Related Articles

Background

Factors associated with the loss of participants in long-term longitudinal studies of ageing, due to refusal or moves, have been discussed less than those with short term follow-up.

Methods

In a population-based study of cognition and ageing (the Medical Research Council Cognitive Function and Ageing Study (MRC CFAS)), factors associated with dropout due to refusal and moving in the first follow-up period (over two years) are compared with factors associated with dropout over ten years. Participants at 10-year follow-up are compared with their age-standardised baseline contemporaries.

Results

Some consistent trends are found over the longer term. Refusers tended to have poorer cognition, less years of education, not have a family history of dementia and be women. Characteristics of people who moved differed between waves, but the oldest and people in worse health moved more. When surviving and responding individuals at ten years are compared with those of the same age at baseline many differences are found. Individuals of lower social class, education, cognitive ability, in residential care, with sight/hearing problems and poor/fair self-reported health are less likely to be seen after 10 years of follow-up. Individuals report more health problems when they participate in multiple interviews.

Conclusion

The characteristics of refusers in the longer term are similar to those refusing to participate over the shorter term. Long-term follow-up studies will under represent the disadvantaged and disabled but represent full health status of participating individuals better. There are advantages and disadvantages to both short-term and long-term follow-up.

OBJECTIVES--To survey current prescribing practice for hormone replacement therapy among general practitioners and to elicit their views on the role of hormone replacement therapy in the prevention of osteoporosis and cardiovascular disease; to determine whether they would participate in randomised controlled trials to evaluate the long term beneficial and adverse effects of hormone replacement therapy. DESIGN--Postal questionnaires to general practitioners throughout the United Kingdom. PARTICIPANTS--1268 general practitioners in the Medical Research Council's general practice research framework. RESULTS--1081 (85%) doctors in 220 (95%) practices responded. The doctors were currently prescribing hormone replacement therapy to an estimated 9% of their female patients aged 40 to 64, and 55% of doctors were prescribing opposed hormone replacement therapy (oestrogen plus progestogen) to more patients than a year previously. Over half the doctors would consider prescribing hormone replacement therapy for prevention of osteoporosis (670, 62%) and cardiovascular disease (611, 57%) to asymptomatic women. Overall, 79% of the doctors (851) would definitely or probably consider entering women who have had a hysterectomy into a randomised controlled trial comparing unopposed (oestrogen only) hormone replacement therapy with opposed hormone replacement therapy; 49% (524) would enter patients with a uterus into such a trial. Among a subsample, 85% (180/210) would consider entering patients without menopausal symptoms into a trial comparing hormone replacement therapy with no treatment (unopposed in patients who have had a hysterectomy, opposed in those with a uterus). CONCLUSION--There is considerable uncertainty among general practitioners as to the balance of beneficial and harmful effects of hormone replacement therapy in the long term, particularly relating to its use for prevention of osteoporosis and cardiovascular disease. Most of these doctors would be prepared to participate in randomised controlled trials to determine the long term effects of this increasingly widely used treatment.

BACKGROUND—Methods of classifying chronic obstructive pulmonary disease (COPD) depend largely upon spirometric measurements but disability is only weakly related to measurements of lung function. With the increased use of pulmonary rehabilitation, a need has been identified for a simple and standardised method of categorising disability in COPD. This study examined the validity of the Medical Research Council (MRC) dyspnoea scale for this purpose.
METHODS—One hundred patients with COPD were recruited from an outpatient pulmonary rehabilitation programme. Assessments included the MRC dyspnoea scale, spirometric tests, blood gas tensions, a shuttle walking test, and Borg scores for perceived breathlessness before and after exercise. Health status was assessed using the St George's Respiratory Questionnaire (SGRQ) and Chronic Respiratory Questionnaire (CRQ). The Nottingham Extended Activities of Daily Living (EADL) score and Hospital Anxiety and Depression (HAD) score were also measured.
RESULTS—Of the patients studied, 32 were classified as having MRC grade 3 dyspnoea, 34 MRC grade 4 dyspnoea, and 34 MRC grade 5 dyspnoea. Patients with MRC grades 1 and 2 dyspnoea were not included in the study. There was a significant association between MRC grade and shuttle distance, SGRQ and CRQ scores, mood state and EADL. Forced expiratory volume in one second (FEV1) was not associated with MRC grade. Multiple logistic regression showed that the determinants of disability appeared to vary with the level of disability. Between MRC grades 3 and 4 the significant covariates were exercise performance, SGRQ and depression score, whilst between grades 4 and 5 exercise performance and age were the major determinants.
CONCLUSIONS—The MRC dyspnoea scale is a simple and valid method of categorising patients with COPD in terms of their disability that could be used to complement FEV1 in the classification of COPD severity.



This paper reports the prognostic significance of clinical and laboratory features recorded at presentation in 485 patients entered into the Medical Research Council's 3rd therapeutic trial in myelomatosis between July 1975 and August 1978. The data were complete up to 1 January 1980, with a median follow-up time of 36 months. The 3 major determinants of prognosis were the blood urea concentration (BUC), the haemoglobin concentration ([Hb]), and the clinical performance status. Three prognostic groups based on these determinants were specified. The groups contained 22%, 56% and 22% of the patients and gave 2-year survival probabilities of 76%, 50% and 9% respectively. Patients in the good-prognosis group had a BUC less than or equal to 8 mM. [Hb] greater than or equal to 100 g/l, and no or minimal symptoms. Those in the poor-prognosis group had either [Hb] less than or equal to 75 g/l or a BUC greater than 10 mM and restricted clinical activity. Patients who had combinations of the 3 determinant features which excluded them from these 2 groups were classified into an intermediate prognosis group.

Background

Although incidence of dementia is known to vary between nations, variation within country has not been explored because most incidence studies are single site or have insufficient numbers to compare sites. Few countries have conducted multisite incidence studies in order to facilitate national comparisons. This study aims to provide robust measures of the variation of the incidence of dementia across sites within England and Wales and produce overall estimates by age and sex.

Methods and Findings

The Medical Research Council Cognitive Function and Ageing Study used identical methodology in five diverse sites across the United Kingdom, each with different risk patterns and mortality rates. Incidence has been estimated using likelihood-based methods between the first two waves of interviews. Incidence rates rise with age, particularly above the age of 75 y, from 7.4 (95% confidence interval, 3.6–16.1) per 1,000 person years at age 65–69 y to 84.9 (95% confidence interval, 63.0–107.8) per 1,000 person years at age 85 y and above. The rate of increase for both sexes is marked, and continues into the oldest age groups. Hence, it is estimated that approximately 180,000 new cases of dementia occur in England and Wales each year. There is no convincing evidence of variation across sites, and incidence rates do not reflect the variations in the prevalence of possible risk factors in these sites.

Conclusion

There is no evidence, within England and Wales, of variation in dementia incidence across sites. Dementia incidence rates do not tail off at the oldest ages.

No evidence for variation in dementia incidence between areas with different vascular disease risk or between men and women, nor for reduced indidence amongst oldest age groups.

Nearly 100 years ago Michaelis and Menten published their now classic paper (Michaelis, L., and Menten, M. L. (1913) Die Kinetik der Invertinwirkung, Biochemische Zeitschrift 49, 333–369), in which they show that the rate of an enzyme-catalyzed reaction is proportional to the concentration of enzyme-substrate complex predicted by the Michaelis-Menten equation. Because the original text was written in German, yet is often quoted by English speaking authors, we undertook a complete translation of the 1913 publication, which we provide as an online supplement (http://pubs.acs.org). Here we introduce the translation, describe the historical context of the work, and show a new analysis of the original data. In doing so, we uncovered several surprises that reveal an interesting glimpse into the early history of enzymology. In particular, our re-analysis of Michaelis and Menten’s data using modern computational methods revealed an unanticipated rigor and precision in the original publication and uncovered a sophisticated, comprehensive analysis that has been overlooked in the century since their work was published. Michaelis and Menten not only analyzed initial velocity measurements, but they also fit their full time course data to the integrated form of the rate equations, including product inhibition, and derived a single global constant to represent all of their data. That constant was not the Michaelis constant, but rather, Vmax/Km, the specificity constant times the enzyme concentration (kcat/Km*E0).

Between 1980 and 2001, the United Kingdom Medical Research Council Childhood Leukemia Working Party has conducted 4 clinical trial in acute lymphoblastic leukemia, which have recruited a total of 6516 patients. UKALL VIII examined the role of daunorubicin in induction chemotherapy, and UKALL X examined the role of post-induction intensification. Both resulted in major improvement in the outcomes. UKALL XI examined the efficacy of different methods of CNS-directed therapy and the effects of an additional intensification. ALL97, which was initially based on the UKALL X D template (two intensification phases), examined the role of different steroids in induction and different thiopurines through continuing chemotherapy. A reappraisal of results from UKALL XI compared to other cooperative group results led to a redesign in 1999, which subsequently resulted in a major improvement in outcomes. Additionally, ALL97 and 97/99 demonstrated a significant advantage for the use of dexamethasone rather than prednisolone; although the use of 6-thioguanine resulted in fewer relapses, this advantage was offset by an increased incidence of deaths in remission. Over the era encompassed by these four trials there has been a major improvement in both event-free and overall survival for children in the UK with ALL.

In their submission to the government in advance of the white paper on science policy in the United Kingdom the Medical Research Council commends the MRC's own approach to managing directly funded research. But a series of semi-structured interviews with the directors of some of the MRC's units suggests a gap between the MRC's model of managed research and the reality. Although such units are theoretically managed from MRC head office (and units are charged an overhead for this), in practice each unit runs its own affairs. Between major reviews average contact time with the head office contact person is seven hours a year. The first paper argues that a purchaser-provider split would recognise the benefits of decentralisation and allow units to bid for research funds from several sources, the successful ones guaranteeing their survival through a rolling series of research programmes. The second paper criticises the MRC's cumbersome peer review system. Reliance on outside experts atrophies the scientific skills of head office staff and builds delays into decision making. A purchaser-provider model would allow the head office scientific staff to act like commercial research and development managers, commissioning research, and using the outcome, rather than peer review, as a criterion for continued funding.

The Agency for Healthcare Research and Quality and its predecessor organizations—collectively referred to here as AHRQ—have a productive history of funding research and development in the field of medical informatics, with grant investments since 1968 totaling $107 million. Many computerized interventions that are commonplace today, such as drug interaction alerts, had their genesis in early AHRQ initiatives.

This review provides a historical perspective on AHRQ investment in medical informatics research. It shows that grants provided by AHRQ resulted in achievements that include advancing automation in the clinical laboratory and radiology, assisting in technology development (computer languages, software, and hardware), evaluating the effectiveness of computer-based medical information systems, facilitating the evolution of computer-aided decision making, promoting computer-initiated quality assurance programs, backing the formation and application of comprehensive data banks, enhancing the management of specific conditions such as HIV infection, and supporting health data coding and standards initiatives.

Other federal agencies and private organizations have also supported research in medical informatics, some earlier and to a greater degree than AHRQ. The results and relative roles of these related efforts are beyond the scope of this review.

The objective of the trial was to determine whether there was any difference in survival rates after operable cases of squamous cell carcinoma of the oesophagus were treated by radiotherapy or surgery. It was designed as a prospective, randomised, multicentre trial in the United Kingdom, after staging as potentially operable, and it was planned to enter 100 patients per annum for 4 years, with a minimum follow-up of 5 years, after pre-entry staging of patients under 75 years of age by barium swallow, chest radiographs, oesophagoscopy, biopsy, bronchoscopy and CT scanning. The protocol was published in July 1986; the trial started in January 1987 and was stopped in June 1988 when only 31 patients from 16 centres were entered, although 30 centres had ethical committees' approval and were willing to start the trial. Interventions were to be as follows: 1. Surgery. According to the practice of that particular surgeon and classified as (a) curative resection if the surgeon considered that no macroscopic tumour was left behind, and (b) palliative if incompletely resected. 2. Radiotherapy. (a) Prescribed minimum corrected tumour dose of 5000 cGy with daily dose of 250 cGy in 20 fractions over 4 weeks. (b) Prescribed minimum corrected tumour dose of 6000 cGy with daily dose of 200 cGy in 30 fractions over 6 weeks. The endpoint was to be survival at 1, 2 and 5 years. The trial was discontinued after 18 months because of lack of recruitment and thus the question whether operable squamous cell cancer of the oesophagus, staged before treatment with CT scanning, is to be treated by radiotherapy or surgical resection remains unanswered.(ABSTRACT TRUNCATED AT 250 WORDS)

To establish whether treatment with diuretic or beta blocker in hypertensive older adults reduces risk of stroke, coronary heart disease, and death.

Randomised, placebo controlled, single blind trial.

226 general practices in the MRC general practice research framework.

4396 patients aged 65-74 randomised to receive diuretic, beta blocker, or placebo. Patients had mean systolic pressures of 160-209 mm Hg and mean diastolic pressures less than 115 mm Hg during an eight week run in and were not taking antihypertensive treatment.

Patients were randomised to atenolol 50 mg daily; hydrochlorothiazide 25 mg or 50 mg plus amiloride 2.5 mg or 5 mg daily; or placebo. The regimens were adjusted to achieve specified target pressures. Mean follow up was 5.8 years.

Strokes, coronary events, and deaths from all causes.

Both treatments reduced blood pressure below the level in the placebo group. Compared with the placebo group, actively treated subjects (diuretic and beta blocker groups combined) had a 25% (95% confidence interval 3% to 42%) reduction in stroke (p = 0.04), 19% (-2% to 36%) reduction in coronary events (p = 0.08), and 17% (2% to 29%) reduction in all cardiovascular events (p = 0.03). After adjusting for baseline characteristics the diuretic group had significantly reduced risks of stroke (31% (3% to 51%) p = 0.04), coronary events (44% (21% to 60%), p = 0.0009), and all cardiovascular events (35% (17% to 49%), p = 0.0005) compared with the placebo group. The beta blocker group showed no significant reductions in these end points. The reduction in strokes was mainly in non-smokers taking the diuretic.

Hydrochlorothiazide and amiloride reduce the risk of stroke, coronary events, and all cardiovascular events in older hypertensive adults.

Summary

Background

In the Medical Research Council (MRC) COIN trial, the epidermal growth factor receptor (EGFR)-targeted antibody cetuximab was added to standard chemotherapy in first-line treatment of advanced colorectal cancer with the aim of assessing effect on overall survival.

Methods

In this randomised controlled trial, patients who were fit for but had not received previous chemotherapy for advanced colorectal cancer were randomly assigned to oxaliplatin and fluoropyrimidine chemotherapy (arm A), the same combination plus cetuximab (arm B), or intermittent chemotherapy (arm C). The choice of fluoropyrimidine therapy (capecitabine or infused fluouroracil plus leucovorin) was decided before randomisation. Randomisation was done centrally (via telephone) by the MRC Clinical Trials Unit using minimisation. Treatment allocation was not masked. The comparison of arms A and C is described in a companion paper. Here, we present the comparison of arm A and B, for which the primary outcome was overall survival in patients with KRAS wild-type tumours. Analysis was by intention to treat. Further analyses with respect to NRAS, BRAF, and EGFR status were done. The trial is registered, ISRCTN27286448.

Findings

1630 patients were randomly assigned to treatment groups (815 to standard therapy and 815 to addition of cetuximab). Tumour samples from 1316 (81%) patients were used for somatic molecular analyses; 565 (43%) had KRAS mutations. In patients with KRAS wild-type tumours (arm A, n=367; arm B, n=362), overall survival did not differ between treatment groups (median survival 17·9 months [IQR 10·3–29·2] in the control group vs 17·0 months [9·4–30·1] in the cetuximab group; HR 1·04, 95% CI 0·87–1·23, p=0·67). Similarly, there was no effect on progression-free survival (8·6 months [IQR 5·0–12·5] in the control group vs 8·6 months [5·1–13·8] in the cetuximab group; HR 0·96, 0·82–1·12, p=0·60). Overall response rate increased from 57% (n=209) with chemotherapy alone to 64% (n=232) with addition of cetuximab (p=0·049). Grade 3 and higher skin and gastrointestinal toxic effects were increased with cetuximab (14 vs 114 and 67 vs 97 patients in the control group vs the cetuximab group with KRAS wild-type tumours, respectively). Overall survival differs by somatic mutation status irrespective of treatment received: BRAF mutant, 8·8 months (IQR 4·5–27·4); KRAS mutant, 14·4 months (8·5–24·0); all wild-type, 20·1 months (11·5–31·7).

Interpretation

This trial has not confirmed a benefit of addition of cetuximab to oxaliplatin-based chemotherapy in first-line treatment of patients with advanced colorectal cancer. Cetuximab increases response rate, with no evidence of benefit in progression-free or overall survival in KRAS wild-type patients or even in patients selected by additional mutational analysis of their tumours. The use of cetuximab in combination with oxaliplatin and capecitabine in first-line chemotherapy in patients with widespread metastases cannot be recommended.

Funding

Cancer Research UK, Cancer Research Wales, UK Medical Research Council, Merck KGgA.

Background

Projections of health and social care need are highly sensitive to assumptions about cohort trends in health and disability. We use a repeated population-based cross-sectional study from the Cambridgeshire centre of the UK Medical Research Council Cognitive Function and Ageing Study to investigate trends in the health of the young-old UK population

Methods

Non-overlapping cohorts of men and women aged 65–69 years in 1991/2 (n = 689) and 1996/7 (n = 687) were compared on: self-reported diseases and conditions; self-rated health; mobility limitation; disability by logistic regression and four-year survival by Cox Proportional Hazards Regression models, with adjustments for differences in socio-economic and lifestyle factors.

Results

Survival was similar between cohorts (HR: 0.91, 95% CI: 0.62 to 1.32). There was a significant increase in the number of conditions reported between cohorts, with more participants reporting 3 or more conditions in the new cohort (14.2% vs. 10.1%). When individual conditions were considered, there was a 10% increase in the reporting of arthritis and a significant increase in the reporting of chronic airways obstruction (OR: 1.36, 95% CI: 1.04 to 1.78).

Conclusion

This study provides evidence of rising levels of ill-health, as measured by the prevalence of self-reported chronic conditions, in the newer cohorts of the young-old. Though changes in diagnosis or reporting of disease cannot, as yet, be excluded, to better understand whether our findings reflect real increases in ill-health, investment should be made into improved population-based databases, linking self-report and objective measures of health and function, and including those in long-term care.

Semi-competing risks data occur frequently in medical research when interest is in simultaneous modelling of two or more processes, one of which may censor the others. We consider the analysis of semi-competing risks data in the presence of interval-censoring and informative loss-to-followup. The work is motivated by a data set from the MRC UK Cognitive Function and Ageing Study, which we use to model two processes, cognitive impairment and death. Analysis is carried out using a multi-state model, which is an extension of that used by Siannis et al. (Statist. Med. 2007; 26:426–442) to model semi-competing risks data with exact transition times, to data which is interval-censored. Model parameters are estimated using maximum likelihood. The role of a sensitivity parameter k, which influences the nature of informative censoring, is explored. Copyright © 2010 John Wiley & Sons, Ltd.

Objectives To evaluate whether country of medical qualification is associated with “higher impact” decisions at different stages of the UK General Medical Council’s (GMC’s) “fitness to practise” process after allowing for other characteristics of doctors and inquiries.

Design Retrospective cohort study.

Setting Medical practice in the United Kingdom.

Participants 7526 inquiries to the GMC concerning 6954 doctors.

Main outcome measures Proportion of inquiries referred for further investigation at initial triage by the GMC, proportion of inquiries investigated that were subsequently referred for adjudication, and proportion of inquiries resulting in doctors being erased or suspended from the medical register; relative odds of higher impact decisions, by country of qualification, adjusted for doctors’ sex, years since primary medical qualification, medical specialty, source and type of inquiry, and nature of allegations.

Results Of 7526 inquiries, 4702 concerned doctors who qualified in the UK, 624 concerned doctors who qualified elsewhere in the European Union (EU), and 2190 concerned doctors who qualified outside the EU. At the initial triage, 30% (n=1398) of inquiries concerning doctors who qualified in the UK had a high impact decision, compared with 43% (267) for doctors who qualified elsewhere in the EU and 46% (998) for those who qualified outside the EU. The adjusted relative odds of an inquiry being referred for further investigation were 1.67 (95% confidence interval 1.28 to 2.17) for doctors who qualified elsewhere in the EU and 1.61 (1.38 to 1.88) for those who qualified outside the EU, compared with doctors who qualified in the UK. At the investigation stage, 5% (228) of inquiries received concerning UK qualified doctors were referred for adjudication, compared with 10% for EU (63) or non-EU (221) qualified doctors. The adjusted relative odds of referral for adjudication were 2.14 (1.46 to 3.16) for doctors who qualified elsewhere in the EU and 1.68 (1.31 to 2.16) for those who qualified outside the EU. At the adjudication stage, 1% (69) of inquiries received concerning UK qualified doctors led to erasure or suspension, compared with 4% (24) for doctors who qualified elsewhere in the EU and 3% (71) for non-EU qualified doctors. The adjusted relative odds of erasure or suspension were 2.16 (1.22 to 3.80) for doctors who qualified elsewhere in the EU and 1.48 (1.00 to 2.19) for those who qualified outside the EU.

Conclusions Inquiries to the GMC concerning doctors qualified outside the UK are more likely to be associated with higher impact decisions at each stage of the fitness to practice process. These associations were not explained by measured inquiry related and doctor related characteristics, but residual confounding cannot be excluded.

The 66-year-old Daniel Hale Williams Medical Reading Club is an independent reading club comprised of 65 physicians in the metropolitan Washington, DC, area. Members representing all specialty fields meet six times a year for dinner and fellowship, to consider topics of common interest to the profession, and to hear a prepared lecture given by a featured essayist. Club members take turns as hosts for each meeting. This article gives a historical list of these meetings, naming the essayist and the topic, the hosts, and the site of the meetings.

From the vantage point of her personal experience, the author examines milestones since the 1960s which have changed the medical library profession and helped shape the Medical Library Association. The advent of automation, including cataloging with OCLC and online literature searching through the SUNY Biomedical Communication Network, was a dramatic event that transformed the work and priorities of librarians, fulfilling the dreams of earlier visionaries. The application of technology in libraries led to an increased demand for education and training for librarians. The Medical Library Association responded with continuing education programs, and a series of important reports influenced how the association filled its role in professional development. Legislation providing federal funding, such as the Medical Library Assistance Act, resulted in a period of expansion for libraries and their services. The Medical Library Association has developed a legislative agenda to influence action in areas such as copyright. In the future, health sciences librarians must take a leadership role.

Two policies of palliative thoracic radiotherapy for NSCLC have been compared in a randomised multicentre controlled trial aimed at simplifying the palliative treatment of patients with poor performance status. A total of 235 patients were entered. They had inoperable, microscopically confirmed disease, too advanced for 'curative' radiotherapy. Their main symptoms were related to the primary intrathoracic tumour even if metastases were present, and they had a poor performance status. Patients were allocated at random to regimens of either 17 Gy given in two fractions of 8.5 Gy 1 week apart (F2 regimen, 117 patients), or a single fraction of 10 Gy (F1 regimen, 118 patients). Two patients (one in each group) were excluded from all analyses because they were found to have had previously treated malignant disease and had been admitted in error. On admission, 95% of the 233 eligible patients had cough, 47% haemoptysis, 59% chest pain, 64% anorexia, and 16% dysphagia. As assessed by the clinicians, these symptoms were palliated in high proportions of patients, ranging in the F2 group from 48% for cough to 75% for haemoptysis, and in the F1 group from 55% for anorexia to 72% for haemoptysis and chest pain. For all five symptoms the median duration of palliation was 50% or more of survival. All these results were similar in the two treatment groups. In contrast, on daily assessment by the patients using a diary card, those treated with the F2 regimen experienced substantially more dysphagia, which was recorded in 56% of the patients compared with 23% in the F1 group (difference 33%: 95% confidence interval 17-48%). The median survival from randomisation was 100 days in the F2 group and 122 days in the F1 group. The F1 regimen, as it requires only a single attendance for treatment, is recommended as a palliative regimen for patients with inoperable NSCLC and a poor performance status.

Splenomegaly was studied retrospectively at the University of California, San Francisco (UCSF), School of Medicine in 301 patients from 1963 to 1995 and compared with the UCSF service of the San Francisco General Hospital Medical Center (SFGH) in 148 patients from 1979 to 1994. The combined 449 patients were classified into several diagnostic groups and were studied by means of several clinical and laboratory associations. Hepatic disease in the percentage of patients at UCSF (with those at SFGH given in parentheses) was associated with splenomegaly in 29% (41%), hematologic disease, 32% (16%); infectious diseases, 16% (36%); congestive or inflammatory disease, 10% (4%); primary splenic disease, 6% (1%); other, 5% (1%); and cause unknown, 2% (1%). Massive splenomegaly occurred in 27% of the patients of the combined series, particularly in patients with hematologic diseases. The acquired immunodeficiency syndrome (AIDS) occurred in more than half of the patients with infectious diseases at SFGH and was four times frequent than in the patients at UCSF. The commonest diseases associated with splenomegaly were hematologic (lymphoma), hepatic (chronic liver disease), infectious diseases (AIDS and endocarditis), congestive (congestive heart failure), primary splenic (splenic vein thrombosis), and other (malignancy not metastatic to the spleen). In 11 patients with AIDS and massive splenomegaly, Mycobacterium avium complex occurred in 8 (73%). Splenectomy was performed in 117 patients (26%), primarily for hematologic amelioration. I conclude that for splenomegaly of unknown origin, the invasive procedure of choice for patients with hematologic associations may be a bone marrow biopsy; for hepatic association, a liver biopsy; and for infectious disease associations, a lymph node biopsy, before any consideration of a diagnostic splenectomy.

Trials have been organized by a Medical Research Council committee to assess the effectiveness and safety for analgesia in labour of oxygen and nitrous oxide mixtures in different proportions. In a preliminary trial concentrations of 50% and 60% v/v nitrous oxide were compared, but, as the replies of 409 mothers revealed little difference between the two, the results of administering either 50% or 70% nitrous oxide to 778 mothers were then compared. The data relating to normal labour, obtained on 501 of the mothers in this main trial, showed that the relief of pain given was much the same. There was a suggestion, however, that the higher concentration of nitrous oxide might be useful in abnormal labour. The proportion of mothers with normal deliveries who lost consciousness, though very small, was significantly higher with 70% nitrous oxide than with the lower concentration. Ninety-two per cent. of mothers found the gas and oxygen machine helpful, and midwives reported complete or good co-operation by 77% of those using it. It is concluded that the 50% oxygen and 50% nitrous oxide mixture can safely be used by unsupervised midwives.

The Council recognize the research needs of Government departments and wish to play their part in meeting them (paragraph 4). The Council have an important role in the national research effort (paragraph 5). Coherent policies in medical research are essential for the best use of resources (paragraph 6). The customer/contractor relationship is inappropriate to most biomedical research (paragraph 8). Transfer of 25% of the Council's budget to departments would, in the long term, hinder the advance of medical practice (paragraph 9). Short-term consequences for universities would be severe (paragraph 10). It would be uneconomical for departments to duplicate machinery for making detailed research policy choices (paragraph 11). A better partnership that will meet the needs of government should be developed between departments and the Council (paragraph 12). Respective responsibilities of departments and the Council in research should be redefined (paragraph 12a). Government funds for medical and related research should be reapportioned in relation to responsibilities (paragraph 12b). A basis is proposed for future partnership with departments, which is not dependent on financial sanctions (paragraph 12c). The Council favour establishment of a board similar to that proposed in the Dainton report (Annex 2).

Cattle besnoitiosis due to the cyst-forming coccidian parasite Besnoitia besnoiti has recently been reported in expansion in Europe since the end of the twentieth century. The B. besnoiti life cycle and many epidemiological traits are still poorly known. Hematophagous flies, including the worldwide-distributed Stomoxys calcitrans, could be mechanical vectors in the contamination of mouthparts after the puncture of cutaneous cysts or ingestion of infected blood. In this study, a protocol is presented to assess more deeply the role of S. calcitrans, reared in laboratory conditions, in parasite transmission. A preliminary trial showed that stable flies could transmit tachyzoites from bovine artificially parasite-enriched blood to B. besnoiti-free blood using glass feeders. Evidence of transmission was provided by the detection of parasite DNA with Ct values ranging between 32 and 37 in the blood recipient. In a second time, a B. besnoiti-infected heifer harboring many cysts in its dermis was used as a donor of B. besnoiti. An interruption of the blood meal taken by 300 stable flies from this heifer was performed. Immediately after the blood meal was interrupted, they were transferred to a glass feeder containing B. besnoiti-free blood from a non-infected heifer. Quantitative PCR and modified direct fluorescence antibody test (dFAT) were used to detect B. besnoiti DNA and entire parasites, respectively, in the blood recipient, the mouthparts, and the gut contents of S. calcitrans at two time intervals: 1 and 24 h after the interrupted blood meal. Parasite DNA was detected at both time intervals (1 and 24 h) in all samples (blood recipient, mouthparts, and gut contents of stable flies) while entire parasites by dFAT were only found in the abdominal compartment 1 h after the interrupted blood meal. Then, S. calcitrans were able to carry B. besnoiti from chronically infected cattle to an artificial recipient in the conditions of the protocol.

Background

We aimed to establish levels of consumer involvement in randomised controlled trials (RCTs), meta-analyses and other studies carried out by the UK Medical Research Council (MRC) Clinical Trials Unit across the range of research programs, predominantly in cancer and HIV.

Methods

Staff responsible for studies that were included in a Unit Progress Report (MRC CTU, April 2009) were asked to complete a semi-structured questionnaire survey regarding consumer involvement. This was defined as active involvement of consumers as partners in the research process and not as subjects of that research. The electronic questionnaires combined open and closed questions, intended to capture quantitative and qualitative information on whether studies had involved consumers; types of activities undertaken; recruitment and support; advantages and disadvantages of involvement and its perceived impact on aspects of the research.

Results

Between October 2009 and April 2010, 138 completed questionnaires (86%) were returned. Studies had been conducted over a 20 year period from 1989, and around half were in cancer; 30% in HIV and 20% were in other disease areas including arthritis, tuberculosis and blood transfusion medicine. Forty-three studies (31%) had some consumer involvement, most commonly as members of trial management groups (TMG) [88%]. A number of positive impacts on both the research and the researcher were identified. Researchers generally felt involvement was worthwhile and some felt that consumer involvement had improved the credibility of the research. Benefits in design and quality, trial recruitment, dissemination and decision making were also perceived. Researchers felt they learned from consumer involvement, albeit that there were some barriers.

Conclusions

Whilst most researchers identified benefits of involving consumers, most of studies included in the survey had no involvement. Information from this survey will inform the development of a unit policy on consumer involvement, to guide future research conducted within the MRC Clinical Trials Unit and beyond.

General Council has reaffirmed its role as the CMA's primary policymaking body. Rejecting key elements of a report from the Committee on Structure that would have made General Council advisory to the Board of Directors, delegates at the 129th annual meeting said the current structure serves members well and does not need to be changed. However, there was considerable support for measures that would provide increased representation for young physicians and medical students. Delegates discussed how to make the annual meeting more representative of CMA members, then referred the report to the Board of Directors.