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Biomedical subjects

D Machin

Publications and source records attributed to D Machin.

At least 55 records · Page 3Linked to original sources

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↗

Season of birth in schizophrenia: no latitude at the equator.

BACKGROUND: If the established winter excess in births of people who subsequently develop schizophrenia is an effect of 'seasonality', this would be testable by examining the pattern of births in an equatorial region with no formal seasons. AIMS: To investigate whether there is any variation in month of birth among patients from equatorial Singapore with a diagnosis of schizophrenia. METHOD: All 9655 patients discharged from Singapore's national psychiatric hospital with a diagnosis of schizophrenia were included (year of birth range 1930-1984). We analysed aggregated data, as well as the data of subsamples grouped according to birth-year periods, in order to examine secular trends. One patient subsample (those born 1960-84) allowed exact matching against the general population data set and close testing of any seasonal influence. RESULTS: Monthly variation in births was evident for both patients and controls; the patterns were very similar, apart from the patient sample showing a trough in March-April. CONCLUSIONS: In an equatorial region, where 'seasons' are absent, no seasonal excess in births of those later developing schizophrenia was evident.

Adult↗

Doctors on tribunals. A confusion of roles.

BACKGROUND: Mental health review tribunals are required to apply legal criteria within a clinical context. This can create tensions within both law and psychiatry. AIMS: To examine the role of the medical member of the tribunal as a possible mediator between the two disciplines. METHOD: Observation of tribunal hearings and panel deliberations and interviews with tribunal members were used to describe the role of the medical member. RESULTS: The dual roles imposed on the medical member as witness and decision-maker and as doctor and legal actor create formal demands and ethical conflicts that are hard, in practice, either to meet or to resolve. CONCLUSIONS: The structure for providing tribunals with access to expert psychiatric input and advice requires reconsideration.

Commitment of Persons with Psychiatric Disorders↗

The role of alternative therapy in the management of partial thickness burns of the face--experience with the use of moist exposed burn ointment (MEBO) compared with silver sulphadiazine.

INTRODUCTION: Conventional management of partial thickness facial burn wounds includes the use of silver sulphadiazine dressings. Silver sulphadiazine forms an overlying slough that makes wound healing assessment difficult. Moist exposed burn ointment (MEBO) has been proposed as the ideal burn wound dressing both for burns of the face and other sites. Proponents of MEBO claim that it accelerates wound healing and results in scarless wound healing and at the same time reduce bacterial colonisation and the need for analgesics. We present here our experience with MEBO in the management of partial thickness burns of the face. MATERIALS AND METHODS: One hundred and fifteen patients with partial thickness burns were randomly assigned to conventional treatment or MEBO. Out of this, 112 were analysed. Thirty-nine patients sustained facial burns; 17 received MEBO and 22 received silver sulphadiazine. Patients were followed up daily until the burn wounds were reduced by 75% of original body surface area (BSA). RESULTS: In patients with facial burns, MEBO was similar to silver sulphadiazine therapy with respect to rate of wound healing. Minimal slough was present over the wounds in MEBO-treated wounds resulting in clearer assessment of healing progression. CONCLUSIONS: Advantages of MEBO as compared to silver sulphadiazine in the management of partial thickness burns of the face include convenient change of dressing and easier assessment of healing progression. This suggests that MEBO is a useful alternative therapy for partial thickness burns of the face.

Anti-Infective Agents, Local↗

Preface

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Journal Article↗

Adjuvant intra-arterial iodine-131-labelled lipiodol for resectable hepatocellular carcinoma: a prospective randomised trial.

BACKGROUND: Resection of hepatocellular carcinoma is potentially curative, but local recurrence is common. In this prospective randomised trial, we aimed to find out if one dose of postoperative adjuvant intra-arterial iodine-131-labelled lipiodol could reduce the rate of local recurrence and increase disease-free and overall survival. METHODS: Patients who underwent curative resection for hepatocellular carcinoma and recovered within 6 weeks were randomly assigned one 1850 MBq dose of 131I-lipiodol or no further treatment (controls). We compared rates of recurrence and disease-free and overall survival (the primary endpoints) between the two groups by intention to treat. We planned an interim analysis when 30 patients (both groups together) had been followed up for a median of 2 years, with the intention of stopping early if the between-group difference in disease-free survival was significant (p=0.029). FINDINGS: Between April, 1992, and August, 1997, we recruited 43 patients: 21 received intra-arterial 131I-lipiodol and 22 received no adjuvant treatment. During a median follow-up of 34.6 (range 14.1-69.7) months, there were six (28.5%) recurrences among the 21 patients in the adjuvant treatment, compared with 13 (59%) in the controls (p=0.04). Median disease-free survival in the treatment and control groups was 57.2 (0.4-69.7) and 13.6 (2.1-68.3) months, respectively (p=0.037). 3-year overall survival in the treatment and control groups was 86.4% and 46.3%, respectively (p=0.039). The interim analysis showed a significant increase in disease-free survival in the treatment group compared with the controls (p=0.01), so we closed the trial early. 131I-lipiodol had no significant toxic effects. INTERPRETATION: In patients with hepatocellular carcinoma, one 1850 MBq dose of intra-arterial 131I-lipiodol given after curative resection significantly decreases the rate of recurrence and increases disease-free and overall survival.

Adolescent↗

A phase II study of cisplatin, ifosfamide and doxorubicin in operable primary, axial skeletal and metastatic osteosarcoma. European Osteosarcoma Intergroup (EOI).

BACKGROUND: Despite advances in the treatment of primary limb osteosarcoma, the outcome of patients with primary metastatic and axial skeletal disease remains poor. The European Osteosarcoma Intergroup have assessed a combination chemotherapy regimen consisting of ifosfamide (IFOS) 3 g/m2/dl-2, doxorubicin (DOX) 25 mg/m2/dl-3 i.v. bolus and cisplatin (CDDP) 100 mg/m2/dl. PATIENTS AND METHODS: One hundred nine previously untreated patients with primary osteosarcoma were registered. Eligibility was confirmed in 103. At presentation, 45 eligible patients had metastatic disease, 15 axial skeletal primary tumours and 43 non-metastatic limb tumours. RESULTS: The major toxicities were myelosuppression (90%, grade 3 or 4) and nausea and vomiting (74%, grade 3 or 4). Overall mean relative dose intensity (RDI) was 80% (88% CDDP, 75% IFOS, 81% DOX). Clinical response as measured by reduction in tumour volume occurred in 36% (95% confidence interval (95% CI): 27%-47%) of primary tumours. Response of pulmonary metastases to chemotherapy was seen in 33% (95% CI: 19%-49%). Good histological response (> or = 90% necrosis of the tumour) occurred in 33% (95% CI: 22%-45%) of resected tumours. Five-year survival was 62% in limb-non-metastatic, 41% in axial skeletal and 16% in limb metastatic patients. CONCLUSIONS: This regimen is active in osteosarcoma but does not appear to be more active than the two-drug CDDP-DOX regimen currently recommended by EOI.

Adolescent↗

Using data from studies of health-related quality of life to describe clinical issues examples from a longitudinal study of patients with advanced stages of cervical cancer.

The focus of the paper is to describe how to present data from studies on health-related quality of life (H-QoL) in a way that is simple and clinically relevant. Data from a longitudinal study of patients with advanced stages of cervix cancer are used. One hundred and eighteen patients filled out questionnaires (including EORTC QLQ-C30) 7 times over a period of 2 years. The following issues are considered: (1) The use of a panel for an initial overview of data. (2) The visual difference between using mean and median values. (3) Box-whisker plots to illustrate the variability of the data. (4) The effect of combining categorical data into fewer categories. (5) Individual patient profiles showing the wide variability among patients. (6) A table showing the change of scores over a one-year period. (7) "Prognostic plots" dividing the initial scores and the following scores. (8) Plotting changes over time. (9) Illustration of the impact of non-random dropout. (10) The effect of drop-out for the patients who fill out two sequential assessments. (11) The use of healthy controls to help answer the question "what is normal?".

Adult↗

Neoadjuvant chemotherapy with doxorubicin and cisplatin in malignant fibrous histiocytoma of bone: A European Osteosarcoma Intergroup study.

PURPOSE: Studies involving small case series have suggested that malignant fibrous histiocytoma of bone (MFH-B) is a chemosensitive tumor and that chemotherapy may improve survival. In this study, we evaluated clinical and pathologic response rates and survival in a series of patients treated with a consistent chemotherapy regimen of doxorubicin and cisplatin (DOX/DDP). PATIENTS AND METHODS: Study patients were required to have biopsy-proven MFH-B, no previous chemotherapy, and primary or metastatic measurable disease and to be </= 65 years of age. Treatment consisted of doxorubicin 25 mg/m(2)/d days 1 through 3 and cisplatin 100 mg/m(2) by 4-hour intravenous infusion every 3 weeks for six cycles. In patients with operable primary tumors, chemotherapy was planned to start within 42 days of biopsy, with definitive surgery performed after three cycles. RESULTS: Forty-one patients had operable nonmetastatic limb sarcomas, and 23 (56%) completed six chemotherapy cycles. Limb salvage was possible in 33 patients (80%), and 16 (42%) of 38 assessable specimens showed a good pathologic response (>/= 90% necrosis). Median time to progression was 56 months, and the 5-year progression-free survival rate was 56% (95% confidence interval [CI], 40% to 72%). Median survival time was 63 months, and the 5-year survival rate was 59% (95% CI, 41% to 77%). Patients with a good pathologic response had longer survival times and times to progression than did those with a poor response. Also treated were two patients with locally recurrent and nine with metastatic disease, and these patients had a median survival time of 17.5 months. CONCLUSION: Our study suggests that adjuvant or neoadjuvant chemotherapy with DOX/DDP is beneficial in MFH-B. Good pathologic response rates and survivals are quite comparable with those for osteosarcoma, a related bone tumor for which adjuvant or neoadjuvant chemotherapy is an accepted practice.

Adolescent↗

The distribution and latency of the auditory P300 in schizophrenia and depression.

In a study of 19 right-handed patients with positive symptoms of schizophrenia, fulfilling DSM-III-R criteria, a deficit in the left central-temporal distribution of the auditory P300 was shown compared to a group of 31 controls, who showed a symmetrical distribution. In contrast, 14 right-handed patients fulfilling DSM-III-R criteria for major depressive illness without any psychotic features showed a deficit in the right auditory P300 distribution. These changes did not appear to depend on either age, gender or amount of medication. There was an increase in the P300 latency of 22 and 10 ms over that of the controls in schizophrenia and depressive patients, respectively. Only for those with schizophrenia was the increased latency statistically significant. This increased latency in the schizophrenic group did not appear to be related to medication.

Acoustic Stimulation↗