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D Machin

Publications and source records attributed to D Machin.

At least 19 recordsLinked to original sources

Competing risks analysis of patients with osteosarcoma: a comparison of four different approaches.

In failure time studies involving a chronic disease such as cancer, several competing causes of mortality may be operating. Commonly, the conventional statistical technique of Kaplan-Meier, which is only meaningfully interpreted by assuming independence of failure types and the censoring mechanism, is employed in clinical research involving competing risks data. Some authors have advocated the use of a cause-specific cumulative incidence function which takes into account the existence of other events within a competing risks framework, without making any assumption about independence. Lunn and McNeil have proposed an approach based on an extension of the Cox proportional hazards regression, which enables direct comparisons between failure types. We have extended this approach to estimate cause-specific cumulative incidence. As it is often not easy to follow competing risks methodology in the literature, this paper sets out systematically the assumptions made and the steps taken to implement four different methods of analysing competing risks data using cumulative incidence rates or the Kaplan-Meier estimates of cause-specific failure probabilities. The data obtained from a randomized trial of patients with osteosarcoma were used to compare these four approaches. As illustrated using the osteosarcoma data, the estimates of the classical Kaplan-Meier methods have larger numerical values than the cause-specific cumulative incidence. On the other hand, estimates of the cause-specific cumulative incidence rates from the conventional method and the modified Cox method are highly comparable.

Adolescent↗

Seasonality of suicide in Singapore: data from the equator.

BACKGROUND: Studies in the northern and southern hemispheres consistently identify seasonal patterns in suicidal deaths. In many such studies, bimodal yearly peaks have been described for females as against unimodal ones for males. The current study examines the monthly variation in suicidal deaths in Singapore to determine if any seasonal patterns exist in an equatorial region. METHODS: Monthly suicidal death data over the decade 1989-98 were examined for the whole sample and for gender- and age-specific subgroups. Both von Mises' distribution and harmonic analysis techniques were used to interpret the data. RESULTS: Among the 2013 male and 1382 female suicides, there was minimal variation in patterning of suicidal deaths. We found a weak suggestion of a later peak for the females in mid-May as opposed to mid-February for the males, and the peaks for those less than 25 years of age were 5-6 months later than for the older age groups. The magnitude of all peaks was, however, very small suggesting chance variation. The harmonic analyses confirmed that patterning was 'randomly' rather than 'seasonally' determined. CONCLUSION: In an equatorial region, there was no evidence of any 'seasonal' patterning of suicidal deaths.

Adult↗

Preface.

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Journal Article↗

Received dose and dose-intensity of chemotherapy and outcome in nonmetastatic extremity osteosarcoma. European Osteosarcoma Intergroup.

PURPOSE: To examine the relationship between received dose, received dose-intensity (RDI), and survival in patients with osteosarcoma. PATIENTS AND METHODS: Between 1983 and 1993, the European Osteosarcoma Intergroup (EOI) conducted two randomized trials involving patients with high-grade, nonmetastatic, biopsy-proven osteosarcoma of the extremity. These trials shared a common treatment arm of doxorubicin (DOX) 75 mg/m(2) and cisplatin (CDDP) 100 mg/m(2) planned for six cycles at 3-week intervals. Definitive surgery was scheduled at week 9, after three cycles. Survival time was calculated from 122 days, the scheduled end of chemotherapy. RESULTS: A total of 287 patients randomized to DOX/CDDP received at least one cycle of chemotherapy, and 232 (81%) received all six cycles. On average, 79% of the intended dose of DOX and 80% of the intended dose of CDDP was given. Mean time to completion of chemotherapy was 1.27 times that specified by the protocol. Mean RDI was 0.64 for DOX (SD = 0.19) and 0.65 for CDDP (SD = 0.18). Progression-free survival was lower for those who received one to five cycles compared with those who completed all six cycles (hazards ratio, 1.69; 95% confidence interval, 1.03 to 2.78). Survival and progression-free survival were lowest for patients with RDI less than 0.6, although these differences were not statistically significant at the 5% level. There was no clear evidence of preoperative dose or dose-intensity influencing histologic response. CONCLUSION: This analysis did not establish a clear survival benefit for increasing received dose or dose-intensity in the context of this two-drug regimen. The hypothesis that increasing dose-intensity may improve survival in osteosarcoma requires prospective evaluation.

Adolescent↗

Anterior chamber depth measurement as a screening tool for primary angle-closure glaucoma in an East Asian population.

OBJECTIVE: To evaluate anterior chamber depth measurement as a method of screening for primary angle-closure glaucoma in an East Asian population. DESIGN: Two-phase, cross-sectional, community-based study. SETTING: Rural and urban locations in the Hovsgol and Omnogobi provinces, Mongolia. PARTICIPANTS: Nine hundred forty-two (94.2%) of 1000 individuals in Hovsgol(1995) and 775 (96.9%) of 1000 individuals in Omnogobi (1997) aged 40 years or older were examined. MAIN OUTCOME MEASURES: Anterior chamber depth was measured by optical pachymetry, slitlamp-mounted A-mode ultrasound, and handheld ultrasound. Gonioscopy was used to detect occludable angles, defined as one in which the trabecular meshwork was visible for less than 90 degrees of angle circumference. Primary open-angle glaucoma was diagnosed in subjects with an occludable angle and glaucomatous optic neuropathy with visual morbidity. The area under the curve in a receiver operating characteristic plot was used to compare test performance. RESULTS: Optical pachymetry outperformed the slitlamp-mounted ultrasound method of anterior chamber depth measurement (area under the curve, 0.93 and 0.90, respectively; z test, P = .001). Handheld ultrasound (area under the curve, 0.86) was inferior to optical measurement (z test, P = .001) but did not differ significantly from slitlamp ultrasound (z test, P = .06). The optical method gave sensitivity of 85% and specificity of 84% at a screening cutoff of less than 2.22 mm for detecting occludable angles. CONCLUSIONS: Measurement of axial anterior chamber depth can detect occludable angles in this Asian population and therefore may have a role in population screening for primary angle-closure glaucoma.

Adult↗

The prevalence of glaucoma in Chinese residents of Singapore: a cross-sectional population survey of the Tanjong Pagar district.

BACKGROUND: Data on prevalence of glaucoma in East Asia are scarce. OBJECTIVE: To determine the prevalence and clinical characteristics of glaucoma in adult Chinese Singaporeans. METHODS: A group of 2000 Chinese people, aged 40 to 79 years, were selected from the electoral register of Tanjong Pagar district in Singapore using a disproportionate, stratified, clustered, random-sampling procedure. Glaucoma was diagnosed in people with an excavated optic neuropathy and a reproducible visual field defect or on the basis of severe structural disc abnormality alone, if reliable field results could not be obtained. The diagnosis was also made in blind subjects with raised intraocular pressure or previous glaucoma surgery. RESULTS: Of 1717 eligible subjects, 1232 were examined, with a response rate of 71.8%. There were 45 cases of glaucoma: 27 were men and 18 were women. The main diagnoses were primary open-angle glaucoma (n = 22 [49%]), primary angle-closure glaucoma (n = 14 [31%]), and secondary glaucoma (n = 7 [16%]). It was not possible to determine the mechanism in 2 (4%). CONCLUSIONS: The age-standardized prevalence of glaucoma was 3.2% (95% confidence interval, 2.3-4.1) in the population 40 years and older. Glaucoma was the leading cause of blindness. Primary angle-closure glaucoma and secondary glaucoma were the most visually destructive forms of the disease. Our findings suggest current projections of glaucoma prevalence among ethnic Chinese are a substantial underestimate. Arch Ophthalmol. 2000;118:1105-1111

Adult↗

Obstructive sleep apnea syndrome in obese Singapore children.

We set out to determine the prevalence of obstructive sleep apnea syndrome (OSAS) among obese Singapore school children and identify risk factors for OSAS. This study was designed as a prospective study in three phases. Parents completed a questionnaire with regards to sleep and daytime symptoms in Phase 1. Children suspected to have OSAS based on the questionnaire and all with a percent ideal body weight (IBW) >/=180 were called for clinic visits in Phase 2. All whose percent IBW >/=180 and those in whom the physicians strongly suspected OSAS were subjected to a polysomnogram in phase 3. The children were recruited from the School Health Nutritional Clinic for obese children. The investigations were carried out at Tan Tock Seng Hospital. In all, 3,671 children were screened with the questionnaire. Of these, 146 were selected to undergo polysomnography. Twenty-six had abnormal sleep studies with apnea/hypoxia indices (AHIs) >5/hr. The significant clinical feature which correlated with OSAS was sleep sitting up (P = 0.005). The risk is higher in morbidly obese (IBW >/=180), with a prevalence of 13.3% (8/60), than in less obese children (IBW <180). One in eight (12.5%) of these children was asymptomatic and would have been missed based on the questionnaire. Presence of adenotonsillar hypertrophy led to increased risk of OSAS. The prevalence of OSAS was 0.7% (26/3,671) among the obese schoolchildren in Singapore, which is similar to the prevalence reported by others. Using discriminant analysis, the estimated prevalence increased to 5.7%. In the morbidly obese (IBW >/=180), the prevalence rate is higher at 13.3%.

Adenoids↗

Neoadjuvant and adjuvant therapy for operable hepatocellular carcinoma.

OBJECTIVES: To determine the efficacy and adverse effects of different neoadjuvant and adjuvant therapies compared to surgery alone or surgery and placebo/supportive therapy when given to improve relapse and survival rates for operable hepatocellular carcinoma. SEARCH STRATEGY: Electronic databases, conference proceedings, bibliographies of identified publications. SELECTION CRITERIA: All truly randomised and quasi-randomised clinical trials that compared hepatocellular carcinoma patients who were given and not given neoadjuvant/adjuvant therapy as a supplement to curative liver resection. DATA COLLECTION AND ANALYSIS: Study data was extracted independently by two reviewers and discrepancies were resolved by consensus. A total of eight randomised controlled clinical trials were identified, totaling 548 randomised patients. Seven of the eight trials reported survival and disease-free survival curves and the results of hypothesis testing (log-rank test). The remaining trial reported only the mean survival times. None reported the hazard ratio and only one did a sample size calculation. The survival and disease-free survival curves were compared using their one, two and three-year survival rates, median survival times and the result of the hypothesis tests. MAIN RESULTS: The size of the randomised clinical trials ranged from 40 to 115 subjects. Both preoperative (neoadjuvant) and postoperative (adjuvant), systemic and locoregional (+/- embolization), chemo- and immunotherapy interventions were tested. None were comparable in terms of both treatment regimen and participants selected, so no pooling was done. Only one regimen using preoperative transcatheter arterial chemoembolization with doxorubicin was approximately duplicated. Seven of the eight trials reported no survival benefit from adjuvant therapy. Only one trial reported a statistically significant difference for survival and disease-free survival for the treatment arm, but the results of both its arms were very poor when compared to other studies. Two of the trials that did not report any absolute survival advantage reported statistically significant differences in disease-free survival. Five of the eight trials did not perform intention-to-treat analysis. The highest toxicity rate was in a trial using oral 1-hexylcarbamoyl 5-fluorouracil which resulted in 12 out of 38 subjects stopping because of adverse events. REVIEWER'S CONCLUSIONS: There is no evidence for efficacy of any of the adjuvant protocols reviewed. In order to detect a realistic treatment advantage, larger trials will have to be conducted.

Antineoplastic Agents↗

Life after radiotherapy: the psychological and social effects experienced by women treated for advanced stages of cervical cancer.

PURPOSE: The aim of this study was to describe the psychological and social reactions of women with advanced stages of cancer of the cervix during and after radiotherapy. METHODS: A questionnaire about health-related quality of life was used, which consisted of the EORTC QLQ-C30 and additional specific questions. One-hundred eighteen patients filled out the questionnaire at the end of treatment and 1, 3, 6, 12, 18, and 24 months later. The scores from the disease-free patients were compared to those from 236 healthy controls. RESULTS: Many patients experience psychological and social consequences at the end of treatment and 1 to 3 months later. Patients continue to think about their illness and treatment throughout the 24-month study period, but find it increasingly hard to share their worries with others. Their score on overall quality of life never reaches that of the controls. CONCLUSION: Disease-free patients treated for cancer of the cervix with radiotherapy have psychological reactions. The interpretation of the results should take into consideration that the patients change their personal frame of reference over the course of time. Professionals should be aware of patients' needs to talk about their disease long after treatment. Patients should be informed about the risk of psychological reactions. The more information about possible symptoms they receive the better their ability to cope with them should they arise.

Adaptation, Psychological↗

Accuracy of clinical estimates of intraocular pressure in Chinese eyes.

PURPOSE: To investigate the validity of clinical estimates of intraocular pressure (IOP) in Chinese people. DESIGN: Prospective, cross-sectional, hospital-based in vivo study. PARTICIPANTS: Twenty-three ethnic Chinese adults (aged 35-82 years) undergoing routine phacoemulsification surgery were examined. TESTING: "True" IOP was measured with a solid-state hemodynamic monitor through a cannula in the anterior chamber. IOP was set successively to 10, 20, and 30 mmHg in each subject, using a reservoir of balanced salt solution. Intraocular pressure was simultaneously estimated by use of a hand-held applanation tonometer (Perkin's) and a Tono-Pen. The association between ocular biometric variables and measurement error was examined. MAIN OUTCOME MEASURES: The median of three readings at each IOP level was taken as the IOP estimate of each instrument. Measurement error was calculated as the mean difference (tonometer minus direct measurement). RESULTS: The error for the hand-held applanation tonometer was -1.6, -4.3 and -5.7 at 10, 20, and 30 mmHg, respectively. For the Tono-Pen the measurement error was +0.4, -2.0, and -4.1 at 10, 20, and 30 mmHg, respectively. We could identify no association between measurement error and corneal thickness or curvature, anterior chamber depth, or axial length. CONCLUSIONS: The applanation tonometer and Tono-Pen underestimate the true IOP in Chinese eyes. Error increases as true IOP increases. These tonometers do not give an accurate estimate of IOP in East Asians.

Adult↗

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↗

Non-steroidal anti-inflammatory drugs, Helicobacter pylori and bleeding gastric ulcer.

BACKGROUND: Helicobacter pylori infection and NSAID usage are considered to be independent risk factors for gastric ulcer (GU). Whether they interact to influence the risk of bleeding in GU is unclear. AIM: To determine the prevalence of H. pylori infection and NSAID ingestion in a group of patients with GU and determine their roles in bleeding and non-bleeding GU. METHODS AND RESULTS: From January 1993 to June 1996, a total of 217 GU patients (150 male, 67 female, median age 61 years, range 26-94) were eligible for the study. Eighty-five per cent were H. pylori-positive and 15% were H. pylori-negative. NSAID usage within 4 weeks prior to endoscopy was present in 30%, more in the H. pylori-negative than H. pylori-positive patients (59% vs. 25% P = 0.0002). Aspirin was most commonly used (43%). One hundred patients bled from GU (69 male, 31 female, mean age 67 years, range 26-94) and 117 did not (81 male, 36 female, mean age 57 years, range 28-86). Univariate logistic regression showed that advanced age (>/= 65 years) and NSAID usage carried an increased risk of bleeding GU (odds ratio 3.4 and 6.8, respectively) while H. pylori infection alone was not associated with additional risk (OR = 0.8). However, when three variables were considered jointly in a multiple logistic regression, the OR associated with H. pylori infection increased to 2.4, suggesting that in the presence of NSAIDs and advanced age, H. pylori also increases the risk of bleeding GU, indicating an interaction between the variables. CONCLUSION: NSAID usage and advanced age are risk factors for bleeding GU, whereas H. pylori infection by itself is not. In the presence of NSAIDs and advanced age, an increased risk of bleeding GU with H. pylori is observed, indicating the possibility of an interaction between these factors.

Adult↗

Use of tamoxifen in hepatocellular carcinoma: a review and paradigm shift.

Hepatocellular carcinoma is often diagnosed at a late, inoperable stage for which there are no uniformly efficacious treatment available presently. The oral anti-oestrogen drug, tamoxifen, has been used in such patients, based on the belief that the growth of hepatocellular carcinoma is promoted by endogenous oestrogen via a receptor-mediated process. In this review, we examine the trials reported in the literature using tamoxifen in hepatocellular carcinoma. Randomized controlled trials with tamoxifen have so far revealed mixed results. We propose that this may be due to the fact that the mechanism of action of tamoxifen in hepatocellular carcinoma is via an oestrogen-receptor independent pathway that requires much higher doses of tamoxifen for activation than those used in the trials so far. Thus there must be a paradigm shift to dissociate the action of tamoxifen from oestrogen receptors in hepatocellular carcinoma. This means that future trials with tamoxifen in hepatocellular carcinoma should use higher doses of tamoxifen, at least four to eight-fold that of the dose that is efficacious in an oestrogen-receptor dependent mechanism.

Antineoplastic Agents, Hormonal↗

Sample sizes for cancer trials where Health Related Quality of Life is the primary outcome.

Health Related Quality of Life (HRQoL) instruments are increasingly important in evaluating health care, especially in cancer trials. When planning a trial, one essential step is the calculation of a sample size, which will allow a reasonable chance (power) of detecting a pre-specified difference (effect size) at a given level of statistical significance. It is almost mandatory to include this calculation in research protocols. Many researchers quote means and standard deviations to determine effect sizes, and assume the data will have a Normal distribution to calculate their required sample size. We have investigated the distribution of scores for two commonly used HRQoL instruments completed by lung cancer patients, and have established that scores do not have the Normal distribution form. We demonstrate that an assumption of Normality can lead to unrealistically sized studies. Our recommendation is to use a technique that is based on the fact that the HRQoL data are ordinal and makes minimal but realistic assumptions.

Antineoplastic Combined Chemotherapy Protocols↗

Detection of gonioscopically occludable angles and primary angle closure glaucoma by estimation of limbal chamber depth in Asians: modified grading scheme.

AIM: To evaluate the performance of limbal chamber depth estimation as a means of detecting occludable drainage angles and primary angle closure, with or without glaucoma, in an east Asian population, and determine whether an augmented grading scheme would enhance test performance. METHOD: A two phase, cross sectional, community based study was conducted on rural and urban areas of Hövsgöl and Omnögobi provinces, Mongolia. 1800 subjects aged 40 to 93 years were selected and 1717 (95%) of these were examined. Depth of the anterior chamber at the temporal limbus was graded as a percentage fraction of peripheral corneal thickness. An "occludable" angle was one in which the trabecular meshwork was seen in less than 90 degrees of the angle circumference by gonioscopy. Primary angle closure (PAC) was diagnosed in subjects with an occludable angle and either raised pressure or peripheral anterior synechiae. PAC with glaucoma (PACG) was diagnosed in cases with an occludable angle combined with glaucomatous optic neuropathy and consistent visual morbidity. RESULTS: Occludable angles were identified in 140 subjects, 28 of these had PACG. The 15% grade (equivalent to the traditional "grade 1") yielded sensitivity and specificity of 84% and 86% respectively for the detection of occludable angles. The 5% grade gave sensitivity of 91% and specificity of 93% for the detection of PACG. The interobserver agreement for this augmented grading scheme was good (weighted kappa 0.76). CONCLUSIONS: The traditional limbal chamber depth grading scheme offers good performance for detecting occludable drainage angles in this population. The augmented scheme gives enhanced performance in detection of established PACG. The augmented scheme has potential for good interobserver agreement.

Adult↗