Number of anticoagulation-naive patients with NVAF who at the moment of inclusion in the START-Register would have been compliant with the lower limit of creatinine clearance declared by the drug companies and with the criteria established from the Italian Regulatory Agency (AIFA), in order to be potentially treated with DOA.

<p>CrCl = creatinine clearance</p><p>*after exclusion of 168 patients with CrCl< 30 ml/min</p><p>**after exclusion of 14 patients with CrCl< 15 ml/min</p><p>^¶after exclusion of 14 patients with CrCl< 15 ml/min</p><p>The criterion regarding the individual difficulties in performing the laboratory control of INR, as well as the percentage of time in range (all the START-Register patients were VKA-naive at inclusion) have not been taken into account for this evaluation.</p

Patients enrolled in the START-Register, indication for anticoagulation and type of treatment.

<p>VKA = vitamin k antagonist; DOAC = direct oral anticoagulant;</p><p>LMWH = light molecular weight heparin</p><p>Patients enrolled in the START-Register, indication for anticoagulation and type of treatment.</p

Clinical characteristics of AF patients in relation to stroke and bleeding risk stratification models.

<p>*all patient were naïve, no time in therapeutic range</p><p>Clinical characteristics of AF patients in relation to stroke and bleeding risk stratification models.</p

Clinical characteristics of NVAF patients included in the START-Register.

<p>VKA = vitamin k antagonist; TIA = Transient ischemic attack</p><p>Clinical characteristics of NVAF patients included in the START-Register.</p

Some characteristics of NVAF patients enrolled in START-Register, compared to those in the GARFIELD Registry and in randomized trials on DOAC.

<p>DOAC = direct oral anticoagulant</p><p>CrCl = creatinine clearance</p><p>Data are expressed as mean ± SD, or median (IQR), or %; NA = not available</p><p>* = patients with CrCl<25 ml/min were excluded</p><p>Some characteristics of NVAF patients enrolled in START-Register, compared to those in the GARFIELD Registry and in randomized trials on DOAC.</p

Additional file 1: of Ebola virus disease complicated with viral interstitial pneumonia: a case report

Laboratory methods

Additional file 3: of Ebola virus disease complicated with viral interstitial pneumonia: a case report

Person and institution involved in the organization and management of the patient

Long Term Effectiveness on Prescribing of Two Multifaceted Educational Interventions: Results of Two Large Scale Randomized Cluster Trials

<div><p>Introduction</p><p>Information on benefits and risks of drugs is a key element affecting doctors’ prescribing decisions. Outreach visits promoting independent information have proved moderately effective in changing prescribing behaviours.</p><p>Objectives</p><p>Testing the short and long-term effectiveness on general practitioners’ prescribing of small groups meetings led by pharmacists.</p><p>Methods</p><p>Two cluster open randomised controlled trials (RCTs) were carried out in a large scale NHS setting. Ad hoc prepared evidence based material were used considering a therapeutic area approach - TEA, with information materials on osteoporosis or prostatic hyperplasia - and a single drug oriented approach - SIDRO, with information materials on me-too drugs of 2 different classes: barnidipine or prulifloxacin. In each study, all 115 Primary Care Groups in a Northern Italy area (2.2 million inhabitants, 1737 general practitioners) were randomised to educational small groups meetings, in which available evidence was provided together with drug utilization data and clinical scenarios. Main outcomes were changes in the six-months prescription of targeted drugs. Longer term results (24 and 48 months) were also evaluated.</p><p>Results</p><p>In the TEA trial, one of the four primary outcomes showed a reduction (prescription of alfuzosin compared to tamsulosin and terazosin in benign prostatic hyperplasia: prescribing ratio −8.5%, p = 0.03). Another primary outcome (prescription of risedronate) showed a reduction at 24 and 48 months (−7.6%, p = 0.02; and −9,8%, p = 0.03), but not at six months (−5.1%, p = 0.36). In the SIDRO trial both primary outcomes showed a statistically significant reduction (prescription of barnidipine −9.8%, p = 0.02; prescription of prulifloxacin −11.1%, p = 0.04), which persisted or increased over time.</p><p>Interpretation</p><p>These two cluster RCTs showed the large scale feasibility of a complex educational program in a NHS setting, and its potentially relevant long-term impact on prescribing habits, in particular when focusing on a single drug. National Health systems should invest in independent drug information programs.</p><p>Trial Registration</p><p>Controlled-Trials.com <a href="http://www.controlled-trials.com/ISRCTN05866587" target="_blank">ISRCTN05866587</a></p></div

% differences in primary outcomes at 6 months (main analysis), 12, 24 and 48 months.

<p>% differences in primary outcomes at 6 months (main analysis), 12, 24 and 48 months.</p

TEA trial: GPs’ mean baseline prescription (in the 3 months preceding the outreach visit) of drugs considered in the primary outcomes, expressed as DDD per 1000 patients.

<p>TEA trial: GPs’ mean baseline prescription (in the 3 months preceding the outreach visit) of drugs considered in the primary outcomes, expressed as DDD per 1000 patients.</p