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D Machin

Publications and source records attributed to D Machin.

At least 55 records · Page 3Linked to original sources
PubMed1998

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↗
PubMed1998

Methodological and statistical issues of quality of life (QoL) and economic evaluation in cancer clinical trials: report of a workshop.

In recent years, quality of life (QoL) and economic evaluations have become increasingly important as additional outcome measures in cancer clinical trials. However, both fields of research are relatively new and in need of finding solutions to a substantial number of specific methodological problems. This paper reports on the proceedings of a symposium aimed at summarising and discussing some of the most contentious methodological and statistical issues in QoL and economic evaluations. In addition, possible solutions are indicated and the most pertinent areas of research are identified. Issues specific to QoL evaluations that are addressed include clinically meaningful changes in QoL scores; how to analyse QoL data and to handle missing and censored data and integration of length of life and QoL outcomes. Issues specific to economic evaluations are the advantages and disadvantages of various outcome measures; statistical methods to analyse economic data and choice of decision criteria and analytical perspective. How to perform QoL and economic evaluations in large and simple trials and whether the gap between QoL and utility measures can be bridged are also discussed.

Clinical Trials as Topic↗
PubMed1998

Young age is not a poor prognostic marker in colorectal cancer.

BACKGROUND: There is still considerable controversy and debate regarding the features and prognosis of colorectal cancer in young patients. METHODS: One hundred and ten patients (5.1 per cent) under the age of 40 years with colorectal cancer (group Y; male: female ratio 48:62) were compared with 2064 patients with colorectal cancer aged 40 years or more (group O; 917 women, 1147 men). Mode of presentation, stage at diagnosis, tumour characteristics and survival were analysed. RESULTS: Predisposing malignant conditions and family history of colorectal cancer were present in 20.9 per cent of patients in group Y versus 2.2 per cent in group O (P < 0.001). Common chief complaints included change in bowel habits, bleeding from the rectum and a significantly higher incidence of abdominal pain in group Y. There was no difference in stage at presentation between the two groups (the proportion of Dukes stage A, B, C and 'D' lesions in group Y was 8.2, 24.5, 37.3 and 30.0 per cent respectively versus 10.5, 27.9, 33.4 and 28.1 per cent in group O). Tumour site and characteristics were similar in both groups. The incidence of mucinous/signet ring cell and poor grade tumours was 6.9 and 11.8 per cent respectively in group Y and 4.5 and 10.5 per cent in group O. With a mean follow-up of 31.8 months, the overall 5-year survival rate was 54.8 per cent in group Y and 54.1 per cent in group O. Comparing stage for stage, survival was not significantly different in the two groups. However, the adjusted hazard ratios of the age groups Y, M (40-59 years), S (60-79 years), and E (80 years and above) were 1.3, 1 (baseline for calculations), 1.4 and 2.4 respectively, suggesting an adverse outcome for patients in group Y compared with patients aged 40-59 years. CONCLUSION: This study revealed no difference in tumour characteristics and survival in patients with colorectal cancer aged less than 40 years compared with those aged above 40 years. However, a higher hazard ratio in the youngest group may connote a worse prognosis than that for those aged 40-59 years. A significant family history of colorectal cancer and predisposing conditions in the young warrants aggressive screening, surveillance and treatment of the underlying conditions. The detection of colorectal cancer in young patients should be no different from that in the old but demands a high index of suspicion.

Adult↗
PubMed1997

Randomised trial of two regimens of chemotherapy in operable osteosarcoma: a study of the European Osteosarcoma Intergroup.

BACKGROUND: A previous trial by the European Osteosarcoma Intergroup (EOI) suggested that a short intensive chemotherapy regimen with doxorubicin and cisplatin might produce survival of operable, non-metastatic osteosarcoma similar to that obtained with complex and longer-duration drug regimens based on the widely used T10 multi-drug protocol. We undertook a randomised multicentre trial to compare these two approaches. METHODS: 407 patients with operable, non-metastatic osteosarcoma were randomly assigned the two-drug regimen (six cycles [18 weeks] of doxorubicin 25 mg/m2 on days 1-3 and cisplatin 100 mg/m2 on day 1) or a multi-drug regimen (preoperatively vincristine, high-dose methotrexate, and doxorubicin; postoperatively bleomycin, cyclophosphamide, dactinomycin, vincristine, methotrexate, doxorubicin, and cisplatin; this protocol took 44 weeks). Surgery was scheduled for week 9 for the two-drug group and week 7 for the multi-drug group. Analyses of survival and progression-free survival were by intention to treat. FINDINGS: Of 407 randomised patients, 391 were eligible and have been followed up for at least 4 years (median 5-6 years). Toxic effects were qualitatively similar with the two regimens. However, 188 (94%) of 199 patients completed the six cycles of two-drug treatment, whereas only 97 (51%) of 192 completed 18 or more of the 20 cycles of the multi-drug regimen. The proportion showing a good histopathological response (> 90% tumour necrosis) to preoperative chemotherapy was about 29% with both regimens and was strongly predictive of survival. Overall survival was 65% at 3 years and 55% at 5 years in both groups (hazard ratio 0.94 [95% CI 0.69-1.27]). Progression-free survival at 5 years was 44% in both groups (hazard ratio 1.01 [0.77-1.33]). INTERPRETATION: We found no difference in survival between the two-drug and multi-drug regimens in operable, non-metastatic osteosarcoma. The two-drug regimen is shorter in duration and better tolerated, and is therefore the preferred treatment. However, 5-year survival is still unsatisfactory and new approaches to treatment, such as dose intensification, are needed to improve results.

Adolescent↗
PubMed1997

Relationship between thermal dose and outcome in thermoradiotherapy treatments for superficial recurrences of breast cancer: data from a phase III trial.

PURPOSE: The objective of this study was to determine whether the thermal dose delivered during hyperthermia treatments and other thermal factors correlate with outcome after combined radiation and hyperthermia of breast carcinoma recurrences. Data were from the combined hyperthermia and radiation treatment arms of four Phase III trials, which when pooled together, demonstrated a positive effect of hyperthermia. METHODS AND MATERIALS: Four Phase III trials addressing the question of whether hyperthermia could improve the local response of superficial recurrent breast cancer to radiation therapy were combined into a single analysis. Thermal dosimetry data were collected from 120 of the 148 breast cancer recurrence patients who received hyperthermia. The data were analyzed for correlations between thermal parameters as well as important clinical parameters and outcome (complete response rate, local disease free survival, time to local failure, and overall survival). RESULTS: Five thermal parameters were tested, all associated with the low regions of the measured temperature distributions. Max(TDmin) and Sum(TDmin) were associated with complete response where TDmin is the minimum thermal dose measured by any of the tumor temperature sensors during a treatment: Max(TDmin) is the maximum of TDmin over a series of treatments. Using a categorical relationship with a cutoff of 10 min for Sum(TDmin), the complete response rate was 77% for Sum(TDmin) > 10 min and 43% for Sum(TDmin) < or = 10 min (p = 0.022, adjusted for study center and significant clinical factors). The overall complete response rate for hyperthermia and radiation was 61% compared to 41% for radiation alone. Either Max(TDmin) or Sum(TDmin) were also associated with local disease free survival, time to local failure and overall survival. CONCLUSIONS: An earlier report of this trial demonstrated a significant benefit when hyperthermia was added to radiation in the treatment of breast cancer recurrences. The analysis of thermal factors demonstrates that parameters representative of the low end of the measured temperature distributions are associated with initial complete response rate, local disease-free survival, time to local failure and overall survival.

Breast Neoplasms↗
PubMed1997

The experience of labour: using ethnography to explore the irresistible nature of the bio-medical metaphor during labour.

OBJECTIVE: taking evidence provided by an ethnographic study based on women's experiences of pregnancy and childbirth, and using ritual theory in the analysis of the relationship between the medical metaphor, inherent in contemporary birth settings, and the views and expectations of childbirth which the women bring with them to that setting. DESIGN: small scale qualitative study using ethnographic research techniques. SETTING: GP surgeries, two consultant-led, hospital-based antenatal units, labour suites and postnatal wards, plus the homes of the women involved from the north east of England. PARTICIPANTS: 40 primigravid women providing two sample groups. Half of the women were actively involved in antenatal class programmes run by the National Childbirth Trust and the NHS and the other half did not attend any antenatal classes. MAIN FINDINGS: within the sample there was a clear cultural diversity which carried significant implications on how the women assembled their understanding of pregnancy and birth antenatally. However, this division lost clarity at the onset of labour, rendering delivery experiences more similar than might have been expected. Ritual theory offers significant insight into this phenomenon, analysing birth as a rite of passage provided a necessary tool to explain why this pattern emerged in the data. KEY CONCLUSIONS AND IMPLICATIONS FOR PRACTICE: cultural diversity suggests an element of caution should be used when advocating the notion of 'informed choice' across the board, sensitivity to existing cultural values is imperative. Despite an emphasis on informed choice, midwifery practice continues to offer the medical metaphor as the dominant cultural prop in the labour ward.

Anthropology, Cultural↗
PubMed1997

Thirty years of Medical Research Council randomized trials in solid tumours.

This paper reviews the survival outcome from the randomized Phase III trials in solid tumours published on behalf of, or in collaboration with, the Cancer Therapy Committee (CTC) of the British Medical Research Council over a 30-year period to 31 December 1995. We review briefly the innovations in statistical methodology that have occurred over the period. We also note the ways in which standards of reporting the trials have improved, with more recent publications including, for example, estimates of the size of effect and confidence intervals. In all, 32 trials, involving over 5000 deaths in more than 8000 patients, have been published. Tumour types have included bladder, bone, brain, cervix, colon and rectum, head and neck, kidney, lung, ovary, prostate and skin. This paper presents a bibliography of these trials and gives details of the treatment comparisons made, the numbers of patients randomized and included in the analysis for each treatment arm, the observed numbers of deaths, and an estimate of the hazard ratio with associated 95% confidence intervals. The bibliography also indicates the main endpoint of each trial, whether recurrence-free survival or survival, and whether the trial was aimed at finding a difference or showing equivalence. The MRC trials have made an impact on both clinical practice and research activities. For example, the lung cancer programme has helped to establish the role of chemotherapy in small cell lung cancer and has developed better palliative treatment for non-small cell lung cancer. Trials of the radiosensitizer misonidazole have demonstrated that it has no role in the treatment of a number of cancers, trials of hyperbaric oxygen have defined the biological activity of this approach, and the appropriate dose of radiotherapy in patients with brain tumours has been found. The individual trials recruited between 44 and 824 patients (median 213). A better measure of the information in a trial is the number of deaths reported, which varied from 28 to 661 (median 145). A large proportion of the comparisons (8/29 or 28%) anticipating a survival difference, demonstrated such a difference at the 5% level of significance. Despite this, it is concluded that some of the trials should have been larger. In such cases, hindsight suggests either that an overoptimistic view of the anticipated survival benefit was taken at the design stage, or, for equivalence trials, the planned confidence interval was too wide for definitive statements to be made. As a consequence, the current CTC profolio of ongoing randomized trials open to patient accrual at 1 January 1996 have a projected median size of 600 and range from 120 to 2000 patients.

Clinical Trials, Phase III as Topic↗
PubMed1997

Quality of life assessment in clinical trials--guidelines and a checklist for protocol writers: the U.K. Medical Research Council experience. MRC Cancer Trials Office.

Many clinical trials groups now routinely consider including Quality of Life (QoL) assessment in trials. Indeed, several have policies stating that QoL should be considered as a potential endpoint in all new trials and that if it is not to be evaluated the applicants should justify not doing so. However, inclusion of QoL in clinical trials presents a number of difficult organisational issues, and serious problems in compliance have frequently been reported. Thus, in multicentre clinical trials many of the expected QoL questionnaires fail to be successfully completed and returned, although a few groups have claimed high success rates. However, it is well recognised that if questionnaires are missing, there may be bias in the interpretation of trial results, and the estimates of treatment differences and the overall level of QoL may be inaccurate and misleading. Hence it is important to seek methods of improving compliance, at the level of both the participating institution and the patient. We describe a number of methods for addressing these issues, which we suggest should be considered by all those writing clinical trial protocols involving QoL assessment. These are based upon over a decade of experience with assessing QoL in Medical Research Council (MRC) cancer clinical trials. In particular, we provide a checklist for points that should be covered in protocols. Examples are given from a range of current MRC Cancer Trials Office protocols, which it is proposed might act as templates when writing new protocols.

Clinical Protocols↗
PubMed1997

Prophylactic cranial irradiation is indicated following complete response to induction therapy in small cell lung cancer: results of a multicentre randomised trial. United Kingdom Coordinating Committee for Cancer Research (UKCCCR) and the European Organization for Research and Treatment of Cancer (EORTC)

Prophylactic cranial irradiation (PCI) reduces the risk of cranial metastasis in small cell lung cancer (SCLC), but the magnitude and value of this reduction, the risks of radiation morbidity and whether PCI influences survival are unclear. We conducted a randomised trial in patients with limited-stage SCLC who had had a complete response to induction therapy. Initially, patients were randomised equally to (1) PCI 36 Gy in 18 daily fractions, (2) PCI 24 Gy in 12 fractions and (3) no PCI; subsequently, to increase the rate of accrual, randomisation was to clinicians' choice of PCI regimen versus no PCI (at a 3:2 ratio). The endpoints were appearance of brain metastases, survival, cognitive function, and quality of life (QoL). Three hundred and fourteen patients (194 PCI, 120 No PCI) were randomised. In the revised design, the most commonly used PCI regimens were 30 Gy in 10 fractions and 8 Gy in a single dose. With PCI, there was a large and highly significant reduction in brain metastases (HR = 0.44, 95% CI 0.29-0.67), a significant advantage in brain-metastasis-free survival (HR = 0.75, 95% CI 0.58-0.96) and a non-significant overall survival advantage (HR = 0.86, 95% CI 0.66-1.12). In both groups, there was impairment of cognitive function and QoL before PCI and additional impairment at 6 months and 1 year, but no consistent difference between the two groups and thus no evidence over 1 year of major impairment attributable to PCI. PCI can safely reduce the risk of brain metastases. Further research is needed to define optimal dose and fractionation and to clarify the effect on survival. Patients with SCLC achieving a complete response to induction therapy should be offered PCI.

Adult↗
PubMed1997

Randomized trials with quality of life endpoints: are doctors' ratings of patients' physical symptoms interchangeable with patients' self-ratings?

The assessment of physical symptoms is a key component of quality of life studies in palliative care, but is often hampered by missing data from patient-completed questionnaires. In two large multicentre randomized trials of palliative treatment conducted by the Medical Research Council Lung Cancer Working Party, Involving over 700 patients, patients completed Rotterdam Symptom Checklists and doctors reported on eleven of the same physical symptoms at each assessment, using the same 4-point severity scale. Ratings by doctors and patients were compared with respect to compliance, severity, and outcomes for the respective trials. Doctors provided more data than patients: 66% vs. 52% in the first 6 months in one trial, 58% vs. 61% in the other. Comparisons of over 33,000 symptom assessments showed 78% complete agreement between doctor and patient, 18% disagreement by one, 4% two, and 1% three grades (complete disagreement). There was no change in levels of agreement over time, but increasing disagreement with increasing symptom severity, and a consistent bias towards doctors underestimating severity. Nevertheless, the two methods of data collection resulted in similar between-treatment conclusions. Therefore, in randomized trials the doctors' assessments of key physical symptoms may be sufficient for the between-treatment comparison. However, the fact that doctors underestimate symptom severity 15% of the time has important implications for palliative interventions.

Attitude of Health Personnel↗