Showing papers by "Guy's and St Thomas' NHS Foundation Trust published in 2015"
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TL;DR: In the Global Burden of Disease Study 2013 (GBD 2013) as discussed by the authors, the authors used the GBD 2010 methods with some refinements to improve accuracy applied to an updated database of vital registration, survey, and census data.
5,792 citations
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Mohammad H. Forouzanfar1, Lily Alexander, H. Ross Anderson, Victoria F Bachman1 +733 more•Institutions (289)
TL;DR: The Global Burden of Disease, Injuries, and Risk Factor study 2013 (GBD 2013) as discussed by the authors provides a timely opportunity to update the comparative risk assessment with new data for exposure, relative risks, and evidence on the appropriate counterfactual risk distribution.
5,668 citations
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TL;DR: In the Global Burden of Disease Study 2013 (GBD 2013) as mentioned in this paper, the authors estimated the quantities for acute and chronic diseases and injuries for 188 countries between 1990 and 2013.
4,510 citations
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Mohammad H. Forouzanfar1, Lily Alexander1, H. Ross Anderson2, Victoria F Bachman1 +718 more•Institutions (295)
TL;DR: The Global Burden of Disease, Injuries, and Risk Factor study 2013 (GBD 2013) as mentioned in this paper provides a timely opportunity to update the comparative risk assessment with new data for exposure, relative risks, and evidence on the appropriate counterfactual risk distribution.
1,656 citations
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Christopher J L Murray1, Ryan M Barber, Kyle J Foreman2, Ayse Abbasoglu Ozgoren +608 more•Institutions (251)
TL;DR: Patterns of the epidemiological transition with a composite indicator of sociodemographic status, which was constructed from income per person, average years of schooling after age 15 years, and the total fertility rate and mean age of the population, were quantified.
1,609 citations
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TL;DR: The Difficult Airway Management Guidelines as discussed by the authors provide a strategy to manage unanticipated difficulty with tracheal intubation and rapid sequence induction, which emphasizes assessment, preparation, positioning, preoxygenation, maintenance of oxygenation, and minimizing trauma from airway interventions.
Abstract: Theseguidelines provide a strategy to manageunanticipated difficulty with tracheal intubation. Theyare foundedon published evidence. Where evidence is lacking, they have been directed by feedback from members of the Difficult Airway Society and based on expert opinion. These guidelines have been informed by advances in the understanding of crisis management; they emphasize the recognition and declaration of difficulty during airway management. A simplified, single algorithm now covers unanticipated difficulties in both routine intubation and rapid sequence induction. Planning for failed intubation should form part of the pre-induction briefing, particularly for urgent surgery. Emphasis is placed on assessment, preparation, positioning, preoxygenation, maintenance of oxygenation, and minimizing trauma from airway interventions. It is recommended that the number of airway interventions are limited, and blind techniques using a bougie or through supraglottic airway devices have been superseded by video- or fibre-optically guided intubation. If tracheal intubation fails, supraglottic airway devices are recommended to provide a route for oxygenation while reviewing how to proceed. Second-generation devices have advantages and are recommended. When both tracheal intubation and supraglottic airway device insertion have failed, waking the patient is the default option. If at this stage, face-mask oxygenation is impossible in the presence of muscle relaxation, cricothyroidotomy should follow immediately. Scalpel cricothyroidotomy is recommended as the preferred rescue technique and should be practised by all anaesthetists. The plans outlined are designed to be simple and easy to follow. They should be regularly rehearsed and made familiar to the whole theatre team.
1,232 citations
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TL;DR: Subcutaneous secukinumab 300 mg and 150 mg improved the signs and symptoms of psoriatic arthritis, suggesting that secuk inumab is a potential future treatment option for patients with this disorder.
683 citations
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TL;DR: In patients who had an inadequate response to or had unacceptable side effects from hydroxyurea, ruxolitinib was superior to standard therapy in controlling the hematocrit, reducing the spleen volume, and improving symptoms associated with polycythemia vera.
Abstract: Background Ruxolitinib, a Janus kinase (JAK) 1 and 2 inhibitor, was shown to have a clinical benefit in patients with polycythemia vera in a phase 2 study. We conducted a phase 3 open-label study to evaluate the efficacy and safety of ruxolitinib versus standard therapy in patients with polycythemia vera who had an inadequate response to or had unacceptable side effects from hydroxyurea. Methods We randomly assigned phlebotomy-dependent patients with splenomegaly, in a 1:1 ratio, to receive ruxolitinib (110 patients) or standard therapy (112 patients). The primary end point was both hematocrit control through week 32 and at least a 35% reduction in spleen volume at week 32, as assessed by means of imaging. Results The primary end point was achieved in 21% of the patients in the ruxolitinib group versus 1% of those in the standard-therapy group (P<0.001). Hematocrit control was achieved in 60% of patients receiving ruxolitinib and 20% of those receiving standard therapy; 38% and 1% of patients in the two g...
649 citations
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TL;DR: Secuk inumab was more effective than placebo in patients with psoriatic arthritis, which validates interleukin-17A as a therapeutic target, and secondary end points, including the ACR50 response and joint structural damage, were significantly better in the secukinumab groups than in the placebo group.
Abstract: ACR20 response rates at week 24 were significantly higher in the group receiving secukinumab at doses of 150 mg (50.0%) and 75 mg (50.5%) than in those receiving placebo (17.3%) (P<0.001 for both comparisons with placebo). Secondary end points, including the ACR50 response and joint structural damage, were significantly better in the secukinumab groups than in the placebo group. Improvements were sustained through 52 weeks. Infections, including candida, were more common in the secukinumab groups. Throughout the study (mean secukinumab exposure, 438.5 days; mean placebo exposure, 128.5 days), four patients in the secukinumab groups had a stroke (0.6 per 100 patient-years; 95% confidence interval [CI], 0.2 to 1.5), and two had a myocardial infarction (0.3 per 100 patientyears; 95% CI, 0.0 to 1.0), as compared with no patients in the placebo group. CONCLUSIONS Secukinumab was more effective than placebo in patients with psoriatic arthritis, which validates interleukin-17A as a therapeutic target. Infections were more common in the secukinumab groups than in the placebo group. The study was neither large enough nor long enough to evaluate uncommon serious adverse events or the risks associated with long-term use. (Funded by Novartis Pharma; ClinicalTrials.gov number, NCT01392326.)
600 citations
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TL;DR: To estimate procedure‐related risks of miscarriage following amniocentesis and chorionic villus sampling (CVS) based on a systematic review of the literature and a meta‐analysis.
Abstract: Objectives To estimate procedure-related risks of miscarriage following amniocentesis and chorionic villus sampling (CVS) based on a systematic review of the literature and a meta-analysis. Methods A search of MEDLINE, EMBASE, CINHAL and The Cochrane Library (2000-2014) was performed to review relevant citations reporting procedure-related complications of amniocentesis and CVS. Only studies reporting data on more than 1000 procedures were included in this review to minimize the effect of bias from smaller studies. Heterogeneity between studies was estimated using Cochran's Q, the I(2) statistic and Egger bias. Meta-analysis of proportions was used to derive weighted pooled estimates for the risk of miscarriage before 24 weeks' gestation. Incidence-rate difference meta-analysis was used to estimate pooled procedure-related risks. Results The weighted pooled risks of miscarriage following invasive procedures were estimated from analysis of controlled studies including 324 losses in 42 716 women who underwent amniocentesis and 207 losses in 8899 women who underwent CVS. The risk of miscarriage prior to 24 weeks in women who underwent amniocentesis and CVS was 0.81% (95% CI, 0.58-1.08%) and 2.18% (95% CI, 1.61-2.82%), respectively. The background rates of miscarriage in women from the control group that did not undergo any procedures were 0.67% (95% CI, 0.46-0.91%) for amniocentesis and 1.79% (95% CI, 0.61-3.58%) for CVS. The weighted pooled procedure-related risks of miscarriage for amniocentesis and CVS were 0.11% (95% CI, -0.04 to 0.26%) and 0.22% (95% CI, -0.71 to 1.16%), respectively. Conclusion The procedure-related risks of miscarriage following amniocentesis and CVS are much lower than are currently quoted.
555 citations
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TL;DR: In this paper, the association between compliance with the Surviving Sepsis Campaign (SSC) performance bundles and mortality was found to be a significant predictor of mortality in the US.
Abstract: Purpose
To determine the association between compliance with the Surviving Sepsis Campaign (SSC) performance bundles and mortality.
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Marjolein J. Peters1, Roby Joehanes2, Luke C. Pilling3, Claudia Schurmann4 +155 more•Institutions (46)
TL;DR: Differences between transcriptomic age and chronological age are associated with biological features linked to ageing, such as blood pressure, cholesterol levels, fasting glucose, and body mass index and the transcriptomic prediction model adds biological relevance and complements existing epigenetic prediction models.
Abstract: Disease incidences increase with age, but the molecular characteristics of ageing that lead to increased disease susceptibility remain inadequately understood. Here we perform a whole-blood gene expression meta-analysis in 14,983 individuals of European ancestry (including replication) and identify 1,497 genes that are differentially expressed with chronological age. The age-associated genes do not harbor more age-associated CpG-methylation sites than other genes, but are instead enriched for the presence of potentially functional CpG-methylation sites in enhancer and insulator regions that associate with both chronological age and gene expression levels. We further used the gene expression profiles to calculate the 'transcriptomic age' of an individual, and show that differences between transcriptomic age and chronological age are associated with biological features linked to ageing, such as blood pressure, cholesterol levels, fasting glucose, and body mass index. The transcriptomic prediction model adds biological relevance and complements existing epigenetic prediction models, and can be used by others to calculate transcriptomic age in external cohorts.
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Nasim Mavaddat1, Paul D.P. Pharoah1, Kyriaki Michailidou1, Jonathan Tyrer1 +239 more•Institutions (68)
TL;DR: The PRS stratifies breast cancer risk in women both with and without a family history of breast cancer, and the observed level of risk discrimination could inform targeted screening and prevention strategies.
Abstract: Background: Data for multiple common susceptibility alleles for breast cancer may be combined to identify women at different levels of breast cancer risk. Such stratification could guide preventive and screening strategies. However, empirical evidence for genetic risk stratification is lacking. Methods: We investigated the value of using 77 breast cancer-associated single nucleotide polymorphisms (SNPs) for risk stratification, in a study of 33 673 breast cancer cases and 33 381 control women of European origin. We tested all possible pair-wise multiplicative interactions and constructed a 77-SNP polygenic risk score (PRS) for breast cancer overall and by estrogen receptor (ER) status. Absolute risks of breast cancer by PRS were derived from relative risk estimates and UK incidence and mortality rates. Results: There was no strong evidence for departure from a multiplicative model for any SNP pair. Women in the highest 1% of the PRS had a three-fold increased risk of developing breast cancer compared with women in the middle quintile (odds ratio [OR] = 3.36, 95% confidence interval [CI] = 2.95 to 3.83). The ORs for ER-positive and ER-negative disease were 3.73 (95% CI = 3.24 to 4.30) and 2.80 (95% CI = 2.26 to 3.46), respectively. Lifetime risk of breast cancer for women in the lowest and highest quintiles of the PRS were 5.2% and 16.6% for a woman without family history, and 8.6% and 24.4% for a woman with a first-degree family history of breast cancer. Conclusions: The PRS stratifies breast cancer risk in women both with and without a family history of breast cancer. The observed level of risk discrimination could inform targeted screening and prevention strategies. Further discrimination may be achievable through combining the PRS with lifestyle/environmental factors, although these were not considered in this report.
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University of Manchester1, George Washington University2, Bradford Royal Infirmary3, Université libre de Bruxelles4, Hospital Italiano de Buenos Aires5, Kaiser Permanente6, Technion – Israel Institute of Technology7, University of Barcelona8, University of Pavia9, Marshfield Clinic10, University of Toronto11, University of Paris12, University Hospitals Coventry and Warwickshire NHS Trust13, University of Angers14, University of Pisa15, University of Liverpool16, McGill University17, French Institute of Health and Medical Research18, University of Oxford19, University of Santiago de Compostela20, St Mary's Hospital21, University of Colorado Boulder22, NHS Ayrshire and Arran23, University of Udine24, University Hospitals of Leicester NHS Trust25, University of Sydney26, Katholieke Universiteit Leuven27, Istituto Giannina Gaslini28, Monash University29, University of Brescia30, Leeds General Infirmary31, Belfast Health and Social Care Trust32, University of Nantes33, Kocaeli University34, Temple University35, Boston Children's Hospital36, University of Paris-Sud37, University of Greifswald38, HealthPartners39, Guy's and St Thomas' NHS Foundation Trust40, University of Helsinki41, Royal Children's Hospital42, University of São Paulo43, Pierre-and-Marie-Curie University44, Princess Margaret Hospital for Children45, Amrita Vishwa Vidyapeetham46, Aarhus University47, University of British Columbia48, Rikshospitalet–Radiumhospitalet49, University of Milan50, University of Liège51, Mater Dei Hospital52, Karolinska Institutet53, Tel Aviv University54, University of Utah55, Nottingham University Hospitals NHS Trust56, University of Basel57, University of Melbourne58, University Hospital of Wales59, Christian Medical College & Hospital60, Casa Sollievo della Sofferenza61, Ghent University62, VU University Amsterdam63, Mount Sinai St. Luke's and Mount Sinai Roosevelt64, University of Nottingham65, McMaster University66, University of Glasgow67
TL;DR: A robust relationship between mutations in all seven genes with increased type I interferon activity in cerebrospinal fluid and serum, and the increased expression of interferOn‐stimulated gene transcripts in peripheral blood is observed.
Abstract: Aicardi-Goutieres syndrome is an inflammatory disease occurring due to mutations in any of TREX1, RNASEH2A, RNASEH2B, RNASEH2C, SAMHD1, ADAR or IFIH1. We report on 374 patients from 299 families with mutations in these seven genes. Most patients conformed to one of two fairly stereotyped clinical profiles; either exhibiting an in utero disease-onset (74 patients; 22.8% of all patients where data were available), or a post-natal presentation, usually within the first year of life (223 patients; 68.6%), characterized by a sub-acute encephalopathy and a loss of previously acquired skills. Other clinically distinct phenotypes were also observed; particularly, bilateral striatal necrosis (13 patients; 3.6%) and non-syndromic spastic paraparesis (12 patients; 3.4%). We recorded 69 deaths (19.3% of patients with follow-up data). Of 285 patients for whom data were available, 210 (73.7%) were profoundly disabled, with no useful motor, speech and intellectual function. Chilblains, glaucoma, hypothyroidism, cardiomyopathy, intracerebral vasculitis, peripheral neuropathy, bowel inflammation and systemic lupus erythematosus were seen frequently enough to be confirmed as real associations with the Aicardi-Goutieres syndrome phenotype. We observed a robust relationship between mutations in all seven genes with increased type I interferon activity in cerebrospinal fluid and serum, and the increased expression of interferon-stimulated gene transcripts in peripheral blood. We recorded a positive correlation between the level of cerebrospinal fluid interferon activity assayed within one year of disease presentation and the degree of subsequent disability. Interferon-stimulated gene transcripts remained high in most patients, indicating an ongoing disease process. On the basis of substantial morbidity and mortality, our data highlight the urgent need to define coherent treatment strategies for the phenotypes associated with mutations in the Aicardi-Goutieres syndrome-related genes. Our findings also make it clear that a window of therapeutic opportunity exists relevant to the majority of affected patients and indicate that the assessment of type I interferon activity might serve as a useful biomarker in future clinical trials.
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Wrocław Medical University1, Transylvania University2, Seconda Università degli Studi di Napoli3, University of North Carolina at Chapel Hill4, National Institutes of Health5, University of Genoa6, French Institute of Health and Medical Research7, Royal Sussex County Hospital8, Monash University9, Guy's and St Thomas' NHS Foundation Trust10, Boston Children's Hospital11, Nippon Medical School12, University of Amsterdam13, Icahn School of Medicine at Mount Sinai14, King's College London15, Hannover Medical School16, Erasmus University Rotterdam17, University of Zurich18
TL;DR: The international community of allergy specialists recognizes the need to develop a comprehensive consensus report to harmonize, disseminate, and implement the best AIT practice.
Abstract: Allergen immunotherapy (AIT) has been used to treat allergic disease since the early 1900s. Despite numerous clinical trials and meta-analyses proving AIT efficacious, it remains underused and is estimated to be used in less than 10% of patients with allergic rhinitis or asthma worldwide. In addition, there are large differences between regions, which are not only due to socioeconomic status. There is practically no controversy about the use of AIT in the treatment of allergic rhinitis and allergic asthma, but for atopic dermatitis or food allergy, the indications for AIT are not well defined. The elaboration of a wider consensus is of utmost importance because AIT is the only treatment that can change the course of allergic disease by preventing the development of asthma and new allergen sensitizations and by inducing allergen-specific immune tolerance. Safer and more effective AIT strategies are being continuously developed both through elaboration of new allergen preparations and adjuvants and alternate routes of administration. A number of guidelines, consensus documents, or both are available on both the international and national levels. The international community of allergy specialists recognizes the need to develop a comprehensive consensus report to harmonize, disseminate, and implement the best AIT practice. Consequently, the International Collaboration in Asthma, Allergy and Immunology, formed by the European Academy of Allergy and Clinical Immunology; the American Academy of Allergy, Asthma & Immunology; the American College of Allergy, Asthma & Immunology; and the World Allergy Organization, has decided to issue an international consensus on AIT.
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TL;DR: Screening of nulliparous women with universal third trimester fetal biometry roughly tripled detection of small-for-gestational-age (SGA) infants.
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King's College London1, HealthPartners2, Obafemi Awolowo University3, University of Washington4, Fred Hutchinson Cancer Research Center5, University of Liverpool6, University of London7, Guy's and St Thomas' NHS Foundation Trust8, University of Texas Southwestern Medical Center9, Memorial Sloan Kettering Cancer Center10, University of Toronto11, Institut Gustave Roussy12, University of Oxford13, Lund University14, Pontifical Catholic University of Chile15, University of Texas at Austin16, Union for International Cancer Control17, Peking University18, Boston Children's Hospital19, Indiana University20, Harvard University21, Cairo University22, University of Zambia23, University of North Carolina at Chapel Hill24, Leiden University25, European Institute of Oncology26, Amrita Institute of Medical Sciences and Research Centre27, Barwon Health28, Deakin University29, Peking Union Medical College30, Guangdong General Hospital31
TL;DR: To deliver safe, affordable, and timely cancer surgery to all, surgery must be at the heart of global and national cancer control planning and wide equity and economic gaps are found.
Abstract: Surgery is essential for global cancer care in all resource settings. Of the 15.2 million new cases of cancer in 2015, over 80% of cases will need surgery, some several times. By 2030, we estimate that annually 45 million surgical procedures will be needed worldwide. Yet, less than 25% of patients with cancer worldwide actually get safe, affordable, or timely surgery. This Commission on global cancer surgery, building on Global Surgery 2030, has examined the state of global cancer surgery through an analysis of the burden of surgical disease and breadth of cancer surgery, economics and financing, factors for strengthening surgical systems for cancer with multiple-country studies, the research agenda, and the political factors that frame policy making in this area. We found wide equity and economic gaps in global cancer surgery. Many patients throughout the world do not have access to cancer surgery, and the failure to train more cancer surgeons and strengthen systems could result in as much as US $6.2 trillion in lost cumulative gross domestic product by 2030. Many of the key adjunct treatment modalities for cancer surgery--e.g., pathology and imaging--are also inadequate. Our analysis identified substantial issues, but also highlights solutions and innovations. Issues of access, a paucity of investment in public surgical systems, low investment in research, and training and education gaps are remarkably widespread. Solutions include better regulated public systems, international partnerships, super-centralisation of surgical services, novel surgical clinical trials, and new approaches to improve quality and scale up cancer surgical systems through education and training. Our key messages are directed at many global stakeholders, but the central message is that to deliver safe, affordable, and timely cancer surgery to all, surgery must be at the heart of global and national cancer control planning.
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TL;DR: Fedratinib therapy significantly reduced splenomegaly and symptom burden in patients with MF and was accompanied by toxic effects in some patients, the most important being encephalopathy of unknown mechanism.
Abstract: Importance Myelofibrosis (MF) is a BCR-ABL –negative myeloproliferative neoplasm characterized by anemia, splenomegaly, debilitating constitutional symptoms, and shortened survival. Fedratinib, a JAK2-selective inhibitor, previously demonstrated clinically beneficial activity in patients with MF in early-phase trials. Objective To evaluate the efficacy and safety of fedratinib therapy in patients with primary or secondary (post–polycythemia vera or post–essential thrombocythemia) MF. Design, Setting, and Participants Double-blind, randomized, placebo-controlled phase 3 study in 94 sites in 24 countries in which 289 adult patients (≥18 years of age) with intermediate-2 or high-risk primary MF, post–polycythemia vera MF, or post–essential thrombocythemia MF were randomly assigned between December 2011 and September 2012 to once-daily oral fedratinib, at a dose of 400 mg or 500 mg, or placebo, for at least 6 consecutive 4-week cycles. Main Outcomes and Measures The primary end point was spleen response (≥35% reduction in spleen volume from baseline as determined by magnetic resonance imaging or computed tomography) at week 24 and confirmed 4 weeks later. The main secondary end point was symptom response (≥50% reduction in total symptom score, assessed using the modified Myelofibrosis Symptom Assessment Form). Results The primary end point was achieved by 35 of 96 (36% [95% CI, 27%-46%]) and 39 of 97 (40% [95% CI, 30%-50%]) patients in the fedratinib 400-mg and 500-mg groups, vs 1 of 96 (1% [95% CI, 0%-3%]) in the placebo group ( P P Conclusions and Relevance Fedratinib therapy significantly reduced splenomegaly and symptom burden in patients with MF. These benefits were accompanied by toxic effects in some patients, the most important being encephalopathy of unknown mechanism. Clinical development of fedratinib was subsequently discontinued. Trial Registration clinicaltrials.gov identifier:NCT01437787
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Felix R. Day1, Katherine S. Ruth2, Deborah J. Thompson1, Kathryn L. Lunetta1 +238 more•Institutions (50)
TL;DR: A dual strategy to identify common and low-frequency protein-coding variation associated with age at natural menopause and enrichment of signals in or near genes involved in delayed puberty are reported, highlighting the first molecular links between the onset and end of reproductive lifespan.
Abstract: Menopause timing has a substantial impact on infertility and risk of disease, including breast cancer, but the underlying mechanisms are poorly understood. We report a dual strategy in ∼70,000 women to identify common and low-frequency protein-coding variation associated with age at natural menopause (ANM). We identified 44 regions with common variants, including two regions harboring additional rare missense alleles of large effect. We found enrichment of signals in or near genes involved in delayed puberty, highlighting the first molecular links between the onset and end of reproductive lifespan. Pathway analyses identified major association with DNA damage response (DDR) genes, including the first common coding variant in BRCA1 associated with any complex trait. Mendelian randomization analyses supported a causal effect of later ANM on breast cancer risk (∼6% increase in risk per year; P = 3 × 10(-14)), likely mediated by prolonged sex hormone exposure rather than DDR mechanisms.
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TL;DR: This guideline is intended to assist in the clinical care of patients with suspected or confirmed ICED infection in the UK, to inform local infection prevention and treatment policies and guidelines and to be used in the development of educational and training material by the relevant professional societies.
Abstract: Infections related to implantable cardiac electronic devices (ICEDs), including pacemakers, implantable cardiac defibrillators and cardiac resynchronization therapy devices, are increasing in incidence in the USA and are likely to increase in the UK, because more devices are being implanted. These devices have both intravascular and extravascular components and infection can involve the generator, device leads and native cardiac structures or various combinations. ICED infections can be life-threatening, particularly when associated with endocardial infection, and all-cause mortality of up to 35% has been reported. Like infective endocarditis, ICED infections can be difficult to diagnose and manage. This guideline aims to (i) improve the quality of care provided to patients with ICEDs, (ii) provide an educational resource for all relevant healthcare professionals, (iii) encourage a multidisciplinary approach to ICED infection management, (iv) promote a standardized approach to the diagnosis, management, surveillance and prevention of ICED infection through pragmatic evidence-rated recommendations, and (v) advise on future research projects/audit. The guideline is intended to assist in the clinical care of patients with suspected or confirmed ICED infection in the UK, to inform local infection prevention and treatment policies and guidelines and to be used in the development of educational and training material by the relevant professional societies. The questions covered by the guideline are presented at the beginning of each section.
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TL;DR: After accounting for relevant covariates, ustekinumab had the highest first-course drug survival, and will aid clinical decision making when choosing biologic therapy for psoriasis patients.
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University Hospitals Birmingham NHS Foundation Trust1, Peter MacCallum Cancer Centre2, Leiden University3, University of Turin4, Memorial Sloan Kettering Cancer Center5, Ohio State University6, University of Wisconsin-Madison7, University of Bordeaux8, Yale University9, University of Paris10, Northwestern University11, University of Barcelona12, National and Kapodistrian University of Athens13, University of Tokyo14, University of Copenhagen15, University of São Paulo16, University of Milan17, Tel Aviv University18, Complutense University of Madrid19, Medical University of Vienna20, University of Florence21, University of Pennsylvania22, University of Bologna23, Autonomous University of Barcelona24, City of Hope National Medical Center25, Guy's and St Thomas' NHS Foundation Trust26, University of Texas MD Anderson Cancer Center27, Stanford University28
TL;DR: This study includes the largest cohort of patients with advanced-stage MF/SS and identifies markers with independent prognostic value, which, used together in a prognostic index, may be useful to stratifyadvanced-stage patients.
Abstract: Purpose Advanced-stage mycosis fungoides (MF; stage IIB to IV) and Sezary syndrome (SS) are aggressive lymphomas with a median survival of 1 to 5 years. Clinical management is stage based; however, there is wide range of outcome within stages. Published prognostic studies in MF/SS have been single-center trials. Because of the rarity of MF/SS, only a large collaboration would power a study to identify independent prognostic markers. Patients and Methods Literature review identified the following 10 candidate markers: stage, age, sex, cutaneous histologic features of folliculotropism, CD30 positivity, proliferation index, large-cell transformation, WBC/lymphocyte count, serum lactate dehydrogenase, and identical T-cell clone in blood and skin. Data were collected at specialist centers on patients diagnosed with advanced-stage MF/SS from 2007. Each parameter recorded at diagnosis was tested against overall survival (OS). Results Staging data on 1,275 patients with advanced MF/SS from 29 international sites ...
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TL;DR: This is the first systematic review of the quality and appropriateness of tools designed to monitor progress and outcomes of young children with ASD and it was not possible to recommend fully robust tools at this stage.
Abstract: BACKGROUND: The needs of children with autism spectrum disorder (ASD) are complex and this is reflected in the number and diversity of outcomes assessed and measurement tools used to collect evidence about children's progress. Relevant outcomes include improvement in core ASD impairments, such as communication, social awareness, sensory sensitivities and repetitiveness; skills such as social functioning and play; participation outcomes such as social inclusion; and parent and family impact. OBJECTIVES: To examine the measurement properties of tools used to measure progress and outcomes in children with ASD up to the age of 6 years. To identify outcome areas regarded as important by people with ASD and parents. METHODS: The MeASURe (Measurement in Autism Spectrum disorder Under Review) research collaboration included ASD experts and review methodologists. We undertook systematic review of tools used in ASD early intervention and observational studies from 1992 to 2013; systematic review, using the COSMIN checklist (Consensus-based Standards for the selection of health Measurement Instruments) of papers addressing the measurement properties of identified tools in children with ASD; and synthesis of evidence and gaps. The review design and process was informed throughout by consultation with stakeholders including parents, young people with ASD, clinicians and researchers. RESULTS: The conceptual framework developed for the review was drawn from the International Classification of Functioning, Disability and Health, including the domains 'Impairments', 'Activity Level Indicators', 'Participation', and 'Family Measures'. In review 1, 10,154 papers were sifted - 3091 by full text - and data extracted from 184; in total, 131 tools were identified, excluding observational coding, study-specific measures and those not in English. In review 2, 2665 papers were sifted and data concerning measurement properties of 57 (43%) tools were extracted from 128 papers. Evidence for the measurement properties of the reviewed tools was combined with information about their accessibility and presentation. Twelve tools were identified as having the strongest supporting evidence, the majority measuring autism characteristics and problem behaviour. The patchy evidence and limited scope of outcomes measured mean these tools do not constitute a 'recommended battery' for use. In particular, there is little evidence that the identified tools would be good at detecting change in intervention studies. The obvious gaps in available outcome measurement include well-being and participation outcomes for children, and family quality-of-life outcomes, domains particularly valued by our informants (young people with ASD and parents). CONCLUSIONS: This is the first systematic review of the quality and appropriateness of tools designed to monitor progress and outcomes of young children with ASD. Although it was not possible to recommend fully robust tools at this stage, the review consolidates what is known about the field and will act as a benchmark for future developments. With input from parents and other stakeholders, recommendations are made about priority targets for research. FUTURE WORK: Priorities include development of a tool to measure child quality of life in ASD, and validation of a potential primary outcome tool for trials of early social communication intervention. STUDY REGISTRATION: This study is registered as PROSPERO CRD42012002223. FUNDING: The National Institute for Health Research Health Technology Assessment programme.
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Public Health England1, University of Manchester2, University of Oxford3, Institute for Health Metrics and Evaluation4, University of London5, John Radcliffe Hospital6, Green Templeton College7, St George's, University of London8, Population Health Research Institute9, University of Birmingham10, King's College London11, Queen Mary University of London12, Anglia Ruskin University13, University of Cambridge14, University of Liverpool15, University of Leicester16, Great Ormond Street Hospital17, University of Southampton18, Guy's and St Thomas' NHS Foundation Trust19, Imperial College London20, University of Sheffield21, University of Bristol22, Ulster University23, Wellcome Trust Centre for Human Genetics24, University College London25, Aintree University Hospitals NHS Foundation Trust26, Swansea University27, University of Cape Town28, University of York29, Newcastle University30, West Hertfordshire Hospitals NHS Trust31, The George Institute for Global Health32, Mid Sweden University33, British Heart Foundation34, Northumbria University35, University of Edinburgh36, Imperial College Healthcare37, NHS England38, University of Nottingham39, Royal Cornwall Hospital40, London School of Economics and Political Science41
TL;DR: In the Global Burden of Disease Study 2013 (GBDDS) as discussed by the authors, knowledge about health and its determinants has been integrated into a comparable framework to inform health policy.
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TL;DR: In resource-limited settings, TB accounts for approximately 40% of facility-based HIV/AIDS-related adult deaths and almost half of this disease remains undiagnosed at the time of death, highlighting the critical need to improve the prevention, diagnosis and treatment of HIV-associated TB globally.
Abstract: Objectives:
Tuberculosis (TB) is estimated to be the leading cause of HIV-related deaths globally. However, since HIV-associated TB frequently remains unascertained, we systematically reviewed autopsy studies to determine the true burden of TB at death.
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TL;DR: This data set reveals traits associated with loci known to confer autoimmune susceptibility, providing mechanistic hypotheses linking immune traits with the etiology of disease, and establishes a bioresource that links genetic control elements associated with normal immune traits to common autoimmune and infectious diseases.
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TL;DR: This work discovers and validate six previously unknown risk loci for PBC and used pathway analysis to identify JAK-STAT/IL12/IL27 signalling and cytokine–cytokine pathways, for which relevant therapies exist.
Abstract: Primary biliary cirrhosis (PBC) is a classical autoimmune liver disease for which effective immunomodulatory therapy is lacking. Here we perform meta-analyses of discovery data sets from genome-wide association studies of European subjects (n=2,764 cases and 10,475 controls) followed by validation genotyping in an independent cohort (n=3,716 cases and 4,261 controls). We discover and validate six previously unknown risk loci for PBC (Pcombined<5 × 10(-8)) and used pathway analysis to identify JAK-STAT/IL12/IL27 signalling and cytokine-cytokine pathways, for which relevant therapies exist.
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TL;DR: Most young ASD children met the criteria for additional psychopathology, and boys were more likely to have oppositional defiant disorder and higher IQ was associated with anxiety disorders and older age with agoraphobia.
Abstract: We employed a clinical sample of young children with ASD, with and without intellectual disability, to determine the rate and type of psychiatric disorders and possible association with risk factors. We assessed 101 children (57 males, 44 females) aged 4.5–9.8 years. 90.5 % of the sample met the criteria. Most common diagnoses were: generalized anxiety disorder (66.5 %), specific phobias (52.7 %) and attention deficit hyperactivity disorder (59.1 %). Boys were more likely to have oppositional defiant disorder (OR 3.9). Higher IQ was associated with anxiety disorders (OR 2.9) and older age with agoraphobia (OR 5.8). Night terrors was associated with parental psychological distress (OR 14.2). Most young ASD children met the criteria for additional psychopathology.
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TL;DR: The BTS Home Oxygen Guideline provides expert consensus opinion in areas where clinical evidence is lacking, and seeks to deliver improved prescribing practice, leading to improved compliance and improved patient outcomes, with consequent increased value to the health service.
Abstract: The British Thoracic Society (BTS) Home Oxygen Guideline provides detailed evidence-based guidance for the use of home oxygen for patients out of hospital. Although the majority of evidence comes from the use of oxygen in patients with chronic obstructive pulmonary disease, the scope of the guidance includes patients with a variety of long-term respiratory illnesses and other groups in whom oxygen is currently ordered, such as those with cardiac failure, cancer and end-stage cardiorespiratory disease, terminal illness or cluster headache. It explores the evidence base for the use of different modalities of oxygen therapy and patient-related outcomes such as mortality, symptoms and quality of life. The guideline also makes recommendations for assessment and follow-up protocols, and risk assessments, particularly in the clinically challenging area of home oxygen users who smoke. The guideline development group is aware of the potential for confusion sometimes caused by the current nomenclature for different types of home oxygen, and rather than renaming them, has adopted the approach of clarifying those definitions, and in particular emphasising what is meant by long-term oxygen therapy and palliative oxygen therapy. The home oxygen guideline provides expert consensus opinion in areas where clinical evidence is lacking, and seeks to deliver improved prescribing practice, leading to improved compliance and improved patient outcomes, with consequent increased value to the health service.
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TL;DR: The available evidence suggests, however, that both EC and secondary inorganic aerosols are associated with adverse health effects.
Abstract: Short-term exposure to fine particle mass (PM) has been associated with adverse health effects, but little is known about the relative toxicity of particle components. We conducted a systematic review to quantify the associations between particle components and daily mortality and hospital admissions. Medline, Embase and Web of Knowledge were searched for time series studies of sulphate (SO4(2-)), nitrate (NO3(-)), elemental and organic carbon (EC and OC), particle number concentrations (PNC) and metals indexed to October 2013. A multi-stage sifting process identified eligible studies and effect estimates for meta-analysis. SO4(2-), NO3(-), EC and OC were positively associated with increased all-cause, cardiovascular and respiratory mortality, with the strongest associations observed for carbon: 1.30% (95% CI: 0.17%, 2.43%) increase in all-cause mortality per 1 μg/m(3). For PNC, the majority of associations were positive with confidence intervals that overlapped 0%. For metals, there were insufficient estimates for meta-analysis. There are important gaps in our knowledge of the health effects associated with short-term exposure to particle components, and the literature also lacks sufficient geographical coverage and analyses of cause-specific outcomes. The available evidence suggests, however, that both EC and secondary inorganic aerosols are associated with adverse health effects.