Witten/Herdecke University

PURPOSE: Empathy is a key element of patient-physician communication; it is relevant to and positively influences patients' health. The authors systematically reviewed the literature to investigate changes in trainee empathy and reasons for those changes during medical school and residency. METHOD: The authors conducted a systematic search of studies concerning trainee empathy published from January 1990 to January 2010, using manual methods and the PubMed, EMBASE, and PsycINFO databases. They independently reviewed and selected quantitative and qualitative studies for inclusion. Intervention studies, those that evaluated psychometric properties of self-assessment tools, and those with a sample size <30 were excluded. RESULTS: Eighteen studies met the inclusion criteria: 11 on medical students and 7 on residents. Three longitudinal and six cross-sectional studies of medical students demonstrated a significant decrease in empathy during medical school; one cross-sectional study found a tendency toward a decrease, and another suggested stable scores. The five longitudinal and two cross-sectional studies of residents showed a decrease in empathy during residency. The studies pointed to the clinical practice phase of training and the distress produced by aspects of the "hidden," "formal," and "informal" curricula as main reasons for empathy decline. CONCLUSIONS: The results of the reviewed studies, especially those with longitudinal data, suggest that empathy decline during medical school and residency compromises striving toward professionalism and may threaten health care quality. Theory-based investigations of the factors that contribute to empathy decline among trainees and improvement of the validity of self-assessment methods are necessary for further research.

'If G-quadruplexes form so readily in vitro, Nature will have found a way of using them in vivo' (Statement by Aaron Klug over 30 years ago).During the last decade, four-stranded helical structures called G-quadruplex (or G4) have emerged from being a structural curiosity observed in vitro, to being recognized as a possible nucleic acid based mechanism for regulating multiple biological processes in vivo. The sequencing of many genomes has revealed that they are rich in sequence motifs that have the potential to form G-quadruplexes and that their location is non-random, correlating with functionally important genomic regions. In this short review, we summarize recent evidence for the in vivo presence and function of DNA and RNA G-quadruplexes in various cellular pathways including DNA replication, gene expression and telomere maintenance. We also highlight remaining open questions that will have to be addressed in the future.

BACKGROUND: Severe trauma continues to represent a global public health issue and mortality and morbidity in trauma patients remains substantial. A number of initiatives have aimed to provide guidance on the management of trauma patients. This document focuses on the management of major bleeding and coagulopathy following trauma and encourages adaptation of the guiding principles to each local situation and implementation within each institution. METHODS: The pan-European, multidisciplinary Task Force for Advanced Bleeding Care in Trauma was founded in 2004 and included representatives of six relevant European professional societies. The group used a structured, evidence-based consensus approach to address scientific queries that served as the basis for each recommendation and supporting rationale. Expert opinion and current clinical practice were also considered, particularly in areas in which randomised clinical trials have not or cannot be performed. Existing recommendations were reconsidered and revised based on new scientific evidence and observed shifts in clinical practice; new recommendations were formulated to reflect current clinical concerns and areas in which new research data have been generated. This guideline represents the fourth edition of a document first published in 2007 and updated in 2010 and 2013. RESULTS: The guideline now recommends that patients be transferred directly to an appropriate trauma treatment centre and encourages use of a restricted volume replacement strategy during initial resuscitation. Best-practice use of blood products during further resuscitation continues to evolve and should be guided by a goal-directed strategy. The identification and management of patients pre-treated with anticoagulant agents continues to pose a real challenge, despite accumulating experience and awareness. The present guideline should be viewed as an educational aid to improve and standardise the care of the bleeding trauma patients across Europe and beyond. This document may also serve as a basis for local implementation. Furthermore, local quality and safety management systems need to be established to specifically assess key measures of bleeding control and outcome. CONCLUSIONS: A multidisciplinary approach and adherence to evidence-based guidance are key to improving patient outcomes. The implementation of locally adapted treatment algorithms should strive to achieve measureable improvements in patient outcome.

Crohn’s disease [CD] is a chronic inflammatory bowel disease [IBD] that can result in progressive bowel damage and disability.1 CD can affect individuals of any age, from children to the elderly,2,3 and may cause significant morbidity and impact on quality of life. Up to one-third of patients present with complicated behaviour [strictures, fistula, or abscesses] at diagnosis.4 Most patients over time will develop a complication, with roughly 50% of patients requiring surgery within 10 years of diagnosis.5–7 As the precise aetiology of CD remains unknown, a curative therapy is not yet available.8 Several agents are available for the medical treatment of CD. Medical agents include mesalazine [5-ASA], locally active steroids [such as budesonide], systemic steroids, thiopurines such as azathioprine [AZA] and mercaptopurine [MP], methotrexate [MTX], and biologic therapies (such as anti-tumour necrosis factor [TNF], anti-integrins, and anti-interleukin [IL] 12/23]. The European Crohn’s and Colitis Organisation [ECCO] produces and regularly updates several guidelines aimed at providing evidence-based guidance on critical aspects of IBD care to all health care professionals who manage patients with IBD. To provide high-quality evidence-based recommendations on medical treatment in CD, ECCO decided to develop these guidelines by adopting the GRADE [Grading of Recommendations Assessment, Development, and Evaluation] approach.9 GRADE is a systematic process for developing guidelines which addresses how to frame the health care questions, summarise the evidence, formulate the recommendations, and grade their strength and the quality of the associated evidence. GRADE increases transparency at all levels of this process and makes explicit the three considerations that lead to a particular recommendation: the quality of the evidence, the balance of benefits and harms, and the patients’ values and preferences. Therefore ECCO reviewed the available high-quality evidence on the medical management of CD and developed evidence-based recommendations on the medical treatment of adult patients with CD. These guidelines do not cover specific situations, such as postoperative management of adult patients with CD, which was already covered in the latest ECCO Guidelines on Crohn’s disease.10 Based on the GRADE workflow, the Guidelines Committee of ECCO [GuiCom] selected a panel of 48 experts supported by a team of methodologists and librarians. Selection was based on IBD expertise, scientific background, and knowledge of the GRADE methodology. All panellists received adequate training in GRADE before starting the process. Additionally, four patients with CD representing the European Federation of Crohn’s and Colitis Associations [EFCCA] were invited to participate in all face-to-face meetings and to provide their experiences and state their preferences. Three domains for medical treatment of CD were identified: 1] induction therapy; 2] maintenance therapy; 3] therapy of fistulising perianal disease. All panellists were assigned to one of three working groups coordinated by one to two working group leaders under the supervision of two Guideline coordinators. The panellists first formulated a series of specific questions using the PICO format [Population, Intervention, Comparator, Outcomes] which were deemed to be clinically important for the medical treatment of CD. The outcomes of all PICO questions were subsequently graded as ‘not important’, ‘important’, or ‘critical’ during a face-to-face kick-off meeting in Vienna, using a Delphi consensus process. A team of professional librarians performed a comprehensive literature search on EMBASE, PubMed/Medline, and Cochrane Central databases using specific search strings for each PICO question [Supplementary Files 1, 2, and 3, available as Supplementary data at ECCO-JCC online]. Two independent working group members [one assigned to the PICO and another one from the same group as a second reviewer] assessed the relevance of each abstract to PICO and included or excluded all the relevant papers for the final data extraction and analysis. Subsequently, the working group members assigned to each PICO question systematically reviewed and summarised the evidence on every outcome, to compile a Summary of Findings [SoF] table for each question. The GRADE method follows a hierarchical approach to synthesise evidence; recent high-quality systematic reviews and meta-analyses of clinical trials were preferentially used to create the recommendations. When these were not available, individual randomised clinical trials [RCTs] followed by observational studies were reviewed; results of individual studies were pooled using random-effects meta-analysis as appropriate and when needed. To define disease activity and severity [mild-to-moderate and moderate-to-severe], we accepted the definitions used by the investigators of the studies selected as an evidence basis for our work. The quality of evidence was classified into the following four categories in accordance with the GRADE approach: ‘high’ [meaning that further research is unlikely to change our in the research may change our in the research to change our in the and [meaning that any of is each PICO the quality of evidence was to the quality of evidence outcomes graded as The strength of each was graded as [meaning the of an the or or as [meaning the balance is the quality of evidence, values or and the outcomes were not in the clinical this was in the To the recommendations, we from the systematic reviews or our group of methodologists performed the All recommendations were to by the panel the ECCO for each with and from a of ECCO members who to the were not selected to be of the The final of all was panel members during a final consensus meeting in and to a final recommendations were at of the panellists with the and associated strength The of the and and the of the were reviewed by two Guideline Committee members and by the ECCO who the final of these The literature search the relevant definitions of and a of the and the the evidence can be in the Supplementary available as Supplementary data at ECCO-JCC As CD is a therapy to in the and in the The that chronic and results in to a recent in medical treatment and disease is that and may patients to their and therapy are to high-quality evidence is not available to this affect the of medical These include disease disease activity and to and of perianal or fistulising the individual for and the individual and the and of each be As is a clinical and is of to disease and therapy at based on and approach will provide the with the to therapy the of of the disease and which is to be to disease to the management of CD a series of health care maintenance be to be and be and appropriate guidance or for and be as in ECCO or the of for induction of of Crohn’s disease performed a meta-analysis of that the of or with in patients with active CD [Supplementary 1, available as Supplementary data at ECCO-JCC online]. The of from to patients with disease with or disease were was significant for induction of clinical [Supplementary 1, available as Supplementary data at ECCO-JCC online]. A recent Cochrane significant and to be in our as was significant in to when with [Supplementary 2, available as Supplementary data at ECCO-JCC online]. the trials of was over for clinical [Supplementary 3, available as Supplementary data at ECCO-JCC online]. significant in to was in trials that [Supplementary available as Supplementary data at ECCO-JCC online]. meta-analysis a significant on clinical the that at of another meta-analysis was to any such A pooled of three trials of a of a in the Crohn’s with the in and was not clinically Two trials with for induction of clinical A pooled a of [Supplementary available as Supplementary data at ECCO-JCC online]. was not by any significant in for [Supplementary available as Supplementary data at ECCO-JCC online]. in trials that the of was to patients with The of or for the treatment of CD not in using for the induction of clinical in patients with active Crohn’s disease to the A Cochrane systematic and included three that at a of with [Supplementary 2, available as Supplementary data at ECCO-JCC online]. Two of these clinical as in or at at was in all three was to for clinical and clinical in patients with active CD in the to the As with steroids which are associated with systemic activity and systemic and and a was to be in the reviewed A Cochrane systematic and meta-analysis from reviewed two that at a of with mesalazine to a mesalazine in patients with active CD [Supplementary 3, available as Supplementary data at ECCO-JCC online]. All trials clinical in or and clinical at was not to mesalazine for clinical in patients with active CD in the [Supplementary available as Supplementary data at ECCO-JCC online]. clinical was in patients in patients mesalazine [Supplementary available as Supplementary data at ECCO-JCC online]. The of was with and in groups [Supplementary and available as Supplementary data at ECCO-JCC online]. studies the of treatment on CD. and to clinical or with the of these the European on the of to or Therefore a was not on to CD, for the treatment of patients with Crohn’s we the of systemic for the induction of clinical and Two on the of systemic or with for the treatment of active available as Supplementary data at ECCO-JCC online]. was at a of 48 and on a basis to and of from to with a of is at over an from these studies in a Cochrane systematic patients on induction of clinical was in patients as with were to be as in clinical in the two studies patients on the of patients from the of systemic was available from one patients with The of was in patients with included of and in patients with and in was for the outcomes to which a quality of evidence the of thiopurines as for the induction of of Crohn’s disease Several studies on the of thiopurines with for induction of and in [Supplementary available as Supplementary data at ECCO-JCC online]. trials the of thiopurines for induction of clinical in with or patients were The active was in four of these and the active was in the The trials were in of of active and of for of the trials for the of The pooled was performed on an basis and for induction of thiopurines and in the active with in the group Three trials on clinical not with of disease these of of disease were of the patients as with of clinical The of clinical was was and to data and the quality of evidence was for this [Supplementary available as Supplementary data at ECCO-JCC online]. one on during The pooled of any was not and thiopurines were in two of of developed The quality of evidence was deemed to a of and on a quality of The groups was at for and for of the trials on at the of the induction data were available that for a pooled trials in of such as or in thiopurines as with a of at and at and for the thiopurines and a of in the group and a significant in in and one relevant was this patients with active CD were randomised to of or for with a of at that was over a [Supplementary available as Supplementary data at ECCO-JCC online]. a of patients with were in clinical The of treatment for and was in with this is by and such as the of studies were that for the induction of of CD. was in the the of for CD and the decided to Three and studies the of and thiopurines for induction of in [Supplementary available as Supplementary data at ECCO-JCC online]. These studies used and of Two studies used at of and and one used at All patients were and received systemic steroids at of the individual studies or the pooled a significant in the to [Supplementary available as Supplementary data at ECCO-JCC online]. the of is with the data are and the quality of evidence is for can be Based on the evidence, on a for the of for clinical in patients with CD not be may be as an for patients with disease when be The to therapy in patients a be the of and to in patients with Crohn’s disease who not to therapy are and therapies for the treatment of CD include and is not in the European for CD, is available in and is a at a of at 2, and during induction and every is a at a of and followed by every is a at a of at 2, and followed by every on agents and from several meta-analyses of their for induction of clinical and clinical [Supplementary available as Supplementary data at ECCO-JCC in patients who not adequate or were to data were available for the induction two studies a the evidence was to on clinical were and data on were by to the of patients included in the meta-analysis on outcomes and and and quality of are was in of The of on and in a that with and were to for induction of The of of biologic agents is a of that patients with fistulising perianal complicated from the of to a of or of agents be the first in disease these results are based on from clinical the of and thiopurines over to clinical and one the of therapy of with as with for the induction of clinical in patients to therapies [Supplementary available as Supplementary data at ECCO-JCC online]. this therapy was not to for clinical therapy was associated with at this was at the of was in to associated with therapy the of used in this was the used in CD patients of therapy with a when starting to in patients with Crohn’s who an to therapy The and Crohn’s the of with over in patients to who to to steroids or [Supplementary available as Supplementary data at ECCO-JCC online]. therapy in of clinical at as with therapy was to result in at this was in for were of in therapy A in clinical is patients who or an to thiopurines and in therapy is in such maintenance in with the benefits in of A of of the of therapy starting therapy in this be in the of evidence, an approach be for induction of in patients with Crohn’s disease with to therapy to therapy high-quality is an that to the by the and CD, induction be using a of systematic and meta-analysis pooled the results from in which was with for induction of in patients with active available as Supplementary data at ECCO-JCC online]. patients with or induction of clinical and induction of clinical at were and a meta-analysis was an of clinical of [Supplementary available as Supplementary data at ECCO-JCC online]. The quality of evidence was The of clinical was [Supplementary available as Supplementary data at ECCO-JCC online]. The quality of evidence was CD patients that of patients at as with of The quality of evidence was on or The pooled of any was not and [Supplementary available as Supplementary data at ECCO-JCC online]. the pooled of any was not and [Supplementary available as Supplementary data at ECCO-JCC the quality of evidence was The of to be for induction of and in patients with Crohn’s disease with to therapy to therapy is a that by the in is at a of at 2, and for and every who do not at can from an at Three randomised trials patients with or on induction of clinical induction of clinical and in adult patients with active available as Supplementary data at ECCO-JCC online]. in these studies were followed for to 10 was in patients with [Supplementary available as Supplementary data at ECCO-JCC online]. clinical was in patients with [Supplementary available as Supplementary data at ECCO-JCC online]. The quality of evidence for these outcomes was of with were not with [Supplementary available as Supplementary data at ECCO-JCC online]. The quality of evidence for this was to from the of or for the treatment of active Crohn’s disease in patients who therapy systematic and meta-analysis performed an of and for induction of in patients with active CD who were or to a of patients with or on induction of clinical and clinical [Supplementary available as Supplementary data at ECCO-JCC online]. The pooled of clinical and clinical were not and the quality of evidence was for a of patients with or on or The pooled of any was not and the pooled of any was not and the quality of evidence was surgery be as an in is for the induction of in patients with CD, as a and of at or a or a Crohn’s of with and is a knowledge on how to CD in of the the and or in patients with disease. Therefore the is to the who the individual and of systemic steroids are in in CD, are by important Additionally, of not disease Therefore we that the of or to steroids the of 10 or within of starting steroids, a within of steroids, or the for a of in all a are not in thiopurines a of and are for in CD patients are with steroids at the of patients with a of steroids and in at and is associated with a of this may be medical and surgery are not or are associated with individual patients with CD as a or with or to therapy we the of These include agents [such as and or All these agents are in and CD The on and and the induction of in the of with thiopurines is for of therapy over was in the performed to The the of or the of and over or in with this be and in The for the of Crohn’s that the of with in patients at of as with a was associated with of and for surgery in patients with A that is associated with to clinical the and of therapy to be a in in the therapy not to be associated with at in the a that therapy is associated with for and as with Therefore the is to the who and to be as specific such as the at for or and at for specific such as patients who or are is evidence on the and in patients with or as a first assessed the and of these agents when used in therapy as with to be in the in was in patients with in patients with CD with disease or to at one surgery be as an the of a for induction of and for using of clinical the or of therapy not on on the disease severity impact of disease in the individual the and for the inflammatory of and disease appropriate studies that the of over a on the of and and that for disease be studies were by this as important research the of for maintenance of in patients with Crohn’s disease for the maintenance of of CD [Supplementary available as Supplementary data at ECCO-JCC online]. significant [Supplementary available as Supplementary data at ECCO-JCC online]. trials that assessed and were from to with trials a of were significant in the of patients an or to or The data were and this [Supplementary available as Supplementary data at ECCO-JCC online]. are for the maintenance of in patients with Crohn’s disease The of maintenance treatment with or to patients with CD who are in one [Supplementary available as Supplementary data at ECCO-JCC online]. meta-analysis included data from trials and A of patients with to were included and followed for to was to in disease activity in was to for the maintenance of in patients outcomes were in four trials and a of patients followed for to The of during maintenance treatment with thiopurines was with The of in patients with thiopurines was and were the the of therapy in patients with Crohn’s disease for that the of thiopurines disease Two studies the of of the for of Crohn’s disease in and the trials [Supplementary available as Supplementary data at ECCO-JCC online]. The excluded from our table was not or the adult patients with a recent of CD were randomised to or to were to active disease in this The results were not significant for any of the critical outcomes of clinical not the two groups patients with and were in The of as and were in patients in the group and in the group methotrexate for the maintenance of in patients with Crohn’s disease on the of are from one patients were of or of for [Supplementary available as Supplementary data at ECCO-JCC online]. with active CD, who to of treatment with were assigned to at a of or for for CD were the of patients who in was in the group in the group 50% of the patients in the group by the of the were in in the group as with the group over the observational [one and the a and patients in the group in the of the was one treatment of these of severity to treatment or from the The of was in patients with Crohn’s disease who with maintenance treatment using the same treatment is Two systematic reviews the of maintenance treatment with and to patients with CD who disease with the same [Supplementary available as Supplementary data at ECCO-JCC online]. trials and were pooled in the meta-analysis from one was on two on and two on A of patients were included and followed for to of the studies included and one included all was as a The of with was The following values were with with and with A significant the three are pooled data available on of all as a performed in the of a Cochrane the for for and were and with is as with for the maintenance of in CD the and of do not the of that may in and observational for clinical in patients with Crohn’s disease who with at every was to in clinical in patients with CD who with [Supplementary available as Supplementary data at ECCO-JCC online]. patients every and patients every were in clinical as with patients and was at clinical and a of with data are to the the of to clinical in patients with Crohn’s disease who with outcomes for the maintenance of with in CD patients [Supplementary available as Supplementary data at ECCO-JCC to in the induction were to every or or a of the patients were in clinical as with of A that at clinical was by of patients every and by of patients every as with in the The treatment every and was and was treatment every and Therefore was every or was in of patients of patients The pooled of any was not patients who were and are data on as this was assessed in a of patients at was significant in patients in the group as with patients in the treatment were during the of were and with significant in the and was an of in the maintenance groups patients in and data are to the are randomised trials or with agents for the maintenance of clinical in patients with CD who or with the same A included trials used the to define clinical with The a time of All were the the the quality of evidence was specific was the in the maintenance Based on is evidence to to or in patients who to induction treatment with any or is a to that and to trials that for the of who from a biologic over the Crohn’s disease patients in clinical under is evidence to for or the of to clinical outcomes as to care from two with a of patients with CD were used to this [Supplementary available as Supplementary data at ECCO-JCC online]. These two of over clinically based for any of our critical clinical [one clinical [one [one [one or [one the a of IBD patients with to maintenance therapy were randomised to or groups were or to a and of the that in patients in clinical a or was in and of in clinical or at were and based the group who received during the patients with CD, with an induction therapy with and were randomised to the following three based on clinical and levels of with of or of or based on clinical The was to a was in clinical with from to in the three in in in studies important in their which the strength of our The outcomes in studies were clinical important such as and to be The in Crohn’s that is on and and that during the induction may outcomes and treatment the that with adequate of patients are Crohn’s disease patients who to an is evidence to for or the of to clinical outcomes to the of in patients on therapy with active to the of of and to clinical was with on clinical in one in a of patients with CD with were randomised to every or based on and levels using the was in clinical the group and the group [Supplementary available as Supplementary data at ECCO-JCC online]. studies a adequate and clinical outcomes from clinical to Based on these observational recent clinical guidelines and a group of experts supported the of the quality of evidence from observational a of patients with active IBD with who and clinical were for and at a of was in of patients in the as with in the clinical was in and in the group another a of the using a of was to a at was this group and a group in which were of was significant in clinical the approach was in the evidence not an a and clinical outcomes a of thiopurines in Crohn’s disease patients in on maintenance as the of is when the treatment is our meta-analysis to the two of in CD patients in on maintenance therapy [Supplementary available as Supplementary data at ECCO-JCC online]. from four trials were included received from to before randomised to or or to or All studies a time of to results that the of clinical is [Supplementary available as Supplementary data at ECCO-JCC online]. meta-analysis for was the data a with of the results were not significant [Supplementary available as Supplementary data at ECCO-JCC online]. for the be performed the data from the To the evidence for the of clinical is in of of as when the treatment was the of was not and from studies that patients treatment for are and this an important research from observational studies and for the of and in patients to treatment with The time and the of patients included in the studies of the meta-analysis are to and that may in the reviewed the literature to the approach of using thiopurines an literature we not evidence the two treatment one was of thiopurines was with thiopurines in the of therapy in patients with IBD. The was as was not to data from and CD specific was patients with Crohn’s disease who with the of and we with A Cochrane based on two the same patients who therapy with or [Supplementary available as Supplementary data at ECCO-JCC online]. The same the of for therapy or These results are to an of in the therapy studies included and studies are to the A of when agents are with the and were as 10 in one meta-analysis of patients included in the patients with Crohn’s disease who with the of and we with the basis of a meta-analysis of studies on by the data included were the and groups to be to the relevant PICO question. The result of this not any in maintenance of clinical therapy and [Supplementary and Supplementary available as Supplementary data at ECCO-JCC online]. this meta-analysis was to of in the studies with a are quality data available for clinical in the which is an that follows the of patients in the on the of were in patients with or at years of The meta-analysis by which was not any in with and therapy [Supplementary available as Supplementary data at ECCO-JCC online]. is evidence to or of therapy in Crohn’s disease patients the to therapy be and and be with the randomised

This paper presents the conclusions of a workshop entitled 'Impact of Molecular Genetics on the Classification of Renal Cell Tumours', which was held in Heidelberg in October 1996. The focus on 'renal cell tumours' excludes any discussion of Wilms' tumour and its variants, or of tumours metastatic to the kidneys. The proposed classification subdivides renal cell tumours into benign and malignant parenchymal neoplasms and, where possible, limits each subcategory to the most commonly documented genetic abnormalities. Benign tumours are subclassified into metanephric adenoma and adenofibroma, papillary renal cell adenoma, and renal oncocytoma. Malignant tumours are subclassified into common or conventional renal cell carcinoma; papillary renal cell carcinoma; chromophobe renal cell carcinoma; collecting duct carcinoma, with medullary carcinoma of the kidney; and renal cell carcinoma, unclassified. This classification is based on current genetic knowledge, correlates with recognizable histological findings, and is applicable to routine diagnostic practice.

Background: Severe traumatic injury continues to present challenges to healthcare systems around the world, and post-traumatic bleeding remains a leading cause of potentially preventable death among injured patients. Now in its fifth edition, this document aims to provide guidance on the management of major bleeding and coagulopathy following traumatic injury and encourages adaptation of the guiding principles described here to individual institutional circumstances and resources.

Background A case report is a narrative that describes, for medical, scientific, or educational purposes, a medical problem experienced by one or more patients. Case reports written without guidance from reporting standards are insufficiently rigorous to guide clinical practice or to inform clinical study design. Objective Develop, disseminate, and implement systematic reporting guidelines for case reports. Methods We used a three‐phase consensus process consisting of (1) pre‐meeting literature review and interviews to generate items for the reporting guidelines, (2) a face‐to‐face consensus meeting to draft the reporting guidelines, and (3) post‐meeting feedback, review, and pilot testing, followed by finalization of the case report guidelines. Results This consensus process involved 27 participants and resulted in a 13‐item checklist—a reporting guideline for case reports. The primary items of the checklist are title, key words, abstract, introduction, patient information, clinical findings, timeline, diagnostic assessment, therapeutic interventions, follow‐up and outcomes, discussion, patient perspective, and informed consent. Conclusions We believe the implementation of the CARE (CAse REport) guidelines by medical journals will improve the completeness and transparency of published case reports and that the systematic aggregation of information from case reports will inform clinical study design, provide early signals of effectiveness and harms, and improve healthcare delivery.

BACKGROUND: A case report is a narrative that describes, for medical, scientific, or educational purposes, a medical problem experienced by one or more patients. Case reports written without guidance from reporting standards are insufficiently rigorous to guide clinical practice or to inform clinical study design.Primary Objective. Develop, disseminate, and implement systematic reporting guidelines for case reports. METHODS: We used a three-phase consensus process consisting of (1) pre-meeting literature review and interviews to generate items for the reporting guidelines, (2) a face-to-face consensus meeting to draft the reporting guidelines, and (3) post-meeting feedback, review, and pilot testing, followed by finalization of the case report guidelines. RESULTS: This consensus process involved 27 participants and resulted in a 13-item checklist-a reporting guideline for case reports. The primary items of the checklist are title, key words, abstract, introduction, patient information, clinical findings, timeline, diagnostic assessment, therapeutic interventions, follow-up and outcomes, discussion, patient perspective, and informed consent. CONCLUSIONS: We believe the implementation of the CARE (CAse REport) guidelines by medical journals will improve the completeness and transparency of published case reports and that the systematic aggregation of information from case reports will inform clinical study design, provide early signals of effectiveness and harms, and improve healthcare delivery.

The aim of this review is to summarize the incidence, prevalence, trend in mortality, and general prognosis of coronary heart disease (CHD) and a related condition, acute coronary syndrome (ACS). Although CHD mortality has gradually declined over the last decades in western countries, this condition still causes about one-third of all deaths in people older than 35 years. This evidence, along with the fact that mortality from CHD is expected to continue increasing in developing countries, illustrates the need for implementing effective primary prevention approaches worldwide and identifying risk groups and areas for possible improvement.

There is need for a brief measure of religiosity that can be included in epidemiological surveys to examine relationships between religion and health outcomes. The Duke University Religion Index (DUREL) is a five-item measure of religious involvement, and was developed for use in large cross-sectional and longitudinal observational studies. The instrument assesses the three major dimensions of religiosity that were identified during a consensus meeting sponsored by the National Institute on Aging. Those three dimensions are organizational religious activity, non-organizational religious activity, and intrinsic religiosity (or subjective religiosity). The DUREL measures each of these dimensions by a separate “subscale”, and correlations with health outcomes should be analyzed by subscale in separate models. The overall scale has high test-retest reliability (intra-class correlation = 0.91), high internal consistence (Cronbach’s alpha’s = 0.78–0.91), high convergent validity with other measures of religiosity (r’s = 0.71–0.86), and the factor structure of the DUREL has now been demonstrated and confirmed in separate samples by other independent investigative teams. The DUREL has been used in over 100 published studies conducted throughout the world and is available in 10 languages.

The removal of the acute appendix is one of the most frequently performed surgical procedures. Open surgery associated with therapeutic efficacy has been the treatment of choice for acute appendicitis. However, in consequence of the evolution of endoscopic surgery, the operation can also be performed with minimally invasive surgery. Due to smaller incisions, the laparoscopic approach may be associated with reduced postoperative pain, reduced wound infection rate, and shorter time until return to normal activity.This is an update of the review published in 2010.

INTRODUCTION: Evidence-based recommendations are needed to guide the acute management of the bleeding trauma patient. When these recommendations are implemented patient outcomes may be improved. METHODS: The multidisciplinary Task Force for Advanced Bleeding Care in Trauma was formed in 2005 with the aim of developing a guideline for the management of bleeding following severe injury. This document represents an updated version of the guideline published by the group in 2007 and updated in 2010. Recommendations were formulated using a nominal group process, the Grading of Recommendations Assessment, Development and Evaluation (GRADE) hierarchy of evidence and based on a systematic review of published literature. RESULTS: Key changes encompassed in this version of the guideline include new recommendations on the appropriate use of vasopressors and inotropic agents, and reflect an awareness of the growing number of patients in the population at large treated with antiplatelet agents and/or oral anticoagulants. The current guideline also includes recommendations and a discussion of thromboprophylactic strategies for all patients following traumatic injury. The most significant addition is a new section that discusses the need for every institution to develop, implement and adhere to an evidence-based clinical protocol to manage traumatically injured patients. The remaining recommendations have been re-evaluated and graded based on literature published since the last edition of the guideline. Consideration was also given to changes in clinical practice that have taken place during this time period as a result of both new evidence and changes in the general availability of relevant agents and technologies. CONCLUSIONS: A comprehensive, multidisciplinary approach to trauma care and mechanisms with which to ensure that established protocols are consistently implemented will ensure a uniform and high standard of care across Europe and beyond.

The aim of these guidelines is to update the 2017 clinical practice guideline (CPG) of the European Society of Intensive Care Medicine (ESICM). The scope of this CPG is limited to adult patients and to non-pharmacological respiratory support strategies across different aspects of acute respiratory distress syndrome (ARDS), including ARDS due to coronavirus disease 2019 (COVID-19). These guidelines were formulated by an international panel of clinical experts, one methodologist and patients' representatives on behalf of the ESICM. The review was conducted in compliance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement recommendations. We followed the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach to assess the certainty of evidence and grade recommendations and the quality of reporting of each study based on the EQUATOR (Enhancing the QUAlity and Transparency Of health Research) network guidelines. The CPG addressed 21 questions and formulates 21 recommendations on the following domains: (1) definition; (2) phenotyping, and respiratory support strategies including (3) high-flow nasal cannula oxygen (HFNO); (4) non-invasive ventilation (NIV); (5) tidal volume setting; (6) positive end-expiratory pressure (PEEP) and recruitment maneuvers (RM); (7) prone positioning; (8) neuromuscular blockade, and (9) extracorporeal life support (ECLS). In addition, the CPG includes expert opinion on clinical practice and identifies the areas of future research.

STUDY DESIGN: Prospective, randomized, controlled study of patients with lumbar disc herniations, operated either in a full-endoscopic or microsurgical technique. OBJECTIVE: Comparison of results of lumbar discectomies in full-endoscopic interlaminar and transforaminal technique with the conventional microsurgical technique. SUMMARY OF BACKGROUND DATA: Even with good results, conventional disc operations may result in subsequent damage due to trauma. Endoscopic techniques have become the standard in many areas because of the advantages they offer intraoperatively and after surgery. With the transforaminal and interlaminar techniques, 2 full-endoscopic procedures are available for lumbar disc operations. METHODS: One hundred seventy-eight patients with full-endoscopic or microsurgical discectomy underwent follow-up for 2 years. In addition to general and specific parameters, the following measuring instruments were used: VAS, German version North American Spine Society Instrument, Oswestry Low-Back Pain Disability Questionnaire. RESULTS: After surgery 82% of the patients no longer had leg pain, and 14% had occasional pain. The clinical results were the same in both groups. The recurrence rate was 6.2% with no difference between the groups. The full-endoscopic techniques brought significant advantages in the following areas: back pain, rehabilitation, complications, and traumatization. CONCLUSION: The clinical results of the full-endoscopic technique are equal to those of the microsurgical technique. At the same time, there are advantages in the operation technique and reduced traumatization. With the surgical devices and the possibility of selecting an interlaminar or posterolateral to lateral transforaminal procedure, lumbar disc herniations outside and inside the spinal canal can be sufficiently removed using the full-endoscopic technique, when taking the appropriate criteria into account. Full-endoscopic surgery is a sufficient and safe supplementation and alternative to microsurgical procedures.

OBJECTIVE: To develop a reporting guideline for overviews of reviews of healthcare interventions. DESIGN: Development of the preferred reporting items for overviews of reviews (PRIOR) statement. PARTICIPANTS: Core team (seven individuals) led day-to-day operations, and an expert advisory group (three individuals) provided methodological advice. A panel of 100 experts (authors, editors, readers including members of the public or patients) was invited to participate in a modified Delphi exercise. 11 expert panellists (chosen on the basis of expertise, and representing relevant stakeholder groups) were invited to take part in a virtual face-to-face meeting to reach agreement (≥70%) on final checklist items. 21 authors of recently published overviews were invited to pilot test the checklist. SETTING: International consensus. INTERVENTION: Four stage process established by the EQUATOR Network for developing reporting guidelines in health research: project launch (establish a core team and expert advisory group, register intent), evidence reviews (systematic review of published overviews to describe reporting quality, scoping review of methodological guidance and author reported challenges related to undertaking overviews of reviews), modified Delphi exercise (two online Delphi surveys to reach agreement (≥70%) on relevant reporting items followed by a virtual face-to-face meeting), and development of the reporting guideline. RESULTS: From the evidence reviews, we drafted an initial list of 47 potentially relevant reporting items. An international group of 52 experts participated in the first Delphi survey (52% participation rate); agreement was reached for inclusion of 43 (91%) items. 44 experts (85% retention rate) completed the second Delphi survey, which included the four items lacking agreement from the first survey and five new items based on respondent comments. During the second round, agreement was not reached for the inclusion or exclusion of the nine remaining items. 19 individuals (6 core team and 3 expert advisory group members, and 10 expert panellists) attended the virtual face-to-face meeting. Among the nine items discussed, high agreement was reached for the inclusion of three and exclusion of six. Six authors participated in pilot testing, resulting in minor wording changes. The final checklist includes 27 main items (with 19 sub-items) across all stages of an overview of reviews. CONCLUSIONS: PRIOR fills an important gap in reporting guidance for overviews of reviews of healthcare interventions. The checklist, along with rationale and example for each item, provides guidance for authors that will facilitate complete and transparent reporting. This will allow readers to assess the methods used in overviews of reviews of healthcare interventions and understand the trustworthiness and applicability of their findings.

INTRODUCTION: Evidence-based recommendations are needed to guide the acute management of the bleeding trauma patient, which when implemented may improve patient outcomes. METHODS: The multidisciplinary Task Force for Advanced Bleeding Care in Trauma was formed in 2005 with the aim of developing a guideline for the management of bleeding following severe injury. This document presents an updated version of the guideline published by the group in 2007. Recommendations were formulated using a nominal group process, the Grading of Recommendations Assessment, Development and Evaluation (GRADE) hierarchy of evidence and based on a systematic review of published literature. RESULTS: Key changes encompassed in this version of the guideline include new recommendations on coagulation support and monitoring and the appropriate use of local haemostatic measures, tourniquets, calcium and desmopressin in the bleeding trauma patient. The remaining recommendations have been reevaluated and graded based on literature published since the last edition of the guideline. Consideration was also given to changes in clinical practice that have taken place during this time period as a result of both new evidence and changes in the general availability of relevant agents and technologies. CONCLUSIONS: This guideline provides an evidence-based multidisciplinary approach to the management of critically injured bleeding trauma patients.

Purpose Within a very short period of time, the worldwide pandemic triggered by the novel coronavirus has not only claimed numerous lives but also caused severe limitations to daily private as well as business life. Just about every company has been affected in one way or another. This first empirical study on the effects of the COVID-19 crisis on family firms allows initial conclusions to be drawn about family firm crisis management. Design/methodology/approach Exploratory qualitative research design based on 27 semi-structured interviews with key informants of family firms of all sizes in five Western European countries that are in different stages of the crisis. Findings The COVID-19 crisis represents a new type and quality of challenge for companies. These companies are applying measures that can be assigned to three different strategies to adapt to the crisis in the short term and emerge from it stronger in the long run. Our findings show how companies in all industries and of all sizes adapt their business models to changing environmental conditions within a short period of time. Finally, the findings also show that the crisis is bringing about a significant yet unintended cultural change. On the one hand, a stronger solidarity and cohesion within the company was observed, while on the other hand, the crisis has led to a tentative digitalization. Originality/value To the knowledge of the authors, this is the first empirical study in the management realm on the impacts of COVID-19 on (family) firms. It provides cross-national evidence of family firms' current reactions to the crisis.

BACKGROUND: Certain drugs are classified as potentially inappropriate medications (PIM) for the elderly because they carry an increased risk of adverse drug events in this patient group. PIM lists from other countries are of limited usefulness in Germany because different drugs are on the market in each country and prescribing practices vary as well. Thus, a list of potentially inappropriate medications for the elderly was developed specifically for use in Germany. METHODS: A preliminary PIM list suitable for the German market was created on the basis of a selective literature search and a qualitative analysis of published international PIM lists. The final German PIM list was developed by means of a comprehensive, structured expert survey in two rounds (a so-called Delphi process). RESULTS: 83 drugs in a total of 18 drug classes were rated as potentially inappropriate for elderly patients. For 46 drugs, the experts came to no clear decision after the second Delphi round. For cases in which the administration of a PIM is clinically necessary, the final PRISCUS list contains recommendations for clinical practice, e.g. monitoring of laboratory values and dose adaptation. Therapeutic alternatives are also listed. CONCLUSION: Potentially inappropriate medications carry the risk of causing adverse drug events in the elderly. A drawback of using a Delphi process to generate a PIM list, as was done for the new German list, is that little scientific evidence is currently available for the evaluation of active substances, potential therapeutic alternatives, and indicated monitoring procedures. Thus, the validity and practicability of the PRISCUS list remain to be demonstrated (and the same holds for PIM lists already published in other countries). It should be used as a component of an overall concept for geriatric pharmacotherapy in which polypharmacy and interacting medications are avoided, and doses are regularly re-evaluated.

Obesity is globaLy prevalent and highly heritable, but its underlying genetic factors remain largely elusive. To identify genetic loci for obesity susceptibility, we examined aSociations betwEn body maS index and ĝ̂1/42.8 miLion SNPs in up to 123,865 individuals with targeted foLow up of 42 SNPs in up to 125,931 aDitional individuals. We confirmed 14 known obesity susceptibility loci and identified 18 new loci aSociated with body maS index (P &lt; 5-10 -8 ), one of which includes a copy number variant near GPRC5B. Some loci (at MC4R, POMC, SH2B1 and BDNF) map near key hypothalamic regulators of energy balance, and one of these loci is near GIPR, an incretin receptor. Furthermore, genes in other newly aSociated loci may provide new insights into human body weight regulation. © 2010 Nature America, Inc. All rights reserved.

Chapter 4 TEP versus TAPP: which is better for the patient? Chapter 5 Laparoscopic surgery in complicated hernia: feasibility, risks, and benefits Chapter 6 Mesh size and recurrence: what is the optimal size? Chapter 7 Selection of mesh material Chapter 8 Cutting or not cutting of mesh: does it influence the recurrence rate? Chapter 9 Mesh fixation modalities: is there an association with acute or chronic pain? Chapter 10 Risk factors and prevention of acute and chronic pain Chapter 11 Urogenital complications associated with laparoscopic/endoscopic hernia repair Chapter 12 Intraperitoneal onlay mesh (IPOM) for inguinal hernia repair-still a therapeutic option? Chapter 13 Role for open preperitoneal mesh repair in the era of laparoscopic inguinal hernia repair Chapter 14 Sportsman hernia-diagnosis and treatment