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A more appropriate approach is to maximise the precision of the epidemiologic investigations by measurement of individual exposure (or water quality) at the place and time of the exposure, as has been done in randomised volunteer studies in the UK and Germany.
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Although a number of studies have explored predictive factors these have been conducted either retrospectively, are based on small sample sizes or have been done in the context of randomised trials which has limitations.
A randomised controlled study in HIV in the pre-HAART era showed a benefit of treating CMV colitis in acquired immunodeficiency syndrome (AIDS) [ 20], but no randomised controlled studies have been done in immunocompetent hosts.
The optimal evaluation will be done in a randomised trial, comparing multidisciplinary treatment with a placebo condition, which is not available for multidisciplinary treatment.
Analysis was done in all 390 randomised patients (ITT) and separately in 169 patients with positive pre-treatment culture (PP).
This could only be done in a controlled randomised trial of antibacterial treatment.
To definitively prove a benefit to the BCSP trends in mortality would need to be assessed instead of survival as was done in the relevant randomised trials that originally investigated the effectiveness of such screening programmes (Hardcastle et al, 1996; Hewitson et al, 2008; Scholefield et al, 2011).
This was done in connection with a randomised study showing that participatory learning of secondary prevention for general practitioners decreased cholesterol levels in their patients with coronary artery disease [ 7].
Even Public Health England says that it is being done "in the absence of direct randomised controlled trial evidence to guide it".
Most of these randomised controlled trials (nine out of 12) were done in Europe.
As NICE guidelines acknowledge, 24 most randomised controlled trials of methadone in the treatment of drug dependence were done in outpatient or inpatient settings or specialist treatment centres.
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