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D Machin

Publications and source records attributed to D Machin.

At least 19 recordsLinked to original sources
PubMed2007

Biometrical aspects of drug development.

Once the activity of a compound has been established in the laboratory (usually by use of experimental animals) the next stage of development is to bring this forward to humans in early-phase clinical trials. A pharmacokinetic study aims to establish an effective dosing regimen for the compound in order to reach concentrations within the therapeutic window as quickly as possible. The aim of the phase I trials is typically to determine a maximal safe dose with which more rigorous investigation of activity in a phase II trial can be conducted. This chapter deals with statistical issues related to the design of phase I studies.

Animals↗
PubMed2006

Socioeconomic status, systolic blood pressure and intraocular pressure: the Tanjong Pagar Study.

BACKGROUND: Lower socioeconomic status (SES) is associated with higher morbidity and mortality in many countries. Present evidence suggests that glaucoma has similar risk factors to major chronic diseases such as cardiovascular disease. This study investigates the association between SES and intraocular pressure (IOP), an important risk factor for glaucoma. METHODS: The Tanjong Pagar Study was a population-based cross-sectional survey of Chinese people aged 40-79 years, who were randomly selected from the Singapore electoral register. Of the 2000 people selected, 1717 were considered eligible and 1090 were examined in clinic and included in the present study. IOP was measured using applanation tonometry. SES was assessed using a standardised questionnaire; education and income were used as the main explanatory variables. The effect of systolic blood pressure (SBP) was also examined. RESULTS: Participants with lower levels of education and income had higher mean IOP (both p<0.01). These associations remained after adjusting for age and central corneal thickness, a strong independent predictor. SBP was strongly associated with both SES and IOP (both p<0.01). Adjusting for SBP attenuated the association between SES and IOP. CONCLUSION: Participants with lower education and income have a higher mean IOP. This effect may be mediated, in part, by an association of education and income with SBP. This is the first study to suggest that there is a social gradient in the distribution of the only major modifiable risk factor for glaucoma. Increasing similarities exist between the causation models of chronic diseases and that of glaucoma.

Adult↗
PubMed2005

Surgery and adjuvant radiotherapy vs concurrent chemoradiotherapy in stage III/IV nonmetastatic squamous cell head and neck cancer: a randomised comparison.

We compared concurrent combination chemotherapy and radiotherapy with surgery and adjuvant radiotherapy in patients with stage III/IV nonmetastatic squamous cell head and neck cancer. Patients with non-nasopharyngeal and nonsalivary resectable squamous cell head and neck cancer were randomised to receive either surgery followed by adjuvant radiotherapy (60 Gy over 30 fractions) or concurrent combination chemotherapy and radiotherapy (66 Gy in 33 fractions). Combination chemotherapy comprised two cycles of i.v. cisplatin 20 mg m(-2) day(-1) and i.v. 5-fluorouracil 1000 mg m(-2) day(-1), both to run over 96 h given on days 1 and 28 of the radiotherapy. A total of 119 patients were randomised. At a median follow-up of 6 years, there was no significant difference in the 3-year disease-free survival rate between the surgery and concurrent chemoradiotherapy (50 vs 40% respectively). The overall organ preservation rate or avoidance of surgery to primary site was 45%. Those with laryngeal/hypopharyngeal disease subsite had a higher organ-preservation rate than the rest (68 vs 30%). Combination chemotherapy and concurrent irradiation with salvage surgery was not superior to conventional surgery and postoperative radiotherapy for resectable advanced squamous cell head and neck cancer. However, this form of treatment schedule with a view to organ-preservation can be attempted especially for those with laryngeal/hypopharyngeal and possibly oropharyngeal disease subsites.

Adult↗
PubMed2005

Discriminative ability of the short-form 36 health survey: a tale of two versions.

BACKGROUND AND OBJECTIVES: Previous studies suggested that the Chinese version of the Short-Form 36 Health Survey (SF-36) had smaller variability in the physical functioning (PF) and physical component summary (PCS) scores than the English SF-36. This may translate into differences in discriminative ability and sample size requirement. MATERIALS AND METHODS: Data were drawn from a community-based survey and a randomised crossover study of Singaporeans bilingual in the Chinese and English languages. The abilities of the two PF and PCS versions in discriminating subjects who reported chronic illness and acute disease symptoms versus those who did not were compared. RESULTS: In all four comparisons (i.e. two health criteria in two studies) the Chinese version of PF showed a larger effect size than the English version. In three out of four comparisons the Chinese version of PCS showed a larger effect size than the English version. CONCLUSIONS: The Chinese version appeared more efficient in detecting a statistically significant difference between groups. Other factors being the same, the Chinese SF-36 may require a smaller sample size than the English SF-36 for the studies of physical aspects of health-related quality of life.

Activities of Daily Living↗
PubMed2004

Establishing long-term survival and cure in young patients with Ewing's sarcoma.

This paper investigates the potential for long-term survivorship for young patients diagnosed with Ewing's sarcoma. Data are examined from two successive UKCCSG Ewing's Tumour studies (ET-1 and ET-2). Patients have been followed for up to 20 years. These studies had suggested that better 5-year survival with ET-2 over the earlier ET-1 was achieved by replacing cyclophosphamide by ifosfamide and increasing the dose of doxorubicin in a four-drug chemotherapy regimen. The updated hazard ratio, stratified for metastatic status at diagnosis, of 0.39 (95% confidence interval 0.12-0.61) confirmed the advantage of the ET-2 regimen in terms of overall survival. Cure models, based on the Weibull distribution, suggested that factors for long-term survival in addition to presence of metastases were age, primary site of tumour and study. Modelling identified the proportion cured with the ET-2 protocol as best at 70% in those who are under 10 years with a nonpelvic primary site and without metastatic disease. This contrasts to only 13% cure in those with the corresponding adverse prognostic indicators. Additionally, the risk of death remains greatest but relatively constant over the first 2 years postdiagnosis, and then declines to a lower but constant value for the next 3 years before reaching the 'cure plateau' at about 5 years. This investigation suggests that 'cure' is possible for patients with Ewing's sarcoma. This is established at approximately 5 years post diagnosis and the proportion cured depends on the presence of metastases, pelvic site and age at diagnosis.

Adolescent↗
PubMed2004

Modelling variability of quality of life scores: a study of questionnaire version and bilingualism.

BACKGROUND AND OBJECTIVES: Modelling variability of quality of life scores can not only improve our understanding of the characteristics of the measurement tools, but also shed light on sample size requirements. Although the English and Chinese versions of the Short Form 36 Health Survey (SF-36) are commonly considered equivalent, they have not been compared in terms of variability. Furthermore, bilingual and monolingual persons may differ in cognition and responses to questionnaires. METHODS: In a community-based survey of quality of life in Singapore, a society where both English and Chinese are widely used and bilingualism is prevalent, 2590 respondents answered either version of the SF-36. We studied the impact of questionnaire version and bilingualism on the variability of SF-36 scores by regression modelling, with adjustment for covariates. RESULTS: The Chinese version had smaller variances in the physical functioning (PF) and the physical component summary scores than the English version. The variance ratios (VRs) were respectively 0.32 and 0.60 (each p < 0.01), controlling for covariates. Bilingualism was not associated with variability in SF-36 scores except PF (VR = 0.78; p < 0.05). CONCLUSIONS: As a result of a smaller variance, using the Chinese version of SF-36 among bilingual Chinese people may require a smaller sample size than using the English version.

Adult↗
PubMed2004

On the evolution of statistical methods as applied to clinical trials.

This paper describes how statistical methods have evolved in parallel with activities associated with randomized control trials. In particular we emphasize the pivotal role of two papers published in British Journal of Cancer, and the paper describing the Cox proportional hazards model. In addition, the importance of early papers on estimating the sample size required for trials is highlighted. Later developments including the increasing roles for competing risks, multilevel modelling and Bayesian methodologies are described. The interplay between computer software and statistical methodological developments is stressed. Finally some future directions are indicated.

Humans↗
PubMed2004

Birthweight and psychological distress in adult twins: a longitudinal study.

AIM: To assess the relation between birthweight and psychological distress as measured by the Malaise Inventory in adult twins. METHODS: Data were drawn from the 1958 British birth cohort study, which included twins followed from birth to age 42 y. We examined the relation between birthweight and psychological distress at ages 23, 33 and 42 y measured by the psychological scale of the Malaise Inventory. Analyses were performed both between subjects (n = 282) and within twin pairs (n = 112). The generalized estimating equations approach was used to handle the repeated measurements. RESULTS: Between the 282 twins, the difference in psychological distress score was -0.45 (95% confidence interval -0.74 to -0.15) per Z-score increase in birthweight-for-gestational age. Within twin pairs, the heavier co-twins tended to have a psychological distress score lower than that of their lighter co-twins, the mean difference being -0.35 (-0.78 to 0.09). CONCLUSION: Results from the between-subject analysis agreed with previous findings from adult singletons that psychological health is related to birthweight. The within-pair analysis suggested a similar relation but did not attain statistical significance.

Adult↗
PubMed2004

Defining "occludable" angles in population surveys: drainage angle width, peripheral anterior synechiae, and glaucomatous optic neuropathy in east Asian people.

BACKGROUND: /aim: A current consensus in epidemiological studies of primary angle closure (PAC) is to diagnose the condition only if the posterior (usually pigmented) trabecular meshwork is seen for less than 90 degrees of the angle circumference, termed an "occludable angle." The authors sought to assess the validity of this epidemiological classification by exploring the relation between drainage angle width, peripheral anterior synechiae (PAS) and glaucomatous optic neuropathy (GON). METHODS: 918 Mongolians and 995 Chinese Singaporeans, both groups aged 40 years and older were examined in two population based surveys. Gonioscopic angle width was graded in five categories (0 = closed to 4 = wide open) according the scheme described by Shaffer. Cases with secondary PAS were excluded. RESULTS: The rate of PAS was between 0.3% and 1.7% in people with wide angles (grades 3 and 4). In those with grade 2 angles, PAS were seen in between 8% of eyes. In eyes with grade 1 angles, the rate rose to 17% in Chinese Singaporeans, and 31% in Mongolians. The odds of PAS were higher in people with narrower angles. However, there was a greater absolute number of people with PAS whose drainage angles were classified as "not occludable" than those classified "occludable." CONCLUSIONS: The traditional view that primary angle closure becomes a significant possibility in drainage angles of < or = grade 2 (approximately 20 degrees ) is valid in east Asians. The definition of an "occludable" angle examined here excludes many people with PAS. This probably serves to underemphasise the role of PAC in population surveys of glaucoma prevalence in Asian people.

Adult↗
PubMed2003

Risk factors for nuclear, cortical and posterior subcapsular cataracts in the Chinese population of Singapore: the Tanjong Pagar Survey.

AIM: To describe risk factors for nuclear, cortical, and posterior subcapsular (PSC) cataracts in Chinese Singaporeans. METHODS: A population based cross sectional study was carried out on ethnic Chinese men and women aged 40-81 years. A stratified, clustered, disproportionate (more weights to older people), random sampling procedure was used to initially select 2000 Chinese names of those aged 40-79 years from the 1996 electoral register in the Tanjong Pagar district in Singapore. Eligible subjects (n = 1717) were invited for a standardised ocular examination and interview at a centralised clinic, following which an abbreviated examination was conducted for non-respondents in their homes. Cataract was graded clinically using to the Lens Opacity Classification System (LOCS) III system. The main outcome measures were adjusted odds ratio for risk factors for specific cataract types (nuclear, cortical and PSC), any cataract and cataract surgery, examined in multiple logistic regression models. RESULTS: Out of the 1232 (71.8%) examined, 1206 (70.2%) provided lens data for this analysis. Increasing age was associated with all cataract types, any cataract, and cataract surgery. There was no significant sex difference in presence of any cataract, specific cataract types or cataract surgery. After controlling for age, sex, and other factors, diabetes was associated with cortical cataract (3.1; 95% CI: 1.6 to 6.1), PSC cataract (2.2; 95% CI 1.2 to 4.1), any cataract (2.0; 95% CI: 0.9 to 4.5), and cataract surgery (2.3; 95% CI: 1.3 to 4.1). Lower body mass index was associated with cortical cataract (1.8; 95% CI: 1.1 to 2.9; lowest versus highest quintile) and any cataract (2.3; 95% CI: 1.3 to 4.0). Current cigarette smoking was associated with nuclear cataract (1.7, 95% CI: 1.0 to 2.9; more than 10 cigarettes per day versus none). A non-professional occupation was associated with nuclear cataract (2.9; 95% CI: 1.5 to 5.8; for production or machine operators and 2.6; 95% CI: 1.2 to 5.5; for labourers or agricultural workers, both versus professionals). Lower education was associated with nuclear cataract (2.3; 95% CI: 1.0 to 5.2, none versus tertiary), while lower household income was associated with PSC cataract (4.7, 95% CI: 1.1 to 20.0; income S$4000). CONCLUSIONS: Age related cataracts are associated with a variety of risk factors among Chinese people in Singapore, similar to those reported in European, Indian, and African derived populations. These data support common aetiological mechanisms for age related cataracts, irrespective of ethnic origin.

Adult↗
PubMed2003

Pilot study using technetium-99m pertechnetate sequential radionuclide-sialography to assess salivary gland function in nasopharyngeal cancer patients on radiation therapy.

INTRODUCTION: Nasopharyngeal carcinoma (NPC) is mainly treated by radiation therapy. A common complication of radiotherapy is xerostomia. Direct measurements of the amount of saliva produced using suction cups and volumetric assessments are cumbersome and time-consuming. Sequential radionuclide sialography is a reproducible and convenient method of measuring salivary function. MATERIALS AND METHODS: Patients with newly diagnosed NPC underwent a pilot study using technetium-99m pertechnetate sequential radionuclide sialography to assess their salivary function before and at 3 months post radiation therapy. From the sialography, time activity curves were obtained for analysis of salivary function. The shape of the time activity curve with citric acid stimulation was classified into 4 types according to the degree of radiation-induced dysfunction. RESULTS: All 14 patients had worse (P < 0.005) time activity curves for both parotids and submandibular glands after radiation therapy. All patients with abnormal curves before radiation therapy presented type IV (non-functioning) curve after radiation therapy. A ratio of pre- and post-stimulation counts allowed for quantification of the degree of stimulatory response. We found a significant decrease in Rc before and after radiation therapy for all salivary glands (P < 0.001). The salivary gland to background ratio, which is a reflection of the degree of salivary gland functional uptake, also had a significant reduction after radiation. CONCLUSION: It is feasible to use technetium-99m pertechnetate in the measurement of salivary gland function in nasopharyngeal cancer patients treated with radiation therapy.

Adult↗
PubMed2002

Association between psychological symptoms in adults and growth in early life: longitudinal follow up study.

OBJECTIVES: To test the hypothesis that birth weight for gestational age and weight gain in early childhood have a long term association with psychological distress in adults. DESIGN: Longitudinal study of 1958 birth cohort followed to age 42 years. SETTING: Population based birth cohort study. PARTICIPANTS: 9731 cohort members with valid perinatal, postnatal, and adult data. MAIN OUTCOME MEASURES: Malaise inventory scores measured at ages 23, 33, and 42 years. Generalised estimating equations approach used to analyse repeated measures. RESULTS: Psychological distress score was inversely related to birthweight z score and weight gain from birth to the age of 7 years. A unit increase in birthweight z score or childhood weight gain was associated with a mean reduction in psychological distress score of 0.10 (95% confidence interval 0.05 to 0.15) and 0.06 (0.02 to 0.10), respectively. Birth weight and weight gain were also inversely related to the odds of having a high level of psychological distress, with odds ratios being 0.90 (0.85 to 0.95) and 0.93 (0.89 to 0.98), respectively. CONCLUSIONS: Psychological health in adults is related to fetal growth and growth in early childhood.

Adult↗
PubMed2002

A review of the rheology of the lamellar phase in surfactant systems.

The rheology of the liquid crystal lamellar phase has been studied in a wide range of systems including non-ionic, anionic and cationic surfactants and block co-polymers. This review summarises the main advances in this area over the past twenty years and includes examples of the rheo-optical techniques, which help to elucidate the changes in microstructural conformation taking place in the lamellar phase during shear. Particular emphasis is given to the microstructural change of the lamellar phase from sheet-like bilayers to dispersed multilamellar vesicles (droplets). Examples of this transition are provided for both surfactant and block co-polymer systems. The review highlights similarities in the rheological signatures of the transition for different systems and also summarises the variation in behaviour of the lamellar phase at different surfactant concentrations and on the addition of salt.

Journal Article↗
PubMed2002

A Bayesian re-assessment of two Phase II trials of gemcitabine in metastatic nasopharyngeal cancer.

The Simon two-stage minimax design is a popular statistical design used in Phase II clinical trials. The analysis of the data arising from the design typically involves the use of frequentist statistics. This paper presents an alternative, Bayesian, approach to the design and analysis of Phase II clinical trials. In particular, we consider how a Bayesian approach could have affected the design, analysis and interpretation of two parallel Phase II trials of the National Cancer Centre Singapore, on the activity of gemcitabine in chemotherapy-naïve and in previously treated patients with metastatic nasopharyngeal carcinoma. We begin by explaining the Bayesian methodology and contrasting it with the frequentist approach. We then carry out a Bayesian analysis of the trial results. The conclusions drawn using the Bayesian approach were in general agreement with those obtained from the frequentist analysis. However they had the advantage of allowing for different and potentially more useful interpretations to be made regarding the trial results, as well as for the incorporation of external sources of information. In particular, using a Bayesian trial design, we were able to take into account the results of the parallel trial results when deciding whether to continue each trial beyond the interim stage.

Antimetabolites, Antineoplastic↗
PubMed2002

Use of the intra-aortic balloon pump for dilatation of benign tracheobronchial strictures.

Tracheobronchial benign stenoses may cause life-threatening emergencies. Here, we will describe a novel technique for the management of tracheal and bronchial stenoses using an intra-aortic balloon pump. The intra-aortic balloon pump was used for dilatation of a postoperative tracheal stricture in a 43-year-old man and a bronchial stricture in a 29-year-old woman with Wegener's granulematosis. There were no intraoperative or postoperative complications in either patient, and the stenosis was relieved successfully in each patient. The intra-aortic balloon pump can be used safely and effectively for the management of difficult tracheobronchial strictures.

Adult↗
PubMed2002

Gemcitabine in metastatic nasopharyngeal carcinoma of the undifferentiated type.

BACKGROUND: We conducted two parallel phase II trials in chemonaïve and previously treated patients with metastatic nasopharyngeal carcinoma (NPC) to evaluate the tumour response, progression-free and overall survival, and toxicity of gemcitabine. PATIENTS AND METHODS: Gemcitabine 1250 mg/m2 was given on days 1 and 8 of a 21-day cycle. Patients with an Eastern Cooperative Oncology Group performance status <2, adequate renal, hepatic and bone marrow function, and radiologically measurable NPC were eligible. RESULTS: Twenty-five chemonaïve and 27 previously treated patients were enrolled. The overall response rate was 28% [95% confidence interval (CI) 14% to 48%] for the chemonaïve and 48% (95% CI 31% to 66%) for previously treated patients. Toxicities greater than or equal to grade 3 occurred in 15 (60%) chemonaïve and 13 (48%) previously treated patients. Neutropenia was uncommon in chemonaïve patients, but occurred in 37% of previously treated patients. The median time to progression was 3.6 months (range 0.9-7.9) for chemonaïve and 5.1 months (0.9-13.1) for previously treated patients. Median overall survival time was 7.2 months (1.4-15.6) and 10.5 months (2.4-15.0) for chemonaïve and previously treated patients, respectively. CONCLUSIONS: Gemcitabine has moderate activity in NPC with minimal toxicity, and is also an effective salvage agent for patients who have failed or progressed after treatment with other agents.

Adult↗