Legal aspects of open disclosure II: Attitudes of health professionals - Findings from a national survey

Objective: To assess the attitudes of health care professionals engaged in open disclosure (OD) to the legal risks and protections that surround this activity. Design and participants: National cross-sectional survey of 51 experienced OD practitioners conducted in mid 2009. Main outcome measures: Perceived barriers to OD; awareness of and attitudes towards medicolegal protections; recommendations for reform. Results: The vast majority of participants rated fears about the medicolegal risks (45/51) and inadequate education and training in OD skills (43/51) as major or moderate barriers to OD. A majority (30/51) of participants viewed qualified privilege laws as having limited or no effect on health professionals' willingness to conduct OD, whereas opinion was divided about the effect of apology laws (state laws protecting expressions of regret from subsequent use in legal proceedings). In four states and territories (Western Australia, South Australia, Tasmania and the Northern Territory), a majority of participants were unaware that their own jurisdiction had apology laws that applied to OD. The most frequent recommendations for legal reform to improve OD were strengthening existing protections (23), improving education and awareness of applicable laws (11), fundamental reform of the medical negligence system (8), and better alignment of the activities of certain legal actors (eg, coroners) with OD practice (6). Conclusions: Concerns about both the medicolegal implications of OD and the skills needed to conduct it effectively are prevalent among health professionals at the leading edge of the OD movement in Australia. The ability of current laws to protect against use of this information in legal proceedings is perceived as inadequate

External validation and recalibration of an incidental meningioma prognostic model – IMPACT: protocol for an international multicentre retrospective cohort study

Introduction: Due to the increased use of CT and MRI, the prevalence of incidental findings on brain scans is increasing. Meningioma, the most common primary brain tumour, is a frequently encountered incidental finding, with an estimated prevalence of 3/1000. The management of incidental meningioma varies widely with active clinical-radiological monitoring being the most accepted method by clinicians. Duration of monitoring and time intervals for assessment, however, are not well defined. To this end, we have recently developed a statistical model of progression risk based on single-centre retrospective data. The model Incidental Meningioma: Prognostic Analysis Using Patient Comorbidity and MRI Tests (IMPACT) employs baseline clinical and imaging features to categorise the patient with an incidental meningioma into one of three risk groups: low, medium and high risk with a proposed active monitoring strategy based on the risk and temporal trajectory of progression, accounting for actuarial life expectancy. The primary aim of this study is to assess the external validity of this model. Methods and analysis: IMPACT is a retrospective multicentre study which will aim to include 1500 patients with an incidental intracranial meningioma, powered to detect a 10% progression risk. Adult patients ≥16 years diagnosed with an incidental meningioma between 1 January 2009 and 31 December 2010 will be included. Clinical and radiological data will be collected longitudinally until the patient reaches one of the study endpoints: intervention (surgery, stereotactic radiosurgery or fractionated radiotherapy), mortality or last date of follow-up. Data will be uploaded to an online Research Electronic Data Capture database with no unique identifiers. External validity of IMPACT will be tested using established statistical methods. Ethics and dissemination: Local institutional approval at each participating centre will be required. Results of the study will be reported through peer-reviewed articles and conferences and disseminated to participating centres, patients and the public using social media

Assessment of fatigue in chronic disease: a bibliographic study of fatigue measurement scales

A large number of fatigue scales exist and there is no consensus on which fatigue measuring scales that are most appropriate for use in assessment of fatigue in different diseases. We aimed to describe the use of fatigue scales in studies of disease-related fatigue during the last three decades. We searched databases from 1975 to 2004 for original studies reporting on disease-related fatigue and extracted information on method used to assess fatigue, diseases under study and year of publication. A total of 2285 papers reported measures of fatigue in chronic non-acute diseases of which 80% were published during the last decade. We identified 252 different ways to measure fatigue, of which 150 were use only once. Multi-symptom scales (n = 156) were used in 670 studies, while 71 scales specifically designed to measure fatigue were applied in 416 studies. The majority of these studies used scales with a multidimensional approach to fatigue, and most studies used scales that were disease-specific or only applied to few different diseases. Research in disease-related fatigue has increased exponentially during the last three decades, even if we adjust for the general increase in publishing activity. The number of scales has also increased and the majority of scales were developed for specific diseases. There is need for measure instruments with different sizes and dimensionality, and due to ceiling and floor effects, the same scale may not be useful for patients with different severity of fatigue. However, since fatigue is an unspecific symptom there should not be need for adopting disease specific fatigue scales for each individual disease. There may be differences in characteristics of fatigue between diseases and generic measurement instruments may facilitate documentation of such differences, which may be of clinical importance

Small but crucial : the novel small heat shock protein Hsp21 mediates stress adaptation and virulence in Candida albicans

Peer reviewedPublisher PD

Addressing quality and usability of surface water bodies in semi-arid regions with mining influences

Water resources management has considerable importance, specifically in the context of climate change. This subject has introduced new challenges in semi-arid regions with water quality problems, such as the Iberian Pyrite Belt, which is one of the largest metallogenetic provinces in the world and one of the driest regions in Europe. Positioned in the Mediterranean context, the region has a high density of polymetallic sulphide mines that promote the degradation of water systems. The present study aims to assess the water quality in the Pyrite Belt, considering a total of 34 surface water bodies, including constructed reservoirs, permanent and ephemeral streams, and mining facilities with accumulated water (e.g., pit lakes and mining dams). The water samples were analysed for physico-chemical properties, including field parameters (pH, electrical conductivity), alkalinity/acidity, hardness, anions, and potential toxic elements. The results were used for hydrochemical classifications and the assessment of suitability for public uses. Statistical methods, such as hierarchical cluster analysis and nearest centroid classifier, were used for grouping and evaluating the similarity between water bodies. Two groups were generated from the analysis: i) constructed lakes with alkaline and sodium signatures; and ii) waters suffering from the influence of mining wastes, e.g., showing high acidity, sulphate and metal contents. Therefore, the loss of water quality in the vicinity of mines reflects the impact of acid mine drainage. The methodological approach used may be applied to the integrated management of water resources in regions with mining influences and where it is necessary to combat drought and water scarcity scenarios.Patricia Gomes acknowledge FCT (Science and Technology Foundation, Portugal) by the research fellowship under the POCH (Programa Operacional Capital Humano) supported by the European Social Fund and National Funds of MCTES (Ministerio da Ciencia, Tecnologia e Ensino Superior) with reference SFRH/BD/108887/2015. This work was co-funded by the European Union through the European Regional Development Fund, based on COMPETE 2020 (Programa Operacional da Competitividade e Internacionalizacao) - project ICT (UID/GEO/04683/2013) with reference POCI-01-0145-FEDER-007690 and project Nano-MINENV number 029259

Fluorescence-Tracking of Activation Gating in Human ERG Channels Reveals Rapid S4 Movement and Slow Pore Opening

Background: hERG channels are physiologically important ion channels which mediate cardiac repolarization as a result of their unusual gating properties. These are very slow activation compared with other mammalian voltage-gated potassium channels, and extremely rapid inactivation. The mechanism of slow activation is not well understood and is investigated here using fluorescence as a direct measure of S4 movement and pore opening. Methods and Findings: Tetramethylrhodamine-5-maleimide (TMRM) fluorescence at E519 has been used to track S4 voltage sensor movement, and channel opening and closing in hERG channels. Endogenous cysteines (C445 and C449) in the S1–S2 linker bound TMRM, which caused a 10 mV hyperpolarization of the VK of activation to 227.562.0 mV, and showed voltage-dependent fluorescence signals. Substitution of S1–S2 linker cysteines with valines allowed unobstructed recording of S3–S4 linker E519C and L520C emission signals. Depolarization of E519C channels caused rapid initial fluorescence quenching, fit with a double Boltzmann relationship, F-VON, with VK,1 = 237.861.7 mV, and VK,2 = 43.567.9 mV. The first phase, VK,1, was,20 mV negative to the conductance-voltage relationship measured from ionic tail currents (G-VK = 218.361.2 mV), and relatively unchanged in a non-inactivating E519C:S620T mutant (V K = 234.461.5 mV), suggesting the fast initial fluorescence quenching tracked S4 voltage sensor movement. The second phase of rapid quenching was absent in the S620T mutant. The E519C fluorescence upon repolarizatio

Transepithelial Transport and Enzymatic Detoxification of Gluten in Gluten-Sensitive Rhesus Macaques

In a previous report, we characterized a condition of gluten sensitivity in juvenile rhesus macaques that is similar in many respects to the human condition of gluten sensitivity, celiac disease. This animal model of gluten sensitivity may therefore be useful toward studying both the pathogenesis and the treatment of celiac disease. Here, we perform two pilot experiments to demonstrate the potential utility of this model for studying intestinal permeability toward an immunotoxic gluten peptide and pharmacological detoxification of gluten in vivo by an oral enzyme drug candidate.Intestinal permeability was investigated in age-matched gluten-sensitive and control macaques by using mass spectrometry to detect and quantify an orally dosed, isotope labeled 33-mer gluten peptide delivered across the intestinal epithelium to the plasma. The protective effect of a therapeutically promising oral protease, EP-B2, was evaluated in a gluten-sensitive macaque by administering a daily gluten challenge with or without EP-B2 supplementation. ELISA-based antibody assays and blinded clinical evaluations of this macaque and of an age-matched control were conducted to assess responses to gluten.Labeled 33-mer peptide was detected in the plasma of a gluten-sensitive macaque, both in remission and during active disease, but not in the plasma of healthy controls. Administration of EP-B2, but not vehicle, prevented clinical relapse in response to a dietary gluten challenge. Unexpectedly, a marked increase in anti-gliadin (IgG and IgA) and anti-transglutaminase (IgG) antibodies was observed during the EP-B2 treatment phase.Gluten-sensitive rhesus macaques may be an attractive resource for investigating important aspects of celiac disease, including enhanced intestinal permeability and pharmacology of oral enzyme drug candidates. Orally dosed EP-B2 exerts a protective effect against ingested gluten. Limited data suggest that enhanced permeability of short gluten peptides generated by gastrically active glutenases may trigger an elevated antibody response, but that these antibodies are not necessarily causative of clinical illness