Showing papers by "University of Calgary published in 2018"
Institute for Systems Biology1, BC Cancer Agency2, University of California, San Francisco3, University of North Carolina at Chapel Hill4, Columbia University5, Discovery Institute6, Massachusetts Institute of Technology7, Arizona State University8, Sage Bionetworks9, Harvard University10, Johns Hopkins University11, Stanford University12, University of Calgary13, Université libre de Bruxelles14, University of Texas MD Anderson Cancer Center15, Medical College of Wisconsin16, Qatar Airways17, Cold Spring Harbor Laboratory18, University of São Paulo19, Henry Ford Hospital20, University of Alabama at Birmingham21, Van Andel Institute22, Stony Brook University23
TL;DR: An extensive immunogenomic analysis of more than 10,000 tumors comprising 33 diverse cancer types by utilizing data compiled by TCGA identifies six immune subtypes that encompass multiple cancer types and are hypothesized to define immune response patterns impacting prognosis.
3,246 citations
Jeffrey D. Stanaway1, Ashkan Afshin1, Emmanuela Gakidou1, Stephen S Lim1 +1050 more•Institutions (346)
TL;DR: This study estimated levels and trends in exposure, attributable deaths, and attributable disability-adjusted life-years (DALYs) by age group, sex, year, and location for 84 behavioural, environmental and occupational, and metabolic risks or groups of risks from 1990 to 2017 and explored the relationship between development and risk exposure.
2,910 citations
University of Southern California1, Stanford University2, University of Iowa3, Brown University4, Ohio State University5, University of Cincinnati6, Medical University of South Carolina7, New York University8, Harvard University9, University of Texas Health Science Center at Houston10, University of Pennsylvania11, Northwestern University12, University of Calgary13
TL;DR: Endovascular thrombectomy for ischemic stroke 6 to 16 hours after a patient was last known to be well plus standard medical therapy resulted in better functional outcomes than standard medical Therapy alone among patients with proximal middle‐cerebral‐artery or internal‐carotid‐arterY occlusion and a region of tissue that was ischeMIC but not yet infarcted.
Abstract: Background Thrombectomy is currently recommended for eligible patients with stroke who are treated within 6 hours after the onset of symptoms. Methods We conducted a multicenter, randomized, open-label trial, with blinded outcome assessment, of thrombectomy in patients 6 to 16 hours after they were last known to be well and who had remaining ischemic brain tissue that was not yet infarcted. Patients with proximal middle-cerebral-artery or internal-carotid-artery occlusion, an initial infarct size of less than 70 ml, and a ratio of the volume of ischemic tissue on perfusion imaging to infarct volume of 1.8 or more were randomly assigned to endovascular therapy (thrombectomy) plus standard medical therapy (endovascular-therapy group) or standard medical therapy alone (medical-therapy group). The primary outcome was the ordinal score on the modified Rankin scale (range, 0 to 6, with higher scores indicating greater disability) at day 90. Results The trial was conducted at 38 U.S. centers and termina...
2,292 citations
Ottawa Hospital Research Institute1, Jewish General Hospital2, McGill University3, University of Ottawa4, University of Amsterdam5, Canadian Agency for Drugs and Technologies in Health6, Paris Descartes University7, University of Birmingham8, Brown University9, Utrecht University10, University of Exeter11, University of Sydney12, Public Health Agency of Canada13, University of Bern14, University of Split15, University of Calgary16, University of Bristol17
TL;DR: A group of 24 multidisciplinary experts used a systematic review of articles on existing reporting guidelines and methods, a 3-round Delphi process, a consensus meeting, pilot testing, and iterative refinement to develop the PRISMA diagnostic test accuracy guideline.
Abstract: Importance Systematic reviews of diagnostic test accuracy synthesize data from primary diagnostic studies that have evaluated the accuracy of 1 or more index tests against a reference standard, provide estimates of test performance, allow comparisons of the accuracy of different tests, and facilitate the identification of sources of variability in test accuracy. Objective To develop the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) diagnostic test accuracy guideline as a stand-alone extension of the PRISMA statement. Modifications to the PRISMA statement reflect the specific requirements for reporting of systematic reviews and meta-analyses of diagnostic test accuracy studies and the abstracts for these reviews. Design Established standards from the Enhancing the Quality and Transparency of Health Research (EQUATOR) Network were followed for the development of the guideline. The original PRISMA statement was used as a framework on which to modify and add items. A group of 24 multidisciplinary experts used a systematic review of articles on existing reporting guidelines and methods, a 3-round Delphi process, a consensus meeting, pilot testing, and iterative refinement to develop the PRISMA diagnostic test accuracy guideline. The final version of the PRISMA diagnostic test accuracy guideline checklist was approved by the group. Findings The systematic review (produced 64 items) and the Delphi process (provided feedback on 7 proposed items; 1 item was later split into 2 items) identified 71 potentially relevant items for consideration. The Delphi process reduced these to 60 items that were discussed at the consensus meeting. Following the meeting, pilot testing and iterative feedback were used to generate the 27-item PRISMA diagnostic test accuracy checklist. To reflect specific or optimal contemporary systematic review methods for diagnostic test accuracy, 8 of the 27 original PRISMA items were left unchanged, 17 were modified, 2 were added, and 2 were omitted. Conclusions and Relevance The 27-item PRISMA diagnostic test accuracy checklist provides specific guidance for reporting of systematic reviews. The PRISMA diagnostic test accuracy guideline can facilitate the transparent reporting of reviews, and may assist in the evaluation of validity and applicability, enhance replicability of reviews, and make the results from systematic reviews of diagnostic test accuracy studies more useful.
1,616 citations
Verneri Anttila1, Verneri Anttila2, Brendan Bulik-Sullivan1, Brendan Bulik-Sullivan2 +717 more•Institutions (270)
TL;DR: It is demonstrated that, in the general population, the personality trait neuroticism is significantly correlated with almost every psychiatric disorder and migraine, and it is shown that both psychiatric and neurological disorders have robust correlations with cognitive and personality measures.
Abstract: Disorders of the brain can exhibit considerable epidemiological comorbidity and often share symptoms, provoking debate about their etiologic overlap. We quantified the genetic sharing of 25 brain disorders from genome-wide association studies of 265,218 patients and 784,643 control participants and assessed their relationship to 17 phenotypes from 1,191,588 individuals. Psychiatric disorders share common variant risk, whereas neurological disorders appear more distinct from one another and from the psychiatric disorders. We also identified significant sharing between disorders and a number of brain phenotypes, including cognitive measures. Further, we conducted simulations to explore how statistical power, diagnostic misclassification, and phenotypic heterogeneity affect genetic correlations. These results highlight the importance of common genetic variation as a risk factor for brain disorders and the value of heritability-based methods in understanding their etiology.
1,357 citations
King's College London1, University of Nottingham2, University of Naples Federico II3, Royal College of Surgeons in Ireland4, Swansea University5, University of Calgary6, University of Melbourne7, Scripps Research Institute8, University of California, San Diego9, Nanjing Medical University10, University of Liverpool11, La Trobe University12, University College London13, Universidade Federal de Minas Gerais14, University of Bath15, Queen Mary University of London16
TL;DR: The guidelines have been simplified for ease of understanding by authors, to make it more straightforward for peer reviewers to check compliance and to facilitate the curation of the journal's efforts to improve standards.
Abstract: This article updates the guidance published in 2015 for authors submitting papers to British Journal of Pharmacology (Curtis et al., 2015) and is intended to provide the rubric for peer review. Thus, it is directed towards authors, reviewers and editors. Explanations for many of the requirements were outlined previously and are not restated here. The new guidelines are intended to replace those published previously. The guidelines have been simplified for ease of understanding by authors, to make it more straightforward for peer reviewers to check compliance and to facilitate the curation of the journal's efforts to improve standards.
1,070 citations
TL;DR: This study offers novel insights into the formation, localization, and release of biogenic SeNS generated by two different Gram-negative bacterial strains under aerobic and metabolically controlled growth conditions.
Abstract: Stenotrophomonas maltophilia SeITE02 and Ochrobactrum sp. MPV1 were isolated from the rhizosphere soil of the selenium-hyperaccumulator legume Astragalus bisulcatus and waste material from a dumping site for roasted pyrites, respectively. Here, these bacterial strains were studied as cell factories to generate selenium-nanostructures (SeNS) under metabolically controlled growth conditions. Thus, a defined medium (DM) containing either glucose or pyruvate as carbon and energy source along with selenite () was tested to evaluate bacterial growth, oxyanion bioconversion and changes occurring in SeNS features with respect to those generated by these strains grown on rich media. Transmission electron microscopy (TEM) images show extra- or intra-cellular emergence of SeNS in SeITE02 or MPV1 respectively, revealing the presence of two distinct biological routes of SeNS biogenesis. Indeed, the stress exerted by upon SeITE02 cells triggered the production of membrane vesicles (MVs), which surrounded Se-nanoparticles (SeNPsSeITE02-G_e and SeNPsSeITE02-P_e with average diameter of 179 ± 56 and 208 ± 60 nm, respectively), as highlighted by TEM and scanning electron microscopy (SEM), strongly suggesting that MVs might play a crucial role in the excreting mechanism of the SeNPs in the extracellular environment. On the other hand, MPV1 strain biosynthesized intracellular inclusions likely containing hydrophobic storage compounds and SeNPs (123 ± 32 nm) under pyruvate conditioning, while the growth on glucose as the only source of carbon and energy led to the production of a mixed population of intracellular SeNPs (118 ± 36 nm) and nanorods (SeNRs; average length of 324 ± 89). SEM, fluorescence spectroscopy, and confocal laser scanning microscopy (CLSM) revealed that the biogenic SeNS were enclosed in an organic material containing proteins and amphiphilic molecules, possibly responsible for the high thermodynamic stability of these nanomaterials. Finally, the biogenic SeNS extracts were photoluminescent upon excitation ranging from 380 to 530 nm, whose degree of fluorescence emission (λem = 416-640 nm) was comparable to that from chemically synthesized SeNPs with L-cysteine (L-cys SeNPs). This study offers novel insights into the formation, localization, and release of biogenic SeNS generated by two different Gram-negative bacterial strains under aerobic and metabolically controlled growth conditions. The work strengthens the possibility of using these bacterial isolates as eco-friendly biocatalysts to produce high quality SeNS targeted to possible biomedical applications and other biotechnological purposes.
955 citations
University of British Columbia1, University of Toronto2, University of Michigan3, University of Minnesota4, McMaster University5, University of Western Ontario6, McGill University7, Dalhousie University8, University of Calgary9, Queen's University10, Kyushu University11, University of São Paulo12, Stanford University13, Case Western Reserve University14, University of Barcelona15, University of Sydney16, George Washington University17, Deakin University18
TL;DR: These 2018 CANMAT and ISBD Bipolar Treatment Guidelines represent the significant advances in the field since the last full edition was published in 2005, including updates to diagnosis and management as well as new research into pharmacological and psychological treatments.
Abstract: The Canadian Network for Mood and Anxiety Treatments (CANMAT) previously published treatment guidelines for bipolar disorder in 2005, along with international commentaries and subsequent updates in 2007, 2009, and 2013. The last two updates were published in collaboration with the International Society for Bipolar Disorders (ISBD). These 2018 CANMAT and ISBD Bipolar Treatment Guidelines represent the significant advances in the field since the last full edition was published in 2005, including updates to diagnosis and management as well as new research into pharmacological and psychological treatments. These advances have been translated into clear and easy to use recommendations for first, second, and third- line treatments, with consideration given to levels of evidence for efficacy, clinical support based on experience, and consensus ratings of safety, tolerability, and treatment-emergent switch risk. New to these guidelines, hierarchical rankings were created for first and second- line treatments recommended for acute mania, acute depression, and maintenance treatment in bipolar I disorder. Created by considering the impact of each treatment across all phases of illness, this hierarchy will further assist clinicians in making evidence-based treatment decisions. Lithium, quetiapine, divalproex, asenapine, aripiprazole, paliperidone, risperidone, and cariprazine alone or in combination are recommended as first-line treatments for acute mania. First-line options for bipolar I depression include quetiapine, lurasidone plus lithium or divalproex, lithium, lamotrigine, lurasidone, or adjunctive lamotrigine. While medications that have been shown to be effective for the acute phase should generally be continued for the maintenance phase in bipolar I disorder, there are some exceptions (such as with antidepressants); and available data suggest that lithium, quetiapine, divalproex, lamotrigine, asenapine, and aripiprazole monotherapy or combination treatments should be considered first-line for those initiating or switching treatment during the maintenance phase. In addition to addressing issues in bipolar I disorder, these guidelines also provide an overview of, and recommendations for, clinical management of bipolar II disorder, as well as advice on specific populations, such as women at various stages of the reproductive cycle, children and adolescents, and older adults. There are also discussions on the impact of specific psychiatric and medical comorbidities such as substance use, anxiety, and metabolic disorders. Finally, an overview of issues related to safety and monitoring is provided. The CANMAT and ISBD groups hope that these guidelines become a valuable tool for practitioners across the globe.
950 citations
University of Melbourne1, University of British Columbia2, New York University3, Federal University of São Paulo4, French Institute of Health and Medical Research5, University of California, Los Angeles6, Albert Einstein College of Medicine7, Children's Hospital Los Angeles8, University of Pavia9, Karolinska Institutet10, University of Calgary11, Peking University12, Royal Hospital for Sick Children13, University of Glasgow14
TL;DR: The International League Against Epilepsy Classification of the Epilepsies has been updated to reflect the gain in understanding of the epilepsies and their underlying mechanisms following the major scientific advances that have taken place since the last ratified classification in 1989.
Abstract: The International League Against Epilepsy (ILAE) classification of the epilepsies has been updated to reflect the gain in understanding of the epilepsies and their underlying mechanisms following the major scientific advances that have taken place since the last ratified classification in 1989. As a critical tool for the practicing clinician, epilepsy classification must be relevant and dynamic to changes in thinking, yet robust and translatable to all areas of the globe. Its primary purpose is for the clinical diagnosis of patients but it is also critical for epilepsy research, development of antiepileptic treatment and communication around the world. The new classification is based on a draft document submitted for public comments in 2013, which was revised to incorporate extensive feedback from the international epilepsy community over several rounds of consultation. It consists of three levels starting with seizure type, where it is assumed that the epileptic seizures of the patient are defined by the new 2017 ILAE seizure classification. After diagnosis of the seizure type, the next step is the diagnosis of the epilepsy type, which includes focal epilepsy, generalized epilepsy, combined generalized and focal epilepsy and also an unclassified epilepsy group. At the third level the disease is assigned to a specific epilepsy syndrome. The new classification incorporates etiology at each stage, emphasizing the need to consider etiology at each step of the diagnosis, as it often carries significant treatment implications. The various etiologies can be assigned to six subgroups, defined with respect to the potential therapeutic consequences. New terminology is introduced, such as developmental and epileptic encephalopathy. The term benign is replaced by the terms self-limiting and pharmacoresponsive, to be used where appropriate. It is hoped that this new framework will assist in improving epilepsy care and research in the twenty-first century.
903 citations
TL;DR: The International Registry of Acute Aortic Dissection (IRAD) was established in 1996 with the mission to raise awareness of this condition and provide insights to guide diagnosis and treatment as mentioned in this paper.
Abstract: Acute aortic dissection (AAD) is a life-threatening condition associated with high morbidity and mortality rates, and it remains a challenge to diagnose and treat. The International Registry of Acute Aortic Dissection was established in 1996 with the mission to raise awareness of this condition and provide insights to guide diagnosis and treatment. Since then, >7300 cases have been included from >51 sites in 12 countries. Although presenting symptoms and physical findings have not changed significantly over this period, the use of computed tomography in the diagnosis has increased, and more patients are managed with interventional procedures: surgery in type A AAD and endovascular therapy in type B AAD; with these changes in care, there has been a significant decrease in overall in-hospital mortality in type A AAD but not in type B AAD. Herein, we summarized the key lessons learned from this international registry of patients with AAD over the past 20 years.
652 citations
Ohio State University1, Washington University in St. Louis2, Duke University3, University of Rochester4, Stanford University5, City of Hope National Medical Center6, Dana Corporation7, University of Chicago8, University of Calgary9, Harvard University10, National Institutes of Health11, Loyola University Chicago12
TL;DR: Among older patients with untreated CLL, treatment with ibrutinib was superior to treatment with bendamustine plus rituximab with regard to progression‐free survival, and there was no significant difference among the three treatment groups with respect to overall survival.
Abstract: Background Ibrutinib has been approved by the Food and Drug Administration for the treatment of patients with untreated chronic lymphocytic leukemia (CLL) since 2016 but has not been compared with chemoimmunotherapy. We conducted a phase 3 trial to evaluate the efficacy of ibrutinib, either alone or in combination with rituximab, relative to chemoimmunotherapy. Methods Patients 65 years of age or older who had untreated CLL were randomly assigned to receive bendamustine plus rituximab, ibrutinib, or ibrutinib plus rituximab. The primary end point was progression-free survival. The Alliance Data and Safety Monitoring Board made the decision to release the data after the protocol-specified efficacy threshold had been met. Results A total of 183 patients were assigned to receive bendamustine plus rituximab, 182 to receive ibrutinib, and 182 to receive ibrutinib plus rituximab. Median progression-free survival was reached only with bendamustine plus rituximab. The estimated percentage of patients wit...
04 Jun 2018
TL;DR: The proposed method, normalized direction-preserving Adam (ND-Adam), enables more precise control of the direction and step size for updating weight vectors, leading to significantly improved generalization performance.
Abstract: Adaptive optimization algorithms, such as Adam and RMSprop, have witnessed better optimization performance than stochastic gradient descent (SGD) in some scenarios. However, recent studies show that they often lead to worse generalization performance than SGD, especially for training deep neural networks (DNNs). In this work, we identify the reasons that Adam generalizes worse than SGD, and develop a variant of Adam to eliminate the generalization gap. The proposed method, normalized direction-preserving Adam (ND-Adam), enables more precise control of the direction and step size for updating weight vectors, leading to significantly improved generalization performance. Following a similar rationale, we further improve the generalization performance in classification tasks by regularizing the softmax logits. By bridging the gap between SGD and Adam, we also hope to shed light on why certain optimization algorithms generalize better than others.
TL;DR: In this article, the authors map the actions towards achieving all of the SDGs that have the potential to improve understanding, measurement, prevention and treatment of kidney disease in all age groups.
Abstract: Kidney disease has been described as the most neglected chronic disease. Reliable estimates of the global burden of kidney disease require more population-based studies, but specific risks occur across the socioeconomic spectrum from poverty to affluence, from malnutrition to obesity, in agrarian to post-industrial settings, and along the life course from newborns to older people. A range of communicable and noncommunicable diseases result in renal complications and many people who have kidney disease lack access to care. The causes, consequences and costs of kidney diseases have implications for public health policy in all countries. The risks of kidney disease are also influenced by ethnicity, gender, location and lifestyle. Increasing economic and health disparities, migration, demographic transition, unsafe working conditions and environmental threats, natural disasters and pollution may thwart attempts to reduce the morbidity and mortality from kidney disease. A multisectoral approach is needed to tackle the global burden of kidney disease. The sustainable development goals (SDGs) emphasize the importance of a multisectoral approach to health. We map the actions towards achieving all of the SDGs that have the potential to improve understanding, measurement, prevention and treatment of kidney disease in all age groups. These actions can also foster treatment innovations and reduce the burden of such disease in future generations.
University of Calgary1, McGill University Health Centre2, Cardiovascular Institute of the South3, University of British Columbia4, Université du Québec à Trois-Rivières5, Université de Montréal6, Laval University7, McMaster University8, Alberta Health Services9, University of Alberta10, McGill University11, University of Toronto12, Heart and Stroke Foundation of Canada13, Population Health Research Institute14, Montreal General Hospital15, University of Western Ontario16, Montreal Heart Institute17, Winnipeg Regional Health Authority18, Université du Québec à Montréal19, Northern Ontario School of Medicine20, St. Michael's Hospital21, University of Manitoba22, Centre for Addiction and Mental Health23, University of Ottawa24, University Health Network25, Concordia University Wisconsin26, Ottawa Hospital Research Institute27, University of Ontario Institute of Technology28, Hôpital Maisonneuve-Rosemont29, University of Saskatchewan30, Centre Hospitalier Universitaire Sainte-Justine31, Children's Hospital of Eastern Ontario32, St Thomas' Hospital33, Mount Sinai Hospital, Toronto34, Université de Sherbrooke35, Brown University36, Concordia Hospital37, University of Pennsylvania38
TL;DR: All individuals with hypertension should have an assessment of global cardiovascular risk to promote health behaviours that lower blood pressure, and an angiotensin receptor-neprilysin inhibitor combination should be used in place of either an ang Elliotensin-converting enzyme inhibitor or angiotENSin receptor blocker in individuals with heart failure.
Hofstra University1, Charité2, University of Verona3, King's College London4, Copenhagen University Hospital5, Lundbeck6, Yale University7, Maastricht University8, University of Hong Kong9, The Feinstein Institute for Medical Research10, SUNY Downstate Medical Center11, Dartmouth College12, Boston University13, University of Calgary14, University of North Carolina at Chapel Hill15, Nathan Kline Institute for Psychiatric Research16, National Institutes of Health17
TL;DR: In this paper, the authors compared early intervention services (EIS) with treatment as usual (TAU) for early-phase psychosis and found that EIS was associated with better outcomes than TAU at the end of treatment for all 13 meta-analyzable outcomes.
Abstract: Importance The value of early intervention in psychosis and allocation of public resources has long been debated because outcomes in people with schizophrenia spectrum disorders have remained suboptimal. Objective To compare early intervention services (EIS) with treatment as usual (TAU) for early-phase psychosis. Data Sources Systematic literature search of PubMed, PsycINFO, EMBASE, and ClinicalTrials.gov without language restrictions through June 6, 2017. Study Selection Randomized trials comparing EIS vs TAU in first-episode psychosis or early-phase schizophrenia spectrum disorders. Data Extraction and Synthesis This systematic review was conducted according to PRISMA guidelines. Three independent investigators extracted data for a random-effects meta-analysis and prespecified subgroup and meta-regression analyses. Main Outcomes and Measures The coprimary outcomes were all-cause treatment discontinuation and at least 1 psychiatric hospitalization during the treatment period. Results Across 10 randomized clinical trials (mean [SD] trial duration, 16.2 [7.4] months; range, 9-24 months) among 2176 patients (mean [SD] age, 27.5 [4.6] years; 1355 [62.3%] male), EIS was associated with better outcomes than TAU at the end of treatment for all 13 meta-analyzable outcomes. These outcomes included the following: all-cause treatment discontinuation (risk ratio [RR], 0.70; 95% CI, 0.61-0.80; P P = .003), involvement in school or work (RR, 1.13; 95% CI, 1.03-1.24; P = .01), total symptom severity (standardized mean difference [SMD], −0.32; 95% CI, −0.47 to −0.17; P P P Conclusions and Relevance In early-phase psychosis, EIS are superior to TAU across all meta-analyzable outcomes. These results support the need for funding and use of EIS in patients with early-phase psychosis.
TL;DR: A quantum-mechanical generalization of majorization is used to derive a complete set of necessary and sufficient conditions for thermal transformations of quantum states, based on natural physical principles, namely, energy conservation, the existence of equilibrium states, and the requirement that quantum coherence be accounted for thermodynamics.
Abstract: What does it mean for one quantum process to be more disordered than another? Interestingly, this apparently abstract question arises naturally in a wide range of areas such as information theory, thermodynamics, quantum reference frames, and the resource theory of asymmetry. Here we use a quantum-mechanical generalization of majorization to develop a framework for answering this question, in terms of single-shot entropies, or equivalently, in terms of semi-definite programs. We also investigate some of the applications of this framework, and remarkably find that, in the context of quantum thermodynamics it provides the first complete set of necessary and sufficient conditions for arbitrary quantum state transformations under thermodynamic processes, which rigorously accounts for quantum-mechanical properties, such as coherence. Our framework of generalized thermal processes extends thermal operations, and is based on natural physical principles, namely, energy conservation, the existence of equilibrium states, and the requirement that quantum coherence be accounted for thermodynamically. Similarly to entropy, majorization allows to quantify deviation from uniformity in a wide range of fields. In this paper, the authors use its generalization to the quantum realm to derive a complete set of necessary and sufficient conditions for thermal transformations of quantum states.
TL;DR: A gap remains in practical guidance on PCC implementation, and several conceptual frameworks for PCC exist, which need to be considered for implementation.
Abstract: Background
Globally, health-care systems and organizations are looking to improve health system performance through the implementation of a person-centred care (PCC) model. While numerous conceptual frameworks for PCC exist, a gap remains in practical guidance on PCC implementation.
Methods
Based on a narrative review of the PCC literature, a generic conceptual framework was developed in collaboration with a patient partner, which synthesizes evidence, recommendations and best practice from existing frameworks and implementation case studies. The Donabedian model for health-care improvement was used to classify PCC domains into the categories of “Structure,” “Process” and “Outcome” for health-care quality improvement.
Discussion
The framework emphasizes the structural domain, which relates to the health-care system or context in which care is delivered, providing the foundation for PCC, and influencing the processes and outcomes of care. Structural domains identified include: the creation of a PCC culture across the continuum of care; co-designing educational programs, as well as health promotion and prevention programs with patients; providing a supportive and accommodating environment; and developing and integrating structures to support health information technology and to measure and monitor PCC performance. Process domains describe the importance of cultivating communication and respectful and compassionate care; engaging patients in managing their care; and integration of care. Outcome domains identified include: access to care and Patient-Reported Outcomes.
Conclusion
This conceptual framework provides a step-wise roadmap to guide health-care systems and organizations in the provision PCC across various health-care sectors.
TL;DR: The liver is a key, frontline immune tissue Ideally positioned to detect pathogens entering the body via the gut, the liver appears designed to detect, capture, and clear bacteria, viruses, and macromolecules.
Abstract: The liver is a key, frontline immune tissue. Ideally positioned to detect pathogens entering the body via the gut, the liver appears designed to detect, capture, and clear bacteria, viruses, and macromolecules. Containing the largest collection of phagocytic cells in the body, this organ is an important barrier between us and the outside world. Importantly, as portal blood also transports a large number of foreign but harmless molecules (e.g., food antigens), the liver's default immune status is anti-inflammatory or immunotolerant; however, under appropriate conditions, the liver is able to mount a rapid and robust immune response. This balance between immunity and tolerance is essential to liver function. Excessive inflammation in the absence of infection leads to sterile liver injury, tissue damage, and remodeling; insufficient immunity allows for chronic infection and cancer. Dynamic interactions between the numerous populations of immune cells in the liver are key to maintaining this balance and overall tissue health.
McMaster University1, Sichuan University2, Ain Shams University3, University Health Network4, Canadian Agency for Drugs and Technologies in Health5, Leonardo6, University of Ottawa7, University of Calgary8, University of Manitoba9, University of Toronto10, Queen Mary University of London11, Tuen Mun Hospital12, Innlandet Hospital Trust13, Jagiellonian University Medical College14, University of Basel15, Isfahan University of Medical Sciences16, Dalhousie University17, Cleveland Clinic18
TL;DR: Evidence from high-quality studies showed that opioid use was associated with statistically significant but small improvements in pain and physical functioning, and increased risk of vomiting compared with placebo, and Comparisons of opioids with nonopioid alternatives suggested that the benefit for pain and functioning may be similar.
Abstract: Importance Harms and benefits of opioids for chronic noncancer pain remain unclear. Objective To systematically review randomized clinical trials (RCTs) of opioids for chronic noncancer pain. Data Sources and Study Selection The databases of CENTRAL, CINAHL, EMBASE, MEDLINE, AMED, and PsycINFO were searched from inception to April 2018 for RCTs of opioids for chronic noncancer pain vs any nonopioid control. Data Extraction and Synthesis Paired reviewers independently extracted data. The analyses used random-effects models and the Grading of Recommendations Assessment, Development and Evaluation to rate the quality of the evidence. Main Outcomes and Measures The primary outcomes were pain intensity (score range, 0-10 cm on a visual analog scale for pain; lower is better and the minimally important difference [MID] is 1 cm), physical functioning (score range, 0-100 points on the 36-item Short Form physical component score [SF-36 PCS]; higher is better and the MID is 5 points), and incidence of vomiting. Results Ninety-six RCTs including 26 169 participants (61% female; median age, 58 years [interquartile range, 51-61 years]) were included. Of the included studies, there were 25 trials of neuropathic pain, 32 trials of nociceptive pain, 33 trials of central sensitization (pain present in the absence of tissue damage), and 6 trials of mixed types of pain. Compared with placebo, opioid use was associated with reduced pain (weighted mean difference [WMD], −0.69 cm [95% CI, −0.82 to −0.56 cm] on a 10-cm visual analog scale for pain; modeled risk difference for achieving the MID, 11.9% [95% CI, 9.7% to 14.1%]), improved physical functioning (WMD, 2.04 points [95% CI, 1.41 to 2.68 points] on the 100-point SF-36 PCS; modeled risk difference for achieving the MID, 8.5% [95% CI, 5.9% to 11.2%]), and increased vomiting (5.9% with opioids vs 2.3% with placebo for trials that excluded patients with adverse events during a run-in period). Low- to moderate-quality evidence suggested similar associations of opioids with improvements in pain and physical functioning compared with nonsteroidal anti-inflammatory drugs (pain: WMD, −0.60 cm [95% CI, −1.54 to 0.34 cm]; physical functioning: WMD, −0.90 points [95% CI, −2.69 to 0.89 points]), tricyclic antidepressants (pain: WMD, −0.13 cm [95% CI, −0.99 to 0.74 cm]; physical functioning: WMD, −5.31 points [95% CI, −13.77 to 3.14 points]), and anticonvulsants (pain: WMD, −0.90 cm [95% CI, −1.65 to −0.14 cm]; physical functioning: WMD, 0.45 points [95% CI, −5.77 to 6.66 points]). Conclusions and Relevance In this meta-analysis of RCTs of patients with chronic noncancer pain, evidence from high-quality studies showed that opioid use was associated with statistically significant but small improvements in pain and physical functioning, and increased risk of vomiting compared with placebo. Comparisons of opioids with nonopioid alternatives suggested that the benefit for pain and functioning may be similar, although the evidence was from studies of only low to moderate quality.
TL;DR: Mendes et al. as discussed by the authors studied the ways feminists have increasingly turned to digital technologies and social media platforms to dialogue, network and organize against contemporary sexism, misogyny and rape culture, and found that survivors took to social media to share their experiences and engage in a 'call-out culture'.
Abstract: On 24 October 2017, the #MeToo hashtag began trending on Twitter. Although the phrase was initiated by African American women’s rights activists Tarana Burke in 2006, it gained widespread attention when actress Alyssa Milano used it as a Twitter hashtag in response to allegations of sexual assault by Hollywood producer Harvey Weinstein. Through the #MeToo hashtag, Milano encouraged members of the public to join in to showcase the magnitude of the problem of sexual violence. Capturing both public and media attention, the hashtag was used 12 million times in the first 24 hours alone (CBS, 2017). Since 2014, we have been studying the ways feminists have increasingly turned to digital technologies and social media platforms to dialogue, network and organize against contemporary sexism, misogyny and rape culture (see Mendes et al., forthcoming). As a research team the sheer volume of attention paid towards this hashtag took us by surprise, but the fact survivors took to social media to share their experiences and engage in a ‘call-out culture’ resonated strongly with our research findings over the past three years. Although #MeToo is perhaps one of the most high-profile examples of digital feminist activism we have yet encountered, it follows a growing trend of the public’s
Emory University1, Johns Hopkins University2, Temple University3, University of Utah4, Swiss Institute of Allergy and Asthma Research5, University of Chicago6, Ghent University7, Humanitas University8, Eskişehir Osmangazi University9, Imperial College London10, University of California, San Diego11, University of North Carolina at Chapel Hill12, Rutgers University13, University of Amsterdam14, University of Missouri15, University of Texas Southwestern Medical Center16, Aarhus University17, Hannover Medical School18, Case Western Reserve University19, Stanford University20, Harvard University21, University of Turku22, University of Colorado Boulder23, University of Texas at Austin24, San Antonio Military Medical Center25, University of Pittsburgh26, University of Texas Health Science Center at Houston27, Ochsner Health System28, Uniformed Services University of the Health Sciences29, Karolinska Institutet30, Wake Forest University31, University of Pavia32, University of Barcelona33, University of Colorado Denver34, Loyola University Chicago35, Nippon Medical School36, Heidelberg University37, Boston University38, Cornell University39, University of Calgary40, Medical University of South Carolina41, Brown University42, George Washington University43, University of Edinburgh44, Oregon Health & Science University45, Mahidol University46, National University of Singapore47, University of Michigan48
TL;DR: To evaluate the existing AR literature, international multidisciplinary experts with an interest in AR have produced the International Consensus statement on Allergy and Rhinology: Allergic Rhinitis (ICAR:AR).
Abstract: BACKGROUND:
Critical examination of the quality and validity of available allergic rhinitis (AR) literature is necessary to improve understanding and to appropriately translate this knowledge to clinical care of the AR patient. To evaluate the existing AR literature, international multidisciplinary experts with an interest in AR have produced the International Consensus statement on Allergy and Rhinology: Allergic Rhinitis (ICAR:AR).
METHODS:
Using previously described methodology, specific topics were developed relating to AR. Each topic was assigned a literature review, evidence-based review (EBR), or evidence-based review with recommendations (EBRR) format as dictated by available evidence and purpose within the ICAR:AR document. Following iterative reviews of each topic, the ICAR:AR document was synthesized and reviewed by all authors for consensus.
RESULTS:
The ICAR:AR document addresses over 100 individual topics related to AR, including diagnosis, pathophysiology, epidemiology, disease burden, risk factors for the development of AR, allergy testing modalities, treatment, and other conditions/comorbidities associated with AR.
CONCLUSION:
This critical review of the AR literature has identified several strengths; providers can be confident that treatment decisions are supported by rigorous studies. However, there are also substantial gaps in the AR literature. These knowledge gaps should be viewed as opportunities for improvement, as often the things that we teach and the medicine that we practice are not based on the best quality evidence. This document aims to highlight the strengths and weaknesses of the AR literature to identify areas for future AR research and improved understanding.
Reading Hospital1, University of Melbourne2, West Virginia University3, Erasmus University Rotterdam4, University of Calgary5, University of Bern6, Harvard University7, Cleveland Clinic8, Brown University9, University of California, San Diego10, Columbia University11, Ochsner Medical Center12, Geisinger Medical Center13
University of Melbourne1, University of Newcastle2, University of Chicago3, University of Calgary4, Complutense University of Madrid5, University of Bordeaux6, Virginia Commonwealth University7, Mayo Clinic8, Johns Hopkins University9, University of Udine10, University of Regensburg11, University of St. Gallen12, University of Washington13, University of Bern14, University of Sydney15
TL;DR: Among premenopausal women with breast cancer, the addition of ovarian suppression to tamoxifen resulted in significantly higher 8‐year rates of both disease‐free and overall survival than tamox ifen alone and the use of exemestane plus ovarian suppression resulted in even higher rates of freedom from recurrence.
Abstract: Background In the Suppression of Ovarian Function Trial (SOFT) and the Tamoxifen and Exemestane Trial (TEXT), the 5-year rates of recurrence of breast cancer were significantly lower among premenopausal women who received the aromatase inhibitor exemestane plus ovarian suppression than among those who received tamoxifen plus ovarian suppression. The addition of ovarian suppression to tamoxifen did not result in significantly lower recurrence rates than those with tamoxifen alone. Here, we report the updated results from the two trials. Methods Premenopausal women were randomly assigned to receive 5 years of tamoxifen, tamoxifen plus ovarian suppression, or exemestane plus ovarian suppression in SOFT and to receive tamoxifen plus ovarian suppression or exemestane plus ovarian suppression in TEXT. Randomization was stratified according to the receipt of chemotherapy. Results In SOFT, the 8-year disease-free survival rate was 78.9% with tamoxifen alone, 83.2% with tamoxifen plus ovarian suppression,...
TL;DR: ASPECTS : Alberta Stroke Program Early Computed Tomography Score mRS : modified Rankin Scale mTICI : modified thrombolysis in cerebral infarction NIHSS : National Institutes of Health Stroke Scale QI : quality improvement SAH : subarachnoid hemorrhage SICH
Abstract: ASPECTS
: Alberta Stroke Program Early Computed Tomography Score
EVT
: endovascular therapy
mRS
: modified Rankin Scale
mTICI
: modified thrombolysis in cerebral infarction
NIHSS
: National Institutes of Health Stroke Scale
QI
: quality improvement
SAH
: subarachnoid hemorrhage
SICH
TL;DR: A moderate level of evidence supports there being beneficial effects of active management goals with avoidance of early palliative care orders, well-coordinated specialist stroke unit care, targeted neurointensive and surgical interventions, early control of elevated blood pressure, and rapid reversal of abnormal coagulation.
Massachusetts Institute of Technology1, Harvard University2, Van Andel Institute3, Vanderbilt University Medical Center4, Memorial Sloan Kettering Cancer Center5, Stanford University6, University of Calgary7, BC Cancer Agency8, University of Texas MD Anderson Cancer Center9, Case Western Reserve University10, Mayo Clinic11, Duke University12, George Washington University13, University of Alabama at Birmingham14, Institute for Systems Biology15
TL;DR: A group of tumors in the colon and rectum lacking hypermutation and aneuploidy termed genome stable and enriched in DNA hypermethylation and mutations in KRAS, SOX9, and PCBP1 is identified.
Duke University1, National Institutes of Health2, University of Texas Health Science Center at Houston3, Vanderbilt University4, RTI International5, University of Michigan6, Case Western Reserve University7, University of California, Los Angeles8, University of Alabama at Birmingham9, Boston University10, University of Virginia11, University of Washington12, Fred Hutchinson Cancer Research Center13, University of Texas MD Anderson Cancer Center14, City of Hope National Medical Center15, Medical University of South Carolina16, Mayo Clinic17, University of Calgary18, Washington University in St. Louis19, Medical College of Wisconsin20, University of Ottawa21, University of Pittsburgh22, University of Toledo23
TL;DR: Myeloablative autologous hematopoietic stem‐cell transplantation achieved long‐term benefits in patients with scleroderma, including improved event‐free and overall survival, at a cost of increased expected toxicity.
Abstract: BackgroundDespite current therapies, diffuse cutaneous systemic sclerosis (scleroderma) often has a devastating outcome. We compared myeloablative CD34+ selected autologous hematopoietic stem-cell transplantation with immunosuppression by means of 12 monthly infusions of cyclophosphamide in patients with scleroderma. MethodsWe randomly assigned adults (18 to 69 years of age) with severe scleroderma to undergo myeloablative autologous stem-cell transplantation (36 participants) or to receive cyclophosphamide (39 participants). The primary end point was a global rank composite score comparing participants with each other on the basis of a hierarchy of disease features assessed at 54 months: death, event-free survival (survival without respiratory, renal, or cardiac failure), forced vital capacity, the score on the Disability Index of the Health Assessment Questionnaire, and the modified Rodnan skin score. ResultsIn the intention-to-treat population, global rank composite scores at 54 months showed the super...
TL;DR: Conceptual advances of the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) working group guidance to evaluate the certainty of evidence from network meta-analysis (NMA) are described.
Stanford University1, University of Calgary2, Centers for Disease Control and Prevention3, George Washington University4, Cleveland Clinic5, Johns Hopkins University School of Medicine6, University of California, Los Angeles7, University of Florida Health Science Center8, Kaiser Permanente9, Emory University10, Icahn School of Medicine at Mount Sinai11, Princeton University12, University of Texas Health Science Center at San Antonio13, Harvard University14, Loma Linda University15, Cincinnati Children's Hospital Medical Center16, University of Washington17, St. Louis Children's Hospital18, University of Utah19, Children's Hospital of Philadelphia20, University of North Carolina at Chapel Hill21, John H. Stroger, Jr. Hospital of Cook County22, Vanderbilt University23, University of Pittsburgh24, Nationwide Children's Hospital25, The Ohio State University Wexner Medical Center26, Boston Children's Hospital27, University of Miami28, University of California, San Diego29, American Academy of Neurology30, University of Kansas31, University of Virginia32, Penn State Milton S. Hershey Medical Center33
TL;DR: This guideline identifies the best practices for mTBI based on the current evidence and creates user-friendly guideline implementation materials that are concise and actionable.
Abstract: Importance Mild traumatic brain injury (mTBI), or concussion, in children is a rapidly growing public health concern because epidemiologic data indicate a marked increase in the number of emergency department visits for mTBI over the past decade. However, no evidence-based clinical guidelines have been developed to date for diagnosing and managing pediatric mTBI in the United States. Objective To provide a guideline based on a previous systematic review of the literature to obtain and assess evidence toward developing clinical recommendations for health care professionals related to the diagnosis, prognosis, and management/treatment of pediatric mTBI. Evidence Review The Centers for Disease Control and Prevention (CDC) National Center for Injury Prevention and Control Board of Scientific Counselors, a federal advisory committee, established the Pediatric Mild Traumatic Brain Injury Guideline Workgroup. The workgroup drafted recommendations based on the evidence that was obtained and assessed within the systematic review, as well as related evidence, scientific principles, and expert inference. This information includes selected studies published since the evidence review was conducted that were deemed by the workgroup to be relevant to the recommendations. The dates of the initial literature search were January 1, 1990, to November 30, 2012, and the dates of the updated literature search were December 1, 2012, to July 31, 2015. Findings The CDC guideline includes 19 sets of recommendations on the diagnosis, prognosis, and management/treatment of pediatric mTBI that were assigned a level of obligation (ie, must, should, or may) based on confidence in the evidence. Recommendations address imaging, symptom scales, cognitive testing, and standardized assessment for diagnosis; history and risk factor assessment, monitoring, and counseling for prognosis; and patient/family education, rest, support, return to school, and symptom management for treatment. Conclusions and Relevance This guideline identifies the best practices for mTBI based on the current evidence; updates should be made as the body of evidence grows. In addition to the development of the guideline, CDC has created user-friendly guideline implementation materials that are concise and actionable. Evaluation of the guideline and implementation materials is crucial in understanding the influence of the recommendations.
Charité1, Boston Children's Hospital2, University of Toronto3, University of Mainz4, University of Calgary5, Semmelweis University6, Hiroshima University7, Campbelltown Hospital8, University of South Florida9, Cambridge University Hospitals NHS Foundation Trust10, University of Texas at Dallas11, Humboldt University of Berlin12, Nippon Medical School13, University of Cape Town14, University of California, San Diego15, University of Alberta16, University of Missouri–Kansas City17, Peking Union Medical College Hospital18, Pennsylvania State University19
TL;DR: The goal of this guideline update and revision is to provide clinicians and their patients with guidance that will assist them in making rational decisions in the management of H AE with deficient C1‐inhibitor (type 1) and HAE with dysfunctional C1-inhibitors (type 2).
Abstract: Hereditary Angioedema (HAE) is a rare and disabling disease. Early diagnosis and appropriate therapy are essential. This update and revision of the global guideline for HAE provides up-to-date consensus recommendations for the management of HAE. In the development of this update and revision of the guideline, an international expert panel reviewed the existing evidence and developed 20 recommendations that were discussed, finalized and consented during the guideline consensus conference in June 2016 in Vienna. The final version of this update and revision of the guideline incorporates the contributions of a board of expert reviewers and the endorsing societies. The goal of this guideline update and revision is to provide clinicians and their patients with guidance that will assist them in making rational decisions in the management of HAE with deficient C1-inhibitor (type 1) and HAE with dysfunctional C1-inhibitor (type 2). The key clinical questions covered by these recommendations are: (1) How should HAE-1/2 be defined and classified?, (2) How should HAE-1/2 be diagnosed?, (3) Should HAE-1/2 patients receive prophylactic and/or on-demand treatment and what treatment options should be used?, (4) Should HAE-1/2 management be different for special HAE-1/2 patient groups such as pregnant/lactating women or children?, and (5) Should HAE-1/2 management incorporate self-administration of therapies and patient support measures?