Maurice McGregor

Probiotic therapy for the prevention and treatment of Clostridium difficile-associated diarrhea: a systematic review

Background: The recent increase in the number and severity of cases of nosocomial Clostridium difficile-associated diarrhea (CDAD) has prompted interest in the use of probiotics for the prevention and treatment of this disease. We performed a systematic review of randomized controlled trials to assess the effectiveness of probiotic therapy. Methods: We searched the PubMed, EMBASE, INAHTA, HEN and Cochrane Collaboration databases to identify trials in which the prevention or treatment of CDAD with probiotic therapy was the primary or secondary outcome. We extracted data on the number of patients randomly assigned to receive probiotic or placebo, the number of patients with CDAD, the type of probiotic, criteria for diagnosing CDAD, persistence of infection after treatment, compliance and adverse effects. Results: We identified 4 eligible studies in which prevention (n = 1) or treatment (n = 3) of CDAD was the primary outcome. The benefit of probiotic therapy seen in 2 of the studies was restricted to subgroups characterized by severe CDAD and increased use of vancomycin. The remaining 2 studies were too methodologically flawed for us to draw meaningful conclusions. We also identified 4 trials in which prevention of antibiotic-associated diarrhea with probiotics was the primary outcome and prevention of CDAD a secondary outcome. These studies were limited primarily by too few CDAD cases and provided no evidence of effective prophylaxis. Overall, heterogeneity in choice and dose of probiotic and in criteria for diagnosing CDAD makes it difficult to synthesize information from the 8 studies. Interpretation: Studies conducted to date provide insufficient evidence for the routine clinical use of probiotics to prevent or treat CDAD. Better designed and larger studies are needed.

Assessing the Impact of Health Technology Assessment

Methodology for evaluation of impact of health technology assessments (HTAs) is outlined and its use illustrated by applying it to 21 HTAs produced by CETS. Impact on policies and technology diffusion was identified in documents, through interviews, questionnaires, and use of data banks. There was evidence that all but three reports influenced policy and that cost-minimization studies caused savings of between

The efficiency frontier approach to economic evaluation of health-care interventions

16 million and

Validity of the hepatojugular reflux as a clinical test for congestive heart failure

27 million annually. Precise estimates of impact will seldom be possible, but systematic documentation of effects is feasible.

Pressure-Flow Relationships in the Coronary Circulation

BACKGROUND IQWiG commissioned an international panel of experts to develop methods for the assessment of the relation of benefits to costs in the German statutory health-care system. PROPOSED METHODS The panel recommended that IQWiG inform German decision makers of the net costs and value of additional benefits of an intervention in the context of relevant other interventions in that indication. To facilitate guidance regarding maximum reimbursement, this information is presented in an efficiency plot with costs on the horizontal axis and value of benefits on the vertical. The efficiency frontier links the interventions that are not dominated and provides guidance. A technology that places on the frontier or to the left is reasonably efficient, while one falling to the right requires further justification for reimbursement at that price. This information does not automatically give the maximum reimbursement, as other considerations may be relevant. Given that the estimates are for a specific indication, they do not address priority setting across the health-care system. CONCLUSION This approach informs decision makers about efficiency of interventions, conforms to the mandate and is consistent with basic economic principles. Empirical testing of its feasibility and usefulness is required.

Indicator-dilution methods in estimation of cardiac output in clinical shock

This study describes observations designed to test the validity of the hepatojugular reflux as an indicator of actual or incipient heart failure. The central venous pressure (CVP) could be predicted from the height of the jugular venous pulsations in 44 of 48 comparisons. In the remaining comparisons, discrepancies ranged from 5 to 7 mm Hg. In patients with normal resting cardiac function, abdominal compression did not cause an increase in CVP of greater than 2 mm Hg (2.7 mm H2O). In 16 of 19 patients with impaired function, CVP increased by greater than or equal to 3 mm Hg. The increase in CVP was estimated from neck veins to within 2 mm Hg in all but 3 instances. CVP stabilized by 10 seconds and did not change over the subsequent 60 seconds. Abdominal compression caused no consistent change in cardiac output. Changes in venous pressure could not be attributed to changes in esophageal pressure or to compression of the heart by elevation of the diaphragm. Observations were consistent with the hypothesis that an increase in right-sided cardiac filling pressures resulting from abdominal compression carried out as described here, reflects both the volume of blood in the abdominal veins and the ability of the ventricles to respond to increased venous return, and constitutes a useful clinical test for detecting congestive cardiac failure. An increase of 3 cm in the height of neck vein distention is a reasonable upper limit of normal.

Measuring the Mortality Impact of Breast Cancer Screening

This study was designed to define more accurately the respective influences of perfusion pressure and flow on coronary resistance. Resistance in a coronary branch, perfused at constant flow, was reduced immediately following temporary perfusion arrest. Large epicardial arteries did not appear to take part in this reaction. In the first 10 to 15 seconds after flow was restored, resistance for that flow was uninfluenced by the duration of the preceding perfusion arrest. That mechanism which caused coronary resistance to fall as a result of metabolic factors, such as reduced availability of oxygen, was thus maximally activated. By observing the relationship of coronary resistance to perfusion pressure at this time, it could be shown that resistance vessels and their surrounding structures showed little evidence of distensibility (resistance constant from 20 to 60 mm Hg). The difference between resistance at steady state and resistance at maximal vasodilatation defines the extent of vasomotion attributable at any flow rate to metabolic factors. Perfusion with venous blood caused a fall of resistance which was greater at any flow rate than could be accounted for by the differences in oxygen delivery rate.

IQWiG methods – a response to two critiques

Abstract In 62 dye curves obtained from 26 patients in shock, comparison was made between cardiac output values derived by the Hamilton and Dow technics for measuring curve area. In normal subjects these values agree within ± 15%. In the presence of shock the conventional Hamilton technic frequently gave substantially lower values. In 1 patient it was shown by a double indicator technic that, following injection of indicator into the vena cava, the greater part of the downslope of the brachial arterial curve might be contaminated by recirculating indicator without the exponential-like decay of the downslope being disturbed. This did not occur when indicator was injected into the pulmonary artery. In seven estimates of cardiac output by dye and direct Fick technics in 4 patients in shock, there was good agreement between dye curve estimates based on Dows formula and direct Fick estimates. When curve area was measured by the conventional Hamilton technic cardiac output was underestimated. Cardiac output cannot be measured accurately in the presence of shock when curve area is measured by Hamiltons technic following right heart injection and brachial arterial sampling. Valid estimates of cardiac output can be obtained either by approximation of the injection and sampling sites or by the use of Dows formula. The presence of error due to recirculation can be suspected when there is failure of the Dow and Hamilton technics to agree within ± 15%.

KTP 532 nm laser for laryngeal lesions. a systematic review.

ObjectivesTo i) estimate how large the mortality reductions would be if women were offered screening from age 50 until age 69; ii) to do so using the same trials and participation rates considered by the Canadian Task Force; iii) but to be guided in our analyses by the critical differences between cancer screening and therapeutics, by the time-pattern that characterizes the mortality reductions produced by a limited number of screens, and by the year-by-year mortality data in the appropriate segment of follow-up within each trial; and thereby iv) to avoid the serious underestimates that stem from including inappropriate segments of follow-up, i.e., too soon after study entry and too late after discontinuation of screening.MethodsWe focused on yearly mortality rate ratios in the follow-up years where, based on the screening regimen employed, mortality deficits would be expected. Because the regimens differed from trial to trial, we did not aggregate the yearly data across trials. To avoid statistical extremes arising from the small numbers of yearly deaths in each trial, we calculated rate ratios for 3-year moving windows.ResultsWe were able to extract year-specific data from the reports of five of the trials. The data are limited for the most part by the few rounds of screening. Nevertheless, they suggest that screening from age 50 until age 69 would, at each age from 55 to 74, result in breast cancer mortality reductions much larger than the estimate of 21% that the Canadian Task Force report is based on.DiscussionBy ignoring key features of cancer screening, several of the contemporary analyses have seriously underestimated the impact to be expected from such a program of breast cancer screening.RésuméObjectifsi) Estimer de combien baisserait la mortalité si l’on proposait aux femmes un dépistage du cancer du sein dès 50 ans et jusqu’à 69 ans; ii) procéder en utilisant les mêmes essais et les mêmes taux de participation que ceux examinés par le Groupe d’étude canadien; iii) mais dans notre analyse, nous guider sur les différences essentielles entre le dépistage et les traitements du cancer, sur l’enchaînement chronologique qui caractérise les baisses de mortalité produites par un nombre limité de dépistages, et sur les données de mortalité annuelles dans le segment de suivi approprié à l’intérieur de chaque essai; et donc iv) éviter les sous-estimations graves qui découlent de l’inclusion de segments de suivi inappropriés, c.-à-d. trop tôt après l’entrée dans l’étude et trop tard après l’abandon du dépistage.MéthodeNous nous sommes concentrés sur les ratios annuels des taux de mortalité dans les années de suivi où, d’après le régime de dépistage employé, on pourrait s’attendre à des déficits de mortalité. Comme les régimes diffèrent d’un essai à l’autre, nous n’avons pas groupé les données annuelles de chaque essai. Pour éviter les valeurs statistiques extrêmes dues au petit nombre de décès annuels dans chaque essai, nous avons calculé les ratios des taux selon des fenêtres mobiles de trois ans.RésultatsNous avons pu extraire des données annuelles dans les rapports de cinq essais. Les données sont limitées pour la plupart par le petit nombre de cycles de dépistage. Néanmoins, elles donnent à penser que le dépistage de 50 à 69 ans résulterait, à chaque âge entre 55 et 74 ans, en une baisse de la mortalité par cancer du sein beaucoup plus importante que l’estimation de 21% sur laquelle se fonde le rapport du Groupe d’étude canadien.AnalyseEn ne tenant pas compte de certaines caractéristiques clés du dépistage du cancer, plusieurs analyses contemporaines sous-estiment gravement l’impact attendu d’un tel programme de dépistage du cancer du sein.

Possible interactions of indomethacin and nitrates in angina pectoris

J. JAIME CARO , ERIK NORD, UWE SIEBERT, ALISTAIR MCGUIRE, MAURICE MCGREGOR, DAVID HENRY, GERARD DE POUVOURVILLE, VINCENZO ATELLA and PETER KOLOMINSKY-RABAS McGill University, Montreal, Canada United Biosource Corporation, Lexington, MA, USA Norwegian Institute of Public Health, Oslo, Norway UMIT – University for Health Sciences, Medical Informatics and Technology, Hall i.T., Austria London School of Economics, London, UK University of Newcastle/ICES, Newcastle, Australia ESSEC Business School, Cergy, France University ‘Tor Vergata’, Rome, Italy IQWiG, Cologne, Germany