Orbital radiotherapy for Graves' ophthalmopathy: useful or useless? Safe or dangerous?

Treatment of Graves' ophthalmopathy does not always provide favorable results. After several decades of efforts, glucocorticoids, orbital radiotherapy (OR) and surgery (orbital decompression) remain the milestones in the management of this disease. OR produce favorable results in about 55-60% of patients. Its effectiveness is increased by the association with systemic glucocorticoids. Recent studies have cast some doubts on its real effectiveness and this is discussed by participants in this Forum. Selection of patients is particularly important to assess treatment outcome, because OR is unlikely to provide beneficial effects in patients with longstanding and inactive eye disease. OR is a safe procedure, with very limited side-effects. It should be used in patients older than 35 years of age. It is recommended that a large, multi-center, prospective, randomized and controlled study with well defined inclusion criteria be carried out to draw sound conclusions on the role of OR in the management of Graves' ophthalmopathy.     

Catecholamine therapy in cardiogenic shock: helpful, useless or dangerous?

Cardiogenic shock is characterized by inadequate organ and tissue perfusion, due to cardiac dysfunction, predominantly following acute myocardial infarction. Mortality rates for patients with cardiogenic shock remain high, ranging from 50-70 % despite effective therapy. Rapid diagnostics, aggressive therapeutic approach (invasive or surgical revascularisation) and pharmacological support are currently used to improve the clinical outcome and survival. In the first line commonly sympathomimetics like dopamine, dobutamine, epinephrine and norepinephrine are used for the pharmacological treatment. They have a high affinity for alpha- and beta adrenergic receptors, leading to a positive inotropic cardiac function, an increase in heart rate, oxygen enhanced demand, and an increase in vasoconstriction. However, there are also some disadvantages in the use of sympathomimetics in patients with cardiogenic shock. Clearly, metabolic acidosis due to the increased oxygen demand can be observed. Vasoconstriction induced by sympathomimetics can lead to perfusion mismatch or even deficit within the microcirculation. Additionally, in some studies which give evidence that the use of sympathomimetics can directly lead to enhanced systemic inflammatory response due to an increased IL-6 expression. However, sympathomimetics are still first line therapeutics for treatment of cardiogenic shock -- with respect to dosage and duration of treatment.     

Overestimation of peer drinking: error of judgement or methodological artefact?

Aims To examine whether inclusion of both self‐ and peer‐referent items in the context of a single social norms drinking questionnaire plays an active role in producing the much‐reported tendency for young people to overestimate the extent of peers' alcohol‐related behaviour and the permissiveness of their attitudes towards alcohol. Design, setting, participants and measurements In a between‐subjects design pupils attending two Scottish secondary schools (n = 1074; 12–18 years; 52.5% male) completed one of three questionnaires designed to measure a range of alcohol‐related behaviours, attitudes and perceptions: a paradigmatic multiple‐target questionnaire included self‐ and peer‐referent items while two single‐target questionnaires included self‐referent or peer‐referent items only. Findings Pupils' self‐reported drinking behaviours and attitudes were similar, regardless of whether multiple or single‐target versions of the questionnaire were used, as were perceptions of peers' frequencies of alcohol use and drunkenness. In contrast, by comparison with pupils who responded to a single‐target version that omitted self‐referent items, use of a multiple‐target questionnaire was significantly more likely to result in reports that peers would consume alcoholic drinks when with friends and hold more permissive or liberal attitudes towards alcohol. Conclusions Social norms research and related health promotion programmes that seek to reduce the extent of overestimation of peer drinking norms are heavily reliant upon multiple‐target drinking questionnaires. The use of such a questionnaire may lead to more distorted or extreme perceptions being reported by pupils compared to single‐target versions, which omit self‐referent drinking items. By implication, use of multiple‐target questionnaires may encourage young people to ‘over‐overestimate’ peer drinking norms.     

DNA fingerprint changes in tuberculosis: reinfection, evolution, or laboratory error?

BACKGROUND: DNA fingerprint patterns of Mycobacterium tuberculosis strains vary within individuals and between epidemiologically linked individuals because of pattern evolution, new infections, and laboratory error. We explored the importance of these factors. METHODS: Cultures from individuals in northern Malawi who had been diagnosed with tuberculosis (TB) during 1996-2001 were fingerprinted with restriction fragment-length polymorphism (RFLP). Probable laboratory error was inferred by use of dates or isolated positive cultures. Pattern evolution was explored within and between individuals, and the relative importance of relapse and reinfection was estimated in individuals with recurrent TB. RESULTS: RFLP results were available for 930 isolates from 806 individuals. The maximum laboratory-error rate was 3.9%. Pattern evolution was more common in linked individuals (17%) than on relapse (11%) or during treatment (3%). Twenty individuals had recurrent TB after completing treatment: in human immunodeficiency virus (HIV)-positive individuals, 7 of 12 recurrences were due to reinfection, compared with 0 of 8 in HIV-negative individuals (P=.01). CONCLUSIONS: The rate of DNA fingerprint-pattern evolution is not linear, and rates of change calculated from repeat cultures within individuals may not be applicable to transmission between individuals. The high proportion of recurrence due to reinfection found in HIV-positive individuals suggests that secondary prophylaxis and/or antiretroviral treatments are needed for such individuals.