The University of Texas at San Antonio Health Science Center

The Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) statement, published in 2009, was designed to help systematic reviewers transparently report why the review was done, what the authors did, and what they found. Over the past decade, advances in systematic review methodology and terminology have necessitated an update to the guideline. The PRISMA 2020 statement replaces the 2009 statement and includes new reporting guidance that reflects advances in methods to identify, select, appraise, and synthesise studies. The structure and presentation of the items have been modified to facilitate implementation. In this article, we present the PRISMA 2020 27-item checklist, an expanded checklist that details reporting recommendations for each item, the PRISMA 2020 abstract checklist, and the revised flow diagrams for original and updated reviews.

The human genome holds an extraordinary trove of information about human development, physiology, medicine and evolution. Here we report the results of an international collaboration to produce and make freely available a draft sequence of the human genome. We also present an initial analysis of the data, describing some of the insights that can be gleaned from the sequence.

The human genome encodes the blueprint of life, but the function of the vast majority of its nearly three billion bases is unknown. The Encyclopedia of DNA Elements (ENCODE) project has systematically mapped regions of transcription, transcription factor association, chromatin structure and histone modification. These data enabled us to assign biochemical functions for 80% of the genome, in particular outside of the well-studied protein-coding regions. Many discovered candidate regulatory elements are physically associated with one another and with expressed genes, providing new insights into the mechanisms of gene regulation. The newly identified elements also show a statistical correspondence to sequence variants linked to human disease, and can thereby guide interpretation of this variation. Overall, the project provides new insights into the organization and regulation of our genes and genome, and is an expansive resource of functional annotations for biomedical research. This overview of the ENCODE project outlines the data accumulated so far, revealing that 80% of the human genome now has at least one biochemical function assigned to it; the newly identified functional elements should aid the interpretation of results of genome-wide association studies, as many correspond to sites of association with human disease. The Encyclopedia of DNA Elements (ENCODE) project has systematically mapped regions of transcription, transcription-factor association, chromatin structure and histone modification. In this overview, the Consortium guides the readers through the project itself, the data and their integrated analyses. Eighty per cent of the human genome now has at least one biochemical function assigned to it. In addition to expanding our understanding of how gene expression is regulated on a genome-wide scale, the newly identified functional elements should help researchers to interpret the results of genome-wide associated studies because many correspond to sites associated with human disease.

Chronic obstructive pulmonary disease (COPD) is a global health problem, and since 2001, the Global Initiative for Chronic Obstructive Lung Disease (GOLD) has published its strategy document for the diagnosis and management of COPD. This executive summary presents the main contents of the second 5-year revision of the GOLD document that has implemented some of the vast knowledge about COPD accumulated over the last years. Today, GOLD recommends that spirometry is required for the clinical diagnosis of COPD to avoid misdiagnosis and to ensure proper evaluation of severity of airflow limitation. The document highlights that the assessment of the patient with COPD should always include assessment of (1) symptoms, (2) severity of airflow limitation, (3) history of exacerbations, and (4) comorbidities. The first three points can be used to evaluate level of symptoms and risk of future exacerbations, and this is done in a way that splits patients with COPD into four categories-A, B, C, and D. Nonpharmacologic and pharmacologic management of COPD match this assessment in an evidence-based attempt to relieve symptoms and reduce risk of exacerbations. Identification and treatment of comorbidities must have high priority, and a separate section in the document addresses management of comorbidities as well as COPD in the presence of comorbidities. The revised document also contains a new section on exacerbations of COPD. The GOLD initiative will continue to bring COPD to the attention of all relevant shareholders and will hopefully inspire future national and local guidelines on the management of COPD.

See the PRISMA 2020 for Abstracts checklist (Table 2).

The Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) statement, published in 2009, was designed to help systematic reviewers transparently report why the review was done, what the authors did, and what they found. Over the past decade, advances in systematic review methodology and terminology have necessitated an update to the guideline. The PRISMA 2020 statement replaces the 2009 statement and includes new reporting guidance that reflects advances in methods to identify, select, appraise, and synthesise studies. The structure and presentation of the items have been modified to facilitate implementation. In this article, we present the PRISMA 2020 27-item checklist, an expanded checklist that details reporting recommendations for each item, the PRISMA 2020 abstract checklist, and the revised flow diagrams for original and updated reviews.

The HER-2/neu oncogene is a member of the erbB-like oncogene family, and is related to, but distinct from, the epidermal growth factor receptor. This gene has been shown to be amplified in human breast cancer cell lines. In the current study, alterations of the gene in 189 primary human breast cancers were investigated. HER-2/neu was found to be amplified from 2- to greater than 20-fold in 30% of the tumors. Correlation of gene amplification with several disease parameters was evaluated. Amplification of the HER-2/neu gene was a significant predictor of both overall survival and time to relapse in patients with breast cancer. It retained its significance even when adjustments were made for other known prognostic factors. Moreover, HER-2/neu amplification had greater prognostic value than most currently used prognostic factors, including hormonal-receptor status, in lymph node-positive disease. These data indicate that this gene may play a role in the biologic behavior and/or pathogenesis of human breast cancer.

The methods and results of systematic reviews should be reported in sufficient detail to allow users to assess the trustworthiness and applicability of the review findings.The Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) statement was developed to facilitate transparent and complete reporting of systematic reviews and has been updated (to PRISMA 2020) to reflect recent advances in systematic review methodology and terminology.Here, we present the explanation and elaboration paper for PRISMA 2020, where we explain why reporting of each item is recommended, present bullet points that detail the reporting recommendations, and present examples from published reviews.We hope that changes to the content and structure of PRISMA 2020 will facilitate uptake of the guideline and lead to more transparent, complete, and accurate reporting of systematic reviews.Systematic reviews are essential for healthcare providers, policy makers, and other decision makers, who would otherwise be confronted by an overwhelming volume of research on which to base their decisions.To allow decision makers to assess the trustworthiness and applicability of review findings, reports of systematic reviews should be transparent and complete.Furthermore, such reporting should allow others to replicate or update reviews.The Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) statement published in 2009 (hereafter referred to as PRISMA 2009) 1-12 was designed to help authors prepare transparent accounts of their reviews, and its recommendations have been widely endorsed and adopted.13 We have updated the PRISMA 2009 statement (to PRISMA 2020) to ensure currency and relevance and to reflect advances in systematic review methodology and terminology. Scope of this guidelineThe PRISMA 2020 statement has been designed primarily for systematic reviews of studies that evaluate the effects of health interventions, irrespective of the design of the included studies.However, the checklist items are applicable to reports of systematic reviews evaluating other non-health-related interventions (for example, social or educational interventions), and many items are applicable to systematic reviews with objectives other than evaluating interventions (such as evaluating aetiology, prevalence, or prognosis).PRISMA 2020 is intended for use in systematic reviews that include synthesis (such as pairwise metaanalysis or other statistical synthesis methods) or do not include synthesis (for example, because only one eligible study is identified).The PRISMA 2020 items are relevant for mixed-methods systematic reviews (which include quantitative and qualitative studies), but reporting guidelines addressing the presentation and synthesis of qualitative data should also be consulted.14 15 PRISMA 2020 can be used for original systematic reviews, updated systematic reviews, or continually updated ("living") systematic reviews.However, for updated and living systematic reviews, there may be some additional considerations that need to be addressed.Extensions to the PRISMA 2009 statement have been developed to guide reporting of network meta-analyses, 16 meta-analyses of individual participant data, 17 systematic reviews of harms, 18 systematic reviews of diagnostic test accuracy studies, 19 and scoping reviews 20 ; for these types of reviews we recommend authors report their review For numbered affiliations see end of the article.

To develop criteria for the classification of fibromyalgia, we studied 558 consecutive patients: 293 patients with fibromyalgia and 265 control patients. Interviews and examinations were performed by trained, blinded assessors. Control patients for the group with primary fibromyalgia were matched for age and sex, and limited to patients with disorders that could be confused with primary fibromyalgia. Control patients for the group with secondary-concomitant fibromyalgia were matched for age, sex, and concomitant rheumatic disorders. Widespread pain (axial plus upper and lower segment plus left- and right-sided pain) was found in 97.6% of all patients with fibromyalgia and in 69.1% of all control patients. The combination of widespread pain and mild or greater tenderness in greater than or equal to 11 of 18 tender point sites yielded a sensitivity of 88.4% and a specificity of 81.1%. Primary fibromyalgia patients and secondary-concomitant fibromyalgia patients did not differ statistically in any major study variable, and the criteria performed equally well in patients with and those without concomitant rheumatic conditions. The newly proposed criteria for the classification of fibromyalgia are 1) widespread pain in combination with 2) tenderness at 11 or more of the 18 specific tender point sites. No exclusions are made for the presence of concomitant radiographic or laboratory abnormalities. At the diagnostic or classification level, the distinction between primary fibromyalgia and secondary-concomitant fibromyalgia (as defined in the text) is abandoned.

Much medical research is observational. The reporting of observational studies is often of insufficient quality. Poor reporting hampers the assessment of the strengths and weaknesses of a study and the generalisability of its results. Taking into account empirical evidence and theoretical considerations, a group of methodologists, researchers, and editors developed the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) recommendations to improve the quality of reporting of observational studies. The STROBE Statement consists of a checklist of 22 items, which relate to the title, abstract, introduction, methods, results and discussion sections of articles. Eighteen items are common to cohort studies, case-control studies and cross-sectional studies and four are specific to each of the three study designs. The STROBE Statement provides guidance to authors about how to improve the reporting of observational studies and facilitates critical appraisal and interpretation of studies by reviewers, journal editors and readers. This explanatory and elaboration document is intended to enhance the use, understanding, and dissemination of the STROBE Statement. The meaning and rationale for each checklist item are presented. For each item, one or several published examples and, where possible, references to relevant empirical studies and methodological literature are provided. Examples of useful flow diagrams are also included. The STROBE Statement, this document, and the associated Web site (http://www.strobe-statement.org/) should be helpful resources to improve reporting of observational research.

BACKGROUND: Type 2 (non-insulin-dependent) diabetes is associated with a marked increase in the risk of coronary heart disease. It has been debated whether patients with diabetes who have not had myocardial infarctions should be treated as aggressively for cardiovascular risk factors as patients who have had myocardial infarctions. METHODS: To address this issue, we compared the seven-year incidence of myocardial infarction (fatal and nonfatal) among 1373 nondiabetic subjects with the incidence among 1059 diabetic subjects, all from a Finnish population-based study. RESULTS: The seven-year incidence rates of myocardial infarction in nondiabetic subjects with and without prior myocardial infarction at base line were 18.8 percent and 3.5 percent, respectively (P<0.001). The seven-year incidence rates of myocardial infarction in diabetic subjects with and without prior myocardial infarction at base line were 45.0 percent and 20.2 percent, respectively (P<0.001). The hazard ratio for death from coronary heart disease for diabetic subjects without prior myocardial infarction as compared with nondiabetic subjects with prior myocardial infarction was not significantly different from 1.0 (hazard ratio, 1.4; 95 percent confidence interval, 0.7 to 2.6) after adjustment for age and sex, suggesting similar risks of infarction in the two groups. After further adjustment for total cholesterol, hypertension, and smoking, this hazard ratio remained close to 1.0 (hazard ratio, 1.2; 95 percent confidence interval, 0.6 to 2.4). CONCLUSIONS: Our data suggest that diabetic patients without previous myocardial infarction have as high a risk of myocardial infarction as nondiabetic patients with previous myocardial infarction. These data provide a rationale for treating cardiovascular risk factors in diabetic patients as aggressively as in nondiabetic patients with prior myocardial infarction.

IDSA/ATS Guidelines for CAP in Adults • CID 2007:44 (Suppl 2) • S31 33.A longer duration of therapy may be needed if initial therapy was not active against the identified pathogen or if it was complicated by extrapulmonary infection, such as meningitis or endocarditis.(Weak recommendation; level III evidence.)Other Treatment Considerations 34.Patients with CAP who have persistent septic shock despite adequate fluid resuscitation should be considered for treatment with drotrecogin alfa activated within 24 h of admission.(Weak recommendation; level II evidence.)35.Hypotensive, fluid-resuscitated patients with severe CAP should be screened for occult adrenal insufficiency.(Moderate recommendation; level II evidence.)36.Patients with hypoxemia or respiratory distress should receive a cautious trial of noninvasive ventilation unless they require immediate intubation because of severe hypoxemia (PaO 2 /FiO 2 ratio, !150) and bilateral alveolar infiltrates.(Moderate recommendation; level I evidence.)37. Low-tidal-volume ventilation (6 cm 3 /kg of ideal body weight) should be used for patients undergoing ventilation who have diffuse bilateral pneumonia or acute respiratory distress syndrome.(Strong recommendation; level I evidence.)Management of Nonresponding Pneumonia Definitions and classification.38.The use of a systematic classification of possible causes of failure to respond, based on time of onset and type of failure (table 11), is recommended.(Moderate recommendation; level II evidence.)As many as 15% of patients with CAP may not respond appropriately to initial antibiotic therapy.A systematic approach to these patients (table 11) will help to determine the cause.Because determination of the cause of failure is more accurate if the original microbiological etiology is known, risk factors for nonresponse or deterioration (table 12) figure prominently in the list of situations in which more aggressive and/ or extensive initial diagnostic testing is warranted (table 5).Prevention (see table 13) 39.All persons у50 years of age, others at risk for influenza complications, household contacts of high-risk persons, and health care workers should receive inactivated influenza vaccine as recommended by the Advisory Committee on Immunization Practices, Centers for Disease Control and Prevention.(Strong recommendation; level I evidence.)40.The intranasally administered live attenuated vaccine is an alternative vaccine formulation for some persons 5-49 years of age without chronic underlying diseases, including immunodeficiency, asthma, or chronic medical conditions.(Strong recommendation; level I evidence.)41.Health care workers in inpatient and outpatient settings and long-term care facilities should receive annual influenza immunization.(Strong recommendation; level I evidence.)42.Pneumococcal polysaccharide vaccine is recommended for persons у65 years of age and for those with selected high-risk concurrent diseases, according to current Advisory Committee on Immunization Practices guidelines.(Strong recommendation; level II evidence.)43.Vaccination status should be assessed at the time of hospital admission for all patients, especially those with medical illnesses.(Moderate recommendation; level III evidence.)44.Vaccination may be performed either at hospital discharge or during outpatient treatment.(Moderate recommendation; level III evidence.)45.Influenza vaccine should be offered to persons at hospital discharge or during outpatient treatment during the fall and winter.(Strong recommendation; level III evidence.)46.Smoking cessation should be a goal for persons hospitalized with CAP who smoke.(Moderate recommendation; level III evidence.)47.Smokers who will not quit should also be vaccinated for both pneumococcus and influenza.(Weak recommendation; level III evidence.)48.Cases of pneumonia that are of public health concern should be reported immediately to the state or local health department.(Strong recommendation; level III evidence.)49.Respiratory hygiene measures, including the use of hand hygiene and masks or tissues for patients with cough, should be used in outpatient settings and EDs as a means to reduce the spread of respiratory infections.(Strong recommendation; level III evidence.)

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PURPOSE: Most patients with advanced pancreas cancer experience pain and must limit their daily activities because of tumor-related symptoms. To date, no treatment has had a significant impact on the disease. In early studies with gemcitabine, patients with pancreas cancer experienced an improvement in disease-related symptoms. Based on those findings, a definitive trial was performed to assess the effectiveness of gemcitabine in patients with newly diagnosed advanced pancreas cancer. PATIENTS AND METHODS: One hundred twenty-six patients with advanced symptomatic pancreas cancer completed a lead-in period to characterize and stabilize pain and were randomized to receive either gemcitabine 1,000 mg/m2 weekly x 7 followed by 1 week of rest, then weekly x 3 every 4 weeks thereafter (63 patients), or to fluorouracil (5-FU) 600 mg/m2 once weekly (63 patients). The primary efficacy measure was clinical benefit response, which was a composite of measurements of pain (analgesic consumption and pain intensity), Karnofsky performance status, and weight. Clinical benefit required a sustained (> or = 4 weeks) improvement in at least one parameter without worsening in any others. Other measures of efficacy included response rate, time to progressive disease, and survival. RESULTS: Clinical benefit response was experienced by 23.8% of gemcitabine-treated patients compared with 4.8% of 5-FU-treated patients (P = .0022). The median survival durations were 5.65 and 4.41 months for gemcitabine-treated and 5-FU-treated patients, respectively (P = .0025). The survival rate at 12 months was 18% for gemcitabine patients and 2% for 5-FU patients. Treatment was well tolerated. CONCLUSION: This study demonstrates that gemcitabine is more effective than 5-FU in alleviation of some disease-related symptoms in patients with advanced, symptomatic pancreas cancer. Gemcitabine also confers a modest survival advantage over treatment with 5-FU.

OBJECTIVE: Several methods have been proposed to evaluate insulin sensitivity from the data obtained from the oral glucose tolerance test (OGTT). However, the validity of these indices has not been rigorously evaluated by comparing them with the direct measurement of insulin sensitivity obtained with the euglycemic insulin clamp technique. In this study, we compare various insulin sensitivity indices derived from the OGTT with whole-body insulin sensitivity measured by the euglycemic insulin clamp technique. RESEARCH DESIGN AND METHODS: In this study, 153 subjects (66 men and 87 women, aged 18-71 years, BMI 20-65 kg/m2) with varying degrees of glucose tolerance (62 subjects with normal glucose tolerance, 31 subjects with impaired glucose tolerance, and 60 subjects with type 2 diabetes) were studied. After a 10-h overnight fast, all subjects underwent, in random order, a 75-g OGTT and a euglycemic insulin clamp, which was performed with the infusion of [3-3H]glucose. The indices of insulin sensitivity derived from OGTT data and the euglycemic insulin clamp were compared by correlation analysis. RESULTS: The mean plasma glucose concentration divided by the mean plasma insulin concentration during the OGTT displayed no correlation with the rate of whole-body glucose disposal during the euglycemic insulin clamp (r = -0.02, NS). From the OGTT, we developed an index of whole-body insulin sensitivity (10,000/square root of [fasting glucose x fasting insulin] x [mean glucose x mean insulin during OGTT]), which is highly correlated (r = 0.73, P < 0.0001) with the rate of whole-body glucose disposal during the euglycemic insulin clamp. CONCLUSIONS: Previous methods used to derive an index of insulin sensitivity from the OGTT have relied on the ratio of plasma glucose to insulin concentration during the OGTT. Our results demonstrate the limitations of such an approach. We have derived a novel estimate of insulin sensitivity that is simple to calculate and provides a reasonable approximation of whole-body insulin sensitivity from the OGTT.

Neural connections, providing the substrate for functional networks, exist whether or not they are functionally active at any given moment. However, it is not known to what extent brain regions are continuously interacting when the brain is "at rest." In this work, we identify the major explicit activation networks by carrying out an image-based activation network analysis of thousands of separate activation maps derived from the BrainMap database of functional imaging studies, involving nearly 30,000 human subjects. Independently, we extract the major covarying networks in the resting brain, as imaged with functional magnetic resonance imaging in 36 subjects at rest. The sets of major brain networks, and their decompositions into subnetworks, show close correspondence between the independent analyses of resting and activation brain dynamics. We conclude that the full repertoire of functional networks utilized by the brain in action is continuously and dynamically "active" even when at "rest."

Background: The Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) Statement, published in 2009, was designed to help systematic reviewers transparently report why the review was done, what the authors did and what they found. Over the last decade, there have been many advances in systematic review methodology and terminology, which have necessitated an update to the guideline.Objectives: To develop the PRISMA 2020 statement for reporting systematic reviews.Methods: We reviewed 60 documents with reporting guidance for systematic reviews to generate suggested modifications to the PRISMA 2009 statement. We sought feedback on the suggested modifications through an online survey of 110 systematic review methodologists and journal editors. The results of the review and survey were discussed at a 21-member in-person meeting. Following the meeting, drafts of the PRISMA 2020 checklist, abstract checklist, explanation and elaboration and flow diagram were generated and refined iteratively based on feedback from co-authors and a convenience sample of 15 systematic reviewers.Results: In this statement paper, we present the PRISMA 2020 27-item checklist, an expanded checklist that details reporting recommendations for each item, the PRISMA 2020 abstract checklist, and the revised flow diagrams for original and updated reviews. The checklist includes new reporting guidance that reflects advances in methods to identify, select, appraise and synthesise studies. The structure and presentation of the items have been modified to facilitate implementation. The PRISMA 2020 statement replaces the 2009 statement.Conclusions: The PRISMA 2020 statement is intended to facilitate transparent, complete and accurate reporting of systematic reviews. Improved reporting should benefit users of reviews, including guideline developers, policy makers, health care providers, patients and other stakeholders. In order to achieve this, we encourage authors, editors and peer-reviewers to adopt the guideline.

Nurse researchers typically provide evidence of content validity for instruments by computing a content validity index (CVI), based on experts' ratings of item relevance. We compared the CVI to alternative indexes and concluded that the widely-used CVI has advantages with regard to ease of computation, understandability, focus on agreement of relevance rather than agreement per se, focus on consensus rather than consistency, and provision of both item and scale information. One weakness is its failure to adjust for chance agreement. We solved this by translating item-level CVIs (I-CVIs) into values of a modified kappa statistic. Our translation suggests that items with an I-CVI of .78 or higher for three or more experts could be considered evidence of good content validity.

The Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) statement, published in 2009, was designed to help systematic reviewers transparently report why the review was done, what the authors did, and what they found.Over the past decade, advances in systematic review methodology and terminology have necessitated an update to

BACKGROUND: Atrial fibrillation is a strong independent risk factor for stroke. PURPOSE: To characterize the efficacy and safety of antithrombotic agents for stroke prevention in patients who have atrial fibrillation, adding 13 recent randomized trials to a previous meta-analysis. DATA SOURCES: Randomized trials identified by using the Cochrane Stroke Group search strategy, 1966 to March 2007, unrestricted by language. STUDY SELECTION: All published randomized trials with a mean follow-up of 3 months or longer that tested antithrombotic agents in patients who have nonvalvular atrial fibrillation. DATA EXTRACTION: Two coauthors independently extracted information regarding interventions; participants; and occurrences of ischemic and hemorrhagic stroke, major extracranial bleeding, and death. DATA SYNTHESIS: Twenty-nine trials included 28,044 participants (mean age, 71 years; mean follow-up, 1.5 years). Compared with the control, adjusted-dose warfarin (6 trials, 2900 participants) and antiplatelet agents (8 trials, 4876 participants) reduced stroke by 64% (95% CI, 49% to 74%) and 22% (CI, 6% to 35%), respectively. Adjusted-dose warfarin was substantially more efficacious than antiplatelet therapy (relative risk reduction, 39% [CI, 22% to 52%]) (12 trials, 12 963 participants). Other randomized comparisons were inconclusive. Absolute increases in major extracranial hemorrhage were small (< or =0.3% per year) on the basis of meta-analysis. LIMITATION: Methodological features and quality varied substantially and often were incompletely reported. CONCLUSIONS: Adjusted-dose warfarin and antiplatelet agents reduce stroke by approximately 60% and by approximately 20%, respectively, in patients who have atrial fibrillation. Warfarin is substantially more efficacious (by approximately 40%) than antiplatelet therapy. Absolute increases in major extracranial hemorrhage associated with antithrombotic therapy in participants from the trials included in this meta-analysis were less than the absolute reductions in stroke. Judicious use of antithrombotic therapy importantly reduces stroke for most patients who have atrial fibrillation.