Reply to Labrie et al. Results of the mortality analysis of the Quebec Randomized/controlled trial (RCT)
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Humans↗
Biomedical subjects
R J Prescott
Publications and source records attributed to R J Prescott.
14 years of follow-up from the Edinburgh randomised trial of breast-cancer screening.
BACKGROUND: The Edinburgh randomised trial of breast-cancer screening recruited women aged 45-64 years from 1978 to 1981 (cohort 1), and those aged 45-49 years during 1982-85 (cohorts 2 and 3). Results based on 14 years of follow-up and 270,000 woman-years of observation are reported. METHODS: Breast-cancer mortality rates in the intervention group (28,628 women offered screening) were compared with those in the control group (26,026) with adjustment for socioeconomic status (SES) of general medical practices. Rate ratios were derived by means of logistic regression for the total trial population and for women first offered screening while younger than 50 years. Analyses were by intention to treat. FINDINGS: Initial unadjusted results showed a difference of just 13% in breast-cancer mortality rates between the intervention and control groups (156 deaths [5.18 per 10,000] vs 167 [6.04 per 10,000]; rate ratio 0.87 [95% CI 0.70-1.06]), but the results were influenced by differences in SES by trial group. After adjustment for SES, the rate ratio was 0.79 (95% CI 0.60-1.02). When deaths after diagnosis more than 3 years after the end of the study were censored the rate ratio became 0.71 (0.53-0.95). There was no evidence of heterogeneity by age at entry and no evidence that younger entrants had smaller or delayed benefit (rate ratio 0.70 [0.41-1.20]). No breast-cancer mortality benefit was observed for women whose breast cancers were diagnosed when they were younger than 50 years. Other-cause mortality rates did not differ by trial group when adjusted for SES. INTERPRETATION: Our findings confirm results from randomised trials in Sweden and the USA that screening for breast cancer lowers breast-cancer mortality. Similar results are reported by the UK geographical comparison, UK Trial of Early Detection of Breast Cancer. The results for younger women suggest benefit from introduction of screening before 50 years of age.
Age Factors↗
Dynamics of reactive oxygen intermediate production in human glioma: n-6 essential fatty acid effects.
BACKGROUND: Reactive oxygen intermediates (ROIs) are important signals controlling cell growth and cell death. Local essential fatty acid (EFA) deficiencies in tumour cells may limit tumour ROI generation. This deficiency may be rectified by the addition of exogenous EFA. MATERIALS AND METHODS: The n-6 EFA effects on tumour ROIs were analysed in terms of kinetics, dose-response and individual cell type responses using flow cytometry of intracellular 2',7'-dichlorofluorescin oxidation. ROI formation in 30 gliomas and five paired samples of normal brain tissue, > 500 000 cells per specimen, was analysed every 10 s for 0-25 min. RESULTS: Tumour cell basal ROI was lower than normal brain tissue ROI from the same subjects (P < 0.00002). Normal and tumour cell ROIs were stimulated by 4-40 micromol L-1 n-6 EFAs, arachidonic acid (AA) and gamma-linolenic acid (GLA). The stimulated ROI rate was exponential, with the maximum dependent on EFA concentration and tumour grade. CONCLUSIONS: EFAs stimulated tumour cells more than normal cells (P < 0.0000017, n = 71) and increased ROIs in glial fibrillary acidic protein-positive cells in tumours. This indicated high sensitivity of glioma cell ROIs to n-6 EFAs.
Adolescent↗
Prospective study of heart rate variability and mortality in chronic heart failure: results of the United Kingdom heart failure evaluation and assessment of risk trial (UK-heart).
BACKGROUND: Patients with chronic heart failure (CHF) have a continuing high mortality. Autonomic dysfunction may play an important role in the pathophysiology of cardiac death in CHF. UK-HEART examined the value of heart rate variability (HRV) measures as independent predictors of death in CHF. METHODS AND RESULTS: In a prospective study powered for mortality, we recruited 433 outpatients 62+/-9.6 years old with CHF (NYHA functional class I to III; mean ejection fraction, 0.41+/-0.17). Time-domain HRV indices and conventional prognostic indicators were related to death by multivariate analysis. During 482+/-161 days of follow-up, cardiothoracic ratio, SDNN, left ventricular end-systolic diameter, and serum sodium were significant predictors of all-cause mortality. The risk ratio for a 41.2-ms decrease in SDNN was 1.62 (95% CI, 1.16 to 2.44). The annual mortality rate for the study population in SDNN subgroups was 5.5% for >100 ms, 12.7% for 50 to 100 ms, and 51.4% for <50 ms. SDNN, creatinine, and serum sodium were related to progressive heart failure death. Cardiothoracic ratio, left ventricular end-diastolic diameter, the presence of nonsustained ventricular tachycardia, and serum potassium were related to sudden cardiac death. A reduction in SDNN was the most powerful predictor of the risk of death due to progressive heart failure. CONCLUSIONS: CHF is associated with autonomic dysfunction, which can be quantified by measuring HRV. A reduction in SDNN identifies patients at high risk of death and is a better predictor of death due to progressive heart failure than other conventional clinical measurements. High-risk subgroups identified by this measurement are candidates for additional therapy after prescription of an ACE inhibitor.
Aged↗
Uptake and acceptability of antenatal HIV testing: randomised controlled trial of different methods of offering the test.
OBJECTIVE: To determine the uptake and acceptability of different methods of a universal offer of voluntary HIV testing to pregnant women. DESIGN: Randomised controlled trial involving four combinations of written and verbal communication, followed by the direct offer of a test. The control group received no information and no direct offer of a test, although testing was available on request. SETTING: Hospital antenatal clinic covering most of the population of the city of Edinburgh. SUBJECTS: 3024 pregnant women booking at the clinic over a 10 month period. MAIN OUTCOME MEASURES: Uptake of HIV testing and women's knowledge, satisfaction, and anxiety. RESULTS: Uptake rates were 6% for those in the control group and 35% for those directly offered the test. Neither the style of leaflet nor the length of discussion had an effect on uptake. Significant independent predictors of uptake were a direct test offer; the midwife seen; and being unmarried, previously tested, and younger age. Knowledge of the specific benefits of testing increased with the amount of information given, but neither satisfaction nor anxiety was affected by the type of offer. CONCLUSIONS: The universal offer of HIV testing is not intrusive and is acceptable to pregnant women. A policy of offering the HIV test to all women resulted in higher uptake and did not increase anxiety or dissatisfaction. Uptake depends more on the midwife than the method of offering the test. Low uptake rates and inadequate detection of HIV infection point to the need to assess a more routine approach to testing.
Adult↗
A slowly enlarging lesion on the abdomen.
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Abdomen↗
The Darlington and Northallerton Prospective Asthma Study: best function predicts mortality during the first 10 years.
The Darlington/Northallerton prospective study of asthmatics referred to secondary care started in 1983, with review and new entry at 5-yr intervals. The principal outcome measures are: mortality (presented here), best function and therapeutic step. All adult asthmatics with > or = 15% peak flow (PEF) reversibility to > or = 200 l min-1 were included. Socio-demographic variables, PEF and spirometry were recorded prospectively. Best vital capacity (FVC) and PEF were assessed according to protocol. The mortality of the original cohort after 10 yr was expressed as standardized mortality ratio (SMR) against the local population, with history and pulmonary function at entry as explanatory variables. Ninety-five per cent follow-up was achieved in 628 subjects, with 173 deaths (29.1% of those traced). The excess death rate was nearly 50% (SMR 1.47, 95% CI 1.26-1.71), with 56% of deaths due to respiratory disease (expected 10%). After allowance for age and sex, there was a consistent inverse relationship between mortality and entry best FVC, increased risk of death 1.51 (95% CI 1.33-1.72) per 10% deficit of best FVC predicted. The risk of respiratory death was eight times greater, and of non-respiratory death three times greater, in the lowest compared with the highest quartile of best FVC. There were no interactions with smoking, but possible enhancement of the effect in the socially deprived. Best FVC was a particularly powerful predictor of mortality in subjects < 65 years at entry, in whom 64% of the excess deaths occurred. Most of the excess in respiratory deaths was not due to acute severe asthma but to the development of chronic obstructive pulmonary disease (COPD), as defined functionally, irrespective of smoking habit which made no further contribution to mortality.
Adult↗
Symptoms and pulmonary function in asthma.
The relationship between symptoms and pulmonary function in asthma is important if the latter is to be held relevant to management guidelines and their audit. Associations between reported symptoms, pulmonary function and therapy were studied in 824 asthmatics (mean FEV1 75.4% predicted; best FEV1 84.6% predicted; and actual/best peak flow (PEF) 87.5%). Bronchodilator usage (reflecting symptomatic wheeze) was evenly distributed up to eight times daily; 22.5% of subjects had nocturnal disturbance and 46.3% persistent daytime symptoms. The univariate relationships between symptoms and function were generally closer with best rather than actual/best. They were further explored using quintiles of function. Symptoms were consistently less as best function increased, but were highly significantly greater in the fifth than in the third and fourth quintiles of actual/best FEV1. There was a trend to a similar U-shaped relationship of actual/best PEF with nocturnal disturbance and daytime symptoms. Best function is a good determinant of expected symptom load in an asthmatic population. Below 85% actual/best function reflects the prevalence of symptoms. In asymptomatic patients a level of at least 85-90% is a useful check of physiological control but will not exclude some symptomatic patients, irrespective of best function.
Adult↗
The effect of monoclonal or ion-exchange purified factor VIII concentrate on HIV disease progression: a prospective cohort comparison.
The CD4 count has been reported to decline less rapidly in HIV-infected haemophiliacs treated with monoclonally purified factor VIII concentrates than in those using intermediate-purity concentrates. No survival advantage has been demonstrated for this effect, and it is unclear whether this effect occurs with all high-purity concentrates. Two cohorts of patients with severe haemophilia A and HIV treated with either ion-exchange-purified or monoclonally-purified concentrates were compared. The CD4 count, survival, AIDS-defining illnesses, CDC category and anti-retroviral therapy were recorded at 6-monthly intervals for 3 years following the change from intermediate to high-purity factor VIII. 116 patients were recruited, 37 of whom were treated with an ion-exchange purified factor VIII concentrate at three centres, mean (SD) age 31.1 (12.2) years, and 79 were treated with monoclonally purified factor VIII concentrate at two centres, mean (SD) age 29.8 (11.2) years. At the start of the study the median CD4 count was (monoclonal v ion-exchange) 0.30 v 0.16 x 10(9)/l. The CD4 count declined in both arms to a median of (monoclonal v ion-exchange) 0.16 v 0.08 x 10(9)/l at the final visit. Analysis of the (CD4 count)(1/2) over time, using a random coefficients model, found that the mean (SE) rates of decline were not statistically significantly different in the two treatment groups (monoclonal v ion exchange: -0.050 (0.008) v -0.034 (0.011) (CD4 count)(1/2) per year, P = 0.24). No statistically significant difference in survival (log-rank test: P = 0.33) was found. There was no difference in the proportion of individuals experiencing one or more AIDS-defining illnesses (P = 0.32) or in the proportion progressing to CDC category IV (P = 0.28) during the study. The CD4 count declined during the study at a rate similar to that previously reported in patients treated with intermediate-purity factor VIII concentrate, and there was no evidence of any difference between the two treatment groups.
Blood Component Transfusion↗
Popliteal vein reflux reduces the healing of chronic venous ulcer.
BACKGROUND: The relationship between deep and superficial venous reflux and healing of venous ulceration by non-operative compression therapy has not been studied previously. METHODS: A total of 155 patients with chronic venous ulcers underwent duplex ultrasonography before treatment with compression bandaging at a hospital-based venous clinic. RESULTS: At 24 weeks, 104 (67 per cent) of ulcers had healed. There was no significant difference in the pattern of either deep or superficial venous reflux between healed and non-healed ulcers except with respect to the popliteal vein. In healed ulcers, 39 scans (38 per cent) indicated competence of the above-knee popliteal vein compared with five (10 per cent) in the non-healing group (P < 0.001, chi 2 test). Similarly, 43 scans (42 per cent) showed below-knee popliteal vein competence in the healed ulcers compared with only five (10 per cent) performed in legs remaining ulcerated (P < 0.001, chi 2 test). CONCLUSION: Popliteal vein incompetence is an indicator of poor response to compression therapy for venous ulceration.
Adult↗
Schwannoma with features mimicking neuroblastoma: report of two cases with immunohistochemical and ultrastructural findings.
OBJECTIVE: A study of two cases of a rare variant of benign schwannoma showing areas mimicking neuroblastoma/peripheral primitive neuroectodermal tumour (PNET). METHODS: Sections of formalin fixed, paraffin embedded specimens were studied by tinctorial stains and immunohistochemistry, and the tissue retrieved from formalin was examined by electronmicroscopy in one case. RESULTS: The tumours were small and subcutaneous. Both showed features of benign schwannoma; one had a multinodular plexiform pattern. In addition, rosette-like structures consisting of collagenous cores surrounded by small round cells or slightly larger epithelioid cells were present. Tumour cells were positive for S100 protein, Leu7, and in one case GFAP, but were negative for neurofilament protein, synaptophysin, and MIC2. Type IV collagen surrounded individual cells. Electronmicroscopy in case 2 confirmed schwannian features (lamina, processes) and failed to show features of neuroblastoma (neuroendocrine granules). CONCLUSIONS: Benign schwannomas may contain rosette-like structures mimicking neuroblastoma/PNET. The techniques used confirmed schwannian differentiation only and eliminated neuroblastoma/PNET. These uncommon variants should be recognised by practising histopathologists to avoid erroneous diagnoses and inappropriate treatment.
Adult↗
Methodological issues in mammography double reading studies.
OBJECTIVES: An examination of the methods used in assessing cancer detection rates in double reading studies to obtain a clear interpretation of the disparate results from differing studies. SETTING: National breast screening programmes. METHODS: Critical appraisal of methodologies used in the comparison of cancer detection rates with single or double reading. RESULTS: The reported improvement in cancer detection rate with double reading varies greatly between studies, depending upon whether the study is blinded and the statistic used. A method of calculating the increase in cancer detection rate due to a second reader is proposed.
Breast Neoplasms↗
Management and control of asthma as assessed by actual/best function and corticosteroid use 1980-1993/4.
This study aimed to determine whether the changes in practice in the management of asthma since the early 1980s have improved standards (as assessed by higher actual/best function) and reduced the need for oral corticosteroids. All asthmatic outpatients were reviewed in 1980, 1983, 1988/89 and 1993/94. Therapeutic step, defined by suppressive medication alone, actual and best peak expiratory flow (PEF) were recorded. Cohorts from 1980, 1983 and 1988/89 were identified in whom best function was established on all subsequent occasions. Changes in practice demonstrated by cross-sectional review of all subjects were interpreted with the aid of longitudinal analysis of the cohorts. Attendance increased from 463 in 1980 to 772 in 1993/94. Between 1983 and 1993/94, the proportion maintained on inhaled corticosteroids increased from 49 to 84% with increased use of higher doses. Mean actual/best PEF rose from 80 to 87%, improving at each therapeutic step. The proportion needing rescue oral corticosteroids fell from 47 to 35% and maintenance oral corticosteroids from 20 to 9%. In the cohorts, there was a similar reduction in use of rescue corticosteroids, but not of maintenance oral corticosteroids. The study confirmed an increase in the use and dose of inhaled corticosteroids, and a better outcome at all treatment steps. The fall in the proportion of subjects dependent on oral corticosteroids was due to attrition, rather than weaning in later years.
Administration, Inhalation↗
Randomized trial comparing infrainguinal polytetrafluoroethylene bypass grafting with and without vein interposition cuff at the distal anastomosis. The Joint Vascular Research Group.
PURPOSE: A multicenter randomized prospective study was undertaken to determine whether an interposition vein cuff improved the short-term and medium-term patency and limb salvage rates of femoral-above-knee and femoral-below-knee popliteal artery polytetrafluoroethylene (PTFE) bypass procedures. METHODS: Two hundred sixty-one bypass operations were randomized (133 to vein cuff and 128 to no vein cuff). One hundred fifty grafts were to the above-knee popliteal artery, 96 to the below-knee popliteal artery, and 15 to tibial vessels. The median follow-up was 617 days. RESULTS: The 12-month patency rates for cuffed and uncuffed above-knee popliteal artery PTFE bypass grafts were 80% and 84%, and the 2-year patency rates were 72% and 70%, respectively. The patency rates for bypass grafts to the below-knee popliteal artery at 12 months were 80% and 65% and at 2 years 52% and 29%, respectively (p = 0.03). At the below-knee site, this was reflected in 24-month difference in limb salvage rates of 84% and 62%, respectively (p = 0.08). CONCLUSIONS: There was no improvement in the patency rate with the use of a distal anastomosis interposition vein cuff in femoral-above-knee popliteal PTFE bypass grafts, but there was a statistically significant advantage when PTFE bypass grafts were anastomosed to the popliteal artery below the knee.
Aged↗
CHOP-based chemotherapy is as effective as alternating PEEC/CHOP chemotherapy in a randomised trial in high-grade non-Hodgkin's lymphoma. Scotland and Newcastle Lymphoma Group.
The aim of this study was to test whether survival for patients with high-grade non-Hodgkin's lymphoma (NHL) can be improved with a non-cross-resistant regimen as compared to a CHOP-based regimen. This is a multicentre study comprising 325 adult patients, median age 58 years, with high-grade non-Hodgkin's lymphoma: patients of any age and performance status were eligible provided they were able to receive the drugs in the regimens. Patients were randomised to either B-CHOP-M (bleomycin, cyclophosphamide, doxorubicin, vincristine, prednisolone and methotrexate) or PEEC-M (methylprednisolone, vindesine, etoposide, chlorambucil and methotrexate) alternating with B-CHOP-M. At a median follow-up of 9 years, there was no significant difference in overall survival or disease-free survival between the two arms. Toxicities for the two regimens were equivalent. This study confirms that for relatively unselected patients with high-grade non-Hodgkin's lymphoma, an alternating multidrug regimen does not improve upon the results obtained with B-CHOP-M.
Adult↗
Glutathione reduces the toxicity and improves quality of life of women diagnosed with ovarian cancer treated with cisplatin: results of a double-blind, randomised trial.
BACKGROUND: Early clinical trials have suggested that glutathione (GSH) offers protection from the toxic effects of cisplatin. PATIENTS AND METHODS: One hundred fifty-one patients with ovarian cancer (stage I-IV) were evaluated in a clinical trial of cisplatin (CDDP) +/- glutathione (GSH). The objective was to determine whether GSH would enhance the feasibility of giving six cycles of CDDP at 100 mg/m2 without dose reduction due to toxicity. RESULTS: When considering the proportion of patients receiving six courses of CDDP at any dose, GSH produced a significant advantage over control--58% versus 39%, (P = 0.04). For these patients there was a significant difference between the reduction in creatinine clearance for GSH treated patients compared with control--74% versus 62% (P = 0.006). Quality of life scores demonstrated that for patients receiving GSH there was a statistically significant improvement in depression, emesis, peripheral neurotoxicity, hair loss, shortness of breath and difficulty concentrating. As an indication of overall activity, these patients were statistically significantly more able to undertake housekeeping and shopping. Clinically assessed response to treatment demonstrated a trend towards a better outcome in the GSH group (73% versus 62%) but this was not statistically significant (P = 0.25). CONCLUSIONS: The results demonstrate that adding GSH to CDDP allows more cycles of CDDP treatment to be administered because less toxicity is observed and the patient's quality of life is improved.
Adult↗
British Thoracic Society study of cryptogenic fibrosing alveolitis: current presentation and initial management. Fibrosing Alveolitis Subcommittee of the Research Committee of the British Thoracic Society.
BACKGROUND: Mortality due to cryptogenic fibrosing alveolitis (CFA) is increasing, particularly in the elderly. Optimum management remains uncertain and previous studies of the disease have largely been from specialist centres. A national study was carried out of the presentation and initial management of CFA in the UK. METHODS: All respiratory physicians in England, Scotland and Wales were invited to enter patients with newly diagnosed CFA over a two year period. CFA was diagnosed on histological grounds or according to clinical criteria which included the absence of a defined connective tissue disorder or pneumoconiosis. Participating physicians (n = 150) completed a questionnaire at patient entry and at all subsequent follow up visits and death. RESULTS: A total of 588 patients (373 men, 63%) were studied of whom 441 (75%) were referrals from primary care. Their mean (SD) age was 67.4 (10.0) years and median duration of symptoms at presentation was 9.0 months. Clubbing was more common in men (203/373; 54%) than in women (86/ 215; 40%); 209 patients (36%) were graded as severely breathless at presentation. A history of dust exposure (organic or inorganic) was present in 274 patients (47%) of whom 87 had had some exposure to asbestos. Subjects exposed to dust were more likely to have smoked and had slightly higher mean lung volumes, but were otherwise indistinguishable from those not exposed in terms of clinical presentation, management, and outcome. Transbronchial biopsy specimens were taken in 164 patients (28%) and open lung biopsy specimens in 73 (12%), but 60% had no histological diagnostic procedure. Biopsy procedures were more likely to be performed in younger patients, those with better lung function, and those with a history of asbestos exposure. At presentation a decision not to initiate specific treatment was made in 284 cases (48%). The decision to initiate treatment was made predominantly on symptomatic grounds. Two years after the close of entry to the study 266 patients (45%) had died. CONCLUSIONS: CFA is predominantly a disease of elderly patients and has a poor prognosis. Physicians generally considered CFA to be a clinical diagnosis and did not initiate treatment in up to half of patients at presentation.
Age Factors↗
Sputum and pulmonary function in asthma.
STUDY OBJECTIVE: To assess the relevance of sputum production to pulmonary function, in particular, persistent obstruction in patients with a primary clinical diagnosis of asthma. DESIGN: Cross-sectional study of all patients currently followed up in secondary care in a defined locality. SETTING: National Health Service and private clinics in north-east England. PATIENTS: All attenders, aged 18 years or older, with asthma, confirmed by reversibility of peak expiratory flow (PEF) by > or =15% and to > or =200 L/min. INTERVENTIONS: Pro forma history. Pulmonary function at attendance. Assessment of best function according to protocol. Measurement of actual FEV1, FVC, and PEF at attendance. MEASUREMENTS AND RESULTS: We studied 772 subjects; 387 (50%) were male; mean age was 55 years; atopic, 51%; current smokers, 11.5%; ex-smokers, 36%; and never smokers, 52.5%. Best pulmonary function was lower in chronic sputum producers (PEF, 83.2 vs 95.8; FVC, 67.9 vs 81.7% predicted). Chronic sputum production and its negative relationship with best function was strongly associated with smoking. There was little relationship between chronic sputum and persistent obstruction in nonsmokers. There were no univariate associations between sputum during attacks, or its color, and pulmonary function, but after allowing for demographic factors, including smoking, green sputum was associated with persistent obstruction. There was little relationship between sputum and actual/best function at attendance. CONCLUSIONS: Chronic sputum production is associated with persistent obstruction principally in those who have smoked, suggesting that the association reflects smoking rather than asthma. There is no interaction with atopy. After allowance for cigarette smoking, there is an association between green sputum production during exacerbations and persistent obstruction. Green sputum during relapse in asthma may indicate inflammation that is relevant to prognosis.
Adult↗