Evidence-based Score Research Articles

Technical standards for the interpretation and reporting of constitutional copy-number variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics (ACMG) and the Clinical Genome Resource (ClinGen)

PurposeCopy-number analysis to detect disease-causing losses and gains across the genome is recommended for the evaluation of individuals with neurodevelopmental disorders and/or multiple congenital anomalies, as well as for fetuses with ultrasound abnormalities. In the decade that this analysis has been in widespread clinical use, tremendous strides have been made in understanding the effects of copy-number variants (CNVs) in both affected individuals and the general population. However, continued broad implementation of array and next-generation sequencing–based technologies will expand the types of CNVs encountered in the clinical setting, as well as our understanding of their impact on human health.This Article was originally published without the accompanying supplementary file “All evaluated CNVs”. This file is now available in the HTML version of the Article; the PDF was correct from the time of publication.A Correction to this paper has been published: https://doi.org/10.1038/s41436-021-01150-9 MethodsTo assist clinical laboratories in the classification and reporting of CNVs, irrespective of the technology used to identify them, the American College of Medical Genetics and Genomics has developed the following professional standards in collaboration with the National Institutes of Health (NIH)–funded Clinical Genome Resource (ClinGen) project. ResultsThis update introduces a quantitative, evidence-based scoring framework; encourages the implementation of the five-tier classification system widely used in sequence variant classification; and recommends “uncoupling” the evidence-based classification of a variant from its potential implications for a particular individual. ConclusionThese professional standards will guide the evaluation of constitutional CNVs and encourage consistency and transparency across clinical laboratories.

11. HIGH CONSISTENCY IN EMBRYO ANEUPLOIDY TESTING OF UNIFORM, MOSAIC AND SEGMENTAL ANEUPLOIDIES WITH THE APPLICATION OF A VALIDATED ALGORITHM

Introduction Detection of mosaic embryos and degree of mosaicism is a hot topic in preimplantation genetic testing of aneuploidy (PGT-A). Several groups have reported healthy life births from mosaic embryos. A key point is the degree of mosaicism that can be detected in a trophectoderm biopsy and the impact of next generation sequencing (NGS) protocol and interpretation of sequencing data. The aim of this study was to determine the robustness of the diagnosis using a validated algorithm to establish the thresholds for mosaicism degree and the minimal resolution for de novo segmental aneuploidies. Material & methods NGS protocol combined automatic library preparation (IonChefTM system, ThermoFisher Scientific), and multiplexing for up to 96 samples (S5-XL sequencer; ThermoFisher). Pools of 4-6 cells with uniform and segmental aneuploidies (10-23 Mb) from cell lines with known karyotypes were employed for platform validation. For mosaicism validation, different proportions of gDNA (0-100%) from cell lines with whole chromosome aneuploidies were sequenced. Quality parameters were evaluated to determine the conditions for accurate detection. Biopsies were diagnosed as mosaic, if only one or two chromosomes fitted the mosaicism thresholds, without uniform aneuploidy for any other chromosome. After validation, results of 34,147 biopsies from 9 diagnostic laboratories using the same diagnostic algorithm were analysed (October 2018-December 2018). Results The minimal resolution for de novo segmental aneuploidies was established at 10 Mb, and the cut-off values for mosaicism detection at 30% and 70%. Biopsies were classified as: euploid ( Finally, we wanted to assess the incidence of mosaicism for chromosomes considered suitable for transfer after genetic and psychological counselling according to Gratti et al (2018). The percentage of low degree mosaicism for low risk chromosomes (1, 3, 4, 5, 10, 12, 19) was 1.1% and for chromosomes with moderate risk (2, 6, 7, 9, 11, 15, 17, 20, 22) was 1.5%. Conclusions High informativity rates were achieved using a high-throughout platform. The application of an internally validated algorithm for PGT-A showed high consistency among different laboratories, avoiding subjectivity and interindividual differences in the diagnosis, and minimizing the risks for overdiagnosis of mosaicism. Low mosaicism rates were identified and even lower if we consider only low mosaics for chromosomes suitable for transfer in the absence of euploid embryos and after proper genetic and psychological counselling. Reference Grati FR, Gallazzi G, Branca L, Maggi F, Simoni G, Yaron Y. An evidence-based scoring system for prioritizing mosaic aneuploid embryos following preimplantation genetic screening. Reprod Biomed Online. 2018 Apr;36(4):442-449.

Recent advances in risk prediction, therapeutics and pathogenesis of IgA nephropathy.

Immunoglobulin A nephropathy (IgAN) is the world's commonest primary glomerular disease with variable clinical presentation and progression rates that are dependent on clinical-pathologic phenotype and duration of follow-up. Overall 4-40% of patients progress to end-stage kidney disease (ESKD) by 10 years. Treatment decisions remain a challenge due to these variations. The ultimate goal of management is to prevent progression to ESKD and of vital importance is the potential reversible early detection of active glomerular inflammation prior to scarring. IgAN is globally, is the most common biopsy proven glomerulonephritis and a leading cause of ESKD. The Oxford pathological classification was devised by a collaborative pathology and nephrology network to provide an evidence-based scoring system with reproducible independent pathology features of predictive value. Clinical variables that alter prognosis include male sex, increasing age, increased body weight, smoking, Pacific Asian ethnicity, hypertension, proteinuria, and complement deficiency. Excellent conservative therapy is the cornerstone of therapy with tight blood control, renin-angiotensin system inhibition, and statin therapy. The role of immunosuppressive therapy including corticosteroids in IgAN remains open with ongoing clinical trials of low dose oral corticosteroids and enteric coated budesonide. Complement activation contributes to the pathogenic process of IgAN with evidence from genetic, serological, histological and in-vitro studies. This knowledge has translated to clinical trials of investigational agents directly targeting the alternative pathway.

Status quo and influencing factors of knowledge, attitude and practice on evidence-based practice in community nurses

Objective To explore the status quo of evidence-based practice in community nurses in terms of knowledge, attitude and practice (KAP) and to analyze its influencing factors. Methods Totally 422 community nurses from Hangzhou and Shenzhen were selected by convenient sampling from October 2017 to April 2018, and their evidence-based KAP was investigated with the evidence-based knowledge, attitude and practice questionnaire. SPSS 20.0 was used for statistical analysis. The total score and scores of various dimensions and items were calculated. The t test and variance analysis were used to compare the scores of community nurses under different conditions, and multivariate linear regression analysis was employed to analyze the influencing factors of evidence-based practice in community nurses. Results The average scores of evidence-based knowledge, attitude and practice in community nurses were (3.86±0.32) , (4.27±0.45) and (3.76±0.25) , respectively. There was statistically significant difference in total KAP scores between community nurses with professional titles, management jobs, research experience and regular reading of literature, in total scores and evidence-based knowledge scores and practice in community nurses with different first degrees, in evidence-based practice scores and total scores between community nurses with different current degrees and in evidence-based attitude scores and total scores between community nurses with or without evidence-based training (P<0.05) . Multivariate linear regression analysis revealed that professional title and evidence-based training experience affected evidence-based knowledge, attitude scores and total scores (P<0.05) , and professional title and current degree affected evidence-based practice in community nurses (P<0.05) . Conclusions The evidence-based practice of community nurses needs to be improved. Degrees have impact on the evidence-based practice of community nurses. The evidence-based practice of community nurses with higher titles is better. Evidence-based training may facilitate the evidence-based knowledge and attitude of community nurses. Key words: Evidence-based medicine; Evidence-based practice; Community nurses; Questionnaire investigation

Current spectrum, challenges and new developments in the surgical care of adults with congenital heart disease.

Today, more than two thirds of patients with congenital heart disease (CHD) are adults. Cardiac surgery plays an essential role in restoring and maintaining cardiac function, aside from evolving medical treatment and catheter-based interventions. The aim of the present publication was to describe the spectrum of operations performed on adults with CHD (ACHD) by reviewing current literature. Currently, surgery for ACHD is predominantly valve surgery, since valvular pathologies are often either a part of the basic heart defect or develop as sequelae of corrective or palliative surgery. Surgical techniques for valve repair, established in patients with acquired heart disease (non-ACHD), can often be transferred to ACHD. New valve substitutes may help to reduce the number of redo operations. Most of valve operations yield good results in terms of survival and quality of life, with the precondition that the ventricular function is preserved. Heart failure due to end-stage CHD is the most frequent cause of mortality in ACHD. However, surgical treatment by means of mechanical circulatory support (MCS) is still uncommon and the mortality exceeds the one following other operations in ACHD. Currently, different devices are used and new technical developments are in progress. However, there still is no ideal assist device available. Therefore, heart transplantation remains the only valid option for end-stage CHD. Despite higher early mortality following heart transplantation in ACHD compared to non-ACHD, the long-term survival compares favorably to non-ACHD. There is room for improvement by refining the indications, the time of listing, and the perioperative care of ACHD transplant patients. Sudden death is the second most frequent cause of mortality in ACHD. Ventricular tachycardia is the most frequent cause of sudden death followed by coronary artery anomaly. Due to the increasing awareness of physicians and the improved imaging techniques, coronary artery anomalies are coming more into the focus of cardiac surgeons. However, the reported experience is limited and it is currently difficult to provide a standardized and generally applicable recommendation for the indication and the adequate surgical technique. With the increasing age and complexity of ACHD, treatment of rhythm disturbances by surgical ablation, pacemaker or implantable cardioverter defibrillator (ICD) implantation and resynchronisation gains importance. A risk score specifically designed for surgery in ACHD is among the newest developments in predicting the outcome of surgical treatment of ACHD. This evidence-based score, derived from and validated with data from the Society of Thoracic Surgeons Congenital Heart Surgery Database, enables comparison of risk-adjusted performance of the whole spectrum of procedures performed in ACHD and helps in understanding the differences in surgical outcomes. The score is thus a powerful tool for quality control and quality improvement. In conclusion, new developments in surgery for ACHD are currently made with regard to valve surgery, which comprises more than half of all operations in ACHD and in treatment of end-stage CHD, which still yields high mortality and morbidity.

On the verge of diagnosis: Detection, reporting, and investigation of de novo variants in novel genes identified by clinical sequencing.

The variable evidence supporting gene-disease associations contributes to the difficulty of accurate variant reporting in a clinical setting. An evidence-based scoring system for evaluating the clinical validity of gene-disease associations, proposed by ClinGen, considers experimental as well as genetic evidence.De novo variants are heavily weighted, given the overall rarity in the genome and their contribution to human disease, however they are reported as "genes of unknown significance" in our center when there is insufficient evidence for the gene-disease assertion. We report a collection of 21de novovariants in genes of unknown clinical significance ascertained via clinical testing, of which eight of 21 (38%) are predicted to cause loss of function. These genes were subjected to ClinGen scoring to assess the strength of gene-disease relationships. Using a cutoff for moderate high or strong, 10 of 21 genes now have sufficient evidence to qualify as likely pathogenic or pathogenic variants. Sharing such cases with phenotypic data is imperative to strengthen available genetic evidence to ultimately upgrade clinical validity classifications and facilitate accurate molecular diagnosis.

How PGS/PGT-A laboratories succeeded in losing all credibility

How PGS/PGT-A laboratories succeeded in losing all credibility

Wednesday, September 26, 2018 7:35 AM–9:00 AM ePosters: P70. Development of a novel scoring system to predict the length of stay for the patients undergoing ACDF surgery

BACKGROUND CONTEXT There has been growing emphasis placed on efficient resource utilization and cost conscious clinical decision-making. As a result of this trend, there has been a growing interest in “outpatient” or “short-stay” spine surgery. However, the cost-savings of selecting these operative venues need to be balanced against patient safety. To our knowledge, there are no evidence-based guidelines to help determine which patients are most appropriate for “outpatient” or “short-stay” surgical procedures. PURPOSE To develop a novel evidence-based scoring system to assist clinicians in selecting the most appropriate surgical setting for patients undergoing one- or two-level anterior cervical decompression and fusion (ACDF). STUDY DESIGN/SETTING Retrospective cohort study. PATIENT SAMPLE The present study was approved by the Institutional Review Board of the Thomas Jefferson University. A review of electronic medical records was performed on 2,220 patients who underwent a primary one- or two-level ACDF for radiculopathy between January 2011 and December 2016. OUTCOME MEASURES Length of stay. METHODS Baseline variables associated with length of stay (LOS) were identified using data from 1104 patients who underwent one- or two-level ACDF surgery. These significant variables were used to develop the ACDF Length of Stay Scoring System (ALSS) for predicting LOS (trichotomized into 1, 2, or 3+ days). Via ordinal regression analysis, as standard practice, all factors that were associated with LOS category at p RESULTS Four independent factors derived from ordinal regression analysis, including the number of fusion levels (one- or two-level), age, uncomplicated hypertension, and depression, were assembled into this ALSS. In this cohort, of the patients with 0 points on the ALSS, 80% stayed 1day in the hospital. The percentage of the patients that stayed 1day in hospital decreased with an increase in the ALSS score. When the ALSS score was five, only 46% of the patients stayed 1day in hospital while 33% stayed for 3 or more days. When APSS score was 6, only 29% of the patients stayed 1day in hospital and 57% for 2days. Spearman's rank-order correlation showed Spearman's correlation coefficient, ρ=0.25, p CONCLUSIONS This study developed a novel scoring system, the ALSS, to help predict the length of stay in patients undergoing ACDF. It is our hope that this system will help provide clinicians evidence-based guidance in selecting and justifying an appropriate operative setting in which to care for their patients. Future studies will be aimed at validating this scoring system in a prospective manner.

An Evidence-Based Scoring System for Prioritizing Mosaic Aneuploid Embryos Following Preimplantation Genetic Screening

(Abstracted from Reprod Biomed Online 2018;36:442–449) Human blastocyst embryos after preimplantation genetic screening (PGS) are comprised of mostly euploid embryos and some mosaic embryos. When there are no euploid cells following PGS, only mosaic embryos are available for transfer.

An evidence-based scoring system for prioritizing mosaic aneuploid embryos following preimplantation genetic screening.

The aim of this study was to devise an evidence-based scoring system for prioritizing mosaic aneuploid embryos for transfer. A retrospective analysis was performed of all sequential cytogenetic and molecular results on chorionic villi samples (n = 72,472) and products of conception (n = 3806) analysed at a single centre. The likelihood that a mosaic aneuploidy detected in chorionic villi samples will involve the fetus, the incidence of clinically significant fetal uniparental disomy in the presence of a mosaic in chorionic villi and the chance of the mosaicism culminating in miscarriage were used to generate a scoring system for prioritizing mosaic aneuploid embryos detected by preimplantation genetic screening. A composite score was obtained for each individual mosaic aneuploidy after assignment of an individual risk score based on the incidence/likelihood of each adverse outcome. A final additional score was assigned to viable full or mosaic aneuploidies with a well-defined phenotype. The higher the composite score the lower the priority for embryo transfer. In conclusion, due to the paucity of prospective studies on the actual transfer of mosaic aneuploid embryos, we suggest using this evidence-based scoring system to provide a useful tool for clinicians, embryologists and patients.

Low Infection-Related Re-Admission Rates in a Retrospective of 4725 Children with Appendicitis Using a Clinical Pathway in a Tertiary Care Pediatric Center.

Standardization of antibiotic management of appendicitis in tertiary care pediatric centers has been associated with improved outcomes. Rady Children's Hospital-San Diego implemented an appendicitis clinical pathway in 2005. We evaluated infection-related re-admission risk factors since 2010, when an electronic medical record was established, with the aim to optimize the clinical pathway. Between January 2010 and August 2015, 4725 children with a diagnosis of appendicitis were evaluated for demographic data, pathology diagnoses, culture results, and inpatient and oral step-down antibiotic therapy regimens. From children originally admitted for appendicitis, those who were re-admitted with infection were compared with those who were not re-admitted for infection. The populations were controlled by severity of infection using a pathology-defined appendicitis severity scale: Grade 0, no appendicitis; grade 1, simple acute appendicitis with gross and microscopic evidence of inflammation, but no perforation; grade 2, gangrenous/necrotizing/micro-perforated appendicitis with subserosal or serosal exudate, but no frank or visually appreciated perforation; and grade 3, frank perforation. Of 4725 children (total population, TP) admitted with a diagnosis of appendicitis, only 199 (4.2%) were re-admitted, with 125 of these admissions for infection (2.65% of the TP). Age, race/ethnicity, language preference, and body mass index were not found to correlate with re-admission for infection. Length of stay significantly differed between the no infection-related re-admission population and infection-related re-admission population (3.02 vs. 4.03 d, p < 0.001). There was a trend toward higher infection-re-admission rates as the pathology grade increased (odds ratio grade 1 vs. grade 3 = 2.28, 95% confidence interval 1.03, 5.03). Infection-related re-admission rates for children on the clinical pathway in our institution were infrequent. The greater association of all-cause and infection-related re-admission rates with pathology grade suggest that defining appendicitis by pathology and clinical severity may provide an evidence-based scoring system to support clinical observation in the use and duration of antibiotic therapy.

MTCTScan: a comprehensive platform for annotation and prioritization of mutations affecting drug sensitivity in cancers.

Cancer therapies have experienced rapid progress in recent years, with a number of novel small-molecule kinase inhibitors and monoclonal antibodies now being widely used to treat various types of human cancers. During cancer treatments, mutations can have important effects on drug sensitivity. However, the relationship between tumor genomic profiles and the effectiveness of cancer drugs remains elusive. We introduce Mutation To Cancer Therapy Scan (mTCTScan) web server (http://jjwanglab.org/mTCTScan) that can systematically analyze mutations affecting cancer drug sensitivity based on individual genomic profiles. The platform was developed by leveraging the latest knowledge on mutation-cancer drug sensitivity associations and the results from large-scale chemical screening using human cancer cell lines. Using an evidence-based scoring scheme based on current integrative evidences, mTCTScan is able to prioritize mutations according to their associations with cancer drugs and preclinical compounds. It can also show related drugs/compounds with sensitivity classification by considering the context of the entire genomic profile. In addition, mTCTScan incorporates comprehensive filtering functions and cancer-related annotations to better interpret mutation effects and their association with cancer drugs. This platform will greatly benefit both researchers and clinicians for interrogating mechanisms of mutation-dependent drug response, which will have a significant impact on cancer precision medicine.

PANLAR Consensus Recommendations for the Management in Osteoarthritis of Hand, Hip, and Knee.

The objective of this consensus is to update the recommendations for the treatment of hand, hip, and knee osteoarthritis (OA) by agreeing on key propositions relating to the management of hand, hip, and knee OA, by identifying and critically appraising research evidence for the effectiveness of the treatments and by generating recommendations based on a combination of the available evidence and expert opinion of 18 countries of America. Recommendations were developed by a group of 48 specialists of rheumatologists, members of other medical disciplines (orthopedics and physiatrists), and three patients, one for each location of OA. A systematic review of existing articles, meta-analyses, and guidelines for the management of hand, hip, and knee OA published between 2008 and January 2014 was undertaken. The scores for Level of Evidence and Grade of Recommendation were proposed and fully consented within the committee based on The American Heart Association Evidence-Based Scoring System. The level of agreement was established through a variation of Delphi technique. Both "strong" and "conditional" recommendations are given for management of hand, hip, and knee OA and nonpharmacological, pharmacological, and surgical modalities of treatment are presented according to the different levels of agreement. These recommendations are based on the consensus of clinical experts from a wide range of disciplines taking available evidence into account while balancing the benefits and risks of nonpharmacological, pharmacological, and surgical treatment modalities, and incorporating their preferences and values. Different backgrounds in terms of patient education or drug availability in different countries were not evaluated but will be important.

Mortality Following Congenital Heart Surgery in Adults Can Be Predicted Accurately by Combining Expert-Based and Evidence-Based Pediatric Risk Scores.

Currently, there are few specific risk stratification models available to predict mortality following congenital heart surgery in adults. We sought to evaluate whether the predictive power of the common pediatric scores is applicable for adults. In addition, we evaluated a new grown-ups with congenital heart disease (GUCH) score specifically designed for adults undergoing congenital heart surgery. Data of all consecutive patients aged 18 years or more, who underwent surgery for congenital heart disease (CHD) between 2004 and 2013 at our institution, were collected. We evaluated the Aristotle Basic Complexity (ABC), the Aristotle Comprehensive Complexity (ACC), the Risk Adjustment in Congenital Heart Surgery (RACHS-1), and the Society of Thoracic Surgeons (STS)-European Association for Cardiothoracic Surgery (EACTS) scores. The proposed GUCH score consists of the STS-EACTS score, the procedure-dependent and -independent factors of the ACC score, and age. The discriminatory power of the scores was assessed using the area under the receiver-operating characteristics curve (c-index). A total of 830 operations were evaluated. Hospital mortality was 2.9%. C-indexes were 0.67, 0.80, 0.62, 0.78, and 0.84 for the ABC, ACC, RACHS-1, STS-EACTS, and GUCH mortality scores, respectively. The evidence-based EACTS-STS score outperforms the expert-based ABC score. The expert-based ACC score is superior to the evidence-based EACTS-STS score since comorbidities are considered. Our proposed GUCH score outperforms all other scores since it integrates the advantages of the evidence-based EACTS-STS score for procedures and the expert-based ACC score for comorbidities. Evidence-based scores for adults with CHD should include comorbidities and patient ages.

Twin-like appearance of an unruptured intracerebral anterior communicating artery (ACom) aneurysm in a male sibling of a patient with a ruptured ACom aneurysm

Increased risk of intracranial aneurysm rupture with subsequent subarachnoid haemorrhage (SAH) is related to several possible factors, including first-grade familial aneurysms. Here we present a case of one ruptured and one unruptured identical twin-like anterior communicating artery (ACom) aneurysm present in two male siblings, without any proven genetic predisposition. According to evidence-based scores, aneurysm rupture risk for the younger (51years old) sibling (with an unruptured ACom aneurysm) would be low, leaving the decision for either treatment or clinical follow-up to the discretion of the treating physician. From a clinical neurosurgical perspective, however, especially since his older brother suffered an aneurysmal SAH at age 57 (i.e. 6 life-years later) from a twin-like-appearing ACom aneurysm, in our opinion rupture seems almost inevitable, thus prompting treatment at an early stage.

GeneAnalytics: An Integrative Gene Set Analysis Tool for Next Generation Sequencing, RNAseq and Microarray Data.

Postgenomics data are produced in large volumes by life sciences and clinical applications of novel omics diagnostics and therapeutics for precision medicine. To move from “data-to-knowledge-to-innovation,” a crucial missing step in the current era is, however, our limited understanding of biological and clinical contexts associated with data. Prominent among the emerging remedies to this challenge are the gene set enrichment tools. This study reports on GeneAnalytics™ (geneanalytics.genecards.org), a comprehensive and easy-to-apply gene set analysis tool for rapid contextualization of expression patterns and functional signatures embedded in the postgenomics Big Data domains, such as Next Generation Sequencing (NGS), RNAseq, and microarray experiments. GeneAnalytics' differentiating features include in-depth evidence-based scoring algorithms, an intuitive user interface and proprietary unified data. GeneAnalytics employs the LifeMap Science's GeneCards suite, including the GeneCards®—the human gene database; the MalaCards—the human diseases database; and the PathCards—the biological pathways database. Expression-based analysis in GeneAnalytics relies on the LifeMap Discovery®—the embryonic development and stem cells database, which includes manually curated expression data for normal and diseased tissues, enabling advanced matching algorithm for gene–tissue association. This assists in evaluating differentiation protocols and discovering biomarkers for tissues and cells. Results are directly linked to gene, disease, or cell “cards” in the GeneCards suite. Future developments aim to enhance the GeneAnalytics algorithm as well as visualizations, employing varied graphical display items. Such attributes make GeneAnalytics a broadly applicable postgenomics data analyses and interpretation tool for translation of data to knowledge-based innovation in various Big Data fields such as precision medicine, ecogenomics, nutrigenomics, pharmacogenomics, vaccinomics, and others yet to emerge on the postgenomics horizon.

The significance of clinical scores and biological markers in disease severity, mortality prediction, and justifying hospital admissions in patients with community-acquired pneumonia

There is a higher prevalence of community-acquired pneumonia (CAP) worldwide. The stratification of the severity and prognosis of CAP is a vital feature as it is one of the most common causes of mortality among other infectious diseases in the developed countries. The mortality rate of patients with CAP depends on the severity of the disease, treatment failure along with the requirement of hospitalization and/or Intensive Care Unit (ICU) management which is quite cost-effective. To improve the outcomes in the management of CAP, there has recently been a significant attention paid to focus on the use and implication of evidence-based scoring systems and biological markers to justify hospital admission in either acute medical settings or ICU, also to classify the disease severity which will help in predicting the mortality rate. We have reviewed the significance of established and newly developed clinical scores, biological markers, and cytokines whether used alone or in conjunction with the clinical severity scores to assess the severity of the disease, prediction of early or late treatment failure, justify the acute in-hospital or ICU admission, and for the identification of short- and long-term mortality. In conclusion, the incorporation of the biological markers in the prognostic scales of the clinical scoring systems may improve the mortality prediction value of patients with CAP requiring acute hospitalization or ICU care and further studies at a larger scale are needed to corroborate the additive value of biological markers.

The Miller–McEntire Score for Molars Provides an Evidence-based Approach to Assigning Periodontal Prognosis for Molar Teeth

Article Title and Bibliographic Information An evidence-based scoring index to determine the periodontal prognosis on molars. Miller PD Jr, McEntire ML, Marlow NM, Gellin RG. J Periodontol 2014;85(2):214-25. Reviewers Martha E. Nunn, DDS, PhD, William G. Carney, DDS, Stuart J. McNally, DDS Purpose/Question To evaluate the evidence for a scoring index used to assign periodontal prognosis of molars based on 102 patients from a private periodontal practice. Source of Funding Supported by National Institutes of Health/National Center for Research Resources Grant P20 RR017696 Type of Study/Design Cohort study Level of Evidence Level 2: Limited-quality, patient-oriented evidence Strength of Recommendation Grade Not applicable

The CDC Clear Communication Index is a new evidence-based tool to prepare and review health information.

This article presents the Centers for Disease Control and Prevention Clear Communication Index (the Index), a tool that emphasizes the primary audience's needs and provides a set of evidence-based criteria to develop and assess public communication products for diverse audiences. The Index consists of four open-ended introductory questions and 20 scored items that affect information clarity and audience comprehension, according to the scientific literature. A research team fielded an online survey to test the Index's validity. Respondents answered 10 questions about either an original health material or one redesigned with the Index. For 9 out of 10 questions, the materials revised using the Index were rated higher than the original materials. Regardless of education level, respondents rated the revised materials more favorably than the original ones. The results indicate that the Index performed as intended and made it more likely that audiences could correctly identify the intended main message and understand the words and numbers in the materials. The results also support the widely held view that audiences are more positive about clearly designed materials. The Index shows that an evidence-based scoring rubric can assess and improve the clarity of health materials.

Screening for Prostate Cancer With the Prostate-Specific Antigen Test

Prostate cancer screening with the prostate-specific antigen (PSA) test remains controversial. To review evidence from randomized trials and related modeling studies examining the effect of PSA screening vs no screening on prostate cancer-specific mortality and to suggest an approach balancing potential benefits and harms. MEDLINE, EMBASE, and the Cochrane Register of Controlled Trials were searched from January 1, 2010, to April 3, 2013, for PSA screening trials to update a previous systematic review. Another search was performed in EMBASE and MEDLINE to identify modeling studies extending the results of the 2 large randomized trials identified. The American Heart Association Evidence-Based Scoring System was used to rate level of evidence. Two trials-the Prostate, Lung, Colorectal and Ovarian (PLCO) screening trial and the European Randomized Study of Screening for Prostate Cancer (ERSPC)-dominate the evidence regarding PSA screening. The former trial demonstrated an increase in cancer incidence in the screening group (relative risk [RR], 1.12; 95% CI, 1.07-1.17) but no cancer-specific mortality benefit to PSA screening after 13-year follow-up (RR, 1.09; 95% CI, 0.87-1.36). The ERSPC demonstrated an increase in cancer incidence with screening (RR, 1.63; 95% CI, 1.57-1.69) and an improvement in the risk of prostate cancer-specific death after 11 years (RR, 0.79; 95% CI, 0.68-0.91). The ERSPC documented that 37 additional men needed to receive a diagnosis through screening for every 1 fewer prostate cancer death after 11 years of follow-up among men aged 55 to 69 years (level B evidence for prostate cancer mortality reduction). Harms associated with screening include false-positive results and complications of biopsy and treatment. Modeling studies suggest that this high ratio of additional men receiving diagnoses to prostate cancer deaths prevented will decrease during a longer follow-up (level B evidence). Available evidence favors clinician discussion of the pros and cons of PSA screening with average-risk men aged 55 to 69 years. Only men who express a definite preference for screening should have PSA testing. Other strategies to mitigate the potential harms of screening include considering biennial screening, a higher PSA threshold for biopsy, and conservative therapy for men receiving a new diagnosis of prostate cancer.