bluuebunny/crossref_metadata_2025 huggingface dataset:
Becoming incapacitated? Long‐term sickness benefit recipients and the construction of stigma and identity narratives
Authors: Garthwaite Kayleigh
Published: December 2014

The transition to becoming ‘incapacitated’ and receiving sickness benefits represents a significant shift in an individual's narrative. Drawing on in‐depth interviews with 25 long‐term sickness benefits recipients in North‐East England, this article focuses upon how individuals perceived and managed becoming ‘incapacitated’, particularly in relation to stigma and identity. The findings show that participants negotiated changes to their identity in varying ways – constructing new dimensions of self, validating their illness and pursuing aspirations. Importantly, the transition onto sickness benefits does not inevitably result in a shift to a negative identity. The term incapacity can include many realities, challenging the notion of sickness benefit recipients as being passively dependent. Instead, an active, sometimes very functional sense of self can be accompanied by a positive identity for recipients, which is especially important, in a context of the rhetoric surrounding ongoing welfare reform and sickness benefits recipients in the UK.
Effect of storage parameters on freeze‐dried kefir grains
Authors: Kök Taş Tuğba
Published: December 2014

The purpose of this study was to use freeze‐drying to preserve microbial activity while extending the shelf life of kefir grains and to determine the best storage temperature. Freeze‐dried kefir grains were lyophilised and were later stored in a multilayer plastic film with a moisture barrier for 90 days at varying temperatures. Microbial activity continued until the 60th day of storage at 4 °C. PCR analysis was performed to determine Lactobacillus kefiranofaciens as an indicator kefir micro‐organism. It was concluded that the conservation of kefir grains by freeze‐drying protects the natural embedded microbiota; therefore, both the shelf life of kefir grains and the consumption of natural kefir increase.
Scandinavian clinical practice guideline on mechanical ventilation in adults with the acute respiratory distress syndrome
Authors: CLAESSON J. , FREUNDLICH M. , GUNNARSSON I. , LAAKE J. H. , VANDVIK P. O. , VARPULA T. , AASMUNDSTAD T. A.
Published: December 2014

Background

The objective of the Scandinavian Society of Anaesthesiology and Intensive Care Medicine (SSAI) task force on mechanical ventilation in adults with the acute respiratory distress syndrome (ARDS) is to formulate treatment recommendations based on available evidence from systematic reviews and randomised trials.

Methods

This guideline was developed according to standards for trustworthy guidelines through a systematic review of the literature and the use of the Grading of Recommendations Assessment, Development and Evaluation system for assessment of the quality of evidence and for moving from evidence to recommendations in a systematic and transparent process.

Results

We found evidence of moderately high quality to support a strong recommendation for pressure limitation and small tidal volumes in patients with ARDS. Also, we suggest positive end‐expiratory pressure (PEEP) > 5 cm H2O in moderate to severe ARDS and prone ventilation 16/24 h for the first week in moderate to severe ARDS (weak recommendation, low quality evidence). Volume controlled ventilation or pressure control may be equally beneficial or harmful and partial modes of ventilatory support may be used if clinically feasible (weak recommendation, very low quality evidence). We suggest utilising recruitment manoeuvres as a rescue measure in catastrophic hypoxaemia only (weak recommendation, low quality evidence). Based on high‐quality evidence, we strongly recommend not to use high‐frequency oscillatory ventilation. We could find no relevant data from randomised trials to guide decisions on choice of FiO2 or utilisation of non‐invasive ventilation.

Conclusion

We strongly recommend pressure‐ and volume limitation and suggest using higher PEEP and prone ventilation in patients with severe respiratory failure.
Acute kidney injury with hydroxyethyl starch 130/0.42 in severe sepsis
Authors: MÜLLER R. B. , HAASE N. , LANGE T. , WETTERSLEV J. , PERNER A.
Published: December 2014

Background

We aimed to detail the effects of hydroxyethyl starch (HES) vs. Ringer's on kidney function including the interaction with mortality in post‐hoc analyses as resuscitation with HES 130/0.42 increased mortality in the Scandinavian Starch for Severe Sepsis/Septic Shock (6S) trial.

Methods

In all 798 randomised patients, we assessed the incidence and effect on mortality of acute kidney injury (AKI) in the HES vs. Ringer's acetate groups using the Kidney Disease: Improving Global Outcome criteria. We also assessed the intervention effect on time to and duration of renal replacement therapy (RRT).

Results

At baseline, the intervention groups were similar. The maximal AKI stage was higher in the HES vs. Ringer's group within the first 5 days after randomisation (P = 0.03), the average difference being 0.2 points (P < 0.01). An increase in AKI stage was associated with mortality (hazard ratio (HR) 1.35; 95% CI 1.22 to 1.49; P < 0.01). Significantly, more patients in the HES group received RRT within the first 5 days (P = 0.01), and the time to initiation of RRT was also shorter compared with the Ringer's group (HR 1.40; 95% CI 1.01–1.93; P = 0.04). The intervention effect of HES on mortality was reduced when adjusting for AKI stage as a time‐dependent covariate (P = 0.15).

Conclusion

In patients with severe sepsis, HES appeared to increase the rate of severe AKI and use of RRT within the first 5 days. The increased mortality observed with HES may have been partly mediated through acute kidney impairment.
Regulation of dopaminergic markers expression in response to acute and chronic morphine and to morphine withdrawal
Authors: García‐Pérez Daniel , Núñez Cristina , Laorden M. Luisa , Milanés M. Victoria
Published: December 2014

Dopamine (DA) is thought to represent a teaching signal and has been implicated in the induction of addictive behaviours. Dysfunction of DA homeostasis leading to high or low DA levels is causally linked to addiction. Previously, it has been proposed that the transcription factors Nurr1 and Pitx3, which are critical for transcription of a set of genes involved in DA metabolism in the mesolimbic pathway, are associated with addiction pathology. Using quantitative real‐time polymerase chain reaction, immunofluorescence and Western blotting, we studied the effects of single morphine administration, morphine dependence and withdrawal on the DA markers DA transporters (DAT), vesicular monoamine transporters (VMAT2) and DA 2 receptor subtype (DRD2), DA 1 receptor subtype as well as tyrosine hydroxylase (TH) in the ventral tegmental area (VTA) and/or nucleus accumbens (NAc). In addition, Nurr1 and Pitx3 expression was also measured. Present data showed a high degree of colocalization of Nurr1 and Pitx3 with TH+ neurons in the VTA. We found that the increased Nurr1 and/or Pitx3 levels during morphine dependence and in morphine‐withdrawn rats were associated to an increase of DAT, VMAT2 and DRD2. Altogether, present data indicate that morphine dependence and withdrawal induced consistent alterations of most of the DA markers, which was correlated with transcription factors involved in the maintenance of DA neurons in drug‐reward pathways, suggesting that Nurr1 and Pitx3 regulation might be associated with controlling adaptation to chronic morphine and to morphine withdrawal‐induced alterations of DA neurons activity in the mesolimbic pathway.
Competition Issues in the Market for Audit and Assurance Services: Are the Concerns Justified?
Authors: Kend Michael , Houghton Keith A. , Jubb Christine
Published: December 2014

Concerns regarding the perceived lack of competition in the market for audit and assurance services has been widely publicised in the popular press on many occasions over many years. The Office of Fair Trading (OFT) in the United Kingdom (UK) decided that competition problems in the audit market warranted a referral to the UK Competition Commission (OFT 115‐11, October 2011). The UK Competition Commission released its report before the end of 2013 for implementation in the near future. This exploratory study investigates in an Australian context the views of stakeholder groups (including regulators, standard setters, audit suppliers, purchasers and financial statement users) regarding the level of competition in the market for audit and assurance services, and what potential remedies could be implemented to deal with such concerns. The findings in this study do not fully support the acceleration in the global debate on audit concentration and competition. Only users of financial reports consider that competition in the audit services market is insufficient. The other stakeholder groups do not share this view, although regulators and standard setters did have concerns over the lack of choice for large company audits. We need to consider the structural benefits and the continued viability of each of these large players (the Big Four), when considering these ‘lack of choice’ concerns. The level of competition is discussed essentially at firm level; however, underlying all of this are the consequences for the efficiency of the capital market.
The molecular spectrum and clinical impact of DIS3 mutations in multiple myeloma
Authors: Weißbach Susann , Langer Christian , Puppe Bernhard , Nedeva Theodora , Bach Elisa , Kull Miriam , Bargou Ralf , Einsele Hermann , Rosenwald Andreas , Knop Stefan , Leich Ellen
Published: December 2014

Multiple myeloma (MM) is a plasma cell neoplasm that presents with a major biological and clinical heterogeneity. We here investigated the spectrum of clonal and subclonal mutations of DIS3, an active part of the exosome complex, that may play a role in the development or progression of MM. The whole coding sequence of DIS3 was subjected to deep sequencing in 81 uniformly‐treated MM patients and 12 MM cell lines and the overall occurrence of DIS3 mutations as well as the presence of DIS3 mutations in minor and major subclones were correlated with cytogenetic alterations and clinical parameters. Our study identified DIS3 mutations in 9/81 patients that were associated with 13q14 deletions and IGH translocations on the cytogenetic level. Specifically, we detected seven novel somatic DIS3 single nucleotide variants (SNVs) and defined three hot spot mutations within the RNB domain. Lastly, we found a trend towards a shorter median overall survival for patients with DIS3 mutations, and patients carrying DIS3 mutations in minor subclones of their tumours showed a significantly worse response to therapy compared to patients with DIS3 mutations in the major subclone.
A compendium of cytogenetic abnormalities in myelofibrosis: molecular and phenotypic correlates in 826 patients
Authors: Wassie Emnet , Finke Christy , Gangat Naseema , Lasho Terra L. , Pardanani Animesh , Hanson Curtis A. , Ketterling Rhett P. , Tefferi Ayalew
Published: December 2014

Among 826 patients with primary myelofibrosis (PMF) and analysable metaphases on cytogenetic studies, 352 (42·6%) had abnormal karyotype, of which 240 (68·2%) were sole aberrations and 48 (13·6%) were complex; the most frequent abnormalities were 20q− (23·3%), 13q− (18·2%), +8 (11·1%), +9 (9·9%), chromosome 1q+ (9·7%) and −7/7q− (7·1%). Phenotypic correlates included: abnormal karyotype with anaemia (P = 0·02), leucopenia (P < 0·01) and thrombocytopenia (P < 0·01); complex karyotype with younger age (P = 0·04) and thrombocytopenia (P < 0·01); leucopenia with 20q−, +8 and −7/7q− and thrombocytopenia with 20q− and −7/7q−. Cytopenias were less likely to occur with 13q−. 476 patients were annotated for JAK2/CALR/MPL mutations; abnormal karyotype frequencies were 43% in JAK2, 42% CALR, 33% MPL mutated and 34% triple‐negative cases (P = 0·3). A proportion of patients were also screened for ASXL1, EZH2, IDH1, IDH2, SRSF2, U2AF1 and SF3B1 mutations; in all instances, mutational frequencies were higher in patients with normal karyotype, reaching significance for ASXL1 (P = 0·02) and U2AF1 (P = 0·01). 13q− was associated with mutant CALR (P = 0·03), +9 with mutant JAK2 (P = 0·02) and 20q− with mutant SRSF2 (P = 0·02). The current PMF study provides detailed cytogenetic information and correlations with mutations and clinical phenotype.
Follow‐up of post‐transplant minimal residual disease and chimerism in childhood lymphoblastic leukaemia: 90 d to react
Authors: Pochon Cécile , Oger Emmanuel , Michel Gérard , Dalle Jean‐Hugues , Salmon Alexandra , Nelken Brigitte , Bertrand Yves , Cavé Hélène , Cayuela Jean‐Michel , Grardel Nathalie , Macintyre Elizabeth , Margueritte Geneviève , Méchinaud Françoise , Rohrlich Pierre , Paillard Catherine , Demeocq François , Schneider Pascale , Plantaz Dominique , Poirée Marilyne , Eliaou Jean‐François , Semana Gilbert , Drunat Séverine , Jonveaux Philippe , Bordigoni Pierre , Gandemer Virginie
Published: December 2014

Relapse after transplantation is a major cause of treatment failure in paediatric acute lymphoblastic leukaemia (ALL). Here, we report the findings of a prospective national study designed to investigate the feasibility of immune intervention in children in first or subsequent remission following myeloablative conditioning. This study included 133 children who received a transplant for ALL between 2005 and 2008. Minimal Residual Disease (MRD) based on T cell receptor/immunoglobulin gene rearrangements was measured on days −30, 30, 90 and 150 post‐transplantation. Ciclosporin treatment was rapidly discontinued and donor lymphocyte infusions (DLI) were programmed for patients with a pre‐ or post‐transplant MRD status ≥10−3. Only nine patients received DLI. Pre‐ and post‐transplant MRD status, and the duration of ciclosporin were independently associated with 5‐year overall survival (OS), which was 62·07% for the whole cohort. OS was substantially higher in patients cleared of MRD than in those with persistent MRD (52·3% vs. 14·3%, respectively). Only pre‐transplant MRD status (Hazard Ratio 2·57, P = 0·04) and duration of ciclosporin treatment (P < 0·001) were independently associated with relapse. The kinetics of chimerism were not useful for predicting relapse, whereas MRD monitoring up to 90 d post‐transplantation was a valuable prognostic tool to guide therapeutic intervention.
Enhanced GABAergic synaptic transmission at VLPAG neurons and potent modulation by oxycodone in a bone cancer pain model
Authors: Takasu Keiko , Ogawa Koichi , Nakamura Atsushi , Kanbara Tomoe , Ono Hiroko , Tomii Takako , Morioka Yasuhide , Hasegawa Minoru , Shibasaki Masahiro , Mori Tomohisa , Suzuki Tsutomu , Sakaguchi Gaku
Published: December 2014

Background and Purpose

We demonstrated previously that oxycodone has potent antinociceptive effects at supraspinal sites. In this study, we investigated changes in neuronal function and antinociceptive mechanisms of oxycodone at ventrolateral periaqueductal gray (VLPAG) neurons, which are a major site of opioid action, in a femur bone cancer (FBC) model with bone cancer‐related pain.

Experimental Approach

We characterized the supraspinal antinociceptive profiles of oxycodone and morphine on mechanical hypersensitivity in the FBC model. Based on the disinhibition mechanism underlying supraspinal opioid antinociception, the effects of oxycodone and morphine on GABAA receptor‐mediated inhibitory postsynaptic currents (IPSCs) in VLPAG neurons were evaluated in slices from the FBC model.

Key Results

The supraspinal antinociceptive effects of oxycodone, but not morphine, were abolished by blocking G protein‐gated inwardly rectifying potassium1 (Kir3.1) channels. In slices from the FBC model, GABAergic synaptic transmission at VLPAG neurons was enhanced, as indicated by a leftward shift of the input–output relationship curve of evoked IPSCs, the increased paired‐pulse facilitation and the enhancement of miniature IPSC frequency. Following treatment with oxycodone and morphine, IPSCs were reduced in the FBC model, and the inhibition of presynaptic GABA release by oxycodone, but not morphine was enhanced and dependent on Kir3.1 channels.

Conclusion and Implications

Our results demonstrate that Kir3.1 channels are important for supraspinal antinociception and presynaptic GABA release inhibition by oxycodone in the FBC model. Enhanced GABAergic synaptic transmission at VLPAG neurons in the FBC model is an important site of supraspinal antinociception by oxycodone via Kir3.1 channel activation.
Cenozoic evolution of the central Myanmar drainage system: insights from sediment provenance in the Minbu Sub‐Basin
Authors: Licht Alexis , Reisberg Laurie , France‐Lanord Christian , Naing Soe Aung , Jaeger Jean‐Jacques
Published: December 2014

Located at the southern edge of the eastern Himalayan syntaxis, the Central Myanmar Basin (CMB) is divided into several Tertiary sub‐basins that have been almost continuously filled since the Indo‐Asia collision. They are currently drained by the Irrawaddy River, which flows down the eastern Tibetan Plateau and the Sino‐Burman Ranges. Tracing sediment provenance from the CMB is thus critical for reconstructing the past denudation of the Himalayan‐Tibetan orogen; it is especially relevant since a popular drainage scenario involves the capture of the Tsangpo drainage system in Tibet by a precursor to the Irrawaddy River. Here, we document the provenance of sediment samples from the Minbu Sub‐Basin at the southern edge of the CMB, which is traversed by the modern stream of the Irrawaddy River. Samples ranging in age from middle Eocene to Pleistocene were investigated using Nd isotopes, trace element geochemistry and sandstone modal compositions. Our data provide no evidence of a dramatic provenance shift; however, sandstone petrography, trace element ratios and isotopic values display long‐term trends indicating a gradual decrease of the volcanic input and its replacement by a dominant supply from the Burmese basement. These trends are interpreted to reflect the progressive denudation of the Andean‐type volcanic arc that extended onto the Burmese margin, along the flank of the modern Sino‐Burman Ranges, where most of the post‐collisional deformation of central Myanmar is located. Though our results do not exclude an ephemeral or diluted contribution from a past Tsangpo‐Irrawaddy connection, sedimentation rates suggest that this hypothesis is unlikely before the development of a stable Tsangpo‐Brahmaputra River in the Miocene. These results thus suggest that the central Myanmar drainage basin has remained restricted to the Sino‐Burman Ranges since the beginning of the India‐Asia collision.
Teamwork and Organizational Innovation: The Moderating Role of the HRM Context
Authors: Fay Doris , Shipton Helen , West Michael A. , Patterson Malcolm
Published: December 2014

Evidence is accumulating on the role of teams in shaping a variety of business outcomes, but our knowledge on the effect of teamwork on organizational innovation is still evolving. This study examines whether the extent to which two staff groups are organized in teams (production staff and management/administrative staff) affects organizational innovation and whether human resource management (HRM) systems, which can be of facilitating or constraining nature, enhance the teamwork/innovation relationships. Hypotheses were tested with lagged and longitudinal data derived from 18 to 45 organizations from the UK manufacturing sector. Results suggest that the more widespread the use of teamwork in organizations, the higher the level of organizational innovation. Furthermore, this effect depends, particularly for production teams, on the overall quality of the HRM systems that exist in their organizations. Teamwork/innovation relationships are further moderated (for management and administrative teams) by an HRM practice that provides teams with time for thoughtful reflection. Thus, HRM systems can be of more or less facilitating or constraining nature for teams in organizations.
Peer support for parents of disabled children part 1: perceived outcomes of a one‐to‐one service, a qualitative study
Authors: Shilling V. , Bailey S. , Logan S. , Morris C.
Published: December 2014

Background

Parents of disabled children are encouraged to seek peer support. Delivering one‐to‐one support requires resources; therefore, investigating how these services may impact on families and those providing the service is important when evaluating such services.

Methods

We carried out a qualitative study involving semi‐structured interviews and focus groups. Participants were 12 parents and 23 befrienders who had contact with the Face2Face one‐to‐one befriending service in Devon and Cornwall during a 12‐month period, and 10 professionals from health, social care and education services.

Findings

Shared experience was perceived central to successful peer support and was a catalyst for other elements of support, enabling parents to (i) learn from the experience of others; (ii) speak freely in a safe and non‐judgemental environment; and (iii) receive support and encouragement from their befriender. These elements underpinned perceived outcomes for both parents providing and receiving support. Outcomes for parents receiving support centred on emotional stability, personal growth and reduced isolation. Supporting parents experienced positive outcomes through their training, mutual support and the feeling that they were helping others. Parents and befrienders appeared to benefit through expanding their social network. Nevertheless providing support was reported to create emotional burden and concerns for befrienders around their performance, and also required a substantial time commitment.

Conclusions

Befrienders as well as parents perceived positive outcomes from their involvement in peer support although there is also potential for less positive impact on those offering support.
Laboratory evaluation of anti-phospholipid syndrome: a preliminary prospective study of phosphatidylserine/prothrombin antibodies in an at-risk patient cohort
Authors: Heikal N M , Jaskowski T D , Malmberg E , Lakos G , Branch D W , Tebo A E
Published: December 2014

Immunoglobulin (Ig)G/IgM autoantibodies to phosphatidylserine/prothrombin (aPS/PT) were evaluated individually and in combination with criteria anti-phospholipid (aPL) tests in a prospectively ascertained cohort of patients at risk for anti-phospholipid syndrome (APS). One hundred and sixty (160) consecutive requests for lupus anti-coagulant (LAC) from the University of Utah Health Sciences Center were identified during 8 weeks. Of these, 104 unique patients had additional requests for cardiolipin (aCL) and/or beta2 glycoprotein I (aβ2GPI) IgG and/or IgM; samples were retained and analysed for aPS/PT, aCL and/or aβ2GPI IgG and IgM antibodies. Following testing, a comprehensive chart review was performed and patients categorized according to their clinical diagnosis. Individual and combined sensitivities, specificities, odd ratios (OR), diagnostic accuracy for specific tests or combinations by receiver operating characteristic (ROC), area under the curve (AUC) analyses and correlations between test results were determined. The sensitivities of aPS/PT IgG/IgM (54·6/45·5%) were lower than LAC (81·8%) but higher relative to aCL IgG/IgM (27·3/0%) or aβ2GPI IgG/IgM (27·3/0%). The best correlation between LAC and any aPL test was observed with aPS/PT (P = 0·002). There was no significant difference in the diagnostic accuracies for any panel with LAC: LAC/aβ2GPI IgG/aCL IgG [AUC 0·979, OR 475·4, 95% confidence interval (CI) 23·1–9056·5, P = 0·0001 and LAC/aβ2GPI IgG/aPS/PT IgG or LAC/aPS/PT IgG/aCL IgG (AUC 0·962, OR 265·3, 14·2–4958·2, P = 0·0001). The high correlation between LAC and aPS/PT IgG/IgM in this preliminary study suggest that this marker may be useful in the evaluation of APS. More studies to determine the optimal aPL antibody tests combination are needed.
The utility of the corticotropin test to diagnose adrenal insufficiency in critical illness: an update
Authors: Venkatesh Balasubramanian , Cohen Jeremy
Published: December 2014

Objective

One of the most common dynamic testing procedures for assessment of adrenocortical function is the standard corticotropin or the cosyntropin test. The aim of this review was to examine the evidence base underlying the corticotropin test in the management of the critically ill patient.

Data synthesis

The principle behind the corticotropin test is the demonstration of aninappropriatelylow cortisol production in response to exogenousACTH, a situation analogous to physiological stress. The corticotropin test was originally described in nonstressed subjects, and its applicability and interpretation in the setting of critical illness continues to generate controversy. Attempting to determine the prevalence of an abnormal corticotropin test in critical illness is complicated by the use of different end‐points and different populations. Moreover, the test result is also influenced by the assay used for measurement of plasma cortisol. Trials assessing the relationship between corticotropin response and severity of stress and organ dysfunction have produced divergent results, which may reflect differences in the methodology and the association being measured. Moreover, controversy exists with respect to the methodology and the interpretation with respect to the following variables: dose of corticotropin, end‐points for assessment of total or free cortisol, effect of plasma cortisol variability, adrenal blood flow and its equivalence with other tests of adrenocortical function.

Conclusions

The corticotropin test is used widely in the evaluation of adrenocortical function in the endocrine clinics. Its role in the critically ill patient is less well established. Several confounding variables exist and to have a ‘one‐size‐fits‐all’ approach with a single end‐point in the face of several methodological and pathophysiological confounders may be flawed and may result in the institution of inappropriate therapy. The current evidence does not support the use of the corticotrophin test in critical illness to assess adrenocortical function and guiding steroid therapy in critical illness.
How meta‐analytic evidence impacts clinical decision making in oral implantology: a Delphi opinion poll
Authors: Pommer Bernhard , Becker Kathrin , Arnhart Christoph , Fabian Ferenc , Rathe Florian , Stigler Robert G.
Published: December 2014

Objectives

To investigate the impact of meta‐analytic evidence in scientific literature on clinical decision making in the field of oral implantology.

Methods

A Delphi opinion poll was performed at the meeting of the “Next Generation” Committees of the Austrian, German and Swiss Societies for Implantology (ÖGI, DGI and SGI). First, the experts gave their opinion on 20 questions regarding routine implant treatment (uninformed decisions), then they were confronted with up‐to‐date Level I evidence from scientific literature on these topics and again asked to give their opinion (informed decisions) as well as to rate the available evidence as satisfactory or insufficient. Topics involved surgical issues, such as immediate implant placement, flapless surgery, tilted and short implants and bone substitute materials, as well as opinions on prosthodontic paradigms, such as immediate loading, abutment materials and platform switching.

Results

Compared to their uninformed decisions prior to confrontation with recent scientific literature, on average, 37% of experts (range: 15–50%) changed their opinion on the topic. When originally favoring one treatment alternative, less than half were still convinced after review of meta‐analytic evidence. Discrepancy between uninformed and informed decisions was significantly associated with insufficient evidence (P = 0.014, 49% change of opinion vs. 26% on topics rated as sufficiently backed with evidence). Agreement regarding strength of evidence could be reached for eight topics (40%), in three issues toward sufficiency and in five issues toward lack of evidence.

Conclusion

Confrontation with literature results significantly changes clinical decisions of implantologists, particularly in cases of ambiguous or lacking meta‐analytic evidence.
Prognostic impact of hyponatraemia in patients with colorectal cancer
Authors: Choi J. S. , Bae E. H. , Ma S. K. , Kweon S. S. , Kim S. W.
Published: December 2014

Aim

Hyponatraemia is a common in surgical practice, but its clinical impact in patients with colorectal cancer has not been evaluated.

Method

We retrospectively assessed 2944 patients who had been admitted to Chonnam National University Hwasun Hospital, Korea with a diagnosis of colorectal cancer. In order to determine the relationship between the serum sodium level and 3‐year mortality, we categorized the patients as having normonatraemia (135–147 mEq/l), or mild (130–134 mEq/l), moderate (125–129 mEq/l) or severe hyponatraemia (< 125 mEq/l).

Results

Hyponatraemia, defined as a serum sodium level of < 135 mEq/l, was evident in 27.6% of patients during hospitalization. Declining serum sodium levels were associated with increasing age, a higher number of comorbidities, a more advanced TNM stage and worsening biochemical parameters. In a multivariate Cox‐proportional regression analysis, the mortality risk was correlated with the severity of hyponatraemia [hazard ratio (HR) 1.65, 95% CI 1.38–1.96; HR 2.24, 95% CI 1.69–2.98; HR 2.20, 95% CI 1.25–3.90, for patients with mild, moderate, and severe hyponatraemia, respectively, compared with patients with normonatraemia]. An independent association between hyponatraemia and long‐term mortality was sustained among various subpopulations and patients with persistent hyponatraemia had a worse prognosis than those with hyponatraemia that resolved.

Conclusion

A substantial proportion of patients developed hyponatraemia during hospitalization, and the long‐term mortality risk increased even in mild cases of hyponatraemia. Hyponatraemia should be considered as an important prognostic factor in colorectal cancer.
Is group pelvic floor retraining as effective as individual treatment?
Authors: Jones H. J. S. , Gosselink M. P. , Fourie S. , Lindsey I.
Published: December 2014

Aim

Traditionally, pelvic floor retraining for faecal incontinence or obstructed defaecation has been delivered to patients through individual sessions with a specialist pelvic floor nurse, a resource‐intensive practice. This study aimed to assess whether a similar outcome can be achieved by delivering retraining to patients in small groups, allowing considerable savings in the use of resources.

Method

Data were collected prospectively in a pelvic floor database. Patients received pelvic floor retraining either individually or in a small group setting and completed baseline and follow‐up questionnaires. Two hundred and fifteen patients were treated, 119 individually and 96 in a small group setting. Scores before and after treatment for the two settings were compared for the Gastrointestinal Quality of Life Index, the Fecal Incontinence Severity Index and the Patient Assessment of Constipation Symptoms. Additionally patients receiving group treatment completed a short questionnaire on their experience.

Results

The median change in Gastrointestinal Quality of Life Index score was 5 (range −62 to 73) for individual treatment and 4 (range −41 to 47) for group treatment, both showing statistically significant improvement. However, there was no significant difference between the settings. Similar results were obtained with the Fecal Incontinence Severity Index and Patient Assessment of Constipation Symptoms scores for the faecal incontinence and obstructed defaecation subgroups respectively.

Conclusion

The majority of patients experienced symptomatic improvement following pelvic floor retraining and there was no significant difference in the resulting improvement according to treatment setting. As treatment costs are considerably less in a group setting, group pelvic floor retraining is more cost‐effective than individual treatment.
Myocardial uptake of bone scintigraphic agents associated with increased pulmonary uptake
Authors: Bach‐Gansmo Tore , Wien Tale N. , Løndalen Ayca , Halvorsen Erling
Published: December 2014

Objective

Due to delivery problems with the most commonly used bone scintigraphic agent medronate‐99mTc‐methylene diphosphonate (MDP) (medronate), several regional institutions changed, at various time points, to 99mTc‐dicarboxypropane diphosphonate (DPD) (Teceos®) from 2010. Extraosseous uptake, in particular, myocardial uptake, was observed in a number of patient examined with DPD, with reduced quality of the bone scans. Additionally, an increase in pulmonary uptake was apparent in many of these patients. The aim of this quality control was to assess pulmonary soft tissue uptake in the patients with high myocardial uptake.

Methods

A retrospective analysis of the 2435 bone scintigraphies performed during a 3‐year period revealed relatively intense myocardial uptake in 10 of the 1195 patients examined with DPD (Teceos®). A comparison of pulmonary uptake in a control group of age‐ and gender‐matched subjects and a control group of patients examined with the same preparation of DPD were assessed.

Results

In patients with cardiac uptake of DPD, it could also be shown a relatively intense background uptake in the lungs with significantly higher uptake ratio over intercostals regions versus the abdomen, compared to the control groups. Furthermore, we found, as already well documented, a significantly lower bone to soft tissue uptake in these patients, as quantified by a femur to surrounding soft tissue ratio.

Conclusion

Cardiac uptake of bone scintigraphic agents is associated with high pulmonary uptake. This may be a sign of pulmonary involvement which may give extraosseous bone tracer uptake its own importance and DPD a new role.
Exercise interventions improve postural control in children with cerebral palsy: a systematic review
Authors: Dewar Rosalee , Love Sarah , Johnston Leanne Marie
Published: December 2014

Aim

The aim of this study was to evaluate the efficacy and effectiveness of exercise interventions that may improve postural control in children with cerebral palsy (CP).

Method

A systematic review was performed using American Academy of Cerebral Palsy and Developmental Medicine (AACPDM) and Preferred Reporting Items for Systematic Reviews and Meta‐Analyses (PRISMA) methodology. Six databases were searched using the following keywords: (‘cerebral palsy’ OR ‘brain injury’); AND (‘postur*’ OR ‘balance’ OR ‘postural balance’ [MeSH]); AND (‘intervention’ OR ‘therapy’ OR ‘exercise’ OR ‘treatment’). Articles were evaluated based on their level of evidence and conduct.

Results

Searches yielded 45 studies reporting 13 exercise interventions with postural control outcomes for children with CP. Five interventions were supported by a moderate level of evidence: gross motor task training, hippotherapy, treadmill training with no body weight support (no‐BWS), trunk‐targeted training, and reactive balance training. Six of the interventions had weak or conflicting evidence: functional electrical stimulation (FES), hippotherapy simulators, neurodevelopmental therapy (NDT), treadmill training with body weight support, virtual reality, and visual biofeedback. Progressive resistance exercise was an ineffective intervention, and upper limb interventions lacked high‐level evidence.

Interpretation

The use of exercise‐based treatments to improve postural control in children with CP has increased significantly in the last decade. Improved study design provides more clarity regarding broad treatment efficacy. Research is required to establish links between postural control impairments, treatment options, and outcome measures. Low‐burden, low‐cost, child‐engaging, and mainstream interventions also need to be explored.
Postencephalitic epilepsy: Clinical characteristics and predictors
Authors: Singh Tarun D. , Fugate Jennifer E. , Hocker Sara E. , Rabinstein Alejandro A.
Published: December 2014

Objective

To describe the etiologies, clinical presentations, outcomes, and predictors of postencephalitic epilepsy (PE) in a large series of adult patients with acute encephalitis.

Methods

We conducted a retrospective review of patients diagnosed with acute encephalitis at Mayo Clinic, Rochester, between January 2000 and December 2012. The patients were categorized into two groups based on the presence or absence ofPEat last follow‐up. Multivariate logistic regression analysis was used to analyze factors associated withPE.

Results

We identified 198 consecutive patients (100 [50.5%] male and 98 [49.5%] female) with a median age of 58 years (range 41.8–69). Etiologies included viral infection (n = 95, 48%), autoimmune (n = 44, 22%), and unknown/others (n = 59, 30%). During hospitalization, seizures were seen in patients with autoimmune encephalitis (n = 24, 54.5%), unknown/others (n = 20, 33.9%), and viral encephalitis (n = 23, 24.2%). Interictal epileptiform discharges on electroencephalography (EEG) were present in 34 (54%), whereas periodic lateralized epileptiform discharges (PLEDs) and generalized periodic discharges (GPDs) were seen in 14 (41.2%) and 2 (5.9%) patients. Forty‐six patients with seizures (70.8%) had fluid‐attenuated inversion recovery (FLAIR)/T2abnormalities, 20 (31.3%) diffusion abnormalities, and 43 (66.2%) cortical involvement. Good outcome at discharge among patients with seizures was seen in 8/23 patients with viral etiology (34.8%), 10/24 patients with autoimmune encephalitis (45.5%), and 12/20 patients with unknown cause (60%).PEwas present in 43 patients (29.9%). On multivariate regression analysis, the factors associated withPEwere generalized seizures during hospitalization (p = 0.03), focal seizures (p ≤ 0.001), and the presence ofFLAIR/T2abnormalities on brain magnetic resonance imaging (MRI) (p = 0.003).

Significance

The presence of seizures during hospitalization and an abnormal brainMRIare the strongest predictors of the development ofPE. The etiology of encephalitis, presence of focal neurologic deficits, and interictalEEGabnormalities did not influence the development ofPE.
Novel therapeutic approaches for haemophilia
Authors: Shetty S. , Ghosh K.
Published: December 2014

The major therapy for haemophilia is plasma derived or recombinant clotting factors which are evolving steadily to increase potency, stability and half‐life. Research in the area of haemophilia therapeutics, however, is not restricted only to modifications in the recombinant products, but alternate therapeutic strategies are being developed which are in different phases of experimental and clinical trials. This chapter reviews the diverse molecular innovations which are being developed for alternate therapeutic approaches in haemophilia. The data is mainly extracted from the literature and the Conference abstracts. Some of the novel therapeutic approaches include inhibition of anticoagulant pathway factors (activated protein C, antithrombin, tissue factor pathway inhibitor) by monoclonal antibodies, peptide inhibitors, DNA or RNA aptamers, use of variant coagulation factors (factor Xa, factor Va) which are more resistant to inactivation or enzymatically more active and antibody‐mediated therapy including a humanized anti‐factor IXa/X bispecific antibody mimicking factor VIII. Other approaches include nonsense mutation suppression, induction of prothrombotic microparticles by P‐selectin‐immunoglobulin chimeras, suppression of fibrinolytic potential either by antifibrinolytics or by the use of mutant molecules of fibrinolytic inhibitors. Few products are proposed as ‘stand alone’ treatment for haemophilia, while a few can be used as adjuvant therapies to recombinant factors with an aim to reduce the amount of factor intake. All efforts are underway to produce an alternate, novel drug for haemophilia which will have an increased half‐life, subcutaneously injectable, non‐immunogenic and effective both in the presence and absence of inhibitors.
Identification of potential clinically significant drug interactions in HIV‐infected patients: a comprehensive therapeutic approach
Authors: Iniesta‐Navalón C , Franco‐Miguel JJ , Gascón‐Cánovas JJ , Rentero‐Redondo L
Published: December 2014

Objectives

The aim of the study was to determine the prevalence of potential clinically significant drug interactions (CSDIs) in HIV‐positive individuals and to identify associated risk factors.

Methods

A cross‐sectional study was conducted including all HIV‐infected out‐patients attending the Pharmacy Service of a regional reference hospital in Murcia, south‐eastern Spain. The complete treatment was screened for possible CSDIs using the Spanish College of Pharmacists' online software resource, bot. Additionally, the severity level of the CSDIs involving antiretroviral (ARV) drugs was compared with that established in the specific antiretroviral database InteraccionesHIV.com. Multivariate logistic regression was used to identify associated risk factors.

Results

Two hundred and sixty‐eight patients were included in the study. A total of 292 potential drug interactions were identified, of which 102 (34.9%) were CSDIs, of which 52.9% involved ARV drugs. Seven therapeutic drug classes were involved in 75% of CSDIs (protease inhibitors, benzodiazepines, nonsteroidal anti‐inflammatory drugs, nonnucleoside reverse transcriptase inhibitors, corticosteroids, antithrombotics and proton pump inhibitors). Factors independently associated with CSDIs were treatment with more than five drugs [odds ratio (OR) 15.1; 95% confidence interval (CI) 6.3–36.2], and treatment with a protease inhibitor (OR 5.3; 95% CI 2.4–11.74).

Conclusions

The findings of this study suggest that the prevalence of clinically relevant drug−drug interactions is high in HIV‐infected patients, and could represent a major health problem. Awareness, recognition and management of drug interactions are important in optimizing the pharmaceutical care of HIV‐infected patients and helping to prevent adverse events and/or loss of efficacy of the drugs administered.
Proteasome‐associated autoinflammatory syndromes: advances in pathogeneses, clinical presentations, diagnosis, and management
Authors: McDermott Amelia , Jacks Jennifer , Kessler Marcus , Emanuel Peter D. , Gao Ling
Published: December 2014

The disease spectrum currently known as the proteasome‐associated autoinflammatory syndromes (PRAAS) was first described in 1939 in patients who presented with recurrent fevers beginning in infancy or early childhood, which were accompanied by nodular erythema, a pernio‐like rash, and joint contractures. Since then, several syndromes, such as chronic atypical neutrophilic dermatosis with lipodystrophy and elevated temperature (CANDLE) syndrome, Nakajo–Nishimura syndrome (NNS), joint contractures, muscle atrophy, microcytic anemia and panniculitis‐induced lipodystrophy (JMP) syndrome, and Japanese autoinflammatory syndrome with lipodystrophy (JASL), have been used to categorize patients with diseases within the same spectrum. Recently, independent studies have identified mutations in the human proteasome subunit β type 8 (PSMB8) gene, which result in a sustained inflammatory response in all syndromes. Further functional studies not only suggest a causative role of PSMB8 mutations but also imply that they represent one disease spectrum, referred to as PRAAS. In this paper, we review the clinical presentations and laboratory findings of PRAAS, as well as the most recent advances in pathogeneses, diagnosis, and treatment options for patients with diseases in this spectrum.
Factors contributing to malnutrition in patients with Parkinson's disease
Authors: Kim Sung R , Chung Sun J , Yoo Sung‐Hee
Published: December 2014

Our objective in this study was to evaluate the nutritional status and to identify clinical, psychosocial, and nutritional factors contributing to malnutrition in Korean patients with Parkinson's disease. We used a descriptive, cross‐sectional study design. Of 102 enrolled patients, 26 (25.5%) were malnourished and 27 (26.5%) were at risk of malnutrition based on Mini‐Nutritional Assessment scores. Malnutrition was related to activity of daily living score, Hoehn and Yahr stage, duration of levodopa therapy, Beck Depression Inventory and Spielberger's Anxiety Inventory scores, body weight, body weight at onset of Parkinson's disease, and body mass index. On multiple logistic regression analysis, anxiety score, duration of levodopa therapy, body weight at onset of Parkinson's disease, and loss of body weight were significant factors predicting malnutrition in Parkinson's disease patients. Therefore, nutritional assessment, including psychological evaluation, is required for Parkinson's disease patients to facilitate interdisciplinary nutritional intervention for malnourished patients.
The atypical MAPK ERK3 controls positive selection of thymocytes
Authors: Sirois Julien , Daudelin Jean‐François , Boulet Salix , Marquis Miriam , Meloche Sylvain , Labrecque Nathalie
Published: December 2014

Extracellular signal‐regulated kinase 3 (ERK3 )is an atypical member of the mitogen‐activated protein kinase (MAPK) family. We have previously shown that ERK3 is expressed during thymocyte differentiation and that its expression is induced in mature peripheral T cells following activation of ERK1/2 by T‐cell receptor (TCR) signalling. Herein, we have investigated whether ERK3 expression is required for proper T‐cell selection. Using a knock‐in mouse model in which the coding sequence of ERK3 is replaced by the gene encoding for the β‐galactosidase reporter, we show that ERK3 is expressed by double‐positive (DP) thymocytes undergoing positive selection. In ERK3‐deficient mice with a polyclonal TCR repertoire, we observe a decrease in positive selection. This reduction in positive selection was also observed when ERK3‐deficient mice were backcrossed to class I‐ and class II‐restricted TCR transgenic mice. Furthermore, the response of DP thymocytes to in vitro TCR stimulation was strongly reduced in ERK3‐deficient mice. Together, these results show that ERK3 expression following TCR signalling is critical for proper thymic positive selection.
A study protocol of a randomized controlled trial examining the efficacy of a symptom self‐management programme for people with acute myocardial infarction
Authors: Klainin‐Yobas Piyanee , Koh Karen Wei Ling , Ambhore Anand Adinath , Chai Ping , Chan Sally Wai‐Chi , He Hong‐Gu
Published: December 2014

Aim

To report a study protocol of a randomized controlled trial examining if a symptom self‐management programme helps patients with acute myocardial infarction self‐manage their physical and psychological symptoms.

Background

In addition to physical conditions, people with acute myocardial infarction often experience psychological symptoms. However, there is limited empirical evidence on how to help individuals self‐manage these psychological symptoms.

Design

A single‐blinded, randomized controlled trial is proposed.

Methods

A convenience sample of 90 will be recruited. Eligible participants will be adult patients with acute myocardial infarction hospitalized at a tertiary hospital in Singapore. Participants will be randomly assigned to one of the three treatment groups: Intervention 1 and standard care (n = 30), Intervention 2 and standard care (n = 30) and standard care alone (n = 30). Data will be collected by self‐reported questionnaires, physiological measures and open‐ended questions. Quantitative data will be analysed by descriptive statistics, t‐test, analysis of covariance and repeated measures analysis of variance. Open‐ended questions will be analysed by content analysis.

Discussion

This study will identify a potentially efficacious symptom self‐management programme for patients with acute myocardial infarction. If the efficacy of the programme is demonstrated, the programme can be integrated into hospital services to improve patient care. A new teaching method (virtual reality–based teaching) and new teaching materials (virtual reality videos and relaxation videos) derived from this study can be offered to patients. Future research with larger samples and multi‐centre recruitment can be undertaken to further test the efficacy of the interventions.