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Biomedical subjects

D McNeil

Publications and source records attributed to D McNeil.

At least 19 recordsLinked to original sources

Applying Cox regression to competing risks.

Two methods are given for the joint estimation of parameters in models for competing risks in survival analysis. In both cases Cox's proportional hazards regression model is fitted using a data duplication method. In principle either method can be used for any number of different failure types, assuming independent risks. Advantages of the augmented data approach are that it limits over-parametrisation and it runs immediately on existing software. The methods are used to reanalyse data from two well-known published studies, providing new insights.

Analysis of Variance

Effects of piped water supply on the incidence of diarrheal diseases in children in southern Thailand.

Simple piped water supply (PWS) is increasingly popular in rural areas of southern Thailand where diarrheal diseases are quite common. The current study was carried out in 1990 in the southern part of Thailand to determine whether the use of PWS could significantly reduce the incidence rate of diarrheal diseases among the children under two years of age. A dynamic cohort study started in January 1990 in seven Muslim villages where PWS was installed for some time and there was a mixture of PWS users and non-users in each village. The cohorts comprised 126 and 137 children using and not using PWS, respectively. They were followed up weekly for one year. The crude incidence rates of diarrhea episodes for children using and not using PWS were 2.54 (SE = 0.21) and 3.52 (SE = 0.18) episodes per child-year, respectively (p < 0.01). The number of diarrheal attacks in each week was modeled as a Poisson variate using a generalized estimating equation, adjusting for correlation within the child. The analysis was carried out for each village separately and meta-analysis was used to combine these analyses. The rate ratio of PWS, adjusted for concurrent age and season, food supplement and common cold, was 0.74 (95% CI = 0.59-0.93), indicating a statistically significant reduction of one quarter. However, the proportion of users decreased with time due to management failure. It was concluded that diarrheal disease in the study area was mild but the incidence rate was high. The effect of PWS on the incidence rate of diarrhea varied with locality.(ABSTRACT TRUNCATED AT 250 WORDS)

Cohort Studies

Evaluation of hookworm control program in southern Thailand.

An intensive hookworm control program providing the rural population of southern Thailand with mass treatment with 300 mg Mebendazole and health education commenced in 1989 with a yearly budget of over US$ 1.2 million. The current research aimed to evaluate the coverage of health education and mass treatment, the effectiveness of mass treatment and the administrative process of the control program, two years after its commencement. This evaluation consisted of three studies. In the first study, 120 villages were randomly selected, from which 840 school children, 843 adults aged between 15-59 and 844 subjects aged over 60 years were interviewed to assess awareness of hookworm, latrine availability, receipt of and compliance with antihelminthics provided, and self-treatment. In the second study, 8 villages from each of the 14 provinces were randomly chosen. Stool samples from randomly selected 4,434 subjects were examined. The third study consisted of interviewing key health planners in Bangkok and 71 health officers/workers from 32 samples villages of 8 sampled provinces. Latrine availability was 80%. Percentages of subjects who had ever heard of hookworm ranged from 70 to 95 in school children, 55 to 80 in adults and 25 to 58 in the older age group. While 63 to 85% had latrines in their homes, 27% to 47% admitted defecation outside in the past month. Percentages of coverage of drug treatment ranged from 82 to 91 in school children, 68 to 80 in adults and 54 to 59 in the older age group.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent

Prognostic value of quality-of-life scores during chemotherapy for advanced breast cancer. Australian New Zealand Breast Cancer Trials Group.

PURPOSE: We observed that quality-of-life (QL) scores, collected to evaluate treatment in a randomized trial in advanced breast cancer, predicted survival duration. This report explores the prognostic associations between QL and survival in more detail. PATIENTS AND METHODS: In a randomized clinical trial comparing intermittent and continuous therapy policies for patients with advanced breast cancer, QL was measured by linear analog self-assessment (LASA) and the Quality-of-Life Index (QLI). Baseline scores and subsequent changes were included in statistical models of survival duration, with and without other prognostic factors. RESULTS: Physician assessment of QLI and patient LASA scores for physical well-being (PWB), mood, nausea and vomiting, appetite, and overall QL (but not pain) at the commencement of treatment were significant predictors of subsequent survival. Scores for PWB and QLI were independent of other prognostic factors. Changes in scores were also prognostically important. Both baseline and change in scores for PWB, mood, pain, and QLI after the first three treatment cycles, but before an arbitrary 180-day time point, were significantly predictive of survival beyond that time. Both QLI and PWB were prognostically independent of tumor response. Although QL improvement was correlated with tumor response, continuous therapy yielded significantly better QL scores, even in nonresponders. CONCLUSION: These findings support the validity of the simple QL measures used in the trial. They are compatible with the simple explanation that patients perceive disease progression before it is clinically evident, but also with a causal relationship between QL and survival duration.

Breast Neoplasms

Reproductive function prior to disease onset in women with scleroderma.

We tested in a retrospective study the hypothesis that women with scleroderma have an increased risk, before disease presentation, of problems in pregnancy. Reproductive history, as reported from a validated postal questionnaire, was obtained from 204 women with scleroderma [mean year of birth (yob) 1942] and compared to that reported by 233 women with primary Raynaud's phenomenon (mean yob 1948) and 189 healthy women from a population register (mean yob 1950). Only pregnancies occurring before symptom onset in the scleroderma group were considered for analysis. All analyses were adjusted for job, social class, age at first pregnancy, smoking habit, and where relevant, parity. The results are expressed as odds ratios (OR) [with 95% confidence limits (CL)] giving the risk of developing scleroderma, with previous exposure to each of the specific reproductive variables analyzed, relative to the 2 comparison groups. The women with scleroderma were more likely than the population women to have had a delay in conception (> or = 12 months): OR 2.6 (1.1, 5.7) or be infertile: OR 2.3 (0.7, 7.2). These differences were not apparent when the scleroderma group was compared to the women with Raynaud's: OR's 0.7 and 1.1, respectively. Similarly there was a greater self report of maternal ill health in pregnancy in the group with scleroderma compared to the population women: OR 2.1 (1.2, 3.5) but not compared to the women with Raynaud's: OR 1.0 (0.7, 1.6).(ABSTRACT TRUNCATED AT 250 WORDS)

Female

On the receiving end--III. Measurement of quality of life during cancer chemotherapy.

From previous studies of the side effects patients identified as important in cancer chemotherapy we identified eight groups of symptoms. Linear analogue self assessment (LASA) scales for these 8 items form a new instrument (GLQ-8) for measuring aspects of quality of life. Patients completed both GLQ-8 and five previously validated LASA scales, together with a new single global quality of life scale (GLQ uniscale) and the visual analogue version of the Spitzer QL Index. This analysis includes 166 patients, with 47 1-hr test-retest and 29 24-hr test-retest pairs. The new scales showed high reliability, with retest correlation coefficients exceeding 0.8 for all items except GLQ uniscale, appetite and anxiety on 1-hour retest, and all except nausea and numbness on 24-hour retest. Correlations were in general higher for the GLQ-8 items than for the 5 older LASA items, while inter-item correlations were lower. Comparisons of the new scales with established instruments and comparisons of new scale scores between known groups supported the validity of the new scales. We conclude that the GLQ-8 and GLQ uniscale are convenient and reliable instruments measuring aspects of quality of life in patients receiving cancer chemotherapy.

Adolescent

Reproducibility of isokinetic muscle strength measurements in normal and arthritic individuals.

The serial reproducibility of an individual's isokinetic torque was assessed in order to establish a reliable baseline value for future comparison. Thirty-two controls and twenty arthritic patients were tested for their peak isokinetic torque on knee flexion and extension and hip flexion at three velocities on five occasions, at fortnightly intervals. The first test was found to provide a reliable baseline for controls and subjects who could generate a peak torque of 54 Newton meters (Nm) or more. The second test was found to be more representative of the series for groups containing weaker subjects. Variation related to torque: for subjects who generate a peak torque of 54 Nm or more, a range of +/- 20% accommodates the variability of 95% of tests. We conclude that a +/- 20% range applied to either the first or second test, depending on the nature of the group to be studied, serves as a representative baseline value.

Aged

Evaluation of zinc complexes on the replication of rhinovirus 2 in vitro.

The effect of zinc salts and complexes were evaluated on the replication of rhinovirus 2 in vitro. Zinc chloride inhibited the replication of rhinovirus 2 at concentrations between 3 and 12 micrograms/ml. Influenza virus was not affected. A number of zinc complexes were tested and compared to zinc chloride. The results indicated that the activity and toxicity of all zinc complexes in the rhinovirus cytopathogenic effect (CPE) assay were directly related to the amount of unbound zinc available.

Cell Line

Environmental factors and chronic unexplained dyspepsia. Association with acetaminophen but not other analgesics, alcohol, coffee, tea, or smoking.

A subgroup of patients with nonulcer dyspepsia (NUD) have no definite cause for their dyspepsia, termed essential dyspepsia. The aim of the present study was to determine if environmental factors are associated with essential dyspepsia. The patterns of ingestion of analgesic drugs (aspirin, acetaminophen, dextropropoxyphene), nonaspirin, nonsteroidal antiinflammatory drugs, alcohol, coffee, tea, and smoking in 113 essential dyspepsia patients were compared with 113 randomly selected community controls matched for age, sex, and social grade. Associations were studied in two six-month periods, before diagnosis in all patients and before the onset of NUD in those patients with a short history of dyspepsia. It was found that acetaminophen ingestion was associated with essential dyspepsia, and this association was present both before the onset of the dyspepsia (OR 3.1, 95% CI 1.3-7.1) and before diagnosis (OR 1.8, 95% CI 1.2-2.6). None of the other environmental factors were associated with essential dyspepsia.

Acetaminophen

Regulation of the growth hormone-independent growth factor-binding protein in children.

Regulation of the diurnal variation of the GH-independent insulin-like growth factor-binding protein (BP-28) was studied in 53 children who underwent various investigations for possible endocrine abnormalities. The plasma BP-28 levels increased 12-fold from 8 +/- 2 (+/-SE) micrograms/L at 2100 h to a peak level of 109 +/- 15 micrograms/L between 0600 and 0800 h. This rise was inversely related to plasma insulin levels and was unrelated to plasma cortisol levels. The overnight rise of plasma BP-28 was significantly altered in children who ate a light meal at 0130 h; in them BP-28 levels started to fall after 0300 h, reached nadir levels at 0400 h, began to rise again by 0700 h, and returned to control levels by 0800 h. Such changes did not occur in children given water alone. From the peak early morning level, plasma BP-28 fell to basal levels in children given oral glucose at 0800 h; the t1/2 of the fall was 55 +/- 9 (+/-SE) min. In children who continued to fast, plasma BP-28 did not fall but, rather, increased from 144 +/- 12 micrograms/L at 0800 h after 10 h of fasting to 239 +/- 30 micrograms/L by 1600 h. The induction of hypoglycemia by insulin given at 0945 h after an overnight fast caused a similar but more rapid rise in plasma BP-28 to 668 +/- 317 micrograms/L (range, 208-1763 micrograms/L) by 1230 h. These results suggest that the diurnal variation of plasma BP-28 concentrations in children is not due to an intrinsic rhythm, but is regulated by the metabolic status of the child.

Adolescent

Exercise-induced anaphylaxis related to food intake.

On one occasion, a healthy, male college athlete ate shrimp three and one-half hours before his usual, strenuous exercise. Several minutes after exercise, generalized anaphylaxis occurred which required emergency medical management. Physicians who work at sites where individuals exercise should be prepared for immediate treatment of this rare but important syndrome in order to avoid possible morbidity and mortality.

Adult

Monitoring distributional assumptions and early stopping for a prospective clinical trial using Monte Carlo simulation.

We have applied the technique of Monte Carlo simulation to the determination of sample size for a partially completed clinical trial of chemotherapy for breast cancer. Simulations based on results observed after the entry of 243 patients in 2 years indicated a power greater than that predicted by the calculations made before the protocol was activated, and allowed a recommendation for an eventual trial closure earlier than would have been permitted by traditional methods. Both estimative and predictive approaches to the simulation of expected survival times for censored patients are presented. The use of simulation is recommended as an aid in reassessing the exact nature of the underlying survival distributions (as these affect the sample size calculations) and in optimizing stopping rules relating to patient accrual to a clinical trial in progress.

Breast Neoplasms

The effects of high Na and Cl concentrations on rat proximal volume and Na fluxes at zero tubular flow.

1. In vivo micropuncture techniques, with and without peritubular capillary perfusion, were used to study the effects of high extracellular Na and Cl concentrations on transepithelial volume (Jv) and sodium (JNa) fluxes in rat proximal tubules. 2. In a double blind manner, the shrinking drop technique of Gertz was used to measure Jv; JNa was calculated from this and the tubular fluid Na concentration. 3. At both 184 and 279 mmol/l pericellular Na concentrations (both inside and outside the tubular epithelium), net Jv decreased significantly by 15 and 64%, respectively. Net JNa remained constant at 184 but decreased by 29% at 279 mmol/l Na concentration. 4. Thus, at both Na concentrations, when translated to free flow conditions, fractional Na reabsorption must have decreased. These findings, also supported by previous results at these Na concentrations, indicate that active Na transport was inhibited by high pericellular Na concentrations. 5. When intratubular Cl concentration was varied between 108 and 138 mmol/l while peritubular Cl was maintained constant (blood perfusing the capillaries), neither Jv nor JNa changed. Thus, at zero tubular flow, differential Cl/HCO3 concentrations do not provide significant driving forces for net Jv or JNa. 6. When only intratubular but not peritubular Na was elevated to 279 mmol/l, Jv and JNa increased markedly by 50 and 187%, providing evidence that a true solvent drag (solute drag) effect does exist in rat proximal tubules. 7. These findings offer a mechanism to explain why Na reabsorption is not increased when the filtered load of Na is increased with an elevation of plasma Na.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Discriminant value of dyspeptic symptoms: a study of the clinical presentation of 221 patients with dyspepsia of unknown cause, peptic ulceration, and cholelithiasis.

This study aims to determine whether the features of dyspepsia can discriminate a subgroup of patients who present with non-ulcer dyspepsia from other diagnostic categories. The following groups were studied: One hundred and thirteen patients with endoscopically confirmed non-ulcer dyspepsia in the absence of clinical, biochemical or radiological evidence of other gastrointestinal diseases or disorders, termed essential dyspepsia; Fifty five patients with symptomatic and endoscopically proven peptic ulceration (32 duodenal ulcers, 23 gastric ulcers); Fifty three patients admitted to hospital with biliary pain and cholelithiasis without other lesion at laparotomy. All patients completed a structured history questionnaire at personal interview. Stepwise logistic regression analysis was done on 19 predefined variables to determine if one or more of these could discriminate between the diagnostic categories. The results suggest that certain groups of symptoms may be of diagnostic value, but many are not. Upper abdominal pain aggravated by food or milk, pain severity, night pain, vomiting, weight loss, and age significantly discriminated essential dyspepsia from the other diagnostic categories. A scoring system was established based on these discriminating symptoms. Using the weighted score, at a sensitivity of 57%, the specificity for a diagnosis of essential dyspepsia was 94%, but only prospective studies will determine if this scoring system is of actual clinical value.

Cholelithiasis