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Background The use of magnetic resonance imaging (MRI) in forensic age estimation has been explored extensively during the past decade. Objective To synthesize the available MRI data for forensic age estimation in living children and young adults, and to provide a comprehensive overview that can guide age estimation practice and future research. Materials and Methods MEDLINE, Embase and Web of Science were searched. Additionally, cited and citing articles and study registers were searched. Two authors independently selected articles, conducted data extraction, and assessed risk of bias. Study populations including living subjects up to 30 years were considered. Results Fifty-five studies were included in qualitative analysis and 33 in quantitative analysis. Most studies suffered from bias, including relatively small European (Caucasian) populations, varying MR-approaches and varying staging techniques. Therefore, pooling of the age distribution data was not appropriate. Reproducibility of staging was remarkably lower in clavicles than in any other anatomical structure. Age estimation performance was in line with the gold standard, which uses radiographs, with mean absolute errors ranging from 0.85 to 2.0 years. The proportion of correctly classified minors ranged from 65% to 91%. Multi-factorial age estimation performed better than based on a single anatomical site. Conclusion More multi-factorial age estimation studies are necessary, together with studies testing if the MRI data can safely be pooled. The current review results can guide future studies, help medical professionals to decide on the preferred approach for specific cases, and help judicial professionals to interpret the evidential value of age estimation results. ispartof: Pediatric Radiology vol:50 issue:12 pages:1-18 ispartof: location:Germany status: published

This umbrella review aims to evaluate the quality, summarize and compare the conclusions of systematic reviews investigating the impact of curative treatment options on health-related quality of life (HRQoL) in muscle-invasive bladder cancer (MIBC). The Cochrane Library, MEDLINE, Embase and Web of Science were searched independently by two authors from inception until 06 January 2020. Systematic reviews and meta-analyses assessing the impact of any curative treatment option on HRQol in MIBC patients were eligible. Risk of bias was assessed using the AMSTAR 2 tool. Thirty-two reviews were included. Robot-assisted RC with extracorporeal urinary diversion and open RC have similar HRQoL (n = 10). Evidence for pelvic organ-sparing RC was too limited (n = 2). Patients with a neobladder showed better overall and physical HRQoL outcomes, but worse urinary function in comparison with ileal conduit (n = 17). Bladder-preserving radiochemotherapy showed slightly better urinary and sexual but worse gastro-intestinal HRQoL outcomes in comparison with RC patients (n = 6). Quality of the reviews was low in more than 50% of the available reviews and most of the studies included in the reviews were nonrandomized studies. This umbrella review gives a comprehensive overview of the available evidence to date.

Background Seriously ill children suffer from numerous symptoms at the end of their lives, including pain, anxiety, and restricted communication. There are currently no comprehensive overviews of which health interventions have proven benefits and which have proven detrimental effects on the quality of life of children in an end-of-life context. In order to identify potential quality indicators to eventually improve care, a systematic review of available evidence is needed. The aim of the current systematic review will be to make an overview of the influence of health interventions on associated outcomes related to quality of life at the end of life in seriously ill children. Methods A systematic search will be conducted in MEDLINE, Embase, CENTRAL, CINAHL, and Web of Science. We will include quantitative empirical designs looking into the influence of a health intervention on (proxies of) quality of life at the end of life in seriously ill children. Three independent authors will review titles and abstracts and screen full texts against eligibility criteria. One reviewer will carry out full data extraction and quality assessment, and a 20% random sample will be extracted and assessed by two independent reviewers. We will use the QualSyst Tool for assessment of the quality of the included studies (QualSyst Tool) for quality assessment; overall strength of the body of evidence will be assessed using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach. An overview table of health interventions will be discussed through narrative synthesis. Should sufficient homogeneous publications arise, we will perform meta-analyses with a random-effects model. Our protocol adheres to the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols (PRISMA-P) checklist for study protocols. Discussion As part of a larger project, we will use the results of this review to identify a first set of quality indicators for the care for children at the end of life. Reviewing the current span of evidence and identifying research gaps will uncover future research priorities into the care for children at the end of life. Systematic review registration PROSPERO CRD42018105109 Electronic supplementary material The online version of this article (10.1186/s13643-019-1059-8) contains supplementary material, which is available to authorized users.

BACKGROUND Children with serious illness suffer from symptoms at the end of life that often fail to be relieved. An overview is required of healthcare interventions improving and decreasing quality of life (QOL) for children with serious illness at the end of life. METHODS A systematic review was performed in five databases, January 2000 to July 2018 without language limit. Reviewers selected quantitative studies with a healthcare intervention, for example, medication or treatment, and QOL outcomes or QOL-related measures, for example, symptoms, for children aged 1-17 years with serious illness. One author assessed outcomes with the QualSyst and GRADE (Grades of Recommendation, Assessment, Development, and Evaluation) Framework; two authors checked a 25% sample. QOL improvement or reduction was categorized. RESULTS Thirty-six studies met the eligibility criteria studying 20 unique interventions. Designs included 1 randomized controlled trial, 1 cross-sectional study, and 34 cohort studies. Patient-reported symptom monitoring increased QOL significantly in cancer patients in a randomized controlled trial. Dexmedetomidine, methadone, ventilation, pleurodesis, and palliative care were significantly associated with improved QOL, and chemotherapy, stem cell transplant, and hospitalization with reduced QOL, in cohort studies. CONCLUSIONS Use of patient-controlled symptom feedback, multidisciplinary palliative care teams with full-time practical support, inhalation therapy, and off-label sedative medication may improve QOL. Curative therapy may reduce QOL. IMPACT QOL for children at the end of life may be improved with patient-controlled symptom feedback, multidisciplinary palliative care teams with full-time practical support, inhalation therapy, and off-label sedative medication. QOL for children at the end of life may be reduced with therapy with a curative intent, such as curative chemotherapy or stem cell transplant. A comprehensive overview of current evidence to elevate currently often-failing QOL management for children at the end of life. New paradigm-level indicators for appropriate and inappropriate QOL management in children at the end of life. New hypotheses for future research, guided by the current knowledge within the field. Various healthcare interventions (as described above) could or might be employed as tools to provide relief in QOL management for children with serious illness, such as cancer, at the end of life, and therefore could be discussed in pediatrician end-of-life training to limit the often-failed QOL management in this population, cave the one-size-fits-all approach for individual cases. Multidisciplinary team efforts and 24/7 presence, especially practical support for parents, might characterize effective palliative care team interventions for children with serious illness at the end of life, suggesting a co-regulating link between well-being of the child partly to that of the parents Hypothesis-oriented research is needed, especially for children with nonmalignant disorders, such as genetic or neurological disorders at the end of life, as well as QOL outcomes for intervention research and psychosocial or spiritual outcomes.

Background: Extensive debate surrounds the practice of continuous sedation until death within end-of-life care. Aim: To provide insight into existing initiatives to support the practice of continuous sedation until death and assess their feasibility and effectiveness. Design: Systematic review and narrative synthesis, registered on PROSPERO (CRD42020149630). Data sources: Records were searched through MEDLINE, EMBASE, CENTRAL, CINAHL, and Web of Science from inception to April 16 2020. Peer-reviewed studies reporting original data on initiatives to support the practice of continuous sedation were included for review. Results: Twenty-one studies met the criteria and were included. Initiatives were focused on assessment tools of consciousness and discomfort (9), the use of guidelines and protocols (8), and expert consultation (3). All initiatives were reported as useful, acceptable, and feasible. Studies on the use of monitoring devices showed that a small proportion of patients were found to be awake, despite the patient being unresponsive according to the observer-based sedation scales. However, the wide range of values of these monitoring devices for comfortable and adequately sedated patients seems to hamper its overall implementation in daily clinical practice. Physicians reported changes in practice conform to guideline recommendations but the shift was modest at best. Expert consultation was regarded as supportive when sufficient expertise is lacking and helpful in avoiding possibly unnecessary sedations. Conclusions: The reviewed initiatives may contribute to improvement of continuous sedation until death, though their evidence base is rather limited. More insight is needed into their feasibility, preconditions for effective implementation and impact in actual practice.

Background & Aims Nonalcoholic fatty liver disease (NAFLD) has become the most common pediatric liver disease. The intrauterine and early life environment can have an important impact on long-term metabolic health. We investigated the impact of maternal prepregnancy obesity, (pre)gestational diabetes, breastfeeding, and birth anthropometrics/preterm birth on the development of NAFLD in children and adolescents. Methods A comprehensive search was performed in MEDLINE, PubMed Central, EMBASE, and grey literature databases through August 2020. The primary outcome was the prevalence of pediatric NAFLD, whereas the histologic severity of steatohepatitis and/or fibrosis were secondary outcomes. Study selection, data extraction, and quality assessment were performed by 2 independent reviewers. Results Our systematic review included 33 articles. Study heterogeneity regarding patient populations, diagnostic tools, and overall quality was considerable. Eight studies determined the impact of maternal prepregnancy overweight/obesity and identified this as a possible modifiable risk factor for pediatric NAFLD. Conversely, 8 studies investigated (pre)gestational diabetes, yet the evidence on its impact is conflicting. Breastfeeding was associated with a reduced risk for NAFLD, steatohepatitis, and fibrosis, especially in studies that evaluated longer periods of breastfeeding. Being born preterm or small for gestational age has an unclear impact on the development of NAFLD, although an early catch-up growth might drive NAFLD. Conclusions In a systematic review, we found that maternal prepregnancy overweight and obesity were associated with an increased risk of pediatric NAFLD. Breastfeeding might be protective against the development of NAFLD when the duration of breastfeeding is sufficiently long (≥6 months).

To provide a comprehensive update on the most prevalent, significant risk factors for neonatal brachial plexus palsy (NBPP).Cochrane CENTRAL, MEDLINE, Web of Science, Embase, and ClinicalTrials.gov were searched for relevant publications up to March 2019. Studies assessing risk factors of NBPP in relation to typically developing comparison individuals were included. Meta-analysis was performed for the five most significant risk factors, on the basis of the PRISMA statement and MOOSE guidelines. Pooled odds ratios (ORs), 95% confidence intervals (CIs), and across-study heterogeneity (ITwenty-two observational studies with a total sample size of 29 419 037 live births were selected. Significant risk factors included shoulder dystocia (OR 115.27; 95% CI 81.35-163.35; IThe incidence of NBPP is decreasing. Shoulder dystocia, macrosomia, maternal diabetes, instrumental delivery, and breech delivery are risk factors for NBPP. Caesarean section appears as a protective factor.The overall incidence of neonatal brachial plexus palsy is 1.74 per 1000 live births. The incidence has declined significantly. Shoulder dystocia, macrosomia, maternal diabetes, instrumental delivery, and breech delivery are the main risk factors. Prevention is difficult owing to unpredictability and often labour-related risk.FACTORES DE RIESGO PARA PARÁLISIS BRAQUIAL NEONATAL: UNA REVISIÓN SISTEMÁTICA Y METAANÁLISIS: OBJETIVO: Proporcionar una actualización completa en los factores de riesgo más prevalentes y significantes para parálisis braquial neonatal (PBN, parálisis de Erb-Duchenne).Se realizaron búsquedas en Cochrane CENTRAL, MEDLINE, páginas de ciencia, Embase, y ClinicalTrials.gov para obtener publicaciones relevantes hasta Marzo del 2019. Se incluyeron estudios que evalúan factores de riesgo para PBN en comparación con niños con desarrollo típico. Se realizó un metaanálisis de los primeros cinco factores de riesgo más significativos sobre la base de declaración PRISMA y las guías MOOSE. Se informaron los odds ratios (OR) agrupados, los intervalos de confianza (IC) del 95 % y la heterogeneidad entra estudios (I2). Se calificó el sesgo de informe y la calidad de la evidencia. Además, evaluamos la incidencia de PBN.Se seleccionaron 22 estudios observacionales con una muestra total de 29.419.037 nacidos vivos. Los factores de riesgo significantes incluyeron: distocia de hombros (OR 115.27; 95% CI 81.35-163.35; I2= 92%), macrosomía (OR 9.75; 95% CI 8.29-11.46; I2= 70%), diabetes gestacional (OR 5.33; 95% CI 3.77-7.55; I2= 59%), parto instrumental (OR 3.8; 95% CI 2.77-5.23 I2= 77%) y presentación podálica (OR 2.49; 95% CI 1.67-3.7; I2= 70%). La cesárea apareció como un factor protector (OR 0.13; 95% CI 0.11-0.16 I2= 41%). La incidencia global combinada de PBN fue de 1.74 por 1000 nacidos vivos. Ha disminuido en los últimos años.La incidencia de PBN está disminuyendo. La distocia de hombros, macrosomía, diabetes gestacional, parto instrumental, y presentación podálica son factores de riesgo para PBN. La cesárea aparece como factor protector.UMA REVISÃO SISTEMÁTICA E METANÁLISE: OBJETIVO: Fornecer uma atualização abrangente sobre os fatores de risco mais prevalentes e significantes para a paralisia neonatal do plexo braquial (PNPP, paralisia de Erb-Duchenne). MÉTODO: Cochrane CENTRAL, MEDLINE, Web of Science, Embase, e ClinicalTrials.gov foram pesquisados quanto a publicações relevantes até março de 2019. Estudos avaliando os fatores de risco para PNPP em relação a indivíduos com desenvolvimento típico foram incluídos. Foi realizada metanálise para os cinco fatores de risco mais significativos, com base nas diretrizes PRISMA e MOOSE. As taxas de risco agrupadas (TRs), intervalos de confiança a 95% (ICs), e heteogeneidade entre estudos (I2) foram reportados. O viés de relato e qualidade da evidência foram pontuados. Adicionalmente, avaliamos a incidência de PNPP.Vinte e dois estudos observacionais com amostra total de 29.419.037 nascidos vivos foram selecionados. Fatores de risco significativos incluíram distocia de ombro, (TR 115,27; IC 95% 81,35-163,35; I2=92%), macrossomia (TR 9,75; IC 95% 8,29-11,46; I2=70%), diabetes (gestational) (TR 5,33; IC 95% 3,77-7,55; I2=59%), parto instrumental (TR 3,8; IC 95% 2,77-5,23; I2=77%), e apresentação pélvica (TR 2,49; IC 95% 1,67-3,7; I2=70%). Parto cesárea foi um fator protetor (TR 0,13; IC 95% 0,11-0,16; I2=41%). A incidência agrupada geral de PNPP foi 1,74 por 1.000 nascidos vivos. A quantidade diminuiu nos últimos anos. INTERPRETAÇÃO: A incidência de PNPP tem diminuído. Distocia de ombro, macrossomia, diabetes materna, parto instrumental e apresentação pélvica são fatores de risco para PNPP. Parto cesárea parece ser um fator protetor.

Chronic diseases are associated with impaired health-related quality of life (HRQoL) outcomes. Comparison of HRQoL outcomes between different diseases and with the general population is of major importance to health economists, epidemiologists, clinicians, and policy makers. The aim of this systematic literature review was to develop a catalogue with EQ-5D scores in chronic non-communicable diseases, and to compare these scores with reference values from the general population. MEDLINE, Embase, and Web of Science were systematically searched independently by two reviewers. Studies were included if they reported mean EQ-5D index values for the adult population and if these scores were compared with the general population. The QualSyst tool for quantitative research was used for quality appraisal. Two hundred and seven articles met the inclusion criteria. An extensive catalogue summarizes the EQ-5D scores in a wide variety of chronic diseases. Mean EQ-5D index values ranged between − 0.20 and 1. Lower EQ-5D scores are reported in chronic diseases compared to the general population, specifically in neurological disorders. Most of the diseases demonstrate a substantial disutility, although a minority of diseases have equal or even higher index scores than the general population. A comprehensive, international catalogue has been developed to provide EQ-5D index scores for diverse chronic diseases compared with reference values based on the available literature. The catalogue gives a clear overview of the existing EQ-5D scores and can be rapidly accessed by researchers worldwide for different applications such as health economic evaluations, decision making, resource allocation, and other policy objectives. Future studies should focus on unexamined diseases and specific patient groups to expand the evidence base on HRQoL in chronic diseases.

This article is part of a new series in this regular feature. The series intend to serve as a road map by sharing expertise and drawing together trends that are relevant to both health science librarians and health informatics professionals. The present article is a collaboration of six medical and health sciences libraries in Belgium and the Flemish library and archive association (VVBAD, n.d., https://www.vvbad.be/). It aims to elucidate the extended, user-tailored approach provided by medical and health sciences libraries in Belgium motivated by the recent changes in user expectations and behaviour.

Background: It is necessary to understand behaviours that contribute to improvement in the quality of end-of-life care; use of behavioural theories allows identification of factors underlying end-of-life care behaviour, but little is known about the extent to which, and in what manner, these theories are used in an end-of-life care research context. Aim: To assess the number of end-of-life care studies that have used behavioural theories, which theories were used, to what extent main constructs were explored/measured and which behavioural outcomes were examined. Design: We conducted a systematic review. The protocol was registered on PROSPERO (CRD42016036009). Data sources: The MEDLINE (PubMed), PsycINFO, EMBASE, Web of Science and CINAHL databases were searched from inception to June 2017. We included studies aimed at understanding or changing end-of-life care behaviours and that explicitly referred to individual behavioural theories. Results: We screened 2231 records by title and abstract, retrieved 43 full-text articles and included 31 studies – 27 quantitative (of which four (quasi-)randomised controlled trials) and four qualitative – for data extraction. More than half used the Theory of Planned Behaviour (9), the Theory of Reasoned Action (4) or the Transtheoretical Model (8). In 9 of 31 studies, the theory was fully used, and 16 of the 31 studies focussed on behaviours in advance care planning. Conclusion: In end-of-life care research, the use of behavioural theories is limited. As many behaviours can determine the quality of care, their more extensive use may be warranted if we want to better understand and influence behaviours and improve end-of-life care.

BACKGROUND Recent literature suggests that more restrictive red blood cell (RBC) transfusion practices are equivalent or better than more liberal transfusion practices. The methodologic quality of guidelines recommending more restrictive transfusion thresholds and their underlying scientific evidence is unclear. Therefore, we aimed to evaluate the quality of the development process of RBC transfusion guidelines and to investigate the underlying evidence of guidelines recommending a more restrictive hemoglobin (Hb) threshold. STUDY DESIGN AND METHODS Via systematic literature screening of relevant databases (NGC, GIN, Medline, and Embase), RBC transfusion guidelines recommending a more restrictive Hb level (

Objective: Summarizing the evidence on the effects of pre- and postoperative exercise and psychosocial rehabilitation interventions on patient-reported outcomes (PROs) and physical fitness in bladder cancer patients undergoing radical cystectomy. Data sources: The Cochrane Central Register of Controlled Trials, MEDLINE, Embase, Web of Science and the Physiotherapy Evidence Database were searched independently by two authors from inception until 10 November 2017. Cited references of the studies and citing references retrieved via Web of Science were also checked. Review methods: Randomized controlled trials (RCTs) and non-randomized studies assessing effects of exercise and psychosocial interventions in bladder cancer patients undergoing radical cystectomy were eligible. Primary outcome measures were PROs and physical fitness. Risk of bias was assessed using the Cochrane Collaboration tool and the Newcastle–Ottawa Scale. Results: Five RCTs (three exercise and two psychosocial studies) and one non-randomized psychosocial study comprising 317 bladder cancer patients were included. Timing of the intervention was preoperative ( n = 2), postoperative ( n = 2) or both pre- and postoperative ( n = 2). Positive effects of exercise were found for physical fitness ( n = 3), some health-related quality-of-life (HRQoL) domains ( n = 2), personal activities in daily living ( n = 1) and muscle strength ( n = 1). Psychosocial interventions showed positive effects on anxiety ( n = 1), fatigue ( n = 1), depression ( n = 1), HRQoL ( n = 1) and posttraumatic growth ( n = 1). Quality assessment showed most shortcomings with sample sizes and strong heterogeneity was observed between studies. Conclusion: The evidence relating to the effects of exercise in bladder cancer is very limited and is even less for psychosocial interventions.

Blood services are reliant upon healthy blood donors to provide a safe and adequate supply of blood products. Inappropriate variables contained within blood donor exclusion criteria can defer potentially appropriate donors. The aim of this systematic review was to examine the effect of low pre-donation blood pressure, as compared with normal blood pressure, on adverse events in allogeneic whole blood donors. A systematic review was performed using highly sensitive search strategies within five databases (Cochrane Central Register of Controlled Trials, CINAHL, Embase, MEDLINE, and Web of Science) from inception date until April 12, 2013. Out of 8305 records, 10 observational studies were identified that addressed the question. Five of these studies (with a combined total of 1,482,020 donations and 2903 donors) included either a statistical analysis or an appropriate study design that controlled for possible confounding factors. Based on the currently available evidence, hypotension has not been shown to be an independent predictive factor for donor complications. However, the overall quality of evidence was rather limited and rated 'low,' using the GRADE approach. In conclusion there is currently no evidence that hypotensive blood donors have a greater risk for donor adverse events compared with their normotensive counterparts.

As part of its strategy Belgian Red Cross-Flanders underpins all its activities with evidence-based guidelines and systematic reviews. The aim of this publication is to describe in detail the methodology used to achieve this goal within an action-oriented organisation, in a timely and cost-effective way.To demonstrate transparency in our methods, we wrote a methodological charter describing the way in which we develop evidence-based materials to support our activities. Criteria were drawn up for deciding on project priority and the choice of different types of projects (scoping reviews, systematic reviews and evidence-based guidelines).While searching for rigorous and realistically attainable methodological standards, we encountered a wide variety in terminology and methodology used in the field of evidence-based practice. Terminologies currently being used by different organisations and institutions include systematic reviews, systematic literature searches, evidence-based guidelines, rapid reviews, pragmatic systematic reviews, and rapid response service. It is not always clear what the definition and methodology is behind these terms and whether they are used consistently. We therefore describe the terminology and methodology used by Belgian Red Cross-Flanders; criteria for making methodological choices and details on the methodology we use are given.In our search for an appropriate methodology, taking into account time and resource constraints, we encountered an enormous variety of methodological approaches and terminology used for evidence-based materials. In light of this, we recommend that authors of evidence-based guidelines and reviews are transparent and clear about the methodology used. To be transparent about our approach, we developed a methodological charter. This charter may inspire other organisations that want to use evidence-based methodology to support their activities.

Chronic diseases are associated with impaired health-related quality of life (HRQoL) outcomes. Comparison of HRQoL outcomes between different diseases and with the general population is of major importance to health economists, epidemiologists, clinicians, and policy makers. The aim of this systematic literature review was to develop a catalogue with EQ-5D scores in chronic non-communicable diseases, and to compare these scores with reference values from the general population. MEDLINE, Embase, and Web of Science were systematically searched independently by two reviewers. Studies were included if they reported mean EQ-5D index values for the adult population and if these scores were compared with the general population. The QualSyst tool for quantitative research was used for quality appraisal. Two hundred and seven articles met the inclusion criteria. An extensive catalogue summarizes the EQ-5D scores in a wide variety of chronic diseases. Mean EQ-5D index values ranged between − 0.20 and 1. Lower EQ-5D scores are reported in chronic diseases compared to the general population, specifically in neurological disorders. Most of the diseases demonstrate a substantial disutility, although a minority of diseases have equal or even higher index scores than the general population. A comprehensive, international catalogue has been developed to provide EQ-5D index scores for diverse chronic diseases compared with reference values based on the available literature. The catalogue gives a clear overview of the existing EQ-5D scores and can be rapidly accessed by researchers worldwide for different applications such as health economic evaluations, decision making, resource allocation, and other policy objectives. Future studies should focus on unexamined diseases and specific patient groups to expand the evidence base on HRQoL in chronic diseases.

Introduction Survivors of muscle invasive bladder cancer (MIBC) experience physical and psychosocial side effects of cancer diagnosis and treatment. These negative side effects have a crucial impact on their health-related quality of life (HRQoL). To date, there is evidence that rehabilitation interventions such as physical activity and psychosocial support have a positive effect on the HRQoL of cancer survivors. Unfortunately, there are no specific guidelines for rehabilitation or survivorship programmes for MIBC survivors. Therefore, this systematic review aims to assess the effects of exercise-based and psychosocial rehabilitation interventions in MIBC survivors. Methods and analysis The approach of this review is consistent with the Cochrane methodology. Randomized controlled trials and non-randomised studies will be included. The population of interest is patients (≥18 years of age) with diagnosis of MIBC or high-risk non-MIBC for whom a radical cystectomy is indicated. There will be two eligible intervention types for inclusion: exercise-based and psychosocial rehabilitation interventions. The primary outcome measures are patient-reported outcomes (eg, HRQoL, fatigue and pain) and physical fitness. Studies will be identified independently by two review authors by searching the Cochrane Central Register of Controlled Trials, MEDLINE, Embase, Web of Science and the Physiotherapy Evidence Database. A third reviewer will be asked by disagreements. Risk of bias will be assessed using the Cochrane Collaboration tool and the Newcastle-Ottawa Scale. Data will be summarised descriptively. If homogeneity of the studies is sufficient, meta-analysis will be undertaken. The broad scope of this review (ie, different interventions and study designs) is needed to have a comprehensive view on effective rehabilitation interventions. Ethics and dissemination Ethics approval is not required, as no primary data will be collected. Results will be disseminated through a peer-reviewed publication.

Inhalation of diesel exhaust particles (DEP) induces an inflammatory reaction in the lung; however, the mechanisms are largely unclear. IL-1β/IL-1RI signaling is crucial in several lung inflammatory responses. Typically, caspase-1 is activated within the NLRP3 inflammasome that recognizes several damage-associated molecular patterns, which results in cleavage of pro–IL-1β into mature IL-1β. In this study, we hypothesized that the NLRP3/caspase-1/IL-1β pathway is critical in DEP-induced lung inflammation. Upon DEP exposure, IL-1RI knockout mice had reduced pulmonary inflammation compared with wild-type mice. Similarly, treatment with rIL-1R antagonist (anakinra) and IL-1β neutralization impaired the DEP-induced lung inflammatory response. Upon DEP exposure, NLRP3 and caspase-1 knockout mice, however, showed similar IL-1β levels and comparable pulmonary inflammation compared with wild-type mice. In conclusion, these data show that the DEP-induced pulmonary inflammation acts through the IL-1β/IL-1RI axis. In addition, DEP initiates inflammation independent of the classical NLRP3/caspase-1 pathway, suggesting that other proteases might be involved.

Chronic obstructive pulmonary disease (COPD) is characterized by pulmonary and extrapulmonary manifestations including systemic inflammation and weight loss. Increased levels of interleukin-6 (IL-6) have been demonstrated in sputum and serum of COPD patients. Therefore, the authors investigated the in vivo role of IL-6 in a murine model of COPD. Wild-type (WT) and IL-6 knockout (KO) mice were exposed subacutely (4 weeks) and chronically (24 weeks) to air or cigarette smoke (CS). Subacute and chronic CS exposure significantly increased pulmonary IL-6 mRNA expression in lung tissue and IL-6 protein levels in bronchoalveolar lavage fluid of WT mice. However, CS-induced accumulation of inflammatory cells at both time points and lymphoid aggregate formation upon chronic CS exposure were independent of IL-6. Chonic CS exposure was associated with a significant failure to gain weight in both WT mice and IL-6 KO mice. Remarkably, air-exposed IL-6 KO mice have lower body weight, serum leptin levels, and adipose tissue mass compared to air-exposed WT mice. In conclusion, IL-6 is of minor importance in CS-induced pulmonary and systemic manifestations in mice, but this study confirms the role for IL-6 as regulator of body weight and body composition.

Leptin, a pleiotropic type I cytokine, was recently demonstrated to be expressed by resident lung cells in chronic obstructive pulmonary disease patients and asymptomatic smokers. To elucidate the functional role of leptin in the onset of chronic obstructive pulmonary disease, we tested leptin-deficient ob/ob mice (C57BL/6), leptin receptor-deficient db/db mice (C57BKS), and littermates in a model of cigarette smoke (CS)-induced pulmonary inflammation. Wild-type (WT) C57BL/6 mice were exposed for 4 or 24 wk to control air or CS. Pulmonary leptin expression was analyzed by immunohistochemistry and real-time PCR. Pulmonary inflammation upon 4 wk CS exposure was evaluated in bronchoalveolar lavage fluid (BALF) and lung tissue of WT, ob/ob, and db/db mice. Immunohistochemical analysis revealed leptin expression in bronchial epithelial cells, pneumocytes, alveolar macrophages, and bronchial/vascular smooth muscle cells. The 4 and 24 wk CS exposure increased leptin expression in bronchial epithelial cells and pneumocytes versus air-exposed WT mice (p < 0.05). The 4 wk CS exposure resulted in increased accumulation of neutrophils, dendritic cells, macrophages, and lymphocytes in BALF and lung tissue of WT, ob/ob, and db/db mice. CS-exposed ob/ob and db/db mice showed in general higher numbers of neutrophils and lower numbers of CD4+, CD8+, and dendritic cells versus CS-exposed WT mice. Consistently, CXCL1 levels were enhanced in BALF of CS-exposed ob/ob and db/db mice versus WT mice (p < 0.05). Exogenous leptin administration completely restored the skewed inflammatory profile in ob/ob mice. These data reveal an important role of leptin in modulating innate and adaptive immunity after CS inhalation in mice.

Recent literature suggests that more restrictive red blood cell (RBC) transfusion practices are equivalent or better than more liberal transfusion practices. The methodologic quality of guidelines recommending more restrictive transfusion thresholds and their underlying scientific evidence is unclear. Therefore, we aimed to evaluate the quality of the development process of RBC transfusion guidelines and to investigate the underlying evidence of guidelines recommending a more restrictive hemoglobin (Hb) threshold.Via systematic literature screening of relevant databases (NGC, GIN, Medline, and Embase), RBC transfusion guidelines recommending a more restrictive Hb level (6,7, or8 g/dL) were included. Four assessors independently evaluated the methodologic quality by scoring the rigor of development domain (AGREE II checklist). The level of evidence served as a reference for the quality of the underlying evidence.The methodologic quality of 13 RBC transfusion guidelines was variable (18%-72%) but highest for those developed by Advancing Transfusion and Cellular Therapies Worldwide (72%), the Task Force of Advanced Bleeding Care in Trauma (70%), and the Dutch Institute for Healthcare Improvement (61%). A Hb level of less than 7 g/dL (intensive care unit patients) or less than 8 g/dL (postoperative patients) were the only thresholds based on high-quality evidence. Only four of 32 recommendations had a high-quality evidence base.Methodologic quality should be guaranteed in future RBC transfusion guideline development to ensure that the best available evidence is captured when recommending restrictive transfusion strategies. More high-quality trials are needed to provide a stronger scientific basis for RBC transfusion guidelines that recommend more restrictive transfusion thresholds.

Background and Objectives Haemochromatosis (HC) is a disorder of iron metabolism, requiring frequent phlebotomy to normalize high serum iron levels. There is currently no consensus relating to the eligibility of these patients to donate blood for transfusion. To gain a better understanding of the policies worldwide, a survey amongst blood services was performed. Materials and Methods A web-based questionnaire was developed and distributed among 44 blood services in 41 countries to identify the different policies relating to patients with HC and blood donation. Results Respondents from 35 blood services (80%) of 33 countries completed the questionnaire. In 24 blood services among them (69%), individuals with genetic susceptibility for HC and/or patients with HC are accepted as blood donors. In approximately one-third of these blood centres (33%), genetic carriers/patients are allowed to donate blood more frequently than regular donors. Prescription from/approval by the patient's treating physician and/or a donor physician is required in the majority of the blood services (87%). Similar policies were identified in a few countries; however, in general, the policies regarding blood donation from patients with HC remain widely variable. Conclusion The results of our survey demonstrate large differences in the blood donation policies regarding carriers/patients with HC illustrating the need for uniform evidence-based and cost-effective policies which could benefit both HC patients and the blood supply around the world.

Chronic obstructive pulmonary disease (COPD) is characterized by infiltration of inflammatory cells, destruction of lung parenchyma, and airway wall remodeling. Hyaluronan (HA) is a component of the extracellular matrix, and low-molecular-weight (LMW) HA fragments have proinflammatory capacities. We evaluated the presence of HA in alveolar and airway walls of C57BL/6 mice that were exposed to air or cigarette smoke (CS) for 4 weeks (subacute) or 24 weeks (chronic). We measured deposition of the extracellular matrix proteins collagen and fibronectin in airway walls and determined the molecular weight of HA purified from lung tissue. In addition, we studied the expression of HA-modulating genes by RT-PCR. HA staining in alveolar walls was significantly enhanced upon chronic CS exposure, whereas HA levels in the airway walls were already significantly higher upon subacute CS exposure and remained elevated upon chronic CS exposure. This differed from the deposition of collagen and fibronectin, which are only elevated at the chronic time point. In lungs of CS-exposed mice, the molecular weight of HA clearly shifted toward more LMW HA fragments. CS exposure significantly increased the mRNA expression of the HA synthase gene Has3 in total lung tissue, whereas the expression of Has1 was decreased. These in vivo studies in an experimental model of COPD show that CS exposure leads to enhanced deposition of (mostly LMW) HA in alveolar and bronchial walls by altering the expression of HA-modulating enzymes. This may contribute to airway wall remodeling and pulmonary inflammation in COPD.

Background Belgian Red Cross-Flanders (BRCFl) is active in many fields including first aid training, for which BRCFl develops evidence-based guidelines according to AGREE II. Objectives Development of evidence-based recommendations for recreational athletes who perform one of 15 sport disciplines, defined by popularity, medical costs and injury risk in Flanders (Belgium). Initiatives concerning wording and accessibility were taken to develop implementable guidelines adapted for laypeople. These guidelines will also be used by the Flemish Government to update its information sources. Methods 10 databases for guidelines, systematic reviews or individual studies were searched and draft recommendations were formulated based on the best current evidence. The quality of evidence was assessed using the GRADE approach. A guideline development group, including a multidisciplinary expert panel (co-authors PV, JB, RM and KP), discussed the draft recommendations while taking into account the evidence, and validated the final recommendations. Results 32 systematic reviews and 2 guidelines that met the methodological criteria were identified as valuable source of studies. Additionally, 73 individual studies were included. The overall quality of the body of evidence varied from moderate to very low. Recommendations, written in active and explicit wording, were organised in a structure in order to be searchable via sports discipline, anatomical localisation, type of intervention, and injury. Discussion Preferences of the target group were taken into account when selecting the sport disciplines and when formulation the evidence-based recommendations. Implications for Guideline Developers/Users Involving the target population is an added value for developing an implementable evidence-based guideline.

Summary Hemochromatosis is a disorder of the iron metabolism, characterized by high body iron content, necessitating frequent phlebotomies to remove excess iron. In some countries, this blood is discarded and not used for blood transfusion because of the non-voluntary character of this donation, and because a potential risk of microbial contamination of the donor blood is assumed. A systematic review was performed in order to collect and critically examine solid evidence with regard to the effectiveness and safety of blood for transfusion when derived from hemochromatosis patients who do not suffer from complications or organ damage. Using three databases (The Cochrane Library, MEDLINE, and Embase) we searched for studies from date of inception until January 2012. Out of 3470 articles, 80 references that were relevant to our question were selected, including many opinion pieces, comments, letters, and narrative reviews. Based on our selection criteria, we finally retained only six observational studies, so evidence on this subject is scarce and furthermore, the strength of the available evidence is low to very low, due to poor study designs. We found no evidence that red blood cell concentrates from hemochromatosis patients without complications of iron overload do not comply with the physiological quality requirements for transfusion, nor that their blood would present a greater risk to recipient safety than blood from non-hemochromatosis donors. However, in vitro findings from two studies suggest that iron-overloaded patients would be more susceptible to bacterial growth, but future in vivo studies are warranted to confirm this. Based on this, we call for harmonization of the blood donor selection policy among countries allowing hemochromatosis patients who do not suffer from complications of iron overload to donate blood, once iron levels are normalized.

Cigarette smoke (CS), the primary risk factor of chronic obstructive pulmonary disease (COPD), leads to pulmonary inflammation through interleukin-1 receptor (IL-1R)I signalling, as determined using COPD mouse models. It is unclear whether interleukin (IL)-1α or IL-1β, activated by the Nlrp3/caspase-1 axis, is the predominant ligand for IL-1RI in CS-induced responses. We exposed wild-type mice (treated with anti-IL-1α or anti-IL-1β antibodies), and IL-1RI knockout (KO), Nlrp3 KO and caspase-1 KO mice to CS for 3 days or 4 weeks and evaluated pulmonary inflammation. Additionally, we measured the levels of IL-1α and IL-1β mRNA (in total lung tissue by RT-PCR) and protein (in induced sputum by ELISA) of never-smokers, smokers without COPD and patients with COPD. In CS-exposed mice, pulmonary inflammation was dependent on IL-1RI and could be significantly attenuated by neutralising IL-1α or IL-1β. Interestingly, CS-induced inflammation occurred independently of IL-1β activation by the Nlrp3/caspase-1 axis. In human subjects, IL-1α and IL-1β were significantly increased in total lung tissue and induced sputum of patients with COPD, respectively, compared with never-smokers. These results suggest that not only IL-1β but also IL-1α should be considered as an important mediator in CS-induced inflammation and COPD.

Background Cigarette smoke (CS) is known to initiate a cascade of mediator release and accumulation of immune and inflammatory cells in the lower airways. We investigated and compared the effects of CS on upper and lower airways, in a mouse model of subacute and chronic CS exposure. Methods C57BL/6 mice were whole-body exposed to mainstream CS or air, for 2, 4 and 24 weeks. Bronchoalveolar lavage fluid (BAL) was obtained and tissue cryosections from nasal turbinates were stained for neutrophils and T cells. Furthermore, we evaluated GCP-2, KC, MCP-1, MIP-3α, RORc, IL-17, FoxP3, and TGF-β1 in nasal turbinates and lungs by RT-PCR. Results In both upper and lower airways, subacute CS-exposure induced the expression of GCP-2, MCP-1, MIP-3α and resulted in a neutrophilic influx. However, after chronic CS-exposure, there was a significant downregulation of inflammation in the upper airways, while on the contrary, lower airway inflammation remained present. Whereas nasal FoxP3 mRNA levels already increased after 2 weeks, lung FoxP3 mRNA increased only after 4 weeks, suggesting that mechanisms to suppress inflammation occur earlier and are more efficient in nose than in lungs. Conclusions Altogether, these data demonstrate that CS induced inflammation may be differently regulated in the upper versus lower airways in mice. Furthermore, these data may help to identify new therapeutic targets in this disease model.

Pentraxin (PTX)3 is involved in antimicrobial defence, apoptotic cell clearance and extracellular matrix stability. As these processes are altered in chronic obstructive pulmonary disease (COPD), we aimed to investigate PTX3 expression in patients with this disease. PTX3 expression was quantified by immunohistochemical staining of lung tissue from never-smokers, smokers without COPD, and in patients with COPD of Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage I, II and III-IV. mRNA expression was examined in total lung tissue by quantitative RT-PCR. PTX3 concentration was measured in induced sputum and plasma by ELISA. PTX3 is mainly localised in the interstitium of the small airways and alveolar walls. There were no significant differences in pulmonary, sputum and plasma PTX3 expression between study groups. However, PTX3 expression in small airways correlated significantly with forced expiratory volume in 1 s (r = 0.35, p = 0.004). In the alveolar walls, PTX3 expression correlated significantly with carbon monoxide transfer coefficient (r = 0.28, p = 0.04). In sputum, PTX3 levels were highly correlated with the number of neutrophils. Finally, systemic levels of PTX3 tended to be lower in severe COPD compared with mild COPD. In COPD, airflow limitation and reduced transfer coefficient for carbon monoxide are associated with lower pulmonary interstitial expression of PTX3.