Adaptation of clinical guidelines: literature review and proposition for a framework and procedure

Purpose. The development and updating of high-quality clinical practice guidelines require substantial resources. Many guideline programmes throughout the world are using similar strategies to achieve similar goals, resulting in many guidelines on the same topic. One method of using resources more efficiently and avoiding unnecessary duplication of effort would be to adapt existing guidelines. The aim was to review the literature on adaptation of guidelines and to propose a systematic approach for adaptation of guidelines. Data sources. We selected and reviewed reports describing the methods and results of adaptation of guidelines from those found by searching Medline, Internet, and reference lists of relevant papers. On the basis of this review and our experience in guideline development, we proposed a conceptual framework and procedure for adaptation of guidelines. Results. Adaptation of guidelines is performed either as an alternative to de novo guideline development or to improve guideline implementation through local tailoring of an international or national guideline. However, no validated process for the adaptation of guidelines produced in one cultural and organizational setting for use in another (i.e. trans-contextual adaptation) was found in the literature. The proposed procedure is a stepwise approach to trans-contextual adaptation, including searching for existing guidelines, quality appraisal, detailed analysis of the coherence between the evidence and the recommendations, and adaptation of the recommendations to the target context of use, taking into account the organization of the health care system and cultural context. Conclusions. Trans-contextual adaptation of guidelines is increasingly being considered as an alternative to de novo guideline development. The proposed approach should be validated and evaluated to determine if it can reduce duplication of effort and inefficient use of resources, although guaranteeing a high-quality product, compared with de novo developmen

Ki-67: level of evidence and methodological considerations for its role in the clinical management of breast cancer: analytical and critical review

Clinicians can use biomarkers to guide therapeutic decisions in estrogen receptor positive (ER+) breast cancer. One such biomarker is cellular proliferation as evaluated by Ki-67. This biomarker has been extensively studied and is easily assayed by histopathologists but it is not currently accepted as a standard. This review focuses on its prognostic and predictive value, and on methodological considerations for its measurement and the cut-points used for treatment decision. Data describing study design, patients’ characteristics, methods used and results were extracted from papers published between January 1990 and July 2010. In addition, the studies were assessed using the REMARK tool. Ki-67 is an independent prognostic factor for disease-free survival (HR 1.05–1.72) in multivariate analyses studies using samples from randomized clinical trials with secondary central analysis of the biomarker. The level of evidence (LOE) was judged to be I-B with the recently revised definition of Simon. However, standardization of the techniques and scoring methods are needed for the integration of this biomarker in everyday practice. Ki-67 was not found to be predictive for long-term follow-up after chemotherapy. Nevertheless, high KI-67 was found to be associated with immediate pathological complete response in the neoadjuvant setting, with an LOE of II-B. The REMARK score improved over time (with a range of 6–13/20 vs. 10–18/20, before and after 2005, respectively). KI-67 could be considered as a prognostic biomarker for therapeutic decision. It is assessed with a simple assay that could be standardized. However, international guidelines are needed for routine clinical use

A Roadmap for HEP Software and Computing R&D for the 2020s

Particle physics has an ambitious and broad experimental programme for the coming decades. This programme requires large investments in detector hardware, either to build new facilities and experiments, or to upgrade existing ones. Similarly, it requires commensurate investment in the R&D of software to acquire, manage, process, and analyse the shear amounts of data to be recorded. In planning for the HL-LHC in particular, it is critical that all of the collaborating stakeholders agree on the software goals and priorities, and that the efforts complement each other. In this spirit, this white paper describes the R&D activities required to prepare for this software upgrade.Peer reviewe

Search for dark matter produced in association with bottom or top quarks in √s = 13 TeV pp collisions with the ATLAS detector

A search for weakly interacting massive particle dark matter produced in association with bottom or top quarks is presented. Final states containing third-generation quarks and miss- ing transverse momentum are considered. The analysis uses 36.1 fb−1 of proton–proton collision data recorded by the ATLAS experiment at √s = 13 TeV in 2015 and 2016. No significant excess of events above the estimated backgrounds is observed. The results are in- terpreted in the framework of simplified models of spin-0 dark-matter mediators. For colour- neutral spin-0 mediators produced in association with top quarks and decaying into a pair of dark-matter particles, mediator masses below 50 GeV are excluded assuming a dark-matter candidate mass of 1 GeV and unitary couplings. For scalar and pseudoscalar mediators produced in association with bottom quarks, the search sets limits on the production cross- section of 300 times the predicted rate for mediators with masses between 10 and 50 GeV and assuming a dark-matter mass of 1 GeV and unitary coupling. Constraints on colour- charged scalar simplified models are also presented. Assuming a dark-matter particle mass of 35 GeV, mediator particles with mass below 1.1 TeV are excluded for couplings yielding a dark-matter relic density consistent with measurements

The hill of health : aspects of community at Waipiata Sanatorium 1923-1961

102 leaves, [21] p. of plates :ill., facsim., map, ports. ; 30 cm. Bibliography: leaves 101-102.Through an investigation of Waipiata Sanatorium from 1923 to 1961, I hope to show that the experiences of both staff and patients were complex and varied, and that the sanatorium experience cannot be dismissed as uniformly unpleasant and ineffective. I also hope to show that analogies with Goffman's 'total institution' are misleading, and that Waipiata Sanatorium is better represented as a unique kind of community, more often resembling a country town than a medical institution. I will argue it was in this creation of community that the real benefit of sanatorium treatment lay, because it provided an atmosphere that was accepting of tuberculosis patients at a time when they suffered from stigma and discrimination. The sanatorium system may have had unpleasant aspects and did not 'cure' all those who participated in the treatment, but at a time when medical science could offer no relief, sanatorium communities provided a way of life that made living with the disease more tolerable. The first two chapters of this work consider the various experiences of the staff and patients who made up the core of the Sanatorium community. They explore the idea that Goffman's central tenet of a total institution, that staff and patients are unequal and opposing groups whose interaction is formally proscribed, does not apply to Waipiata Sanatorium, Instead staff and patients were fluid and interchanging members of a community that was dedicated to the wellbeing of the patients and to making life with tuberculosis as tolerable as possible, balancing the need for institutional structures with an understanding of the emotional and psychological needs of both staff and patients. The third chapter looks in more detail at aspects of community at Waipiata, both within the Sanatorium itself and its place within the wider Maniototo Plains. It also compares the experiences of Sanatorium patients with those of tuberculosis sufferers who remained outside these communities. [extract from Introduction

A trivalent, inactivated influenza vaccine (Vaxigrip®): summary of almost 50 years of experience and more than 1.8 billion doses distributed in over 120 countries

Introduction: Vaxigrip, a trivalent split-virion, inactivated vaccine available since 1968 has been in use longer than any other influenza vaccine. It is the most widely-used influenza vaccine, with more than 1.8 billion doses distributed in more than 120 countries. Areas covered: The significant body of evidence that confirms the efficacy, effectiveness, immunogenicity, and safety of Vaxigrip in healthy individuals of all ages and at-risk populations is summarized. The results from at least 15 randomized efficacy trials and 15 other studies have demonstrated that vaccination with Vaxigrip is efficacious against various clinical endpoints. It was estimated that more than 37 million laboratory-confirmed influenza episodes, 476,000 influenza-related hospitalizations, and 67,000 influenza-related deaths have been avoided by the more than 1.8 billion doses of Vaxigrip that have been distributed, emphasizing its important public health impact. Expert commentary: This strong evidence base in favor of Vaxigrip provides a robust foundation to support the implementation of the quadrivalent formulation. This quadrivalent formulation of Vaxigrip contains two A and two B influenza strains (VaxigripTetra), and has a similar immunogenicity and safety profile to the trivalent formulation while offering broader protection due to the addition of the second influenza B strain

Thermally induced osteocyte damage initiates a remodelling signaling cascade

Thermal elevations experienced by bone during orthopaedic procedures, such as cutting and drilling, exothermal reactions from bone cement, and thermal therapies such as tumor ablation, can result in thermal damage leading to death of native bone cells (osteocytes, osteoblasts, osteoclasts and mesenchymal stem cells). Osteocytes are believed to be the orchestrators of bone remodeling, which recruit nearby osteoclast and osteoblasts to control resorption and bone growth in response to mechanical stimuli and physical damage. However, whether heat-induced osteocyte damage can directly elicit bone remodelling has yet to be determined. This study establishes the link between osteocyte thermal damage and the remodeling cascade. We show that osteocytes directly exposed to thermal elevations (47 degrees C for 1 minute) become significantly apoptotic and alter the expression of osteogenic genes (Opg and Cox2). The Rankl/Opg ratio is consistently down-regulated, at days 1, 3 and 7 in MLO-Y4s heat-treated to 47 degrees C for 1 minute. Additionally, the pro-osteoblastogenic signaling marker Cox2 is significantly up-regulated in heat-treated MLO-Y4s by day 7. Furthermore, secreted factors from heat-treated MLO-Y4s administered to MSCs using a novel co-culture system are shown to activate pre-osteoblastic MSCs to increase production of the pro-osteoblastic differentiation marker, alkaline phosphatase (day 7, 14), and calcium deposition (day 21). Most interestingly, an initial pro-osteoclastogenic signaling response (increase Rankl and Rankl/Opg ratio at day 1) followed by later stage pro-osteoblastogenic signaling (down-regulation in Rankl and the Rankl/Opg ratio and an up-regulation in Opg and Cox2 by day 7) was observed in non-heat-treated MLO-Y4s in co-culture when these were exposed to the biochemicals produced by heat-treated MLO-Y4s. Taken together, these results elucidate the vital role of osteocytes in detecting and responding to thermal damage by means of thermally induced apoptosis followed by a cascade of remodelling responses.Funding from the National University of Ireland, Galway Fellowship Scheme, the National University of Ireland Travelling Scholarships in Engineering, the European Research Council (ERC) (under grant no. 258992;BONEMECHBIO)