Publishing interim results of randomised clinical trials in peer-reviewed journals

Background: Interim analyses of randomised controlled trials are sometimes published before the final results are available. In several cases, the treatment effects were noticeably different after patient recruitment and follow-up completed. We therefore conducted a literature review of peer-reviewed journals to compare the reported treatment effects between interim and final publications and to examine the magnitude of the difference. Methods: We performed an electronic search of MEDLINE from 1990 to 2014 (keywords: ‘clinical trial’ OR ‘clinical study’ AND ‘random*’ AND ‘interim’ OR ‘preliminary’), and we manually identified the corresponding final publication. Where the electronic search produced a final report in which the abstract cited interim results, we found the interim publication. We also manually searched every randomised controlled trial in eight journals, covering a range of impact factors and general medical and specialist publications (1996–2014). All paired articles were checked to ensure that the same comparison between interventions was available in both. Results: In all, 63 studies are included in our review, and the same quantitative comparison was available in 58 of these. The final treatment effects were smaller than the interim ones in 39 (67%) trials and the same size or larger in 19 (33%). There was a marked reduction, defined as a ≥20% decrease in the size of the treatment effect from interim to final analysis, in 11 (19%) trials compared to a marked increase in 3 (5%), p = 0.057. The magnitude of percentage change was larger in trials where commercial support was reported, and increased as the proportion of final events at the interim report decreased in trials where commercial support was reported (interaction p = 0.023). There was no evidence of a difference between trials that stopped recruitment at the interim analysis where this was reported as being pre-specified versus those that were not pre-specified (interaction p = 0.87). Conclusion: Published interim trial results were more likely to be associated with larger treatment effects than those based on the final report. Publishing interim results should be discouraged, in order to have reliable estimates of treatment effects for clinical decision-making, regulatory authority reviews and health economic analyses. Our work should be expanded to include conference publications and manual searches of additional journal publications

On the characterisation of a Bragg spectrometer with X-rays from an ECR source

Narrow X-ray lines from helium-like argon emitted from a dedicated ECR source have been used to determine the response function of a Bragg crystal spectrometer equipped with large area spherically bent silicon (111) or quartz (10$\bar{1}$) crystals. The measured spectra are compared with simulated ones created by a ray-tracing code based on the expected theoretical crystal's rocking curve and the geometry of the experimental set-up.Comment: Version acceptee (NIM

Effects of Urea, Borax and Ammonium Chloride on Flame Retarding Properties of Cellulosic Ceiling Board

This work involves the impregnation of urea, borax and ammonium chloride solutions prepared in varying concentrations into strips of cellulosic ceiling board. A formulated solution was also made of equal concentration of urea and borax solution and impregnated into strips of cellulosic ceiling board. The treated and blank samples were dried and investigated for ignitability, flame propagation and afterglow time. Urea was found to give a good effect for ignitability after 28.00sec than borax, ammonium chloride and blank after 26.00sec, 25.00sec and 16.80sec respectively. Urea gave a better effect for flame propagation of 0.13x10-2cm/sec than borax, ammonium chloride and blank which has 0.24x10-2cm/sec, 0.28x10-2cm/sec and 1.95x10-2cm/sec respectively and also urea has afterglow time of 0.22x102sec than borax (0.60 x102sec), ammonium chloride (0.70x102sec) and blank (2.25 x102sec). The formulated solution drastically improved the ignitability from 16.80sec (blank) to 34.00sec and zero flame propagation and afterglow time was recorded. With this result, urea was found to give a better retarding effect, hence could be incorporated in cellulosic ceiling board during production. Keywords: Urea, borax, ceiling board, ignitability, flame propagation, afterglow time

Highly Charged Ion Production Using an Electrode in Biased and Floating Modes

One of the most popular ways to obtain higher beam intensities in ECR ion sources is to install an electrode (usually disc) into the plasma chamber. Examined this method in detail we found that majority of the groups observed the beam intensity improvement by supplying a suitable biased voltage to the electrode and an electron current was injected into the plasma. A few groups observed the enhancement, however, when the electrode operated at floating potential - without being an electron donor. Only a few (and sometimes contradictionary) information was found on the optimised properties of the electrodes, i.e. position, dimension, shape, material. In spite of the great success of the "biased-disc" method, the mechanism is still not completely clear. In this contribution, as one step of understanding, we examine what condition we observed the above mentioned two modes. The experiments were performed at the 18 GHz RIKEN and at the 14.5 GHz ATOMKI ECR ion sources. It was found that effect of the electrode is strongly depends on the local plasma parameters and on the position of the electrode. At certain mirror ratios and electrode positions we needed to negatively bias the electrode and inject electrons into the plasma. The electrode operated as an electron source (Electron Donor ED mode). At higher mirror ratios and other axial positions the electrode works by directly changing the plasma potential dip (Potential Tuner PT mode). These two modes were checked and successfully found both in continuos and in pulsed mode operation. In both (ED and PT) modes we generated higher highly charged ion currents in the RIKEN-ECRIS than without the electrode

Recent Developments for ECR Ion Sources at HIMAC

Two ECR ion sources are installed for the Heavy Ion Medical Accelerator in Chiba (HIMAC) at the National Institute of Radiological Sciences (NIRS). One of them, the NIRS-ECR, is a 10GHz ECR ion source, and is mainly operated to produce C4+ ions for the daily clinical treatment. The other source, the NIRS-HEC, is an 18GHz ECR ion source, and is expected to produce heavier ion species. In order to realize the uniform ion-density distribution at the extraction aperture for the higher beam intensity, the radial magnetic field given by the permanent sextupole magnet has been optimized. In the case of the optimized magnetic configuration of the NIRS-HEC, the extracted intensities of Ar8+ and Ar9+ ions increased from 250 and 150 up to 800 and 400 electric micro A, respectively. An optimized sextupole magnet for the NIRS-ECR is under construction. Other developments for increasing the beam intensity and extension of producible ion species are now in progress. An aluminum chamber, which is exchanged for the old copper chamber of the NIRS-HEC, has been tested. An additional microwave-injection system with a wide frequency range of 10 to 18GHz, which allows to investigate the effects of two-frequency heating, has been installed

The Use of eHealth for Pharmacotherapy Management With Patients With Respiratory Disease, Cardiovascular Disease, or Diabetes:Scoping Review

Background: eHealth is increasingly considered an important tool for supporting pharmacotherapy management.Objective: We aimed to assess the (1) use of eHealth in pharmacotherapy management with patients with asthma or chronic obstructive pulmonary disease (COPD), diabetes, or cardiovascular disease (CVD); (2) effectiveness of these interventions on pharmacotherapy management and clinical outcomes; and (3) key factors contributing to the success of eHealth interventions for pharmacotherapy management.Methods: We conducted a scoping review following the PRISMA-ScR (Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for scoping review) statement. Databases searched included Embase, MEDLINE (PubMed), and Cochrane Library. Screening was conducted by 2 independent researchers. Eligible articles were randomized controlled trials and cohort studies assessing the effect of an eHealth intervention for pharmacotherapy management compared with usual care on pharmacotherapy management or clinical outcomes in patients with asthma or COPD, CVD, or diabetes. The interventions were categorized by the type of device, pharmacotherapy management, mode of delivery, features, and domains described in the conceptual model for eHealth by Shaw at al (Health in our Hands, Interacting for Health, Data Enabling Health). The effectiveness on pharmacotherapy management outcomes and patient- and clinician-reported clinical outcomes was analyzed per type of intervention categorized by number of domains and features to identify trends.Results: Of 63 studies, 16 (25%), 31 (49%), 13 (21%), and 3 (5%) included patients with asthma or COPD, CVD, diabetes, or CVD and diabetes, respectively. Most (38/63, 60%) interventions targeted improving medication adherence, often combined for treatment plan optimization. Of the 16 asthma or COPD interventions, 6 aimed to improve inhaled medication use. The majority (48/63, 76%) of the studies provided an option for patient feedback. Most (20/63, 32%) eHealth interventions combined all 3 domains by Shaw et al, while 25% (16/63) combined Interacting for Health with Data Enabling Health. Two-thirds (42/63, 67%) of the studies showed a positive overall effect. Respectively, 48% (23/48), 57% (28/49), and 39% (12/31) reported a positive effect on pharmacotherapy management and clinician- and patient-reported clinical outcomes. Pharmacotherapy management and patient-reported clinical outcomes, but not clinician-reported clinical outcomes, were more often positive in interventions with ≥3 features. There was a trend toward more studies reporting a positive effect on all 3 outcomes with more domains by Shaw et al. Of the studies with interventions providing patient feedback, more showed a positive clinical outcome, compared with studies with interventions without feedback. This effect was not seen for pharmacotherapy management outcomes.Conclusions: There is a wide variety of eHealth interventions combining various domains and features to target pharmacotherapy management in asthma or COPD, CVD, and diabetes. Results suggest feedback is key for a positive effect on clinician-reported clinical outcomes. eHealth interventions become more impactful when combining domains.</p