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Biomedical subjects

David Machin

Publications and source records attributed to David Machin.

At least 19 recordsLinked to original sources
PubMed2006

Are Asians comfortable with discussing death in health valuation studies? A study in multi-ethnic Singapore.

BACKGROUND: To characterize ease in discussing death (EID) and its influence on health valuation in a multi-ethnic Asian population and to determine the acceptability of various descriptors of death and "pits"/"all-worst" in health valuation. METHODS: In-depth interviews (English or mother-tongue) among adult Chinese, Malay and Indian Singaporeans selected to represent both genders and a wide range of ages/educational levels. Subjects rated using 0-10 visual analogue scales (VAS): (1) EID, (2) acceptability of 8 descriptors for death, and (3) appropriateness of "pits" and "all-worst" as descriptors for the worst possible health state. Subjects also valued 3 health states using VAS followed by time trade-off (TTO). The influence of sociocultural variables on EID and these descriptors was studied using univariable analyses and multiple linear regression (MLR). The influence of EID on VAS/TTO utilities with adjustment for sociocultural variables was assessed using MLR. RESULTS: Subjects (n = 63, 35% Chinese, 32% Malay, median age 44 years) were generally comfortable with discussing death (median EID: 8.0). Only education significantly influenced EID (p = 0.045). EID correlated weakly with VAS/TTO scores (range: VAS: -0.23 to 0.07; TTO: -0.14 to 0.11). All subjects felt "passed away", "departed" and "deceased" were most acceptable (median acceptability: 8.0) while "sudden death" and "immediate death" were least acceptable (median acceptability: 5.0). Subjects clearly preferred "all-worst" to "pits" (63% vs. 19%, p < 0.001). CONCLUSION: Singaporeans were generally comfortable with discussing death and had clear preferences for several descriptors of death and for "all-worst". EID is unlikely to influence health preference measurement in health valuation studies.

Adult↗
PubMed2006

Immediate nephrectomy versus preoperative chemotherapy in the management of non-metastatic Wilms' tumour: results of a randomised trial (UKW3) by the UK Children's Cancer Study Group.

PURPOSE: To determine if patients receiving preoperative chemotherapy with vincristine and actinomycin D for non-metastatic Wilms' tumour have a more advantageous stage distribution and so need less treatment compared to patients who have immediate nephrectomy, without adversely affecting outcome. METHODS: Between 1991 and 2001, a total of 205 patients with newly diagnosed non-metastatic renal tumours, of which 186 had Wilms' histologies, were randomly assigned either to immediate surgery or to 6 weeks preoperative chemotherapy and then delayed surgery. Both groups of children received postoperative chemotherapy according to tumour stage and histology determined at the time of nephrectomy. RESULTS: There was a significant improvement in the stage distribution for patients with Wilms' histologies receiving delayed surgery compared to those having immediate nephrectomy (stage I: 65.2% versus 54.3%; stage II: 23.9% versus 14.9%; stage III: 9.8% versus 29.8%, chi2 test for trend=7.02, p=0.008). This improvement resulted in 20% fewer children receiving radiotherapy or doxorubicin yet event-free and overall survivals at 5 years of 79.6% and 89.0%, respectively, were similar in the two groups. CONCLUSION: Six weeks of preoperative chemotherapy with vincristine and actinomycin D results in a significant shift towards a more advantageous stage distribution and hence reduction in therapy, while maintaining excellent event free and overall survival in children with non-metastatic Wilms' tumour. Around 20% of survivors were therefore spared the late-effects of doxorubicin or radiotherapy. Our results suggest that all children with non-metastatic Wilms' tumour should receive chemotherapy prior to tumour resection.

Adolescent↗
PubMed2006

Late periorbital haemorrhage following functional endoscopic sinus surgery: a caution for potential day case surgery.

BACKGROUND: Orbital complications following functional endoscopic sinus surgery (FESS) are fortunately rare. They are usually easily and rapidly recognizable. CASE PRESENTATION: We present an unusual case of a forty-five year old woman who underwent routine FESS and was not packed nasally after the procedure. Six hours later she started bleeding and nasal packs were inserted. She soon developed unilateral periorbital bruising and within hours her condition had worsened so much that the viability of the eye was thrown into question. She underwent medial and lateral canthotomies and made an uneventful post-operative recovery. CONCLUSION: This rare case demonstrates that late, brisk post-operative bleeding can occur after FESS with potentially catastrophic consequences. Clinicians should be aware that discharging patients after FESS too early may lead to medico-legal problems.

Journal Article↗
PubMed2006

On the application of the von Mises distribution and angular regression methods to investigate the seasonality of disease onset.

This paper describes an approach to summarize the data arising from studies investigating the pattern of disease onset within a calendar year. Such data have been traditionally summarized into monthly counts summated over the complete years studied and patterns often examined by use of Pearson's chi(2) tests with 11 degrees of freedom. This test and others commonly used in practice are reviewed. As an alternative, we suggest that by first representing the date of onset for an individual as a point on a unit circle that the von Mises distribution with a single peak may provide a useful description of such data. Further an extension to angular regression including covariates, analogous to that used routinely in other areas of clinical research, potentially allows a more systematic and detailed investigation of possible seasonal patterns in patient subgroups. The methodology is applied to examples from the date of onset of primary angle-closure glaucoma and date of diagnosis of acute lymphoblastic leukaemia and examines in both situations how the peak onset varies with covariates. Difficulties associated with convergence to the maximum likelihood estimates of the associated parameters are described. Finally, we emphasize the need for individualized (rather than grouped) patient data to be available for study, a clear specification of the particular 'onset' time studied, and suggest that further case studies are required to evaluate the approach.

Adult↗
PubMed2006

A randomized controlled trial to compare steroid with cyclosporine for the topical treatment of oral lichen planus.

OBJECTIVE: To compare the effectiveness of cyclosporine solution versus triamcinolone acetonide in orabase in the treatment of oral lichen planus (OLP) in reducing signs and symptoms. STUDY DESIGN: One hundred thirty-nine biopsy-proven OLP patients were randomly assigned to cyclosporine (68) or steroid (71) applied onto the target lesion and affected areas. Assessments were at weeks 0, 2, 4, 8 by clinical scoring and grid measurement of the target lesion (reticulation, erythema, ulceration). Patients ranked severity of pain and burning sensation using visual analog scales. RESULTS: Although clinical response, pain, burning sensation, area of reticulation, erythema, and ulceration at week 4 were all worse in patients receiving cyclosporine than in those receiving steroid, the differences were not statistically significant. Large patient-to-patient variability was evident over the observation period, with little evidence of marked changes in levels over time in both treatment groups. CONCLUSION: Topical cyclosporine appears no more effective than steroid in the treatment of oral lichen planus.

Administration, Topical↗
PubMed2006

Detection of narrow angles and established angle closure in Chinese residents of Singapore: potential screening tests.

PURPOSE: To assess the performance of peripheral and central anterior chamber depth (ACD) measurements, and autorefraction, in identifying Chinese people with occludable drainage angles or established primary angle closure. DESIGN: Population-based cross-sectional analysis. METHODS: Subjects aged 40 years and older were drawn from a representative sample of Chinese Singaporean residents. Limbal chamber depth (LCD) was estimated and central ACD was measured using optical pachymetry and ultrasound. An autorefraction was taken for all subjects. Angle width and the presence of peripheral anterior synechiae were determined by gonioscopy. Receiver operating characteristic curves were generated to show the performance of these tests in detecting occludable angles. RESULTS: A total of 1090 subjects were examined. The prevalence of occludable angles was 6.5%. LCD measurement performed best in detecting occludable angles (area under the curve [AUC] 0.904, 95% confidence interval [CI] 0.870, 0.937). Optical pachymetry and ultrasound measurement of ACD performed less well (AUC 0.859 and 0.810, respectively), and autorefraction performed poorly in detecting occludable angles (AUC 0.632). LCD also gave the best performance in detecting primary angle closure (AUC 0.782, 95% CI 0.727, 0.837). CONCLUSIONS: Limbal LCD estimation outperforms other methods of measuring ACD as a screening tool for the detection of occludable drainage angles in the Chinese population of Singapore.

Adult↗
PubMed2006

A Bayesian dose finding design for dual endpoint phase I trials.

We propose a dose-finding weighted design for an early clinical trial which aims to determine the optimal dose, selected on the basis of both efficacy and toxicity, to be used in patients entering subsequent studies in a drug development process. The goal is to identify the optimal dose, while using a minimal number of subjects. For each dose under test, a decision table is defined with a utility value attached to each possible decision. The relationship between the utility and the target probability for each outcome is shown. A Dirichlet prior is used and we illustrate the process of maximizing the expected utility under the resulting posterior distribution to find the optimal decision at each stage of the trial. We show how this affects the eventual choice of optimal dose in various scenarios. Properties of our design are discussed and compared with a current standard design.

Anti-HIV Agents↗
PubMed2006

A randomized, placebo-controlled trial of thymosin-alpha1 and lymphoblastoid interferon for HBeAg-positive chronic hepatitis B.

Combination therapy between two immunomodulators used for treatment of chronic hepatitis B was explored based on reported therapeutic efficacy of interferon-alpha, and thymosin-alpha1 as monotherapeutic agents to determine if combination therapy was superior to interferon alone. This double-blinded, randomized, placebo-controlled trial compares the addition of thymosin-alpha1, 1.6 microg taken three times per week (combination therapy) or thymosin placebo (monotherapy) to lymphoblastoid interferon (Wellferon), 5 million international units (MIU) taken three times per week, for 24 weeks. Entry criteria included positive hepatitis B e antigen (HBeAg); alanine aminotransferease (ALT) > or = 1.5 x upper normal limit, but < or = 10 x upper normal limit; positive HBV DNA; absence of cirrhosis; treatment naivety and no co-morbid factors. A total of 98 HBeAg-positive patients were recruited, of which 48 were randomized to combination therapy and 50 to monotherapy. The primary endpoint was the loss of HBeAg at 72 weeks. The secondary endpoints were HBeAg seroconversion, normalization of ALT, loss of HBV DNA and improvement in histology. The HBeAg loss was 45.8% and 28.0% for combination therapy and monotherapy, respectively (difference, 17.8%; 95% CI -1.2%-35.3%, P = 0.067). There was a trend towards HBeAg loss when using combination therapy. There were also no statistically significant differences between the different therapies with respect to the secondary endpoints of HBeAg seroconversion, changes in histology, normalization of ALT or loss of HBV DNA. In conclusion, this trial showed a 17.8% improvement in HBeAg loss rates using combination therapy over interferon monotherapy. This could clinically indicate a potential important difference that would need confirmation in subsequent trials.

Adult↗
PubMed2005

Randomized trial of Alemtuzumab for prevention of graft rejection and preservation of renal function after kidney transplantation.

BACKGROUND: A randomized, multicenter, controlled trial was undertaken to evaluate the safety and efficacy of Alemtuzumab, a powerful lytic agent for both T and B lymphocytes, in the prophylaxis of rejection in renal transplantation (RTx). METHODS: Thirty patients were randomized to receive Alemtuzumab together with low-dose cyclosporine (CsA) monotherapy (CAMPATH, n = 20) or to full doses of CsA with azathioprine and corticosteroids (Standard, n = 10). CsA was administered at doses to achieve whole-blood trough CsA levels of 90 to 110 ng/mL and 180 to 225 ng/mL in CAMPATH and Standard groups, respectively. RESULTS: Per protocol, CsA trough levels were lower in patients assigned to CAMPATH post-RTx (median trough level of 119 vs. 166 ng/mL at 6 months, CAMPATH vs. Standard; 95% confidence interval, -92 to -34). At 6 months post-RTx, serum creatinine, graft and patient survivals, incidence of biopsy proven acute rejection (25% vs. 20%, CAMPATH vs. Standard), overall treatment failure, and severe and moderate infections were comparable. Whereas all patients receiving Standard therapy required maintenance corticosteroids at 6 months, of the 17 of 20 patients with functioning grafts in CAMPATH, 15 (88%, 95% confidence interval, 53%-97%) were steroid free. CONCLUSION: These results suggest that Alemtuzumab is an effective induction agent that permits low-dose steroid-free immunosuppression in RTx.

Adolescent↗
PubMed2005

Randomized trial of radiotherapy versus concurrent chemoradiotherapy followed by adjuvant chemotherapy in patients with American Joint Committee on Cancer/International Union against cancer stage III and IV nasopharyngeal cancer of the endemic variety.

PURPOSE: The Intergroup 00-99 Trial for nasopharyngeal cancer (NPC) showed a benefit of adding chemotherapy to radiotherapy. However, there were controversies regarding the applicability of the results to patients in endemic regions. This study aims to confirm the findings of the 00-99 Trial and its applicability to patients with endemic NPC. PATIENTS AND METHODS: Between September 1997 and May 2003, 221 patients were randomly assigned to receive radiotherapy (RT) alone (n = 110) or chemoradiotherapy (CRT; n = 111). Patients in both arms received 70 Gy in 7 weeks using standard RT portals and techniques. Patients on CRT received concurrent cisplatin (25 mg/m2 on days 1 to 4) on weeks 1, 4, and 7 of RT and adjuvant cisplatin (20 mg/m2 on days 1 to 4) and fluorouracil (1,000 mg/m2 on days 1 to 4) every 4 weeks (weeks 11, 15, and 19) for three cycles after completion of RT. All patients were analyzed by intent-to-treat analysis. The median follow-up time was 3.2 years. RESULTS: Distant metastasis occurred in 38 patients on RT alone and 18 patients on CRT. The difference in 2-year cumulative incidence was 17% (95% CI, 14% to 20%; P = .0029). The hazard ratio (HR) for disease-free survival was 0.57 (95% CI, 0.38 to 0.87; P = .0093). The 2- and 3-year overall survival (OS) rates were 78% and 85% and 65% and 80% for RT alone and CRT, respectively. The HR for OS was 0.51 (95% CI, 0.31 to 0.81; P = .0061). CONCLUSION: This report confirms the findings of the Intergroup 00-99 Trial and demonstrates its applicability to endemic NPC. This study also confirms that chemotherapy improves the distant metastasis control rate in NPC.

Adolescent↗
PubMed2005

Variation in the seasonal diagnosis of acute lymphoblastic leukemia: evidence from Singapore, the United States, and Sweden.

This study investigated, by summing data over successive years, the evidence for the seasonal diagnosis of acute lymphoblastic leukemia. To do so, the authors estimated the dates of peak diagnosis over a range of geographic locations including Singapore (1968-1999), Hawaii and mainland United States (1973-1999), and western Sweden (1977-1994) at latitudes of 1.16 degrees N to 58.24 degrees N. In contrast to other studies, the authors used case-by-case information on dates, gender, and age rather than grouped data for analysis. The seasonal pattern was estimated by fitting a von Mises distribution to the data from each location. No seasonal pattern was found in Singapore, which is close to the equator and does not have marked climatic changes. Likewise, seasonality was not demonstrated in Hawaii or mainland United States despite a 26.18 degrees range of latitudes. In contrast, a significant peak (early January) was observed for western Sweden that appeared strongest for males (December 22, 95% confidence interval: November 16, January 16) and those less than age 20 years (January 14, 95% confidence interval: December 8, March 27). Thus, despite a wide geographic range of localities, there is little evidence of any seasonality in the diagnosis of acute lymphoblastic leukemia in most populations studied and no strong evidence of any influence of climate (as expressed by latitude).

Adolescent↗
PubMed2005

Anterior chamber depth and the risk of primary angle closure in 2 East Asian populations.

OBJECTIVE: To evaluate the risk of peripheral anterior synechiae (PAS) and glaucomatous optic neuropathy attributable to primary angle closure at varying anterior chamber depths (ACDs) in two East Asian populations. METHODS: Participants 40 years and older were from 2 population-based glaucoma surveys in Mongolia and Singapore. Central ACD was measured by optical pachymetry. Presence of PAS was determined by dynamic gonioscopy. Cases with secondary PAS were excluded. Glaucomatous optic neuropathy was diagnosed in subjects with structural and functional evidence of glaucoma. RESULTS: A total of 2032 subjects, consisting of 942 Mongolians and 1090 Chinese Singaporeans, were included in this study. A logistic model of the relationship between ACD and PAS among Singaporeans showed a consistent, incremental increase in PAS across the entire range of ACD. In deeper anterior chambers the rate of PAS exceeded that seen in Mongolians. In Mongolians, there was a clear threshold for ACD (2.4 mm) at or above which PAS were very uncommon. With ACD less than 2.4 mm, the rate of PAS rose rapidly to overtake that seen in Singaporeans. CONCLUSIONS: Shallow anterior chambers are a significant risk factor for angle closure in East Asians, although the nature of the association is specific to the individual population. There was a trend toward higher rates of glaucomatous optic neuropathy in people with the shallowest anterior chambers.

Adult↗
PubMed2005

Does being bilingual in English and Chinese influence changes in quality of life scale scores? Evidence from a prospective, population based study.

BACKGROUND: Bilinguals differ from monolinguals in language use, but the influence of bilingualism on changes in Health-Related Quality of Life (HRQoL) scores is not known. OBJECTIVE: To determine the influence of bilingualism on changes in HRQoL scores. RESEARCH DESIGN: A prospective cohort study of a population-based, disproportionately stratified random sample of monolingual or bilingual ethnic Chinese who completed the Short-Form 36 Health Survey (SF-36) in English or Chinese twice in 2 years. Least squares regression models were used to assess the influence of bilingualism on SF-36 scores, while adjusting for the influence of questionnaire language and determinants of HRQoL. RESULTS: Usable English and Chinese questionnaires were returned by 1013 and 910 subjects respectively (aged 21-65 years, 48.5% female, 52.8% bilingual). Bilinguals differed from monolinguals in known determinants of HRQoL (being younger and better educated), changes in determinants of HRQoL over 2 years (more bilinguals had changes in work or marital status) and had mean SF-36 scores that were up to 10 points higher than monolinguals. After adjusting for these differences, bilingualism did not influence 2 year change scores for any of 8 SF-36 scales. CONCLUSION: Bilingualism did not influence changes in HRQoL scores over 2 years in this large, population-based study of subjects fluent in English and/or Chinese (representing an alphabet and/or pictogram based language respectively).

Adult↗
PubMed2005

Performance of polymethyl pentene oxygenators for neonatal extracorporeal membrane oxygenation: a comparison with silicone membrane oxygenators.

OBJECTIVE: To review the performance of polymethyl pentene versus silicone oxygenators in terms of efficiency in priming and oxygenation, oxygenator resistance, requirements for coagulation proteins and consumption of blood products, for neonatal extracorporeal membrane oxygenation (ECMO) patients. STUDY DESIGN: Forty consecutive neonates were selected retrospectively pre- and post-introduction of the new polymethyl pentene (PMP) oxygenators. They formed two equal groups. After calculation of the sample size, data were collected from ELSO registry forms and patient records. Results were analysed using parametric and non-parametric tests. RESULTS: Neonatal PMP (N-PMP) oxygenators were smaller, faster and easier to prime. They were less efficient than silicone oxygenators, especially in carbon dioxide elimination, and, therefore, required higher sweeps. The preservation of coagulation proteins was significantly better, but there was no reduction in the consumption of blood products, despite having less than half the surface area and significantly lower blood path resistance. CONCLUSION: Small PMP oxygenators (Medos Hilite 800 LT) provide adequate gas exchange and offer technical advantages in terms of more efficient priming, reduced haemodynamic resistance and better control and preservation of coagulation proteins than silicone oxygenators.

Equipment Design↗
PubMed2005

A potential propensity for failure secondary to clot embolism in neonatal ECMO.

OBJECTIVE: To report a single case of oxygenator failure caused by clot embolism originating from the bladder; and to discuss some preventative options. CASE REPORT: A 2.5 kg neonate with a diagnosis of influenza A received veno-arterial (V-A) extracorporeal membrane oxygenation (ECMO) for cardiorespiratory support. Halfway through treatment, she underwent an elective circuit change for numerous clots in her circuit. The patient continued to consume vast quantities of platelets and developed a fatal oxygenator failure after 18 days. DISCUSSION: Amongst the factors influencing the outcome in events of a sudden unexpected oxygenator failure are the severity of patient illness, the size of the clot relative to the size of the oxygenator, the availability of a previously primed circuit and the ease and speed of priming a new oxygenator. CONCLUSION: There is a need for improvement in the design of small oxygenators and ECMO circuits. Adjustment of the coagulation parameters and lowering the tolerance towards clots in the circuit by electively changing them may reduce the incidence of sudden unexpected oxygenator failure. However, using a slightly larger Medos oxygenator may gain valuable time needed to arrange an oxygenator/circuit change.

Equipment Design↗
PubMed2005

The effect of temperature and aprotinin during cardiopulmonary bypass on three different methods of activated clotting time measurement.

The activated clotting time (ACT) is used frequently for monitoring blood anticoagulant response with heparin before, during, and after cardiopulmonary bypass (CPB). Many cardiac procedures involving CPB require reduction of the patient's blood temperature and use of the serine protease inhibitor, aprotinin. Three different methods of ACT measurement were compared to show the effects of different CPB temperatures and the presence of aprotinin. A total of 42 patients were included in the study: 14 received CPB at 28 degrees C, 14 received CPB at 32 degrees C, and 14 normothermic (37 degrees C) CPB. Within each temperature group, seven received aprotinin. The ACT in each group of patients was measured by a celite activator (C-ACT), a kaolin activator (K-ACT), and a celite, kaolin and glass activator (MAX-ACT). All three methods of ACT measurement showed significant increases (p < .05) in clotting times at hypothermic CPB compared with normothermic groups. During heparinization the C-ACT was significantly increased (p < .05) in the presence of aprotinin. Comparability between the 3 ACT measurement methods showed a very high correlation between C-ACT and K-ACT clotting times (R2 = .8962), and slightly lower correlation between MAX-ACT and C-ACT (R2 = .7780), and MAX-ACT and K-ACT (R2 = .7827). All ACT measurements are affected by changes in blood temperature. The C-ACT measurement is prolonged with aprotinin, whereas the MAX-ACT and K-ACT method of measurement in the presence of aprotinin are not significantly altered. It appears that the MAX-ACT produces lower values and may necessitate additional heparin therapy for ACT target values considered safe during CPB. Further study is required from these additional findings.

Adult↗