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Biomedical subjects

R Milroy

Publications and source records attributed to R Milroy.

At least 19 recordsLinked to original sources
PubMed2006

The relationship between an inflammation-based prognostic score (Glasgow Prognostic Score) and changes in serum biochemical variables in patients with advanced lung and gastrointestinal cancer.

BACKGROUND: The Glasgow Prognostic Score (GPS), an inflammation-based prognostic score formed from standard thresholds of C reactive protein (CRP) and albumin, has prognostic value in patients with advanced cancer. Little is known about the general biochemical disturbance associated with the systemic inflammatory response in cancer. AIM: To examine the relationship between the GPS and blood biochemistry in patients with advanced lung and gastrointestinal cancer. METHODS: The GPS (albumin <35 g/l = 1 and CRP >10 mg/l = 1 combined to form a prognostic score of 0 (normal) and 1 or 2 (abnormal)) and a variety of biochemical variables were examined in patients (n = 50) with advanced lung or gastrointestinal cancer and in a healthy control group (n = 13). RESULTS: The GPS was normal in all the controls, but abnormal in 78% of the cancer group. Serum levels of sodium, chloride, creatine kinase, zinc and vitamin D were lower in the cancer group (all p<0.01), whereas levels of calcium, copper (both p<0.05), alkaline phosphatase, gamma-glutamyl transferase (both p<0.001) and lactate dehydrogenase (p<0.10) were raised. In the patient group, with increasing GPS, there was a median reduction in Karnofsky Performance Status (25%), haemoglobin (22%), sodium (3%), zinc (15%) and survival (93%, all p<0.05) and a median increase in white cell count (129%), alkaline phosphatase (217%), gamma-glutamyl transferase (371%) and lactate dehydrogenase (130%, all p<0.05). CRP levels were strongly and similarly correlated with alkaline phosphatase and gamma-glutamyl transferase, accounting for more than 25% of the variation in their activities. CONCLUSION: Several correlations were seen between biochemical variables and increasing GPS. In particular, chronic activation of the systemic inflammatory response in cancer was associated with increase in gamma-glutamyl transferase and alkaline phosphatase activity in patients with advanced lung and gastrointestinal cancer.

Adult↗
PubMed2005

Assessment of quality of life in the supportive care setting of the big lung trial in non-small-cell lung cancer.

PURPOSE: The Big Lung Trial (BLT) was a large, pragmatic trial to evaluate the addition of chemotherapy to primary treatment (ie, surgery, radical radiotherapy, or supportive care) in non-small-cell lung cancer (NSCLC). In the supportive care group, there was a small but significant survival benefit in patients treated with chemotherapy compared with supportive care alone (no chemotherapy). A substudy was undertaken to evaluate the quality of life (QoL) implications of the treatment options. QoL was assessed using European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaires C30 (QLQ-C30) and LC17, and daily diary cards. PATIENTS AND METHODS: EORTC QLQ-C30 and LC17 were collected at 0, 6 to 8, 12, 18, and 24 weeks. Diary cards were completed during the first 12 weeks of the study. The primary end point was global QoL at 12 weeks. RESULTS: A total of 273 patients were randomly assigned: 138 to no chemotherapy and 135 to chemotherapy. There was no evidence of a large detrimental effect on QoL of chemotherapy. No statistically significant differences in global QoL or physical/emotional functioning, fatigue and dyspnea, and pain were detected at 12 weeks. Higher rates of palliative radiotherapy in the no chemotherapy arm may have lessened differences in QoL. Global QoL, role functioning, fatigue, appetite loss, and constipation were prognostic indicators of survival at 12 weeks. CONCLUSION: There were no important adverse effects of chemotherapy on QoL.

Aged↗
PubMed2004

Chemotherapy for patients with non-small cell lung cancer: the surgical setting of the Big Lung Trial.

OBJECTIVES: The non-small cell lung cancer (NSCLC) meta-analysis suggested a survival benefit for cisplatin-based chemotherapy when given in addition to surgery, radical radiotherapy or 'best supportive care'. However, it included many small trials and trials with differing eligibility criteria and chemotherapy regimens. The aim of the Big Lung Trial was therefore to run a large pragmatic trial to confirm the survival benefits seen in the meta-analysis. METHODS: In the surgery setting, a total of 381 patients were randomised to chemotherapy (C, 192 patients) or no chemotherapy (NoC, 189 patients). C was three 3-weekly cycles of cisplatin/vindesine, mitomycin/ifosfamide/cisplatin, mitomycin/vinblastine/cisplatin or vinorelbine/cisplatin. RESULTS: Chemotherapy was given before surgery in 3% of patients whilst 97% received adjuvant chemotherapy. Baseline characteristics were: median age 61 years, 69% male, 48% squamous cell, 93% WHO PS 0-1, 27% stage I, 38% stage II, and 34% stage III. Complete resection was achieved in approximately 95% of patients. In the C group, 13% received no chemotherapy, 21% one or two cycles, and 64% all three cycles of their prescribed chemotherapy (60% of the latter with no delays or modification). 30% had grade 3/4 toxicity, mainly haematological, nausea/vomiting and neutropenic fever, and six patients were reported as having a treatment-related death. 198 (52%) of patients have died, but there is currently no evidence of a benefit in overall survival to the C group: HR 1.02 (95% CI 0.77-1.35), P = 0.90). CONCLUSIONS: This trial has failed to observe a survival benefit with adjuvant chemotherapy following complete resection of stage I-III NSCLC. However, the hazard ratio and 95% confidence intervals are consistent with the previously reported meta-analysis and two large recently reported trials, which suggest a small survival benefit with cisplatin-based chemotherapy.

Aged↗
PubMed2004

Chemotherapy versus supportive care in advanced non-small cell lung cancer: improved survival without detriment to quality of life.

BACKGROUND: In 1995 a meta-analysis of randomised trials investigating the value of adding chemotherapy to primary treatment for non-small cell lung cancer (NSCLC) suggested a small survival benefit for cisplatin-based chemotherapy in each of the primary treatment settings. However, the meta-analysis included many small trials and trials with differing eligibility criteria and chemotherapy regimens. METHODS: The aim of the Big Lung Trial was to confirm the survival benefits seen in the meta-analysis and to assess quality of life and cost in the supportive care setting. A total of 725 patients were randomised to receive supportive care alone (n = 361) or supportive care plus cisplatin-based chemotherapy (n = 364). RESULTS: 65% of patients allocated chemotherapy (C) received all three cycles of treatment and a further 27% received one or two cycles. 74% of patients allocated no chemotherapy (NoC) received thoracic radiotherapy compared with 47% of the C group. Patients allocated C had a significantly better survival than those allocated NoC: HR 0.77 (95% CI 0.66 to 0.89, p = 0.0006), median survival 8.0 months for the C group v 5.7 months for the NoC group, a difference of 9 weeks. There were 19 (5%) treatment related deaths in the C group. There was no evidence that any subgroup benefited more or less from chemotherapy. No significant differences were observed between the two groups in terms of the pre-defined primary and secondary quality of life end points, although large negative effects of chemotherapy were ruled out. The regimens used proved to be cost effective, the extra cost of chemotherapy being offset by longer survival. CONCLUSIONS: The survival benefit seen in this trial was entirely consistent with the NSCLC meta-analysis and subsequent similarly designed large trials. The information on quality of life and cost should enable patients and their clinicians to make more informed treatment choices.

Adult↗
PubMed2003

The approach to the surgical management of cancer in four European countries.

Outcome of lung cancer appears poorer in the UK than elsewhere in Europe. This may be due to a less aggressive approach in treatment. This study investigated whether clinicians' perceptions of their approach differed between European countries. A questionnaire was circulated to cancer specialists in four countries (Belgium, Greece, Switzerland and the UK) asking about management. An aggression score was calculated using the proportion of standard cases that would proceed to operation at different ages and levels of pulmonary function. The principle problems suggested by most of the 314 respondents were inoperability before symptoms (particularly in the UK) and confounding effects of comorbidity. Surgeons particularly blamed delay in referral. The aggression scores (Belgium 54%, UK 49%, Switzerland 47% and Greece 37%) did not suggest the UK is an outlier, but the UK was more conservative in its approach to N2 disease and isolated cerebral metastasis. The aggression scores of surgeons were greater than those of the others (51% versus 42%). Lung cancer was felt to present late with potentially confounding symptoms, but delay in the clinical process was thought to be less important. Although the UK was more conservative with special cases, its approach to typical cases could account for differences in patient survival.

Data Collection↗
PubMed2003

Lung cancer: the importance of seeing a respiratory physician.

Patients with lung cancer present to and are managed by a variety of clinicians. In this study the effect of involvement by a respiratory physician on the diagnosis, staging, treatment and survival of a large unselected group of lung cancer patients was investigated. The study population was derived from the Scottish Cancer Registry. A total of 3,855 patients diagnosed during 1995 with lung cancer were studied. The data were validated and supplemented by references to medical records. The study found that a respiratory physician had been involved in the initial management of 2,901 (75.3%) patients. These patients were found more likely to have had the cancer diagnosis confirmed by histological methods and to have received active treatment with surgery, radiotherapy or chemotherapy. Survival, 1 yr after diagnosis was higher in patients who saw a respiratory physician (24.4 versus 11.1%) and benefit was found to have remained 3 yrs after diagnosis (8.1 versus 3.7%). Although the patients who had not seen a respiratory physician were generally older, and had more extensive disease, after correcting for age, stage and other prognostic factors, the relative hazard ratio of death for those not managed by a respiratory physician was 1.44. The data from this study supports the recommendations of recent lung cancer guidelines for the early involvement by a respiratory physician.

Adult↗
PubMed2002

The systemic inflammatory response, weight loss, performance status and survival in patients with inoperable non-small cell lung cancer.

The relationship between the magnitude of systemic inflammatory response and the nutritional/functional parameters in patients with inoperable non-small cell lung cancer were studied. The extent of weight loss, albumin, C-reactive protein, performance status and quality of life was measured in 106 patients with inoperable non-small cell lung cancer (stages III and IV). Survival analysis was performed using the Cox proportional hazard model. The majority of patients were male and almost 80% had elevated circulating C-reactive protein concentrations (>10 mg x l(-1)). On multivariate analysis, age (P=0.012), tumour type (0.002), weight loss (P=0.056), C-reactive protein (P=0.047), Karnofsky performance status (P=0.002) and fatigue (P=0.046) were independent predictors of survival. The patients were grouped according to the magnitude of the C-reactive protein concentrations (< or =10, 11-100 and >100 mg x l(-1)). An increase in the magnitude of the systemic inflammatory response was associated with increased weight loss (P=0.004), reduced albumin concentrations (P=0.001), reduced performance status (P=0.060), increased fatigue (P=0.011) and reduced survival (HR 1.936 95%CI 1.414-2.650, P<0.001). These results indicate that the majority of patients with inoperable non-small cell lung cancer have evidence of a systemic inflammatory response. Furthermore, an increase in the magnitude of the systemic inflammatory response resulted in greater weight loss, poorer performance status, more fatigue and poorer survival.

Adult↗
PubMed2001

Longitudinal study of resting energy expenditure, body cell mass and the inflammatory response in male patients with non-small cell lung cancer.

The aim of this study was to examine the inter-relationship between the inflammatory response and resting energy expenditure in patients with non-small cell lung cancer (NSCLC) before and after the onset of weight loss. Healthy subjects (n=7) and patients with NSCLC without weight loss (n=12) were studied. Resting energy expenditure adjusted for metabolically active tissue, as measured by total body potassium, was approximately 15% higher in the NSCLC group (P<0.01). Moreover, the resting energy expenditure, correlated with the magnitude of the inflammatory response (r=0.753, P<0.01). Six cancer patients subsequently lost weight and the relationship between resting energy expenditure and the inflammatory response was maintained. These results highlight the impact of the inflammatory response on the increase in the resting energy expenditure which precedes the onset of weight loss in patients with NSCLC.

Adult↗
PubMed2001

Management and survival of patients with lung cancer in Scotland diagnosed in 1995: results of a national population based study.

BACKGROUND: The prognosis of patients with lung cancer in Scotland is poor and not improving. This study was designed to document factors influencing referral, diagnostic evaluation, treatment, and survival in patients with lung cancer. METHODS: Patients diagnosed during 1995 were identified from the Scottish Cancer Registry and their medical records were reviewed. Adequate records were available in 91.2% of all potentially eligible cases. RESULTS: In 1995, patients in Scotland with lung cancer had a high rate of microscopic verification (74.1%) and 75.3% were assessed by a respiratory physician; however, only 56.8% received active treatment (resection 10.7%, radiotherapy 35.8%, chemotherapy 16.1%) and 2.9% participated in a clinical trial. Survival was poor with a median of 3.6 months; 21.1% (95% CI 19.8% to 22.4%) were alive at 1 year and 7.0% (95% CI 6.2% to 7.8%) at 3 years. Management by respiratory physician, oncologist, or thoracic surgeon was an independent predictor of access to potentially curative treatment and better survival. CONCLUSION: This national population based study demonstrates low use of treatment, poor survival, and the influence of process of care on survival. Implementation of evidence-based guidelines will require substantial changes in practice. Increasing the number of patients who receive treatment may improve survival.

Adult↗
PubMed2000

Route choices, anticipated forgetting, and interface design for on-line reference documents.

Preference and usability are imperfectly correlated when choice among procedures depends on anticipating cognitive difficulties. Navigation choices were explored by offering 2 routes through an on-line price catalog. The harder route never varied, but interface features of the easier route varied across readers. In Experiment 1, readers chose the easier route (82% trials) when it was visually salient but otherwise preferred the harder route from the active window. This suggested that visual factors influenced decisions. Experiment 2 equated visual factors, but choice of the easier route fell significantly when it needed an activation click. Navigating the harder route increased readers' use of an on-line notebook (i.e., people more often anticipated forgetting prices while reading). People choose easier procedures unless interface design miscues anticipated effort. Thus, usability evaluation needs to include factors influencing choices among methods.

Adult↗
PubMed2000

Gemcitabine plus best supportive care (BSC) vs BSC in inoperable non-small cell lung cancer--a randomized trial with quality of life as the primary outcome. UK NSCLC Gemcitabine Group. Non-Small Cell Lung Cancer.

Three hundred patients with symptomatic, locally advanced or metastatic NSCLC not requiring immediate radiotherapy were enrolled into this randomized multicentre trial comparing gemcitabine + BSC vs BSC alone. Patients allocated gemcitabine received 1000 mg/m2 on days 1, 8 and 15 of a 28-day cycle, for a maximum of six cycles. The main aim of this trial was to compare patient assessment of a predefined subset of commonly reported symptoms (SS14) from the EORTC QLQ-C30 and LC13 scales. The primary end-points were defined as (1) the percentage change in mean SS14 score between baseline and 2 months and (2) the proportion of patients with a marked (> or = 25%) improvement in SS14 score between baseline and 2 months sustained for > or =4 weeks. The secondary objectives were to compare treatments with respect to overall survival, and multidimensional QL parameters. The treatment groups were balanced with regard to age, gender, Karnofsky performance status (KPS) and disease stage (40% had metastatic disease). The percentage change in mean SS14 score from baseline to 2 months was a 10% decrease (i.e. improvement) for gemcitabine plus BSC and a 1% increase (i.e. deterioration) for BSC alone (P = 0.113, two-sample t-test). A sustained (> or = 4 weeks) improvement (> or =25%) on SS14 was recorded in a significantly higher proportion of gemcitabine + BSC patients (22%) than in BSC alone patients (9%) (P = 0.0014, Pearson's chi-squared test). The QLQ-C30 and L13 subscales showed greater improvement in the gemcitabine plus BSC arm (in 11 domains) than in the BSC arm (one symptom item). There was greater deterioration in the BSC alone arm (six domains/items) than in the gemcitabine + BSC arm (three QL domains). Tumour response occurred in 19% (95% CI 13-27) of gemcitabine patients. There was no difference in overall survival: median 5.7 months (95% CI 4.6-7.6) for gemcitabine + BSC patients and 5.9 months (95% CI 5.0-7.9) (log-rank, P = 0.84) for BSC patients, and 1 -year survival was 25% for gemcitabine + BSC and 22% for BSC. Overall, 74 (49%) gemcitabine + BSC patients and 119 (79%) BSC patients received palliative radiotherapy. The median time to radiotherapy was 29 weeks for gemcitabine + BSC patients and 3.8 weeks for BSC. Patients treated with gemcitabine + BSC reported better QL and reduced disease-related symptoms compared with those receiving BSC alone. These improvements in patient-assessed QL were significant in magnitude and were sustained.

Adult↗
PubMed1999

Is small cell lung cancer the perfect target for anti-telomerase treatment?

Small cell lung cancer (SCLC) is common in men and women, has a very poor prognosis, and is therefore a major cause of premature mortality. As such, any prospects for improved therapy are of great significance. The promise of telomerase as a therapeutic target is now close to realization with extremely encouraging preclinical studies aimed at the RNA component (hTR) of telomerase. The rational integration of telomerase therapeutics into clinical trials will therefore require tumours to be well characterized for hTR expression. Despite the large number of cancer types now characterized for telomerase or telomerase component gene expression, only a handful of SCLC samples have been analysed. Given the major clinical problem with treating SCLC, we specifically set out to address the issue of hTR expression in neuroendocrine tumours. Our study covers 91 pulmonary neuroendocrine tumours (62 SCLC and 29 carcinoid tumours). We present data to show that upregulation of the RNA component of telomerase occurs in 98% of human SCLCs. Interestingly, the less aggressive carcinoid tumours of the lung had a significantly lower frequency of hTR expression (P < 0.01). Importantly, we compare hTR expression in this series to the well characterized biological targets p53 and BCL2, and show hTR to be expressed more frequently. Therapies directed at the RNA component of human telomerase are in active development and these data show SCLC to be a prime target for such therapies.

Carcinoid Tumor↗
PubMed1998

Lung cancer--management and outcome in Glasgow, 1991-92.

Current practice and outcome for patients with lung cancer were determined by retrospective case note review of a random sample of all lung cancer cases registered for a calendar year and augmented by review of all surgical and radical radiotherapy cases. A total of 262 patients - 231 patients less than 75 years of age and 31 patients more than 75 years of age - represented 83% of the random sample. Eighty-three per cent of patients were seen within 2 weeks of referral. One-third reported symptoms occurring for less than 1 month and one-third had experienced symptoms for more than 3 months. The median time interval from first hospital contact until the making of a management decision was 18 days. The median interval from first contact to surgery was 63 days, and to starting radical radiotherapy 70 days. Histological confirmation was obtained in 69% of patients. Ten per cent of all lung cancer patients were calculated to have received chemotherapy. Five per cent of the whole cohort had definitive surgery and 64% of these were judged to be free of the disease at 3 years. Overall survival was 9% at 3 years, with no differences relating to cell type or area of residence. Many areas of good practice have been identified, but the lack of tumour staging or performance status data, the low proportion receiving chemotherapy or definitive surgery and the poor outcome after radical radiotherapy indicate the need for prospective audit and feedback of results. The long time interval from management decision to surgery and radiotherapy suggests organizational issues which need attention.

Adult↗
PubMed1998

Longitudinal study of body cell mass depletion and the inflammatory response in cancer patients.

There is recent evidence that the inflammatory response may be important in the disproportionate loss of body cell mass in cancer patients. To examine this further, 18 male patients with lung or gastrointestinal cancer were studied over a 12-week period. In addition to weight, anthropometry, C-reactive protein (marker of the inflammatory response), albumin, and total body potassium were measured at baseline and 12 weeks. When those patients who lost total body potassium were compared with those who had not, there was a significant increase in the baseline and 12-week C-reactive protein concentrations (p < 0.05). The reduction in total body potassium was also associated with a reduction in triceps skinfold thickness (p < 0.05). There were significant correlations between the mean C-reactive protein concentration and the relative (r = -0.846, p < 0.001) and absolute (r = -0.806, p < 0.001) change in total body potassium over the follow-up period. This study demonstrates the association of a chronic inflammatory response with the rate of loss of body cell mass observed in cancer patients.

Aged↗
PubMed1998

A structured approach to the interpretation and reporting of ventilation/perfusion scans.

The aim of this study was to develop a structured approach to the reporting and in particular the clinical interpretation of ventilation/perfusion (V/Q) scan results. An initial audit indicated that there were significant variations in the clinical management of patients particularly after a non-diagnostic V/Q scan report. There were also differences in the approaches used to interpret the scan itself. In an attempt to improve this, a set of interpretation guidelines was produced based on the revised PIOPED data. To combat the problems with clinical interpretation, a standard method for assessing the pre-test clinical probability of pulmonary embolism was established. This clinical risk was then combined with the V/Q scan result to give an overall probability for the presence of pulmonary embolism. The more precise risk stratification which resulted allowed explicit clinical advice on patient management to be incorporated into the final report. A second audit was performed with the revised methodology in place. The level of inter-observer variability for scan reporting decreased from 30% to 12%. The prior assessment of clinical risk and the standardized method of combining this with the scan result led to an improvement in patient management. This was particularly true for the non-diagnostic group, in whom additional investigations were more appropriately used. A structured approach which allows the pre-test probability of pulmonary embolism to be combined in an explicit fashion with the V/Q scan result can provide a more precise risk stratification allowing appropriate recommendations to be made. Such an approach can result in improved patient management.

Anticoagulants↗
PubMed1996

Understanding patients: let's talk about it. A study of cancer communication.

As part of a project on quality of life in patients with lung cancer, an investigation was carried out to examine how patients reacted to the study. A group of 82 patients attending a chest clinic were interviewed by means of a short questionnaire. They were asked to indicate whether an interview was preferable to filling in a questionnaire and whether a home visit was preferable to a clinic interview, and their feelings about interviews. In addition, we documented our observations during the study period. All patients agreed to participate in the study, of whom, 56 patients (68%) preferred to be interviewed, 8 (10%) preferred to fill in a questionnaire by themselves, and the remaining 18 (22%) expressed no preference. Forty-one patients (50%) preferred to be interviewed at their homes, 13 (16%) in the clinic, and 28 (34%) expressed no preference. Nearly all patients (96%) indicated that they found being interviewed very or quite comfortable. Our observations indicated that patients were pleased to talk about and discuss their perceived cultural and social values or daily life experiences. The findings suggest that, despite the strenuous attempts by clinicians to deliver effective health care, proper communication with patients remains limited. The finding has some implications for community care.

Adult↗