenase multienzyme complex (EC 1.6.5.3). The increase in the redox energy of the mitochondrial cofactor couples paralleled the increase in the free energy of cytosolic ATP hydrolysis, delta GATP. The potential of the mitochondrial relative to the cytosolic phases, Emito/cyto, calculated from delta GATP and delta pH on the assumption of a 4 H+ transfer for each ATP synthesized, was -143 mV during perfusion with glucose or glucose plus insulin, and decreased to -120 mV on addition of ketones. Viewed in this light, the moderate ketosis characteristic of prolonged fasting or type II diabetes appears to be an elegant compensation for the defects in mitochondrial energy transduction associated with acute insulin deficiency or mitochondrial senescence.

Animals↗
PubMed1995

A community study of snoring and sleep-disordered breathing. Symptoms.

Four hundred forty-one subjects 34 to 69 yr of age were recruited from a random sample of the community. The sample was biased in favor of men, snorers, and subjects with subjective sleep complaints. They answered a questionnaire and were monitored in their homes for sleep-disordered breathing (SDB). This report concerns the presence of symptoms associated with the obstructive sleep apnea (OSA) syndrome in the subjects with SDB detected in this community sample. Most of the symptoms commonly recognized as occurring in OSA were associated with SDB in our sample: snoring that disturbed the sleep of other persons, reports of apnea, reports of gasping or choking sounds during sleep, and finding the bedclothes in disarray in the mornings had significant univariate associations with SDB. Nocturnal choking and morning headache were negatively associated with SDB. Excessive daytime somnolence (EDS) was reported by 41% of those with SDB, but it was also reported by 37% of snorers without SDB and by 37% of nonsnorers. We conclude that the symptoms seen in clinic patients with OSA also occur in subjects with SDB who have not presented for medical attention. Enumeration of these symptoms by questionnaire, however, is a poor test for OSA in the community. EDS was reported by a higher than expected proportion of subjects not affected by SDB, suggesting that causes of self-reported EDS other than SDB may be common.

Accidents, Traffic↗
PubMed1995

A community study of snoring and sleep-disordered breathing. Prevalence.

We conducted a study of the prevalence of sleep-disordered breathing in subjects derived from a random sample of the population. A total of 2,202 subjects 35 to 69 yr of age were approached. Four hundred forty-one answered a questionnaire concerning their sleep symptoms, general health, and habits such as alcohol consumption, and they were monitored for sleep-disordered breathing (SDB). The sample was biased in favor of snorers and those with other subjective sleep complaints. Fifty-six percent of the subjects were men. Of the 441 subjects 79 (17.9%) had SDB (more than 15 episodes of apnea or hypopnea per hour: respiratory distress index [RDI] > or = 15), 289 were snorers but had RDI < 15, and 73 were nonsnorers. The prevalence of SDB in this sample was therefore at least 3.6% (79 of 2,204). The minimum prevalence in men was 5.7%, and in women it was 1.2%. Logistic regression identified only male sex as an independent predictor of snoring without SDB (adjusted odds ratio [OR], 3.24; 95% CI, 1.33 to 7.82), body mass index (adjusted OR for an increase of 5 kg/m2, 0.95; 95% CI, 0.85 to 1.05), and alcohol consumption (adjusted OR for an increase of 10 g/day, 1.05; 95% CI, 0.84 to 1.37) were not significant predictors of snoring. The independent predictors of SDB among snorers were age (adjusted OR for an increase of 5 yr, 1.26; 95% CI, 1.08 to 1.47) and neck circumference (adjusted OR for an increase of 2 cm, 1.53; 95% CI, 1.16 to 2.00).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1995

A community study of snoring and sleep-disordered breathing. Health outcomes.

Four hundred forty-one subjects 34 to 69 yr of age were recruited from a random sample of the community. They answered a questionnaire and were monitored in their homes for sleep-disordered breathing (SDB). This report concerns the association between observed SDB and arterial hypertension and vascular disease. Hypertension was defined as self-report of a diagnosis of hypertension made by a physician, current treatment for hypertension, or a systolic pressure greater than 150 mm Hg or a diastolic pressure greater than 90 mm Hg. Coronary artery disease was defined by self-report of angina or myocardial infarction of "heart attack." There were few cases of stroke or claudication, and a category of "occlusive vascular disease" was defined by self-report of coronary artery disease or of "blocked arteries" or stroke. Subjects were classified as snorers (n = 289) or nonsnorers (n = 73) by self-report of regular snoring, and as having SDB (n = 79) if more than 15 abnormal respiratory events were recorded per hour of recording. There were significant increases in the prevalence of hypertension, coronary artery disease, and occlusive vascular disease from nonsnorers (26, 7, and 10%, respectively) through snorers (39, 12, and 17%) to subjects with SDB (57, 20, and 28%). The crude odds ratio for SDB versus nonsnorers was 3.8 (95% CI, 1.9 to 7.5) for hypertension, 3.5 (1.2 to 10.0) for coronary artery disease, and 3.7 (1.5 to 9.1) for occlusive vascular disease.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗