Translation of mRNA into protein is a unidirectional information flow process. Analysing the input (mRNA) and output (protein) of translation, we find that local protein structure information is encoded in the mRNA nucleotide sequence. The Coding Sequence and Structure (CSandS) database developed in this work provides a detailed mapping between over 4000 solved protein structures and their mRNA. CSandS facilitates a comprehensive analysis of codon usage over many organisms. In assigning translation speed, we find that relative codon usage is less informative than tRNA concentration. For all speed measures, no evidence was found that domain boundaries are enriched with slow codons. In fact, genes seemingly avoid slow codons around structurally defined domain boundaries. Translation speed, however, does decrease at the transition into secondary structure. Codons are identified that have structural preferences significantly different from the amino acid they encode. However, each organism has its own set of ‘significant codons’. Our results support the premise that codons encode more information than merely amino acids and give insight into the role of translation in protein folding.

SummaryThe importance of serum immunoglobulin (Ig)G concentration in IgG replacement therapy for primary immunodeficiency diseases is established in certain settings. Generally, IgG is infused via the intravenous (IVIG) or subcutaneous (SCIG) route. For IVIG infusion, published data demonstrate that higher IgG doses and trough levels provide patients with improved protection from infection. The same conclusions are not yet accepted for SCIG; data from two recent Phase III studies and a recent post-hoc analysis, however, suggest the same correlation between higher SCIG dose and serum IgG concentration and decreased incidence of infection seen with IVIG. Other measures of clinical efficacy have not been considered similarly. Thus, combined analyses of these and other published SCIG studies were performed; a full comparison of the 13 studies was, however, limited by non-standardized definitions and reporting. Despite these limitations, our analyses indicate that certain clinical outcomes improve at higher SCIG doses and associated higher serum IgG concentrations, and suggest that there might be opportunity to improve patient outcomes via SCIG dose adjustment.

Background and AimsSeveral meta-analyses comparing ciclosporin with tacrolimus have been conducted since the 1994 publication of the tacrolimus registration trials, but most captured data from randomized controlled trials (RCTs) predating recent improvements in waiting list prioritization, induction protocols and concomitant medications. The present study comprised a systematic review and meta-analysis of ciclosporin and tacrolimus in liver transplant recipients using studies published since January 2000.MethodsSearches of PubMed, the Cochrane Library and EMBASE identified RCTs of tacrolimus and ciclosporin as the immunosuppressant in adult primary liver transplant recipients, published between January 2000 and August 6, 2014. A random effects meta-analysis was conducted to evaluate the relative risk of death, graft loss, acute rejection (AR), new-onset diabetes after transplantation (NODAT) and hypertension with tacrolimus relative to ciclosporin at 12 months.ResultsThe literature search identified 11 RCTs comparing ciclosporin with tacrolimus. Relative to ciclosporin, tacrolimus was associated with significantly improved outcomes in terms of patient mortality (risk ratio [RR] with ciclosporin of 1.26; 95% confidence interval [95%CI] 1.01–1.58). Tacrolimus was superior to ciclosporin in terms of hypertension (RR with ciclosporin 1.26; 95%CI 1.07–1.47), but inferior in terms of NODAT (RR with ciclosporin 0.60; 95%CI 0.47–0.77). There were no significant differences between ciclosporin and tacrolimus in terms of graft loss or AR.ConclusionsMeta-analysis of RCTs published since 2000 showed tacrolimus to be superior to ciclosporin in terms of patient mortality and hypertension, while ciclosporin was superior in terms of NODAT. No significant differences were identified in terms of graft loss or AR. These findings provide further evidence supporting the use of tacrolimus as the cornerstone of immunosuppressive therapy in liver transplant recipients.

ObjectiveTo evaluate the effect of capnography monitoring on sedation-related adverse events during procedural sedation and analgesia (PSA) administered for ambulatory surgery relative to visual assessment and pulse oximetry alone.Design and settingSystematic literature review and random effects meta-analysis of randomised controlled trials (RCTs) reporting sedation-related adverse event incidence when adding capnography to visual assessment and pulse oximetry in patients undergoing PSA during ambulatory surgery in the hospital setting. Searches for eligible studies published between 1 January 1995 and 31 December 2016 (inclusive) were conducted in PubMed, the Cochrane Library and EMBASE without any language constraints. Searches were conducted in January 2017, screening and data extraction were conducted by two independent reviewers, and study quality was assessed using a modified Jadad scale.InterventionsCapnography monitoring relative to visual assessment and pulse oximetry alone.Primary and secondary outcome measuresPredefined endpoints of interest were desaturation/hypoxaemia (the primary endpoint), apnoea, aspiration, bradycardia, hypotension, premature procedure termination, respiratory failure, use of assisted/bag-mask ventilation and death during PSA.ResultsThe literature search identified 1006 unique articles, of which 13 were ultimately included in the meta-analysis. Addition of capnography to visual assessment and pulse oximetry was associated with a significant reduction in mild (risk ratio (RR) 0.77, 95% CI 0.67 to 0.89) and severe (RR 0.59, 95% CI 0.43 to 0.81) desaturation, as well as in the use of assisted ventilation (OR 0.47, 95% CI 0.23 to 0.95). No significant differences in other endpoints were identified.ConclusionsMeta-analysis of 13 RCTs published between 2006 and 2016 showed a reduction in respiratory compromise (from respiratory insufficiency to failure) during PSA with the inclusion of capnography monitoring. In particular, use of capnography was associated with less mild and severe oxygen desaturation, which may have helped to avoid the need for assisted ventilation.

Analysis using the CORE Diabetes Model showed that improvements in glycaemic control associated with sensor-augmented pump use led to a reduced incidence of diabetes-related complications and a longer life expectancy. Use of the sensor-augmented pump was associated with an incremental cost-effectiveness ratio of 367,571 SEK per quality-adjusted life year gained, which is likely to represent good value for money in the treatment of Type 1 diabetes in Sweden.

SWA of bolus insulin should be considered a beneficial and cost-saving alternative to FBB therapy for the intensification of treatment in type 2 diabetes.

In this review of the Korean cloning scandal involving Woo-Suk Hwang, the nature of the disaster is documented and reasons why it occurred are suggested. The general problems it raises for scientific research are highlighted and six possible ways of improving practice are offered in the light of this case: (1) better education of science students; (2) independent monitoring and validation; (3) guidelines for tissue donation for research; (4) fostering of debate about ethically contentious research in science journals; (5) development of an international code of ethical research practice; (6) fostering of public involvement in ethical review and debate through the web.

Background: Health-technology assessment (HTA) is a recognized mechanism to determine the relative benefits of innovative medical technologies. One aspect is their health-economic impact. While the process and methodology for pharmaceuticals is well-established, guidance for medical devices is sparse.Aim: To provide an overview of the health-economic aspect in current European HTA guidelines concerning medical devices and identifying issues raised and potential improvements proposed in recent literature.Methodology: Available guidelines by European agencies were each reviewed and summarized. To complement this, a full systematic review of current literature concerning potential improvements to existing HTA practices for medical devices, from PubMed and EMBASE, was conducted; the focus was on health economics. Authors could only review documents in English, French, or German. The systematic review yielded 518 unique articles concerning HTA for medical devices, 32 of which were considered for full-text review after screening of all abstracts.Results: There is very limited consensus in—and mostly a complete lack of—guidance specific to medical devices in official HTA guidelines, for both clinical and economic analyses. Twenty two of 41 European countries had published official HTA guidance in English, French, or German. Among these only 4 (England, France, the Netherlands, and Sweden) dedicated a chapter or separate document to medical devices. In the literature, there is sufficient evidence to suggest medical devices need to be addressed separately from pharmaceuticals. However, mostly challenges are discussed rather than implementable solutions offered. We present the following set of frequently discussed issues and summarize any solutions that pertain to them: a weak evidence base, learning-curve effects, organizational impact, incremental innovation, diversity of devices, dynamic pricing, and transferability. We further combine reviewed information to suggest a set of possible best practices for health-economic assessment of medical devices.Conclusion: For greater efficiency in medical-device innovation, European agencies should look to (re-)address the specific requirements of medical devices in their HTA guidelines. When both the health-economic and data requirements for the HTA of medical devices are defined, the development of practical solutions will likely follow.