Evidence-based Definition Research Articles

Defining Clinical Excellence for Palliative Care Specialists: A Concept Whose Time Has Come.

Experts in the field of palliative care in the United States (U.S.) have defined competence, or "good," mainly for programs, trainees, or providers of primary palliative care. Our interprofessional workgroup of palliative care specialists proposes that setting a standard for clinical excellence, or "great," applicable to palliative care specialists of all professions will elevate the field in the U.S. by providing an aspirational target usable for individual assessment and self-assessment, highlighting the common ground between team roles, and promoting a deeper understanding of teamwork, utilization, and productivity. We call for research that utilizes inclusive methods and broad representation of diverse voices to design a vivid, practical, and evidence-based definition of clinical excellence for palliative care specialists.

An evidence-based definition of anemia for singleton, uncomplicated pregnancies.

BackgroundThe definition for anemia in pregnancy is outdated, derived from Scandinavian studies in the 1970’s to 1980’s. To identity women at risk of blood transfusion, a common cause of Severe Maternal Morbidity, a standard definition of anemia in pregnancy in a modern, healthy United States cohort is needed.ObjectiveTo define anemia in pregnancy in a United States population including a large county vs. private hospital population using uncomplicated patients.Materials and methodsInclusion criteria were healthy women with the first prenatal visit before 20 weeks. Exclusion criteria included preterm birth, preeclampsia, hypertension, diabetes, short interval pregnancy (<18 months), multiple gestation, abruption, and fetal demise. All women had iron fortification (Ferrous sulfate 325 mg daily) recommended. The presentation to care and pre-delivery hematocrits were obtained, and the percentiles determined. A total of 2000 patients were included, 1000 from the public county hospital and 1000 from the private hospital. Each cohort had 250 patients in each 2011, 2013, 2015, and 2018. The cohorts were compared for differences in the fifth percentile for each antepartum epoch. Student’s t-test and chi-squared statistical tests were used for analysis, p-value of ≤0.05 was considered significant.ResultsIn the public and private populations, 777 and 785 women presented in the first trimester while 223 and 215 presented in the second. The women at the private hospital were more likely to be older, Caucasian race, nulliparous, and present earlier to care. The fifth percentile was compared between the women in the private and public hospitals and were clinically indistinguishable. When combining the cohorts, the fifth percentile for hemoglobin/hematocrit was 11 g/dL/32.8% in the first trimester, 10.3 g/dL/30.6% in the second trimester, and 10.0 g/dL/30.2% pre-delivery.ConclusionsFifth percentile determinations were made from a combined cohort of normal, uncomplicated pregnancies to define anemia in pregnancy. Comparison of two different cohorts confirms that the same definition for anemia is appropriate regardless of demographics or patient mix.

Development and implementation of a hemovigilance program at a university veterinary teaching hospital.

To describe the development and implementation of a small animal hemovigilance program at a university veterinary teaching hospital. Retrospective observational descriptive study performed between October 2014 and March 2019. University teaching hospital. Dogs and cats receiving blood product transfusions . None. A hemovigilance working group composed of veterinary specialists in clinical pathology, internal medicine, and emergency and critical care was established. This group developed evidence-based definitions of transfusion reactions, reaction classification systems, and a transfusion reaction reporting form. The reporting form contained sections for patient information, transfusion information, administration details, and reaction details. Reaction events were classified by reaction type, severity grade, and imputability to the transfusion. Following implementation of the hemovigilance program, transfusion reaction data were collected and examined for the period spanning October 2014 and March 2019. During the study period, 718 canine transfusions (4 whole blood, 400 packed RBC [pRBC], 300 fresh frozen plasma [FFP], 7 platelet rich plasma, and 7 cryoprecipitate) and 124 feline transfusions (5 whole blood, 95 pRBC, and 24 FFP) were administered. There were 32 total reactions (27 canine and 5 feline), with the most common reaction being febrile nonhemolytic transfusion reactions (19/32; 59%). The incidence rate of transfusion reactions was found to be 3.8% in dogs and 4.0% in cats. For the confirmed reactions, classification criteria for case definition, reaction severity grade, and imputability were able to be determined and recorded. This allowed targeted interventions to be implemented in order to potentially reduce future reactions. A hemovigilance program can be instituted successfully in a veterinary hospital setting and once developed, standardized reporting tools could be utilized by multiple hospitals and provide the basis for more widespread reaction reporting in veterinary medicine.

Re-thinking benign inflammation of the lactating breast: A mechanobiological model.

Despite the known benefits of breastfeeding for both infant and mother, clinical support for problems such as inflammation of the lactating breast remains a research frontier. Breast pain associated with inflammation is a common reason for premature weaning. Multiple diagnoses are used for inflammatory conditions of the lactating breast, such as engorgement, blocked ducts, phlegmon, mammary candidiasis, subacute mastitis, mastitis and white spots, which lack agreed or evidence-based aetiology, definitions and treatment. This is the first in a series of three articles which review the research literature concerning benign lactation–related breast inflammation. This article investigates aetiological models. A complex systems perspective is applied to analyse heterogeneous and interdisciplinary evidence elucidating the functional anatomy and physiology of the lactating breast; the mammary immune system, including the human milk microbiome and cellular composition; the effects of mechanical forces during lactation; and the interactions between these. This analysis gives rise to a mechanobiological model of breast inflammation, in which very high intra-alveolar and intra-ductal pressures are hypothesized to strain or rupture the tight junctions between lactocytes and ductal epithelial cells, triggering inflammatory cascades and capillary dilation. Resultant elevation of stromal tension exerts pressure on lactiferous ducts, worsening intraluminal backpressure. Rising leucocyte and epithelial cell counts in the milk and alterations in the milk microbiome are signs that the mammary immune system is recruiting mechanisms to downregulate inflammatory feedback loops. From a complex systems perspective, the key mechanism for the prevention or treatment of breast inflammation is avoidance of excessively high intra-alveolar and intra-ductal pressures, which prevents a critical mass of mechanical strain and rupture of the tight junctions between lactocytes and ductal epithelial cells.

Re-thinking benign inflammation of the lactating breast: Classification, prevention, and management.

Despite the known benefits of breastfeeding for both infant and mother, clinical support for problems such as benign inflammation of the lactating breast remain a research frontier. Breast pain associated with inflammation is a common reason for premature weaning. Multiple diagnoses are used for benign inflammatory conditions of the lactating breast which lack agreed or evidence-based aetiology, definitions, and treatment. This article is the second in a three-part series. This second review analyses the heterogeneous research literature concerning benign lactation-related breast inflammation from the perspectives of the mechanobiological model and complexity science, to re-think classification, prevention, and management of lactation-related breast inflammation. Benign lactation-related breast inflammation is a spectrum condition, either localized or generalized. Acute benign lactation-related breast inflammation includes engorgement and the commonly used but poorly defined diagnoses of blocked ducts, phlegmon, mammary candidiasis, subacute mastitis, and mastitis. End-stage (non-malignant) lactation-related breast inflammation presents as the active inflammations of abscess, fistula, and septicaemia, and the inactive condition of a galactocoele. The first preventive or management principle of breast inflammation is avoidance of excessively high intra-alveolar and intra-ductal pressures, which prevents strain and rupture of a critical mass of lactocyte tight junctions. This is achieved by frequent and flexible milk removal. The second preventive or management principle is elimination of the mechanical forces which result in high intra-alveolar pressures. This requires elimination of conflicting vectors of force upon the nipple and breast tissue during milk removal; avoidance of focussed external pressure applied to the breast, including avoidance of lump massage or vibration; and avoidance of other prolonged external pressures upon the breast. Three other key preventive or management principles are discussed. Conservative management is expected to be effective for most, once recommendations to massage or vibrate out lumps, which worsen micro-vascular trauma and inflammation, are ceased.

International Continence Society (ICS) report on the terminology for sexual health in men with lower urinary tract (LUT) and pelvic floor (PF) dysfunction.

The terminology for sexual health in men with lower urinary tract (LUT) and pelvic floor (PF) dysfunction has not been defined and organized into a clinically based consensus terminology report. The aim of this terminology report is to provide a definitional document within this context that will assist clinical practice and research. This report combines the input of the members of sexual health in men with LUT and PF Dysfunction working group of the International Continence Society (ICS), assisted at intervals by external referees. Appropriate core clinical categories and a sub-classification were developed to give coding to definitions. An extensive process of 18 rounds of internal and external review was involved to exhaustively examine each definition, with decision-making by collective opinion (consensus). The Committee retained evidence-based definitions, identified gaps, and updated or discarded outdated definitions. Expert opinions were used when evidence was insufficient or absent. A terminology report for sexual health in men with LUT and PF dysfunction, encompassing 198 (178 NEW) separate definitions, has been developed. It is clinically based with the most common diagnoses defined. Clarity and user-friendliness have been key aims to make it interpretable by practitioners and trainees in all the different speciality groups involved. Conservative and surgical managements are major additions and appropriate figures have been included to supplement and clarify the text. Emerging concepts and measurements, in use in the literature and offering further research potential, but requiring further validation, have been included as an appendix. Interval (5-10 years) review is anticipated to keep the document updated. A consensus-based terminology report for sexual health in men with LUT and PF dysfunction has been produced to aid clinical practice and research. The definitions that have been adopted are those that are most strongly supported by the literature at this time or are considered clinical principles or consensus of experts' opinions.

Respiratory Dysfunction Criteria in Critically Ill Children: The PODIUM Consensus Conference.

Respiratory dysfunction is a component of every organ failure scoring system developed, reflecting the significance of the lung in multiple organ dysfunction syndrome. However, existing systems do not reflect current practice and are not consistently evidence based. We aimed to review the literature to identify the components of respiratory failure associated with outcomes in children, with the purpose of developing an operational and evidence-based definition of respiratory dysfunction. Electronic searches of PubMed and Embase were conducted from 1992 to January 2020 by using a combination of medical subject heading terms and text words to define respiratory dysfunction, critical illness, and outcomes. We included studies of critically ill children with respiratory dysfunction that evaluated the performance of metrics of respiratory dysfunction and their association with patient-centered outcomes. Studies in adults, studies in premature infants (≤36 weeks' gestational age), animal studies, reviews and commentaries, case series with sample sizes ≤10, and studies not published in English in which we were unable to determine eligibility criteria were excluded. Data were abstracted into a standard data extraction form. We provided binary (no or yes) and graded (no, nonsevere, or severe) definitions of respiratory dysfunction, prioritizing oxygenation and respiratory support. The proposed criteria were approved by 82% of members in the first round, with a score of 8 of 9 (interquartile range 7-8). Exclusion of non-English publications, heterogeneity across the pediatric age range, small sample sizes, and incomplete handling of confounders are limitations. We propose definitions for respiratory dysfunction in critically ill children after an exhaustive literature review.

Advancing the Science on Unexpected Episodes of Clarity and Lucidity in People With Dementia

People with late-stage Alzheimer’s disease and related dementias (ADRD) have been reported, largely by way of anecdote, to exhibit unexpected episodes of spontaneous, meaningful, and relevant communication or behavior. These episodes of lucidity (EL) are characterized by spontaneous mental clarity in people living with dementia (PLWD) who are assumed to have lost coherent cognitive capacity. Given the transient nature and limited understanding of underlying mechanisms responsible for this phenomenon, these episodes are frequently overlooked and have received little scientific attention. Few studies have documented EL among PLWD with precision; scientific understanding is limited to anecdotes and case studies, which have not operationalized EL. Thus, there is a critical need for an evidence-based understanding and systematic operationalization of EL. Precise and robust operationalizations of EL will allow future research to assess if EL has different effects on ADRD prognosis or alters how family members manage and adapt to ADRD progression in their care recipient. The National Institute on Aging (NIA) has funded six studies to advance the scientific understanding of EL in dementia. These studies use a variety of methodological approaches to capture EL experiences, and together, they will provide evidence-based operational definitions of EL, novel approaches for measurement of this phenomenon, and estimates of its prevalence. This symposium will provide an overview of the funded studies and three different methodological approaches that are being used to better operationalize and understand EL.

Acute Atherosis Lesions at the Fetal-Maternal Border: Current Knowledge and Implications for Maternal Cardiovascular Health.

Decidua basalis, the endometrium of pregnancy, is an important interface between maternal and fetal tissues, made up of both maternal and fetal cells. Acute atherosis is a uteroplacental spiral artery lesion. These patchy arterial wall lesions containing foam cells are predominantly found in the decidua basalis, at the tips of the maternal arteries, where they feed into the placental intervillous space. Acute atherosis is prevalent in preeclampsia and other obstetric syndromes such as fetal growth restriction. Causal factors and effects of acute atherosis remain uncertain. This is in part because decidua basalis is challenging to sample systematically and in large amounts following delivery. We summarize our decidua basalis vacuum suction method, which facilitates tissue-based studies of acute atherosis. We also describe our evidence-based research definition of acute atherosis. Here, we comprehensively review the existing literature on acute atherosis, its underlying mechanisms and possible short- and long-term effects. We propose that multiple pathways leading to decidual vascular inflammation may promote acute atherosis formation, with or without poor spiral artery remodeling and/or preeclampsia. These include maternal alloreactivity, ischemia-reperfusion injury, preexisting systemic inflammation, and microbial infection. The concept of acute atherosis as an inflammatory lesion is not novel. The lesions themselves have an inflammatory phenotype and resemble other arterial lesions of more extensively studied etiology. We discuss findings of concurrently dysregulated proteins involved in immune regulation and cardiovascular function in women with acute atherosis. We also propose a novel hypothesis linking cellular fetal microchimerism, which is prevalent in women with preeclampsia, with acute atherosis in pregnancy and future cardiovascular and neurovascular disease. Finally, women with a history of preeclampsia have an increased risk of premature cardiovascular disease. We review whether presence of acute atherosis may identify women at especially high risk for premature cardiovascular disease.

A pragmatic, evidence-based approach to coding for abdominal wall reconstruction

PurposeAmbiguity exists defining abdominal wall reconstruction (AWR) and associated Current Procedural Terminology code usage in the context of ventral hernia repair (VHR), especially with recent adoption of laparoscopic and robotic-assisted AWR techniques. Current guidelines have not accounted for the spectrum of repair complexity and have relied on expert opinion. This study aimed to develop an evidence-based definition and coding algorithm for AWR based on myofascial releases performed.MethodsThree vignettes and associated outcomes were evaluated in adult patients who underwent elecive VHR with mesh between 2013 and 2020 in the Abdominal Core Health Quality Collaborative including: (1) no myofascial release (NR), (2) posterior rectus sheath myofascial release (PRS), and (3) PRS with transversus abdominis release or external oblique release (PRS-TA/EO). The primary outcome measure was operative time based on the following categories (min): 0–59, 60–119, 120–179, 180–239, and 240 + ; secondary outcomes included disease severity measures and 30-day postoperative outcomes.Results15,246 patients were included: 7287(NR), 2425(PRS), and 5534(PRS-TA/EO). Operative time increased based on myofascial releases performed: 180–239 min (p < 0.05): NR(5%), PRS(23%), PRS-TA/EO(28%) and greater than 240 min (p < 0.05): NR (4%), PRS (17%), PRS-TA/EO(44%). A dose–response effect was observed for all secondary outcome measures indicative of three distinct levels of patient complexity and outcomes for each of the three vignettes.ConclusionAWR is defined as VHR including myofascial release. Coding for AWR should reflect the actual effort used to manage these patients. We propose an evidence-based approach to AWR coding that focuses on myofascial release and is inclusive of minimally invasive techniques.

Creating an operational definition for prolonged postoperative opioid use through the use of concept analysis

AimTo develop an evidence-based operational definition for Prolonged Postoperative Opioid Use (PPOU). BackgroundIn the United States, opioids are a mainstay of postoperative pain management, and are prescribed to over 90% of patients following surgery. Recent literature has highlighted the risk for prolonged postoperative opioid use (PPOU) after many surgical procedures. However, reported rates of PPOU vary greatly across studies, due in part to inconsistent operational definitions. Recent literature identified 29 distinct definitions for PPOU, which resulted in incidence ranging from 0.01% to 14.7% when applied to the same cohort of opioid naïve patients. MethodsWe followed the eight-step method described by Walker & Avant, using an iterative literature search process with the following databases: PubMed, CINAHL, Google Scholar. English-language peer-reviewed publications through August 2020 were included in the analysis. ResultsThe four defining attributes of PPOU are (1) use of opioids greater than 90 days following surgery, (2) treatment of postoperative (non-cancer) pain, (3) in opioid-naïve patients, (4) with legal prescription use. We identified four antecedents and four consequences to PPOU. ConclusionThe definition of PPOU in current literature varies greatly and has had significant impact on the interpretation and reliability of research findings. We propose the following working definition: PPOU is the legal prescription use of any opioid for greater than 90 days following surgery, for the purposes of treating post-operative pain, by a patient who opioid naïve in the year prior to surgery.

Reassessment of climate zones for high-level pavement analysis using machine learning algorithms and NASA MERRA-2 data

Incorporating climate impact into pavement distress initiation and propagating modeling and management, suffers from the extent of weather data available, and ability to process into a useable form in a time and computationally inexpensive manner. Analysts have overcome this challenge by partitioning large geographic areas into regions with similarities in climate impact on pavement distress initiation and propagation. Historically, large geographical areas have been empirically carved out into smaller regions with similar climates by experienced geographers and climatologists. The availability of extensive weather data, comprising hundreds of meteorological variables reported with a high spatial and temporal resolution, has made the use of empirical methodologies for establishing climate regions obsolete and untenable.This paper presents a new machine learning methodology for (1) establishing pavement-specific climate regions and (2) accurately separating predictor climate attributes into climate regions for use in the pavement management and high-level analyses. The new methodology comprises stochastic and machine learning algorithms: correlation analysis, principal factor analysis, cluster analysis, and decision tree. It entails preprocessing and transforming of raw climate data into uncorrelated scores that represent the majority of variance in original climate data, performing cluster analysis to partition large geographical areas into regions with similar climatic effects on pavement distress initiation and propagation, and development and extraction of if-then-else rules from a DT classifier capable of separating predictor climate attribute into identified climate regions. The methodology is tested using National Aeronautics and Space Administration (NASA) Modern-Era Retrospective analysis for Research and Applications, Version 2 (MERRA-2) weather data. The outcome is the identification and prediction of seven distinct pavement-specific climate regions with 88.1 percent accuracy. This methodology assures an evidence-based definition of climate regions based on the similarity of climatic effect on pavement distress initiation and propagation and improves historical empirical partitioning methods. Methodology outcomes inform pavement managers on (1) the positive and negative impact of local climate on pavement distress initiation and propagation and (2) measures required to mitigate adverse impacts of climate.

Multimodal Strategy to Improve Hand Hygiene Compliance to Practices among Staff Nurses

Introduction and Background: Healthcare-acquired infections [HCAI] account for 10-30% of all hospitaladmissions, according to the World Health Organization [WHO]. An estimated 1.4 million people are infected withHCAI at any given time.1 As the burden of health-care-associated infections grows, so does the seriousness of diseaseand treatment difficulty, which is exacerbated by multi-drug-resistant pathogen infections.2 Health care providersare reverting to the fundamentals of infection control by employing common steps such as hand hygiene.3 TheWHO’s global initiative on patient safety programmers has made “Clean Care is Safer Care” a top priority.it is timefor developing countries to formulate the much-needed policies for implementation of basic infection preventionpractices in health care set-up.4Nurses, the “nucleus of the health-care system,” spend more time with patients than any other health-care worker, andtheir adherence to hand-washing protocols appears to be more important in preventing disease transmission amongpatients. Hand hygiene is thought to be the most important factor in preventing healthcare-associated infections(HAI). Hand hygiene programmes with a variety of components have been shown to increase compliance amonghealthcare workers and, as a result, minimise infections. One such initiative is the World Health Organization’simplementation of an evidence-based definition called “My five moments for hand hygiene.”5The investigator seeks to study the compliance to hand hygiene practices among staff nurses, working in the obstetricaland gynaecological wards. The research is an endeavour to increase the awareness and educate nurses about the needfor compliance to hand hygiene practices.Aim: A.The aim of this study was to see how well health care workers in the intensive care unit kept their handsclean (ICU)B. To determine the causes of noncompliance, andC. To investigate the effectiveness of a multimodal intervention approach in enhancing compliance.Methodology: This Quasi experimental one group pre-intervention and post intervention study compares thecompliance to hand hygiene practices before and after a multimodal interventional strategySetting: The study was conducted in ICU ward in hospitalResult: The study needed a sample size of 64 nurses to achieve an 80 percent power and a 5% error rate. A t testwas used to compare the mean pre- and post-test scores. ANOVA was used to examine the relationships betweenthe baseline variables. Hand hygiene enforcement among staff nurses increased dramatically from 45.31 percentto 65.78 percent following multimodal intervention strategies. (P0.0001) Hand hygiene techniques have improvedsignificantly (hand wash technique mean score increased from 5.97 + 1.284 to 8.16 + 1.158 (p 0.05) and hand rubtechnique score increased from 4.52 + 0.992 to 6.69 + 1.489 (p 0.05)).The private wards had considerably better handhygiene than the general wards.XI. Conclusion: The results of this study show that when multimodal interventional interventions were used, handhygiene compliance improved.

P–065 Advanced paternal age does affect egg donation program outcomes?

Abstract Study question Does increasing paternal age has a negative impact in fertilization (FR), blastulation (BR), clinical pregnancy (CPR) and miscarriage (MR) rates in an egg donation program? Summary answer The increase paternal age in an egg donation program has not a negative impact in fertilization rate, blastulation rate, clinical pregnancy rates and miscarriage rates. What is known already It is well documented that semen quality is affected with increasing paternal age but there is no evidence-based definition of what is advanced paternal age. There is controversial information about if the increasing paternal age affects in vitro fertilization results, and when this negative impact could begin. Study design, size, duration This was a single center retrospective cohort study, involving 485 first single embryo transfer of an egg donation program, from January 2017 to December 2019. Participants/materials, setting, methods All first embryo transfer of egg donation cycles performed at CEGyR, Buenos Aires, Argentina were included. Elevated sperm DNA fragmentation (TUNEL &amp;gt;20), sperm bank, and testicular biopsy cycles were excluded. Patients were divided according to male partner age: (1) &amp;lt;41, (2) 41–44, (3) 45–50 and (4) &amp;gt;50 years old. Group (1) was considered the control group. Statistical analyses were performed for FR and BR with ANOVA and CPR and MR with chi-squared tests. Main results and the role of chance The number of patients in group (1) was 200, in (2) 130, in (3) 117 and in (4) 38. Male average age was 36,8 in group (1), 42,2 in (2) 47,1 in (3) and 54,2 in group (4). The FR in group (1) was 72,60%, in group (2) was 73%, in (3) was 75% and 73% in (4). ANOVA results for FR: F = 0,65 (p: 0,58). The BR, defined as the relation between the total number of blastocysts over the number of fertilized oocytes in a cycle, was in group (1) 46,35%, in group (2) was 45%, in group (3) 46%, and in group (4) 42%. ANOVA results for BR F = 0,36 (p:0,78). The CPR in group (1) was 42,19%. Comparing with the other groups: group (2) was 37,09% (chi-square statistic=0,64 p:0,43); group (3) 34,58% (2,32 p:0,13); and group (4) was 32,43% (1,48 p:0,22). The MR in group (1) was 12,49%. Comparing with the other groups: group (2) was 18,55% (chi-square statistic=2,31 p:0,12); group (3) 14,94% (1,01 p:0,32); and group (4) was 15,85% (0,91 p:0,33). For all results analyzed there were not a statistically difference between groups. Limitations, reasons for caution The main limitation of this study was its retrospective design based on data from a single center which may be subject of bias. Wider implications of the findings: Further large prospective studies are required to make meaningful comparisons. Our findings give no support for a general recommendation. Trial registration number Not applicable

Defining Dravet syndrome: An essential pre-requisite for precision medicine trials.

ObjectiveThe classical description of Dravet syndrome, the prototypic developmental and epileptic encephalopathy, is of a normal 6‐month‐old infant presenting with a prolonged, febrile, hemiclonic seizure and showing developmental slowing after age 1 year. SCN1A pathogenic variants are found in >80% of patients. Many patients have atypical features resulting in diagnostic delay and inappropriate therapy. We aimed to provide an evidence‐based definition of SCN1A‐Dravet syndrome in readiness for precision medicine trials.MethodsEpilepsy patients were recruited to the University of Melbourne Epilepsy Genetics Research Program between 1995 and 2020 by neurologists from around the world. Patients with SCN1A pathogenic variants were reviewed and only those with Dravet syndrome were included. Clinical data, including seizure and developmental course, were analyzed in all patients with SCN1A‐Dravet syndrome.ResultsTwo hundred and five patients were studied at a median age of 8.5 years (range 10 months to 60 years); 25 were deceased. The median seizure‐onset age was 5.7 months (range 1.5–20.6 months). Initial seizures were tonic‐clonic (52%) and hemiclonic (35%), with only 55% being associated with fever. Only 34% of patients presented with status epilepticus (seizure lasting ≥30 minutes). Median time between first and second seizure was 30 days (range 4 hours to 8 months), and seven patients (5%) had at least 6 months between initial seizures. Median ages at onset of second and third seizure types were 9.1 months (range 3 months–25.4 years) and 15.5 months (range 4 months–8.2 years), respectively. Developmental slowing occurred prior to 12 months in 27%.SignificanceAn evidence‐based definition of SCN1A‐Dravet syndrome is essential for early diagnosis. We refine the spectrum of Dravet syndrome, based on patterns of seizure onset, type, and progression. Understanding of the full spectrum of SCN1A‐Dravet syndrome presentation is essential for early diagnosis and optimization of treatment, especially as precision medicine trials become available.

Toward an Evidence-Based Definition and Classification of Carbohydrate Food Quality: An Expert Panel Report.

Carbohydrate-containing crops provide the bulk of dietary energy worldwide. In addition to their various carbohydrate forms (sugars, starches, fibers) and ratios, these foods may also contain varying amounts and combinations of proteins, fats, vitamins, minerals, phytochemicals, prebiotics, and anti-nutritional factors that may impact diet quality and health. Currently, there is no standardized or unified way to assess the quality of carbohydrate foods for the overall purpose of improving diet quality and health outcomes, creating an urgent need for the development of metrics and tools to better define and classify high-quality carbohydrate foods. The present report is based on a series of expert panel meetings and a scoping review of the literature focused on carbohydrate quality indicators and metrics produced over the last 10 years. The report outlines various approaches to assessing food quality, and proposes next steps and principles for developing improved metrics for assessing carbohydrate food quality. The expert panel concluded that a composite metric based on nutrient profiling methods featuring inputs such as carbohydrate–fiber–sugar ratios, micronutrients, and/or food group classification could provide useful and informative measures for guiding researchers, policymakers, industry, and consumers towards a better understanding of carbohydrate food quality and overall healthier diets. The identification of higher quality carbohydrate foods could improve evidence-based public health policies and programming—such as the 2025–2030 Dietary Guidelines for Americans.

Genomic Complexity in Chronic Lymphocytic Leukemia Defined By Array-Based Analysis: Definitions, Associations with Other Biomarkers and Clinical Impact

Background: The advent of efficacious but also very expensive novel treatment regimens for high-risk chronic lymphocytic leukemia (CLL), has highlighted the need for accurate risk-stratification. Published evidence indicates that classic chromosome banding analysis (CBA) offers valuable complementary information to the routinely performed FISH analysis in CLL, potentially improving risk assessment. Indeed, recent studies identified complex karyotype (CK; defined as ≥3 abberations) as an independent predictive marker for refractoriness to ibrutinib and venetoclax, although for CLL, a precise evidence-based definition of genomic complexity (GC) is yet to be made. Array-based (CGH/SNP) analysis is capable of globally assessing the CLL genome, does not require in vitro mitogens, offers increased detection depth, and allows for easier standardization.Aims: 1. Determine a prognostic relevant definition of GC in CLL by array-based analysis. 2. Head-to-head comparison of the sensitivity of CBA versus array-based analysis.Methods: 1911 CLL and monoclonal B-cell lymphocytosis (MBL) patients (CLL=1895, 99% and MBL=16, 1%, respectively) were analyzed with CGH or SNP arrays mostly performed within the first year from diagnosis and before treatment administration (66% and 84%, respectively). For a subgroup (N=206) both CBA and array results were available (<1 year in between analyses). Main features of the studied cohort: median age: 60.7 years, males: 1252 (68%), Binet: A/B/C:623/324/141 (57%/30%/13%), IGHV-mutated CLL (M-CLL): 536/1082 (50%), del(13q): 1020/1910 (53%), del(11q): 353/1911 (19%), TP53 aberrations (TP53 abs, deletions and/or mutations of the TP53 gene): 205/1911 (11%). Recurrent chromosomal aberrations i.e. del(13)(q14), del(11)(q22.3) and del(17)(p13.1) defined by array were included in all analyses irrespective of size, while the cut-off for other aberrations are indicated.Results: First, analysis was performed using a size cut-off ≥5Mb according to Schoumans et al (Genes Chrom Cancer 2016). Applying the criteria ≥3 structural and/or numerical aberrations to define GC, 451/1911 cases (24%) displayed GC analyzed with CGH/SNP arrays. GC was significantly related (p<0.001) with advanced clinical stage (Binet B/C), IGHV-unmutated CLL (U-CLL), del(11q), del(13q) and TP53 abs. On univariate analysis, GC was associated with inferior OS (median: 10.0 vs 12.2 (p<0.001) years). GC cases were stratified into those with 3 (‘low-GC’, N=174, 39%), 4 (‘intermediate-GC’, N=103, 23%) and ≥5 (‘high-GC’, N=174, 39%) aberrations. High-GC cases differed significantly (p<0.05) from the other two subgroups, being enriched for U-CLL and TP53 abs (84% and 45%, respectively). The median OS was 5.8 years for the high-GC vs 10 years for the low- and 8.1 years for the intermediate-GC group (p<0.01). Only ‘high-GC’ remained significant (p<0.01) on multivariate analysis along with TP53 abs and IGHV status (see table).Lowering the array cut-off to 1Mb (N=353) resulted in detection of a higher number of aberrations (3.04 vs 2.34) compared to 5Mb cut-off (95% CI paired differences 0.475-0.924). Although a lower array cut-off resulted in upstaging of high risk GC (22 vs 12%), the median OS in the ‘high risk’ group was increased as compared to the cut-off of 5Mb (8.4 vs 5.5 years).Array-analysis (5Mb cut-off) showed a higher number of total detected aberrations as compared to CBA (2.35 vs 1.84, 95% CI paired differences 0.221-0.798). With array more patients were defined as GC with higher discriminatory power regarding survival (concordance index: 58 vs 55%) than with CBA. Prognostic impact of array vs CBA and of specific aberrations is currently being analyzed.Conclusion: According to this largest performed array-based analyses, current definitions for CK defined by the presence of ≥3 structural or numerical aberrations based on classical cytogenetic approaches may be suboptimal when applied for cases analyzed by array techniques. Instead, ≥5 aberrations detected by arrays were linked to high-risk disease, independent of clinical stage, IGHV and TP53 status. Since a lower array cut-off resulted in the detection of additional aberrations, without however been accompanied by the same dismal outcome as the 5Mb cut-off, further studies are warranted in order to define the actual prognostic relevance of smaller aberrations. [Display omitted] DisclosuresEldering:Roche: Research Funding; Gilead: Research Funding; Celgene: Research Funding. Ghia:Pharmacyclics LLC, an AbbVie Company: Consultancy; Janssen: Consultancy, Research Funding; Gilead: Consultancy, Research Funding, Speakers Bureau; Adaptive: Consultancy; AbbVie: Consultancy; Roche: Consultancy; Novartis: Research Funding. Stamatopoulos:Janssen Pharmaceuticals: Honoraria, Research Funding; Novartis SA: Research Funding; Gilead: Consultancy, Honoraria, Research Funding; Abbvie: Honoraria, Research Funding. Haferlach:MLL Munich Leukemia Laboratory: Employment, Equity Ownership. Strefford:Roche: Research Funding. Kater:Celgene: Consultancy, Research Funding; Johnson & Johnson: Research Funding; Abbvie: Research Funding.

Evidence-based Definition for Extensively Drug-Resistant Tuberculosis.

Rationale: Until 2020, extensively drug-resistant tuberculosis (XDR-TB) was defined as TB with resistance to rifampicin and isoniazid (multidrug-resistant TB [MDR-TB]), any fluoroquinolone (FQ), and any second-line injectable drug (SLID). In 2019, the World Health Organization issued new recommendations for treating patients with drug-resistant TB, substantially limiting the role of SLIDs in MDR-TB treatment and thus putting the definition of XDR-TB into question. Objectives: To propose an up-to-date definition for XDR-TB. Methods: We used a large data set to assess treatment outcomes for patients with MDR-TB exposed to any type of longer regimen. We included patients with bacteriologically confirmed MDR-TB and known FQ and SLID resistance results. We performed logistic regression to estimate the adjusted odds ratios (aORs) for an unfavorable treatment outcome (failure, relapse, death, loss to follow-up), and estimates were stratified by the resistance pattern (FQ and/or SLID) and group A drug use (moxifloxacin/levofloxacin, linezolid, and/or bedaquiline). Measurements and Main Results: We included 11,666 patients with MDR-TB; 4,653 (39.9%) had an unfavorable treatment outcome. Resistance to FQs increased the odds of an unfavorable treatment outcome (aOR, 1.91; 95% confidence interval [CI], 1.63-2.23). Administration of bedaquiline and/or linezolid improved treatment outcomes regardless of resistance to FQs and/or SLIDs. Among patients with XDR-TB, compared with persons receiving no group A drug, aORs for an unfavorable outcome were 0.37 (95% CI, 0.20-0.69) with linezolid only, 0.40 (95% CI, 0.21-0.77) with bedaquiline only, and 0.21 (95% CI, 0.12-0.38) with both. Conclusions: Our study supports a new definition of XDR-TB as MDR-TB and additional resistance to FQ plus bedaquiline and/or linezolid and helps assess the adequacy of this definition for surveillance and treatment choice.

Follow-up definitions in clinical orthopaedic research : a systematic review.

AimsThe follow-up interval of a study represents an important aspect that is frequently mentioned in the title of the manuscript. Authors arbitrarily define whether the follow-up of their study is short-, mid-, or long-term. There is no clear consensus in that regard and definitions show a large range of variation. It was therefore the aim of this study to systematically identify clinical research published in high-impact orthopaedic journals in the last five years and extract follow-up information to deduce corresponding evidence-based definitions of short-, mid-, and long-term follow-up.MethodsA systematic literature search was performed to identify papers published in the six highest ranked orthopaedic journals during the years 2015 to 2019. Follow-up intervals were analyzed. Each article was assigned to a corresponding subspecialty field: sports traumatology, knee arthroplasty and reconstruction, hip-preserving surgery, hip arthroplasty, shoulder and elbow arthroplasty, hand and wrist, foot and ankle, paediatric orthopaedics, orthopaedic trauma, spine, and tumour. Mean follow-up data were tabulated for the corresponding subspecialty fields. Comparison between means was conducted using analysis of variance.ResultsOf 16,161 published articles, 590 met the inclusion criteria. Of these, 321 were of level IV evidence, 176 level III, 53 level II, and 40 level I. Considering all included articles, a long-term study published in the included high impact journals had a mean follow-up of 151.6 months, a mid-term study of 63.5 months, and a short-term study of 30.0 months.ConclusionThe results of this study provide evidence-based definitions for orthopaedic follow-up intervals that should provide a citable standard for the planning of clinical studies. A minimum mean follow-up of a short-term study should be 30 months (2.5 years), while a mid-term study should aim for a mean follow-up of 60 months (five years), and a long-term study should aim for a mean of 150 months (12.5 years).Level of Evidence: Level I.Cite this article: Bone Jt Open 2021;2(5):344–350.

2021 ACC/AHA Key Data Elements and Definitions for Heart Failure: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Data Standards (Writing Committee to Develop Clinical Data Standards for Heart Failure).

2021 ACC/AHA Key Data Elements and Definitions for Heart Failure: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Data Standards (Writing Committee to Develop Clinical Data Standards for Heart Failure).