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Biomedical terminologies play a vital role in managing biomedical data. Missing IS-A relations in a biomedical terminology could be detrimental to its downstream usages. In this paper, we investigate an approach combining logical definitions and lexical features to discover missing IS-A relations in two biomedical terminologies: SNOMED CT and the National Cancer Institute (NCI) thesaurus. The method is applied to unrelated concept-pairs within non-lattice subgraphs: graph fragments within a terminology likely to contain various inconsistencies. Our approach first compares whether the logical definition of a concept is more general than that of the other concept. Then, we check whether the lexical features of the concept are contained in those of the other concept. If both constraints are satisfied, we suggest a potentially missing IS-A relation between the two concepts. The method identified 982 potential missing IS-A relations for SNOMED CT and 100 for NCI thesaurus. In order to assess the efficacy of our approach, a random sample of results belonging to the "Clinical Findings" and "Procedure" subhierarchies of SNOMED CT and results belonging to the "Drug, Food, Chemical or Biomedical Material" subhierarchy of the NCI thesaurus were evaluated by domain experts. The evaluation results revealed that 118 out of 150 suggestions are valid for SNOMED CT and 17 out of 20 are valid for NCI thesaurus. [ABSTRACT FROM AUTHOR]

Background: Chronic lung disease of prematurity (CLD) is the most prevalent complication of preterm birth and indicates an increased likelihood of long-term pulmonary complications. The accurate diagnosis of this condition is critical for long-term health management. Numerous definitions define CLD with different clinical parameters and radiology findings, making diagnosis of the disease ambiguous and potentially inaccurate. Methods: 95 patients were identified for this study, as determined by the diagnosis or confirmation of CLD in the impression of the radiologist's report on chest x-ray. Pulmonary function and complications were recorded at multiple benchmark timeframes within each patient's first few months of life and used for determining eligibility under each definition. Results: Each clinical definition of CLD had a high sensitivity for patients identified to have CLD by radiologists, correctly fitting over 90% of patients. Most patients included required invasive mechanical ventilation or positive pressure ventilation at 36 weeks postmenstrual age, indicating patients with radiographically confirmed CLD tended to have more severe disease. Radiologists tended to diagnose CLD before 36 weeks postmenstrual age, a timepoint used by multiple standard clinical definitions, with cases called earlier fitting under a larger percentage of definitions than those called later. Conclusions: Radiologists tend to diagnose CLD in young patients with severe respiratory compromise, and can accurately diagnose the condition before developmental milestones for clinical definitions are met. [ABSTRACT FROM AUTHOR]

Objective: To determine the prevalence and associated risk factors of undiagnosed metabolic syndrome (MetS) using three different definitions among apparently healthy adults of Karachi, Pakistan. Methods: This community-based cross-sectional survey was conducted in Karachi, Pakistan, from January 2022 to August 2022. A total of 1065 healthy individuals aged 25–80 years of any gender were consecutively included. MetS was assessed using the National Cholesterol Education Program for Adult Treatment Panel (NCEP-ATP) III guidelines, International Diabetes Federation (IDF), and modified NCEP-ATP III. Results: The prevalence of MetS was highest with the modified NCEP-ATP III definition at 33.9% (95% CI: 31–36), followed by the IDF definition at 32.2% (95% CI: 29–35). In contrast, the prevalence was lower at 22.4% (95% CI: 19–25) when using the NCEP ATP III definition. The risk of MetS significantly increases with higher BMI, as defined by the IDF criteria (adjusted OR [ORadj] 1.13, 95% CI 1.09–2.43), NCEP-ATP III criteria (ORadj 1.15, 95% CI 1.11–1.19), and modified NCEP-ATP III criteria (ORadj 1.16, 95% CI 1.12–1.20). Current smokers had significantly higher odds of MetS according to the IDF (ORadj 2.72, 95% CI 1.84–4.03), NCEP-ATP III (ORadj 3.93, 95% CI 2.55–6.06), and modified NCEP-ATP III (ORadj 0.62, 95% CI 0.43–0.88). Areca nut use was associated with higher odds of MetS according to both IDF (ORadj 1.71, 95% CI 1.19–2.47) and modified NCEP-ATP III criteria (ORadj 1.58, 95% CI 1.10–2.72). Furthermore, low physical activity had significantly higher odds of MetS according to the NCEP-ATP III (ORadj 1.36, 95% CI 1.01–1.84) and modified NCEP-ATP III criteria (ORadj 1.56, 95% CI 1.08–2.26). Conclusion: One-third of the healthy individuals were diagnosed with MetS based on IDF, NCEP-ATP III, and modified NCEP-ATP III criteria. A higher BMI, current smoking, areca nut use, and low physical activity were significant factors. [ABSTRACT FROM AUTHOR]

Background: A uniform definition of continence is urgently needed to allow the comparison of study results and to estimate patient outcomes after radical prostatectomy (RP). To identify a practical definition that includes both objective and subjective aspects in a tangible way, we assessed different continence definitions and evaluated which best reflects the patients' subjective perception of continence. Methods: Our analyses included 718 patients that underwent either robot-assisted radical prostatectomy (RARP) or laparoscopic radical prostatectomy (LRP) in a multicenter randomized patient-blinded trial. Continence was assessed through patient questionnaires prior to and at 3, 6 and 12 months after surgery which included the number of pads used per day, the ICIQ-SF and the question "Do you suffer from incontinence? (yes/no)" to assess subjective continence. We used Krippendorff's Alpha to calculate the agreement of different continence definitions with the subjective perception. Results: At 3 months, the "0/safety pad" definition shows the highest agreement by alpha = 0.70 (vs. 0.63 for "0 pads" and 0.37 for "0–1 pad"). At 6 and 12 months "0 pads" is the better match, with alpha values of 0.69 (vs. 0.62 and 0.31) after 6 months and 0.70 (vs. 0.65 and 0.32) after 12 months. The ICIQ-SF score shows good correlation with the subjective continence at 3 months (alpha = − 0.79), the coefficient then decreasing to − 0.69 and − 0.59 at 6 and 12 months. Conclusion: The best continence definition according to the patients' perspective changes over time, "0 pads" being the superior criterion in the long-term. We recommend using the 0-pad definition for standardized continence reporting, as it is simple yet as accurate as possible given the inevitably high subjectivity of continence perception. Trial registration The LAP-01 trial was registered with the U.S. National Library of Medicine clinical trial registry (clinicaltrials.gov), NCT number: NCT03682146, and with the German Clinical Trial registry (Deutsches Register Klinischer Studien), DRKS ID number: DRKS00007138 [ABSTRACT FROM AUTHOR]

Background: The definition of irreparable rotator cuff tear (IRCT) is controversial. This scoping review provides definitions used to describe IRCT in the literature. This scoping review (1) identified criteria used in the definition of IRCT and (2) investigated the current state of those criteria in prospective surgical therapeutic trials. Methods: This scoping review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews. PubMed, Scopus, and Web of Science were searched in March 2023. Studies were screened against predetermined inclusion and exclusion criteria. Criteria regarding clinical symptoms, preoperative images, and intraoperative findings were captured respectively. Results: A total of 41 prospective studies were eligible for inclusion, and 35 studies (85.4%) defined IRCT. IRCT was defined on the basis of the following main criteria: preoperative image findings (28/35), intraoperative findings (24/35), and symptoms (16/35). With regard to preoperative images, IRCT was mainly defined on the basis of retraction of the tendon in the coronal plane (22/28), the severity of fatty degeneration (19/28), and ruptured tendon number or width of the defect in the sagittal plane (17/28). Conclusion: This scoping review highlights the lack of a standardized definition for IRCT in clinical practice, with common predictive criteria including a duration of over 6 months, retraction beyond 5 cm, Goutallier grade 3 fatty infiltration, and the rupture of two or more tendons. However, surgeons should apply more than one criterion when examining preoperative images and confirm reparability during surgery. A more objective manner of evaluating intraoperative reparability is necessary. [ABSTRACT FROM AUTHOR]

Background: Despite the recognised health benefits of physical activity, the physical activity levels of children and adolescents continue to decline. The concept of physical literacy (PL) is a promising holistic approach to physical activity promotion that addresses affective and cognitive domains in addition to physical and motor domains. In Germany, however, no uniform or widely used method exists for assessing PL in children. This research was conducted to compile information on international PL assessment systems for children and adolescents (up to 18 years of age), including their underlying definitions, structural designs and development processes, for the purpose of developing such a tool in Germany. Methods: A scoping review was conducted using PubMed, Web of Science and SPORTDiscus database entries. The initial search was conducted in July 2022, with a follow-up search performed in May 2023. Articles that operationalised the construct of PL and at least two of the three domains were identified and included. The procedure and assessment tools used to evaluate the individual domains and the overall PL construct were extracted from all selected articles. Results: A total of 882 articles were identified; five were added after a manual search. After duplicates were removed, 563 articles were screened by title and abstract, and 40 articles met the inclusion criteria and were included in the review. In a review of these articles, 23 different assessment procedures were identified. Eight assessment procedures included PL as a superordinate construct. Twenty-two of the 23 procedures assessed the affective and physical domains, only 14 assessed the cognitive domain. Conclusion: Approximately half of the identified PL assessment systems addressed all three domains. Motor performance was most frequently integrated into the test procedures. Future developments in Germany should integrate all domains in the assessment to produce a holistic conceptualisation as the basis for appropriate funding. [ABSTRACT FROM AUTHOR]

Background: Since 1997, research on Gulf War illness (GWI) has predominantly used 3 case definitions—the original Research definition, the CDC definition, and modifications of the Kansas definition—but they have not been compared against an objective standard. Methods: All 3 case definitions were measured in the U.S. Military Health Survey by a computer-assisted telephone interview in a random sample (n = 6,497) of the 1991 deployed U.S. military force. The interview asked whether participants had heard nerve agent alarms during the conflict. A random subsample (n = 1,698) provided DNA for genotyping the PON1 Q192R polymorphism. Results: The CDC and the Modified Kansas definition without exclusions were satisfied by 41.7% and 39.0% of the deployed force, respectively, and were highly overlapping. The Research definition, a subset of the others, was satisfied by 13.6%. The majority of veterans meeting CDC and Modified Kansas endorsed fewer and milder symptoms; whereas, those meeting Research endorsed more symptoms of greater severity. The group meeting Research was more highly enriched with the PON1 192R risk allele than those meeting CDC and Modified Kansas, and Research had twice the power to detect the previously described gene-environment interaction between hearing alarms and RR homozygosity (adjusted relative excess risk due to interaction [aRERI] = 7.69; 95% CI 2.71–19.13) than CDC (aRERI = 2.92; 95% CI 0.96–6.38) or Modified Kansas without exclusions (aRERI = 3.84; 95% CI 1.30–8.52) or with exclusions (aRERI = 3.42; 95% CI 1.20–7.56). The lower power of CDC and Modified Kansas relative to Research was due to greater false-positive disease misclassification from lower diagnostic specificity. Conclusions: The original Research case definition had greater statistical power to detect a genetic predisposition to GWI. Its greater specificity favors its use in hypothesis-driven research; whereas, the greater sensitivity of the others favor their use in clinical screening for application of future diagnostic biomarkers and clinical care. [ABSTRACT FROM AUTHOR]

Although the defining elements of "acute respiratory distress syndrome" (ARDS) have been known for over a century, the syndrome was first described in 1967. Since then, despite several revisions of its conceptual definition, it remains a matter of debate whether ARDS is a discrete nosological entity. After almost 60 years, it is appropriate to examine how critical care has modeled this fascinating syndrome and affected patient's outcome. Given that the diagnostic criteria of ARDS (e.g., increased pulmonary vascular permeability and diffuse alveolar damage) are difficult to ascertain in clinical practice, we believe that a step forward would be to standardize the assessment of pulmonary and extrapulmonary involvement in ARDS to ensure that each patient can receive the most appropriate and effective treatment. The selection of treatments based on arbitrary ranges of PaO2/FiO2 lacks sufficient sensitivity to individualize patient care. [ABSTRACT FROM AUTHOR]

Background: In the USA, access to quality healthcare varies greatly across racial and ethnic groups, resulting in significant health disparities. A new term, "racial health equity" (RHE), is increasingly reported in the medical literature, but there is currently no consensus definition of the term. Additionally, related terms such as "health disparities," "health inequities," and "equality" have been inconsistently used when defining RHE. Methods: The primary purpose of this scoping review is to investigate the current use and underlying concepts used to define racial health equity. The study will address two key questions: (1) "What terminology and definitions have been used to characterize RHE?" and (2) "What knowledge gaps and challenges are present in the current state of RHE research and theory?" The review will collect and analyze data from three sources: (1) websites from key national and international health organizations, (2) theoretical and narrative published articles, and (3) evidence synthesis studies addressing interventions targeting racial health equity and minority stakeholder engagement. Discussion: Defining "racial health equity" and related terminology is the first step to advancing racial health equity within the USA. This review aims to offer an improved understanding of RHE constructs and definitions, bringing greater unity to national racial health equity research efforts across disciplines. Systematic review registration: This protocol is registered with the Open Science Framework at https://osf.io/7pvzq. [ABSTRACT FROM AUTHOR]

Background: A comprehensive and agreed-upon definition of vaccine literacy (VL) could support the understanding of vaccination and help policy-makers and individuals make informed decisions about vaccines. Methods: To shed some light on this debate and provide clarity, a scoping review was conducted to collect, summarize, and analyse available definitions of VL. Based on the findings of the scoping review, a new and comprehensive definition was proposed by a panel of experts. Results: Fifty-three articles were included, and two of them appeared to be the milestones around which the other definitions were grouped. The new definition proposed by the panel of experts included not only the personal perspective, but also the community, population, and organizational perspectives. Moreover, due to the increasing complexity of the social context with respect to the ability to navigate, understand, and use information and services, the definition of organizational vaccine literacy and the attributes of a vaccine literate healthcare organization have been proposed. Conclusion: The new definition can contribute to the overall paradigm of health literacy and its distinct component of vaccine literacy, possibly improving the implementation of public health strategies to allow vaccination to be understood as a social practice by the entire community. This study describes the conceptual foundations, the competencies, and the civic orientation to be considered when developing measurement tools devoted to assessing VL at the different levels and in different contexts. [ABSTRACT FROM AUTHOR]

Background: KDIGO and pRIFLE classifications are commonly used in pediatric acute kidney injury (AKI). As a novel AKI definition, pROCK considered the high variability of serum creatinine in children. This study aimed to compare the above three definitions for AKI in infants undergoing cardiac surgery. Methods: We analyzed a clinical cohort of 413 infants undergoing cardiac surgery. AKI was defined and staged according to pRIFLE, KDIGO, and pROCK, respectively. Incidence differences and diagnostic agreement across definitions were assessed. The association between postoperative outcomes and AKI by each definition was investigated. Results: Postoperative AKI was identified in 185 (44.8%), 160 (38.7%), and 77 (18.6%) patients according to pRIFLE, KDIGO, and pROCK, respectively. The agreement between pRIFLE and KDIGO was almost perfect (κ = 0.88), while there was only a slight agreement between pROCK and them. AKI by pROCK was independently associated with adverse outcomes (p = 0.003) and prolonged mechanical ventilation (p = 0.002). Conclusions: There were considerable differences in AKI incidence and staging among definitions. Compared with pRIFLE and KDIGO, AKI defined by pROCK was significantly reduced and better associated with postoperative adverse outcomes. [ABSTRACT FROM AUTHOR]

Background: A unified clinical definition of feeding intolerance (FI) is urged for better management of enteral nutrition (EN) in critically ill patients. We aimed to identify optimum clinical FI definitions based on reported evidence. Methods: We searched clinical studies comparing FI with non-FI with a clear definition, summarized the evidence by random-effect meta-analyses, and rated the certainty of evidence by the Grading of Recommendations Assessment, Development and Evaluation frameworks. Results: Five thousand five hundred twenty-five records were identified, of which 26 eligible studies enrolled 25,189 adult patients. Most patient-centered outcomes were associated with FI overall. Low to very low certainty evidence established FI defined as large gastric residual volume (GRV) ≥ 250 ± 50 mL combined with any other gastrointestinal symptoms (GIS) had a significant association with high mortalities in particular all-cause hospital mortality (odds ratio [OR] 1.90, 95% confidence interval [CI] 1.40–2.57), the incidence of pneumonia (OR 1.54, 95% CI 1.13–2.09) and prolonged length of hospital stay (mean difference 4.20, 95% CI 2.08–6.32), with a moderate hospital prevalence (41.49%, 95% CI 31.61–51.38%). 3-day enteral feeding (EF) delivered percentage < 80% had a moderate hospital prevalence (38.23%, 95% CI 24.88–51.58) but a marginally significant association with all-cause hospital mortality (OR 1.90, 95% CI 1.03–3.50). Conclusions: In critically ill adult patients receiving EN, the large-GRV-centered GIS to define FI seemed to be superior to 3-day EF-insufficiency in terms of both close associations with all-cause hospital mortality and acceptable hospital prevalence (Registered PROSPERO: CRD42022326273). Trial registration: The protocol for this review and meta-analysis was registered with PROSPERO: CRD42022326273. Registered 10 May 2022. [ABSTRACT FROM AUTHOR]

Background: Along with other types of research, it has been stated that the extent of redundancy in systematic reviews has reached epidemic proportions. However, it was also emphasized that not all duplication is bad, that replication in research is essential, and that it can help discover unfortunate behaviors of scientists. Thus, the question is how to define a redundant systematic review, the harmful consequences of such reviews, and what we could do to prevent the unnecessary amount of this redundancy. Main body: There is no consensus definition of a redundant systematic review. Also, it needs to be defined what amount of overlap between systematic reviews is acceptable and not considered a redundancy. One needs to be aware that it is possible that the authors did not intend to create a redundant systematic review. A new review on an existing topic, which is not an update, is likely justified only when it can be shown that the previous review was inadequate, for example, due to suboptimal methodology. Redundant meta-analyses could have scientific, ethical, and economic questions for researchers and publishers, and thus, they should be avoided, if possible. Potential solutions for preventing redundant reviews include the following: (1) mandatory prospective registration of systematic reviews; (2) editors and peer reviewers rejecting duplicate/redundant and inadequate reviews; (3) modifying the reporting checklists for systematic reviews; (4) developing methods for evidence-based research (EBR) monitoring; (5) defining systematic reviews; (6) defining the conclusiveness of systematic reviews; (7) exploring interventions for the adoption of methodological advances; (8) killing off zombie reviews (i.e., abandoned registered reviews); (9) better prevention of duplicate reviews at the point of registration; (10) developing living systematic reviews; and (11) education of researchers. Conclusions: Disproportionate redundancy of the same or very similar systematic reviews can lead to scientific, ethical, economic, and societal harms. While it is not realistic to expect that the creation of redundant systematic reviews can be completely prevented, some preventive measures could be tested and implemented to try to reduce the problem. Further methodological research and development in this field will be welcome. [ABSTRACT FROM AUTHOR]

Background: Definitions are important in healthcare. Unfortunately, problems can be found withall existing definitions of manipulation. Methods: This paper derives a set of eligibility criteria from prior definitions of manipulation to inform what should (and should not) be incorporated within a valid definition. These criteria were then used to select components from currently available empirical data to create a new definition. Results: The resulting definition of manipulation is: "Separation (gapping) of opposing articular surfaces of a synovial joint, caused by a force applied perpendicularly to those articular surfaces, that results in cavitation within the synovial fluid of that joint." The corresponding definition for the mechanical response of a manipulation is: "Separation (gapping) of opposing articular surfaces of a synovial joint that results in cavitation within the synovial fluid of that joint." In turn, the action of a manipulation can be defined as: "A force applied perpendicularly to the articular surfaces." Conclusions: We believe these definitions to be valid (derived from and consistent with all available empirical data), complete (containing all necessary components), minimally sufficient (minimal redundancy, and sufficient to distinguish manipulation from other physical interventions), and robust (able to withstand important limitations embodied within sensible eligibility criteria). It is hoped that the simplicity and clarity of these definitions, and the transparency of their formation, will encourage their wide adoption in clinical, research, educational and professional settings. [ABSTRACT FROM AUTHOR]

In 2016, we published a conceptual framework outlining the conclusions of our work in defining pilot and feasibility studies. Since then, the CONSORT extension to randomised pilot and feasibility trials has been published and there have been further developments in the pilot study landscape. In this paper, we revisit and extend our framework to incorporate the various feasibility pathways open to researchers, which include internal pilot studies. We consider, with examples, when different approaches to feasibility and pilot studies are more effective and efficient, taking into account the pragmatic decisions that may need to be made. The ethical issues involved in pilot studies are discussed. We end with a consideration of the funders' perspective in making difficult resource decisions to include feasibility work and the policy implications of these; throughout, we provide examples of the uncertainties and compromises that researchers have to navigate to make progress in the most efficient way. [ABSTRACT FROM AUTHOR]

When considering the manner of death, two categories can be distinguished, namely natural death and unnatural death. Though most physicians think that the distinction between the two is evident, this is not the case.When comparing the Netherlands, Belgium, England and Germany it is noticed that the terms natural and unnatural might be used in law but are not defined by law. In practice, the term unnatural death is used when there is an external cause of death, but even that turns out to not be sufficient in making an obvious difference between the two terms. Different countries may even label the same death differently. A, at times philosophical and semantic, discussion shows that when it comes to causes of death a very large grey area exists between natural and unnatural causes of death. The Netherlands, Belgium and Germany even have the possibility to label a death as natural (or unnatural) without actually knowing the cause of death.In conclusion, we recommend a new system in which the circumstances surrounding a death are properly investigated. This should lead to a report to an independent legal expert, who is able to decide if and what conclusion can be drawn, from a judicial and a public point of view, thereby, making the distinction and the use of the terms natural and unnatural/nonnatural obsolete. [ABSTRACT FROM AUTHOR]

Background: There has recently been a push for recovery-focused research in the eating disorder (ED) field, starting with a consensus definition of recovery. One definition, in particular, proposed by Bardone-Cone et al. [21] has received considerable attention given its transdiagnostic nature and validation studies. However, no studies to date have elicited lived experience views of this definition. The goal of the current study was to examine perspectives on this definition of recovery from individuals with a past or present ED and to determine whether participant agreement with the model differed based on diagnostic history or current symptom severity. Methods: Sixty-two individuals (95.2% women; 91.9% White/European) participated in a 1–2 h interview aimed at capturing their perspectives on ED recovery. Transcripts were analyzed using qualitative content analysis and codebook thematic analysis to examine agreement with and thoughts on Bardone-Cone's definition of recovery, respectively. Chi-squared tests of independence and binary logistic regression were computed to determine whether agreement with the definition differed across diagnostic history and self-reported symptoms. Results: Although some participants indicated acceptance of the definition, the majority expressed concerns related to its categorical nature, proposed criteria, feasibility, language, and applications. There were no differences in acceptance based on diagnostic history or current symptom severity. Conclusion: A single definition of recovery does not seem to fit individuals' lived ED experience. Future research may benefit from distinguishing between recovery as an individually-defined phenomenon and related constructs such as remission (i.e., loss of diagnosis or absence of clinical symptoms). A more comprehensive multi-faceted, and person-centered model of recovery may have merit in clinical settings. Plain English Summary: Eating disorder recovery has been defined as reaching a specific body weight, while also refraining from eating disorder behaviours and reporting lessened eating disorder thoughts. Although this seems reasonable, no studies have asked people who have or have had eating disorders if this fits with their lived experience. We presented participants with a specific definition of eating disorder recovery which includes weight, behaviour, and thought criteria and asked them about their perspectives. Though some people felt this definition was sufficient, the majority expressed concerns. These ranged from concerns about the specific criteria (e.g., using body weight is outdated and not informative) to the applications of the definition (e.g., such specific criteria may limit some people from receiving services). These findings point toward the inclusion of lived experience voices in eating disorder recovery definitions. [ABSTRACT FROM AUTHOR]

Background: Metabolic syndrome (MetS) is characterized by a cluster of signs of metabolic disturbance and has caused a huge burden on the health system. The study aims to explore the prevalence and characteristics of MetS defined by different criteria in the Chinese population.Methods: Using the data of the China Hypertension Survey (CHS), a nationally representative cross-sectional study from October 2012 to December 2015, a total of 28,717 participants aged 35 years and above were included in the analysis. The MetS definitions of the International Diabetes Federation (IDF), the updated US National Cholesterol Education Program Adult Treatment Panel III (the revised ATP III), and the Joint Committee for Developing Chinese Guidelines (JCDCG) on Prevention and Treatment of Dyslipidemia in Adults were used. Multivariable logistic regression was used to identify factors associated with MetS.Results: The prevalence of MetS diagnosed according to the definitions of IDF, the revised ATP III, and JCCDS was 26.4%, 32.3%, and 21.5%, respectively. The MetS prevalence in men was lower than in women by IDF definition (22.2% vs. 30.3%) and by the revised ATP III definition (29.2% vs. 35.4%), but the opposite was true by JCDCG (24.4%vs 18.5%) definition. The consistency between the three definitions for men and the revised ATP III definition and IDF definition for women was relatively good, with kappa values ranging from 0.77 to 0.89, but the consistency between the JCDCG definition and IDF definition (kappa = 0.58) and revised ATP III definition (kappa = 0.58) was poor. Multivariable logistic regression showed that although the impact and correlation intensity varied with gender and definition, area, age, education, smoking, alcohol use, and family history of cardiovascular disease were factors related to MetS.Conclusions: The prevalence and characteristics of the MetS vary with the definition used in the Chinese population. The three MetS definitions are more consistent in men but relatively poor in women. On the other hand, even if estimated according to the definition of the lowest prevalence, MetS is common in China. [ABSTRACT FROM AUTHOR]

Background: The algorithm for proven and young (APY) has been suggested as a solution for recursively computing a sparse representation for the inverse of a large genomic relationship matrix (G). In APY, a subset of genotyped individuals is used as the core and the remaining genotyped individuals are used as noncore. Size and definition of the core are relevant research subjects for the application of APY, especially given the ever-increasing number of genotyped individuals. Methods: The aim of this study was to investigate several core definitions, including the most popular animals (MPA) (i.e., animals with high contributions to the genetic pool), the least popular males (LPM), the least popular females (LPF), a random set (Rnd), animals evenly distributed across genealogical paths (Ped), unrelated individuals (Unrel), or based on within-family selection (Fam), or on decomposition of the gene content matrix (QR). Each definition was evaluated for six core sizes based on prediction accuracy of single-step genomic best linear unbiased prediction (ssGBLUP) with APY. Prediction accuracy of ssGBLUP with the full inverse of G was used as the baseline. The dataset consisted of 357k pedigreed Duroc pigs with 111k pigs with genotypes and ~ 220k phenotypic records. Results: When the core size was equal to the number of largest eigenvalues explaining 50% of the variation of G (n = 160), MPA and Ped core definitions delivered the highest average prediction accuracies (~ 0.41−0.53). As the core size increased to the number of eigenvalues explaining 99% of the variation in G (n = 7320), prediction accuracy was nearly identical for all core types and correlations with genomic estimated breeding values (GEBV) from ssGBLUP with the full inversion of G were greater than 0.99 for all core definitions. Cores that represent all generations, such as Rnd, Ped, Fam, and Unrel, were grouped together in the hierarchical clustering of GEBV. Conclusions: For small core sizes, the definition of the core matters; however, as the size of the core reaches an optimal value equal to the number of largest eigenvalues explaining 99% of the variation of G, the definition of the core becomes arbitrary. [ABSTRACT FROM AUTHOR]

Background: Metabolic syndrome (MetS) is a public health problem in Europe, affecting all age groups. Several MetS definitions are available. The aim of this study was to compare four different MetS definitions in the Finnish adult population, to assess their agreement and to evaluate the impact of the choice of the definition on the prevalence of MetS. Methods: Data from FinHealth 2017, a cross-sectional national population health survey, focusing on adults aged 25 years or older were used in the analysis (n=5687). Measured data on anthropometrics, blood pressure and biomarkers together with questionnaire data were used to classify the participants into the MetS categories according to the four definitions. The definitions chosen for the comparison were those by the World Health Organization (WHO) (1998), National Cholesterol Education Program Adult Treatment Panel III (NCEP-ATP III) (2004), International Diabetes Federation (IDF) (2005), and Joint Interim Statement (JIS) (2009). Results: The four MetS definitions resulted in substantially different MetS prevalence: 17.7% by WHO, 33.3% by NCEP-ATP III, 41.5% by IDF, and 43.0% by JIS. Regardless of the definition used, the prevalence of MetS increased with age. The prevalence of the different components varied between the definitions, depending on the different cut-off points adopted. Out of all participants, only 13.6% were identified to have MetS according to all four definitions. Agreement between participants recognised by different MetS definitions, estimated through kappa coefficients, was almost perfect for IDF vs. JIS (0.97), strong for JIS vs. NCEP-ATP III (0.80), moderate for IDF vs. NCEP-ATP III (0.76) and weak for WHO vs. NCEP-ATP III (0.42), WHO vs. IDF (0.41) and WHO vs. JIS (0.40). Conclusions: Differences between observed prevalence of MetS in Finnish men and women using different MetS definitions were large. For cross-country comparisons, as well as for trend analyses within a country, it is essential to use the same MetS definition to avoid discrepancies in classification due to differences in used definitions. [ABSTRACT FROM AUTHOR]

Background: Biomedical named entity recognition (NER) is a fundamental task of biomedical text mining that finds the boundaries of entity mentions in biomedical text and determines their entity type. To accelerate the development of biomedical NER techniques in Spanish, the PharmaCoNER organizers launched a competition to recognize pharmacological substances, compounds, and proteins. Biomedical NER is usually recognized as a sequence labeling task, and almost all state-of-the-art sequence labeling methods ignore the meaning of different entity types. In this paper, we investigate some methods to introduce the meaning of entity types in deep learning methods for biomedical NER and apply them to the PharmaCoNER 2019 challenge. The meaning of each entity type is represented by its definition information. Material and method: We investigate how to use entity definition information in the following two methods: (1) SQuad-style machine reading comprehension (MRC) methods that treat entity definition information as query and biomedical text as context and predict answer spans as entities. (2) Span-level one-pass (SOne) methods that predict entity spans of one type by one type and introduce entity type meaning, which is represented by entity definition information. All models are trained and tested on the PharmaCoNER 2019 corpus, and their performance is evaluated by strict micro-average precision, recall, and F1-score. Results: Entity definition information brings improvements to both SQuad-style MRC and SOne methods by about 0.003 in micro-averaged F1-score. The SQuad-style MRC model using entity definition information as query achieves the best performance with a micro-averaged precision of 0.9225, a recall of 0.9050, and an F1-score of 0.9137, respectively. It outperforms the best model of the PharmaCoNER 2019 challenge by 0.0032 in F1-score. Compared with the state-of-the-art model without using manually-crafted features, our model obtains a 1% improvement in F1-score, which is significant. These results indicate that entity definition information is useful for deep learning methods on biomedical NER. Conclusion: Our entity definition information enhanced models achieve the state-of-the-art micro-average F1 score of 0.9137, which implies that entity definition information has a positive impact on biomedical NER detection. In the future, we will explore more entity definition information from knowledge graph. [ABSTRACT FROM AUTHOR]

Background: The 6th World Symposium on Pulmonary Hypertension (Nice 2018) proposed a new definition of pre-capillary pulmonary hypertension (PH) as a condition with mean pulmonary artery pressure (mPAP) > 20 mmHg, pulmonary artery wedge pressure  ≤ 15 mmHg, and pulmonary vascular resistance (PVR) ≥ 3 Wood units (WU). The characteristics and prognosis of patients with pre-capillary PH, according to this new definition, is unclear. Therefore, we determined the characteristics and survival of patients with borderline pre-capillary PH.Methods: We retrospectively enrolled 683 patients who underwent their first right heart catheterization at Chiba University, Japan. Among them, 489 patients met the pre-capillary PH requirement with mPAP ≥ 25 mmHg (conventional pre-capillary PH group), while 22 patients met the borderline pre-capillary PH criteria (borderline pre-capillary PH group). Additionally, 16 patients with a mean PAP of 20-25 and PVR of 2-3 WU were also examined.Results: The borderline pre-capillary PH group comprised 4.3% of the total patients with pre-capillary PH, and the majority was in Group 3 (40.9%) or 4 (45.5%). The survival of the borderline pre-capillary PH group tended to be better than that of the conventional pre-capillary PH group. The prognosis of Group3 PH was the worst among the patients with borderline precapillary PH. There was no significant difference in survival between the borderline pre-capillary PH group with PVR ≥ 3 WU and that with PVR of 2-3 2WU, although none of the patients in the latter group died due to right heart failure.Conclusions: This is the first study conducted in a PH center in an Asian country to reveal the characteristics of patients with pre-capillary PH, according to the Nice 2018 definition. They comprised 4.3% of the total population with pre-capillary PH, and the majority of the pre-capillary PH cases were in either Group3 or 4. The prognosis may be affected by the patients' underlying diseases. Further prospective studies are needed to determine whether the new definition, including the PVR cut-off, is beneficial in clinical practice. [ABSTRACT FROM AUTHOR]

Background: Patient-Reported Outcomes (PROs) are standardized questionnaires used to measure subjective outcomes such as quality of life in healthcare. They are considered paramount to assess the results of therapeutic interventions. However, because their calibration is relative to internal standards in people's mind, changes in PRO scores are difficult to interpret. Knowing the smallest value in the score that the patient perceives as change can help. An estimator linking the answers to a Patient Global Rating of Change (PGRC: a question measuring the overall feeling of change) with change in PRO scores is frequently used to obtain this value. In the last 30 years, a plethora of methods have been used to obtain these estimates, but there is no consensus on the appropriate method and no formal definition of this value.Methods: We propose a model to explain changes in PRO scores and PGRC answers.Results: A PGRC measures a construct called the Perceived Change (PC), whose determinants are elicited. Answering a PGRC requires discretizing a continuous PC into a category using threshold values that are random variables. Therefore, the populational value of the Minimal Perceived Change (MPC) is the location parameter value of the threshold on the PC continuum defining the switch from the absence of change to change.Conclusions: We show how this model can help to hypothesize what are the appropriate methods to estimate the MPC and its potential to be a rigorous theoretical basis for future work on the interpretation of change in PRO scores. [ABSTRACT FROM AUTHOR]

Background: In contrast to the hospital setting, today little work has been directed to the definition, measurement, and improvement of the quality of out-patient medical and therapeutic care. We developed a set of indicators to measure the quality of out-patient neuropsychological therapy after stroke. Methods: The indicators cover core and interdisciplinary aspects of out-patient neuropsychological work such as mediation of patients into social care in case of need. Selection of the quality-indicators was done together with a consensus group of out-patient therapists and supported by evidence, validity, reliability as well as estimated relevance and variability with the quality of care. The set of indicators was further tested in a retrospective cohort study. Anonymous data of 104 patients were collected from out-patient clinical records of five clinics between November 2017 and April 2018. Associations between process and outcome quality were estimated exploitatively. Results: Results allowed for the identification of areas with greater variability in the quality of process care and indicated that attention training as recommended by current guidelines had the lowest overall rate for meeting the quality-aim (met in 44% of the cases). This was followed by time < 1 month until the start of therapy (63% met) and mediation into social care in case of need (65% met). We further observed that overall quality and involving relatives in the therapy was associated with higher rates of professional reintegration (p-value = 0.03). However, the need for mediation into social care was associated with a reduced chance for successful professional reintegration (p-value = 0.009). Conclusion: In conclusion, we describe a first set of quality indicators which cover different aspects of out-patient neuropsychological therapy and sufficient variability with care. First data further suggests that meeting the specified quality aims may indeed have relevant effects on outcomes. [ABSTRACT FROM AUTHOR]

Ongoing and future hydroclimatic changes have large environmental and societal impacts. In terrestrial ecosystems, these changes are usually described with the terms 'wetter' and 'drier', which refer to the change in the quantity and/or presence of water, either as water fluxes or stocks. We conducted a literature review of almost 500 recent climate change studies to quantitatively investigate the consistency of the use of these terms across disciplines, regarding the hydroclimatic variables they are related to. We found that although precipitation is prevalently used to describe 'wetter' and 'drier' conditions, many other variables are also used to refer to changes in water availability between research fields, pointing to a varied perspective on the use of these terms. Some studies do not define the terms at all. In order to facilitate meta-analyses across disciplines, we therefore highlight the need to explicitly state which hydroclimatic variables authors are referring to. In this way, we hope that the terms 'wetter' and 'drier' used in scientific studies are easier to relate to hydroclimatic processes, which should facilitate the application by authorities and policy makers. [ABSTRACT FROM AUTHOR]

Background: In 2017, the European Commission's Joint Research Centre (JRC) started developing a methodological framework for a guideline-based quality assurance (QA) scheme to improve cancer quality of care. During the first phase of the work, inconsistency emerged about the use of terminology for the definition, the conceptual underpinnings and the way QA relates to health questions that are answered in guidelines. The objective of this final of three articles is to propose a conceptual framework for an integrated approach to guideline and QA development and clarify terms and definitions for key elements. This work will inform the upcoming European Commission Initiative on Colorectal Cancer (ECICC).Methods: A multidisciplinary group of 23 experts from key organizations in the fields of guideline development, performance measurement and quality assurance participated in a mixed method approach including face-to-face dialogue and several rounds of virtual meetings. Informed by results of a systematic literature review that indicated absence of an existing framework and practical examples, we first identified the relations of key elements in guideline-based QA and then developed appropriate concepts and terminology to provide guidance.Results: Our framework connects the three key concepts of quality indicators, performance measures and performance indicators integrated with guideline development. Quality indicators are constructs used as a guide to monitor, evaluate, and improve the quality of the structure, process and outcomes of healthcare services; performance measures are tools that quantify or describe measurable elements of practice performance; and performance indicators are quantifiable and measurable units or scores of practice, which should be guided by guideline recommendations.Conclusions: The inconsistency in the way key terms of QA are used and defined has confused the field. Our conceptual framework defines the role, meaning and interactions of the key elements for improving quality in healthcare. It directly builds on the questions asked in guidelines and answered through recommendations. These findings will be applied in the forthcoming ECICC and for the future updates of ECIBC. These are large-scale integrated projects aimed at improving healthcare quality across Europe through the development of guideline-based QA schemes; this will help in implementing and improving our approach. [ABSTRACT FROM AUTHOR]

Background: Influenza is a major cause of morbidity and mortality in Africa. However, a lack of epidemiological data remains for this pathology, and the performances of the influenza-like illness (ILI) case definitions used for sentinel surveillance have never been evaluated in Senegal. This study aimed to i) assess the performance of three different ILI case definitions, adopted by the WHO, USA-CDC (CDC) and European-CDC (ECDC) and ii) identify clinical factors associated with a positive diagnosis for Influenza in order to develop an algorithm fitted for the Senegalese context.Methods: All 657 patients with a febrile pathological episode (FPE) between January 2013 and December 2016 were followed in a cohort study in two rural villages in Senegal, accounting for 1653 FPE observations with nasopharyngeal sampling and influenza virus screening by rRT-PCR. For each FPE, general characteristics and clinical signs presented by patients were collected. Sensitivity, Specificity, Positive Predictive Value (PPV) and Negative Predictive Value (NPV) for the three ILI case definitions were assessed using PCR result as the reference test. Associations between clinical signs and influenza infection were analyzed using logistic regression with generalized estimating equations. Sore throat, arthralgia or myalgia were missing for children under 5 years.Results: WHO, CDC and ECDC case definitions had similar sensitivity (81.0%; 95%CI: 77.0-85.0) and NPV (91.0%; 95%CI: 89.0-93.1) while the WHO and CDC ILI case definitions had the highest specificity (52.0%; 95%CI: 49.1-54.5) and PPV (32.0%; 95%CI: 30.0-35.0). These performances varied by age groups. In children < 5 years, the significant predictors of influenza virus infection were cough and nasal discharge. In patients from 5 years, cough, nasal discharge, sore throat and asthenia grade 3 best predicted influenza infection. The addition of "nasal discharge" as a symptom to the WHO case definition decreased sensitivity but increased specificity, particularly in the pediatric population.Conclusion: In summary, all three definitions studies (WHO, ECDC & CDC) have similar performance, even by age group. The revised WHO ILI definition could be chosen for surveillance purposes for its simplicity. Symptomatic predictors of influenza virus infection vary according the age group. [ABSTRACT FROM AUTHOR]

Background: Neurological forms of Gaucher disease, the inherited disorder of β-Glucosylceramidase caused by bi-allelic variants in GBA1, is a progressive disorder which lacks a disease-modifying therapy. Systemic manifestations of disease are effectively treated with enzyme replacement therapy, however, molecules which cross the blood-brain barrier are still under investigation. Clinical trials of such therapeutics require robust, reproducible clinical endpoints to demonstrate efficacy and clear phenotypic definitions to identify suitable patients for inclusion in trials. The single consistent clinical feature in all patients with neuronopathic disease is the presence of a supranuclear saccadic gaze palsy, in the presence of Gaucher disease this finding serves as diagnostic of 'type 3' Gaucher disease.Methods: We undertook a study to evaluate saccadic eye movements in Gaucher patients and to assess the role of the EyeSeeCam in measuring saccades. The EyeSeeCam is a video-oculography device which was used to run a protocol of saccade measures. We studied 39 patients with non-neurological Gaucher disease (type 1), 21 patients with type 3 (neurological) disease and a series of 35 healthy controls. Mean saccade parameters were compared across disease subgroups.Results: We confirmed the saccadic abnormality in patients with type 3 Gaucher disease and identified an unexpected subgroup of patients with type 1 Gaucher disease who demonstrated significant saccade parameter abnormalities. These patients also showed subtle neurological findings and shared a GBA1 variant.Conclusions: This striking novel finding of a potentially attenuated type 3 Gaucher phenotype associated with a specific GBA1 variant and detectable saccadic abnormality prompts review of current disease classification. Further, this finding highlights the broad spectrum of neuronopathic Gaucher phenotypes relevant when designing inclusion criteria for clinical trials. [ABSTRACT FROM AUTHOR]

Background: Patients benefit from access to their medical records. However, clinical notes and letters are often difficult to comprehend for most lay people. Therefore, functionality was implemented in the patient portal of a Dutch university medical centre (UMC) to clarify medical terms in free-text data. The clarifications consisted of synonyms and definitions from a Dutch medical terminology system. We aimed to evaluate to what extent these lexical clarifications match the information needs of the patients. Secondarily, we evaluated how the clarifications and the functionality could be improved.Methods: We invited participants from the patient panel of the UMC to read their own clinical notes. They marked terms they found difficult and rated the ease of these terms. After the functionality was activated, participants rated the clarifications provided by the functionality, and the functionality itself regarding ease and usefulness. Ratings were on a scale from 0 (very difficult) to 100 (very easy). We calculated the median number of terms not understood per participant, the number of terms with a clarification, the overlap between these numbers (coverage), and the precision and recall.Results: We included 15 participants from the patient panel. They marked a median of 21 (IQR 19.5-31) terms as difficult in their text files, while only a median of 2 (IQR 1-4) of these terms were clarified by the functionality. The median precision was 6.5% (IQR 2.3-14.25%) and the median recall 8.3% (IQR 4.7-13.5%) per participant. However, participants rated the functionality with median ease of 98 (IQR 93.5-99) and a median usefulness of 79 (IQR 52.5-97). Participants found that many easy terms were unnecessarily clarified, that some clarifications were difficult, and that some clarifications contained mistakes.Conclusions: Patients found the functionality easy to use and useful. However, in its current form it only helped patients to understand few terms they did not understand, patients found some clarifications to be difficult, and some to be incorrect. This shows that lexical clarification is feasible even when limited terms are available, but needs further development to fully use its potential. [ABSTRACT FROM AUTHOR]

Background: The National Cancer Institute (NCI) Thesaurus provides reference terminology for NCI and other systems. Previously, we proposed a hybrid prototype utilizing lexical features and role definitions of concepts in non-lattice subgraphs to identify missing IS-A relations in the NCI Thesaurus. However, no domain expert evaluation was provided in our previous work. In this paper, we further enhance the hybrid approach by leveraging a novel lexical feature-roots of noun chunks within concept names. Formal evaluation of our enhanced approach is also performed.Method: We first compute all the non-lattice subgraphs in the NCI Thesaurus. We model each concept using its role definitions, words and roots of noun chunks within its concept name and its ancestor's names. Then we perform subsumption testing for candidate concept pairs in the non-lattice subgraphs to automatically detect potentially missing IS-A relations. Domain experts evaluated the validity of these relations.Results: We applied our approach to 19.08d version of the NCI Thesaurus. A total of 55 potentially missing IS-A relations were identified by our approach and reviewed by domain experts. 29 out of 55 were confirmed as valid by domain experts and have been incorporated in the newer versions of the NCI Thesaurus. 7 out of 55 further revealed incorrect existing IS-A relations in the NCI Thesaurus.Conclusions: The results showed that our hybrid approach by leveraging lexical features and role definitions is effective in identifying potentially missing IS-A relations in the NCI Thesaurus. [ABSTRACT FROM AUTHOR]

Background: Previous studies on the persistence of child and adolescent mental healthcare do not consider the role of time-invariant individual characteristics. Estimating persistence of healthcare using standard linear models yields biased estimates due to unobserved heterogeneity and the autoregressive structure of the model. This study provides estimates of the persistence of child and adolescent mental healthcare taking these statistical issues into account.Methods: We use registry data of more than 80,000 Dutch children and adolescents between 2000 and 2012 from the Psychiatric Case Registry Northern Netherlands (PCR-NN). In order to account for autocorrelation due to the presence of a lagged dependent variable and to distinguish between persistence caused by time-invariant individual characteristics and a direct care effect we use difference GMM-IV estimation. In further analyses we assess the robustness of our results to policy reforms, different definitions of care and diagnosis decomposition.Results: All estimation results for the direct care effect (true state-dependence) show a positive coefficient smaller than unity with a main effect of 0.215 (p<0.01), which indicates that the process is stable. Persistence of care is found to be 0.065 (p<0.05) higher for females. Additionally, the majority of persistence of care appears to be associated with time-invariant characteristics. Further analyses indicate that (1) results are robust to different definitions of care and (2) persistence of care does not differ significantly across subgroups.Conclusions: The results indicate that the majority of mental healthcare persistence for children and adolescents is due to time-invariant individuals characteristics. Additionally, we find that in the absence of further shocks a sudden increase of 10 care contacts in the present year is associated with an average of less than 3 additional care contacts at some point in the future. This result provides essential information about the necessity of budget increases for future years in the case of exogenous increases in healthcare use. [ABSTRACT FROM AUTHOR]

Background: Chronic kidney disease has emerged as a strong cardiovascular risk factor, and in many current guidelines, it is already considered as a coronary heart disease (CHD) equivalent. Routinely, creatinine has been used as the main marker of renal function, but recently, cystatin C emerged as a more promising marker. The aim of this study was to assess the comparative cardiovascular and mortality risk of chronic kidney disease (CKD) using cystatin C-based and creatinine-based equations of the estimated glomerular filtration rate (eGFR) in participants of population-based and disease cohorts.Methods: The present study has been conducted within the BiomarCaRE project, with harmonized data from 20 population-based cohorts (n = 76,954) from 6 European countries and 3 cardiovascular disease (CVD) cohorts (n = 4982) from Germany. Cox proportional hazards models were used to assess hazard ratios (HRs) for the various CKD definitions with adverse outcomes and mortality after adjustment for the Systematic COronary Risk Evaluation (SCORE) variables and study center. Main outcome measures were cardiovascular diseases, cardiovascular death, and all-cause mortality.Results: The overall prevalence of CKD stage 3-5 by creatinine- and cystatin C-based eGFR, respectively, was 3.3% and 7.4% in the population-based cohorts and 13.9% and 14.4% in the disease cohorts. CKD was an important independent risk factor for subsequent CVD events and mortality. For example, in the population-based cohorts, the HR for CVD mortality was 1.72 (95% CI 1.53 to 1.92) with creatinine-based CKD and it was 2.14 (95% CI 1.90 to 2.40) based on cystatin-based CKD compared to participants without CKD. In general, the HRs were higher for cystatin C-based CKD compared to creatinine-based CKD, for all three outcomes and risk increased clearly below the conventional threshold for CKD, also in older adults. Net reclassification indices were larger for a cystatin-C based CKD definition. Differences in HRs (between the two CKD measures) in the disease cohorts were less pronounced than in the population-based cohorts.Conclusion: CKD is an important risk factor for subsequent CVD events and total mortality. However, point estimates of creatinine- and cystatin C-based CKD differed considerably between low- and high-risk populations. Especially in low-risk settings, the use of cystatin C-based CKD may result in more accurate risk estimates and have better prognostic value. [ABSTRACT FROM AUTHOR]

Background: Many of the strategies designed to reduce "low-value care" have been implemented without a consensus on the definition of the term "value". Most "low value care" lists are based on the comparative effectiveness of the interventions.Main Text: Defining the value of an intervention based on its effectiveness may generate an inefficient use of resources, as a very effective intervention is not necessarily an efficient intervention, and a low effective intervention is not always an inefficient intervention. The cost-effectiveness plane may help to differentiate between high and low value care interventions. Reducing low value care should include three complementary strategies: eliminating ineffective interventions that entail a cost; eliminating interventions whose cost is higher and whose effectiveness is lower than that of other options (quadrant IV); and eliminating interventions whose incremental or decremental cost-effectiveness is unacceptable in quadrants I and III, respectively. Defining low-value care according to the efficiency of the interventions, ideally at the level of subgroups and individuals, will contribute to develop true value-based health care systems.Conclusion: Cost-effectiveness rather than effectiveness should be the main criterion to assess the value of health care services and interventions. Payment-for-value strategies should be based on the definition of high and low value provided by the cost-effectiveness plane. [ABSTRACT FROM AUTHOR]

Background: The periprosthetic joint infection (PJI) is a severe complication in the field of arthroplasty. Despite the rising number of primary joint replacements, no unified therapeutic standard has been established for the treatment of PJI yet.Methods: A survey on the principles of treatment of PJI in Germany was conducted. A total of 515 EndoProthetikZentren (EPZ) were included, resulting in a response rate of 100%.Results: For early infections 97.6% of the centers use prosthesis-preserving procedures (DAIR). A one-stage exchange was implemented by less than 50% of the centers. If implemented, this treatment entails a prior selection of patients for a successful treatment. The two-stage exchange is performed in all centers, and most centers proceed with the implantation of a cemented spacer between stages. 75% of the centers proceed with a center-based concept for the treatment of PJI.Conclusion: The aim of a uniform PJI standard at the centers has not yet been fully achieved. Further improvements within the certification were initiated. The most relevant treatment options in Germany are displayed. The two-stage revision with a cemented spacer is the most widely implemented treatment. This exposition of principles could help for the further development of standardized treatment guidelines and definitions. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the applicability and estimate the radiobiological parameters of linear-quadratic Poisson tumour control probability (TCP) model for primary prostate cancer patients for two relevant target structures (prostate gland and GTV). The TCP describes the dose-response of prostate after definitive radiotherapy (RT). Also, to analyse and identify possible significant correlations between clinical and treatment factors such as planned dose to prostate gland, dose to GTV, volume of prostate and mpMRI-GTV based on multivariate logistic regression model.Methods: The study included 129 intermediate and high-risk prostate cancer patients (cN0 and cM0), who were treated with image-guided intensity modulated radiotherapy (IMRT) ± androgen deprivation therapy with a median follow-up period of 81.4 months (range 42.0-149.0) months. Tumour control was defined as biochemical relapse free survival according to the Phoenix definition (BRFS). MpMRI-GTV was delineated retrospectively based on a pre-treatment multi-parametric MR imaging (mpMRI), which was co-registered to the planning CT. The clinical treatment planning procedure was based on prostate gland, delineated on CT imaging modality. Furthermore, we also fitted the clinical data to TCP model for the two considered targets for the 5-year follow-up after radiation treatment, where our cohort was composed of a total number of 108 patients, of which 19 were biochemical relapse (BR) patients.Results: For the median follow-up period of 81.4 months (range 42.0-149.0) months, our results indicated an appropriate α/β = 1.3 Gy for prostate gland and α/β = 2.9 Gy for mpMRI-GTV. Only for prostate gland, EQD2 and gEUD2Gy were significantly lower in the biochemical relapse (BR) group compared to the biochemical control (BC) group. Fitting results to the linear-quadratic Poisson TCP model for prostate gland and α/β = 1.3 Gy were D50 = 66.8 Gy with 95% CI [64.6 Gy, 69.0 Gy], and γ = 3.8 with 95% CI [2.6, 5.2]. For mpMRI-GTV and α/β = 2.9 Gy, D50 was 68.1 Gy with 95% CI [66.1 Gy, 70.0 Gy], and γ = 4.5 with 95% CI [3.0, 6.1]. Finally, for the 5-year follow-up after the radiation treatment, our results for the prostate gland were: D50 = 64.6 Gy [61.6 Gy, 67.4 Gy], γ = 3.1 [2.0, 4.4], α/β = 2.2 Gy (95% CI was undefined). For the mpMRI-GTV, the optimizer was unable to deliver any reasonable results for the expected clinical D50 and α/β. The results for the mpMRI-GTV were D50 = 50.1 Gy [44.6 Gy, 56.0 Gy], γ = 0.8 [0.5, 1.2], α/β = 0.0 Gy (95% CI was undefined). For a follow-up time of 5 years and a fixed α/β = 1.6 Gy, the TCP fitting results for prostate gland were D50 = 63.9 Gy [60.8 Gy, 67.0 Gy], γ = 2.9 [1.9, 4.1], and for mpMRI-GTV D50 = 56.3 Gy [51.6 Gy, 61.1 Gy], γ = 1.3 [0.8, 1.9].Conclusion: The linear-quadratic Poisson TCP model was better fit when the prostate gland was considered as responsible target than with mpMRI-GTV. This is compatible with the results of the comparison of the dose distributions among BR and BC groups and with the results achieved with the multivariate logistic model regarding gEUD2Gy. Probably limitations of mpMRI in defining the GTV explain these results. Another explanation could be the relatively homogeneous dose prescription and the relatively low number of recurrences. The failure to identify any benefit for considering mpMRI-GTV as the target responsible for the clinical response is confirmed when considering a fixed α/β = 1.6 Gy, a fixed follow-up time for biochemical response at 5 years or Gleason score differentiation. [ABSTRACT FROM AUTHOR]

Background: Partially methylated domains (PMDs) are a hallmark of epigenomes in reproducible and specific biological contexts, including cancer cells, the placenta, and cultured cell lines. Existing methods for deciding whether PMDs exist in a sample, as well as their identification, are few, often tailored to specific biological questions, and require high coverage samples for accurate identification. Results: In this study, we outline a set of axioms that take a step towards a functional definition for PMDs, describe an improved method for comparable PMD detection across samples with substantially differing sequencing depths, and refine the decision criteria for whether a sample contains PMDs using a data-driven approach. Applying our method to 267 methylomes from 7 species, we corroborated recent results regarding the general association between replication timing and PMD state, and report identification of several reproducibly "escapee" genes within late-replicating domains that escape the reduced expression and hypomethylation of their immediate genomic neighborhood. We also explored the discordant PMD state of orthologous genes between human and mouse, and observed a directional association of PMD state with gene expression and local gene density. Conclusions: Our improved method makes low sequencing depth, population-level studies of PMD variation possible and our results further refine the model of PMD formation as one where sequence context and regional epigenomic features both play a role in gradual genome-wide hypomethylation. [ABSTRACT FROM AUTHOR]

Background: Loss of muscle mass and function may be more pronounced in older adults with chronic kidney disease (CKD) and with albuminuria. Thus, we investigated the prevalence of sarcopenia among community-dwelling older adults according to kidney function and grade of albuminuria. We also explored differences in the prevalence of sarcopenia according to three different equations for the estimation of glomerular filtration rate (eGFR).Methods: A cross-sectional analysis of 1420 community-dwelling older adults (≥75 years old) included in the SCOPE study, a multicenter prospective cohort study, was conducted. Comprehensive geriatric assessment including short physical performance battery (SPPB), handgrip strength test and bioelectrical impedance analysis (BIA) was performed. Sarcopenia was defined using the updated criteria of the European Working Group on Sarcopenia in Older People (EWGSOP2). eGFR was calculated using Berlin Initiative Study (BIS), Chronic Kidney Disease Epidemiological Collaboration (CKD-EPI) and Full Age Spectrum (FAS) equations, and urinary albumin-to-creatinine ratio (ACR) was collected to categorize CKD according to Kidney Disease Improving Global Outcomes guidelines.Results: Median age was 79.5 years (77.0-83.0), 804 (56.6%) were women. Using EWGSOP2 definition, 150 (10.6%) participants met diagnostic criteria for sarcopenia. Moreover, 85 (6%) participants had severe sarcopenia. Sarcopenia was more prevalent in participants with more advanced stages of CKD according to BIS eq. (9.6% in stages 1 and 2 and 13.9% in stages 3a, 3b and 4, p = 0.042), and also according to CKD-EPI (9.8% vs. 14.2%, p = 0.042) and FAS although not reaching statistical signification (9.8% vs. 12.7%, p = 0.119). Thus, differences in prevalence are observed among CKD categories as estimated by different equations. Prevalence of sarcopenia was also higher with increasing albuminuria categories: 9.3% in normoalbuminuric, 13.2% in microalbuminuric and 16.8% in macroalbuminuric participants, (p = 0.019).Conclusions: Sarcopenia is common among community-dwelling older adults, especially among those with more advanced CKD categories, with prevalence estimates differing slightly depending on the equation used for the estimation of eGFR; as well as among those with higher albuminuria categories. [ABSTRACT FROM AUTHOR]

Background: Multiple definitions are used to investigate injuries in musicians, resulting in a wide range of prevalence rates. The aim of this study is to establish the impact of different injury definitions on the prevalence of injuries and disability in classical music students. Moreover, the practical implications of using different injury definitions are considered.Methods: A prospective cohort study among first-year classical music students was performed using bi-monthly questionnaires focusing on injuries. Three injury definitions were used: 1) all MSK complaints injury (any MSK complaint resulting in a VAS pain score > 0 in the past eight weeks), 2) medical attention injury (any MSK complaint that resulted in a student consulting a health provider in the past eight weeks), 3) time-loss injury (any MSK complaint that resulted in partly/completely missing music classes or activities in the past eight weeks). For all injury definitions prevalences were calculated and compared. Furthermore, the Disabilities of the Arm, Shoulder and Hand performing arts module (DASH-pa) was used to calculate disability scores for all three injury definitions.Results: Twenty-nine classical music students participated in the current study. The total response rate over one academic year was 85.3%. One year prevalences of all MSK complaints, medical attention and time-loss were 96.6, 17.2 and 13.8% respectively. The bi-monthly prevalences ranged from 74.1 to 96.0% for all MSK complaints, from 5.6 to 11.5% for medical attention injuries and from 0 to 11.5% for time loss injuries. Scores on the DASH-pa ranged from 15.6 to 26.9 for MSK complaints, 33.3 to 50 for medical attention and 47.9 to 62.5 for time-loss injuries.Conclusion: The choice of injury definition is a critical factor affecting the outcome of music injury surveillance studies. To reach a consensus, it is therefore important to consider the different injury definitions depending on the goal of the injury surveillance and the practical implications. [ABSTRACT FROM AUTHOR]

Background: Pregnancy-associated breast cancer (PABC) is defined as breast cancer that is diagnosed during pregnancy and/or the postpartum period. Definitions of the duration of the postpartum period have been controversial, and this variability may lead to diverse results regarding prognosis. Moreover, evidence on the dose-response association between the time from the last pregnancy to breast cancer diagnosis and overall mortality has not been synthesized.Methods: We systematically searched PubMed, Embase, and the Cochrane Library for observational studies on the prognosis of PABC published up to June 1, 2019. We estimated summary-adjusted hazard ratios (HRs) and the corresponding 95% confidence intervals (CIs). Subgroup analyses based on diagnosis time, PABC definition, geographic region, year of publication and estimation procedure for HR were performed. Additionally, dose-response analysis was conducted by using the variance weighted least-squares regression (VWLS) trend estimation.Results: A total of 54 articles (76 studies) were included in our study. PABC was associated with poor prognosis for overall survival (OS), disease-free survival (DFS) and cause-specific survival (CSS), and the pooled HRs with 95% CIs were 1.45 (1.30-1.63), 1.39 (1.25-1.54) and 1.40 (1.17-1.68), respectively. The corresponding reference category was non-PABC patients. According to subgroup analyses, the varied definition of PABC led to diverse results. The dose-response analysis indicated a nonlinear association between the time from the last delivery to breast cancer diagnosis and the HR of overall mortality (P < 0.001). Compared to nulliparous women, the mortality was almost 60% higher in women with PABC diagnosed at 12 months after the last delivery (HR = 1.59, 95% CI 1.30-1.82), and the mortality was not significantly different at 70 months after the last delivery (HR = 1.14, 95% CI 0.99-1.25). This finding suggests that the definition of PABC should be extended to include patients diagnosed up to approximately 6 years postpartum (70 months after the last delivery) to capture the increased risk.Conclusion: This meta-analysis suggests that PABC is associated with poor prognosis, and the definition of PABC should be extended to include patients diagnosed up to approximately 6 years postpartum. [ABSTRACT FROM AUTHOR]

Background: Administrative healthcare databases are widespread and are often standardized with regard to their content and data coding, thus they can be used also as data sources for surveillance and epidemiological research. Chronic dialysis requires patients to frequently access hospital and clinic services, causing a heavy burden to healthcare providers. This also means that these patients are routinely tracked on administrative databases, yet very few case definitions for their identification are currently available. The aim of this study was to develop two algorithms derived from administrative data for identifying incident chronic dialysis patients and test their validity compared to the reference standard of the regional dialysis registry.Methods: The algorithms are based on data retrieved from hospital discharge records (HDR) and ambulatory specialty visits (ASV) to identify incident chronic dialysis patients in an Italian region. Subjects are included if they have at least one event in the HDR or ASV databases based on the ICD9-CM dialysis-related diagnosis or procedure codes in the study period. Exclusion criteria comprise non-residents, prevalent cases, or patients undergoing temporary dialysis, and are evaluated only on ASV data by the first algorithm, on both ASV and HDR data by the second algorithm. We validated the algorithms against the Emilia-Romagna regional dialysis registry by searching for incident patients in 2014 and performed sensitivity analyses by modifying the criteria to define temporary dialysis.Results: Algorithm 1 identified 680 patients and algorithm 2 identified 676 initiating dialysis in 2014, compared to 625 patients included in the regional dialysis registry. Sensitivity for the two algorithms was respectively 90.8 and 88.4%, positive predictive value 84.0 and 82.0%, and percentage agreement was 77.4 and 74.1%.Conclusions: Algorithms relying on retrieval of administrative records have high sensitivity and positive predictive value for the identification of incident chronic dialysis patients. Algorithm 1, which showed the higher accuracy and has a simpler case definition, can be used in place of regional dialysis registries when they are not present or sufficiently developed in a region, or to improve the accuracy and timeliness of existing registries. [ABSTRACT FROM AUTHOR]

Background: The spatial spread of many mosquito-borne diseases occurs by focal spread at the scale of a few hundred meters and over longer distances due to human mobility. The relative contributions of different spatial scales for transmission of chikungunya virus require definition to improve outbreak vector control recommendations.Methods: We analyzed data from a large chikungunya outbreak mediated by the mosquito Aedes albopictus in the Lazio region, Italy, consisting of 414 reported human cases between June and November 2017. Using dates of symptom onset, geographic coordinates of residence, and information from epidemiological questionnaires, we reconstructed transmission chains related to that outbreak.Results: Focal spread (within 1 km) accounted for 54.9% of all cases, 15.8% were transmitted at a local scale (1-15 km) and the remaining 29.3% were exported from the main areas of chikungunya circulation in Lazio to longer distances such as Rome and other geographical areas. Seventy percent of focal infections (corresponding to 38% of the total 414 cases) were transmitted within a distance of 200 m (the buffer distance adopted by the national guidelines for insecticide spraying). Two main epidemic clusters were identified, with a radius expanding at a rate of 300-600 m per month. The majority of exported cases resulted in either sporadic or no further transmission in the region.Conclusions: Evidence suggest that human mobility contributes to seeding a relevant number of secondary cases and new foci of transmission over several kilometers. Reactive vector control based on current guidelines might allow a significant number of secondary clusters in untreated areas, especially if the outbreak is not detected early. Existing policies and guidelines for control during outbreaks should recommend the prioritization of preventive measures in neighboring territories with known mobility flows to the main areas of transmission. [ABSTRACT FROM AUTHOR]

The incidence of gluten-related disorders (GRDs) continues to increase and its global prevalence is estimated at approximately 5% of the population. Celiac disease (CD), dermatitis herpetiformis (DH), gluten ataxia (GA), wheat allergy (WA), and non-celiac gluten sensitivity (NCGS) are the five major GRDs that present with a wide range of clinical manifestations. The diagnosis of GRDs can be challenging because the typical and atypical clinical manifestations of the GRDs overlap. In this review, the current definitions of gluten-related disorders, focusing on their clinical features, diagnostic and therapeutic approaches are presented. We concluded that GRDs are usually diagnosed using a combination of clinical features, serological tests, and histopathological findings. Treatment usually involves dietary modification. [ABSTRACT FROM AUTHOR]

Background: In randomized trials, the term "double-blind" (and its derivatives, single- and triple-blind, fully blind, and partially blind or masked) has no standard or widely accepted definition. Agreement about which groups are blinded is poor, and authors using these terms often do not identify which groups were blinded, despite specific reporting guidelines to the contrary. Nevertheless, many readers assume-incorrectly-that they know which groups are blinded. Thus, the term is ambiguous at best, misleading at worst, and, in either case, interferes with the accurate reporting, interpretation, and evaluation of randomized trials. The problems with the terms have been thoroughly documented in the literature, and many authors have recommended that they be abandoned.Proposal: We and our co-signers suggest eliminating the use of adjectives that modify "blinding" in randomized trials; a trial would be described as either blinded or unblinded. We also propose that authors report in a standard table which groups or individuals were blinded, what they were blinded to, how blinding was implemented, and whether blinding was maintained. Individuals with dual responsibilities, such as caregiving and data collecting, would also be identified. If blinding was compromised, authors should describe the potential implications of the loss of blinding on interpreting the results.Conclusion: "Double blind" and its derivatives are terms with little to recommend their continued use. Eliminating the use of adjectives that impart a false specificity to the term would reduce misinterpretations, and recommending that authors report who was blinded to what and how in a standard table would require them to be specific about which groups and individuals were blinded. [ABSTRACT FROM AUTHOR]

Background: Participants in clinical research studies often do not reflect the populations for which healthcare interventions are needed or will be used. Enhancing representation of under-served groups in clinical research is important to ensure that research findings are widely applicable. We describe a multicomponent workstream project to improve representation of under-served groups in clinical trials.Methods: The project comprised three main strands: (1) a targeted scoping review of literature to identify previous work characterising under-served groups and barriers to inclusion, (2) surveys of professional stakeholders and participant representative groups involved in research delivery to refine these initial findings and identify examples of innovation and good practice and (3) a series of workshops bringing together key stakeholders from funding, design, delivery and participant groups to reach consensus on definitions, barriers and a strategic roadmap for future work. The work was commissioned by the UK National Institute for Health Research Clinical Research Network. Output from these strands was integrated by a steering committee to generate a series of goals, workstream plans and a strategic roadmap for future development work in this area.Results: 'Under-served groups' was identified and agreed by the stakeholder group as the preferred term. Three-quarters of stakeholders felt that a clear definition of under-served groups did not currently exist; definition was challenging and context-specific, but exemplar groups (e.g. those with language barriers or mental illness) were identified as under-served. Barriers to successful inclusion of under-served groups could be clustered into communication between research teams and participant groups; how trials are designed and delivered, differing agendas of research teams and participant groups; and lack of trust in the research process. Four key goals for future work were identified: building long-term relationships with under-served groups, developing training resources to improve design and delivery of trials for under-served groups, developing infrastructure and systems to support this work and working with funders, regulators and other stakeholders to remove barriers to inclusion.Conclusions: The work of the INCLUDE group over the next 12 months will build on these findings by generating resources customised for different under-served groups to improve the representativeness of trial populations. [ABSTRACT FROM AUTHOR]

Background: Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a debilitating disease with unknown causes. From the perspectives on the etiology and pathophysiology, ME/CFS has been labeled differently, which influenced changes in case definitions and terminologies. This review sought to feature aspects of the history, developments, and differential symptoms in the case definitions.Methods: A search was conducted through PubMed published to February 2020 using the following search keywords: case definition AND chronic fatigue syndrome [MeSH Terms]. All reference lists of the included studies were checked. Of the included studies, the number of citations and the visibility in the literatures of the definitions were considered for comparisons of the criteria.Results: Since the first 'ME' case definition was developed in 1986, 25 case definitions/diagnostic criteria were created based on three conceptual factors (etiology, pathophysiology, and exclusionary disorders). These factors can be categorized into four categories (ME, ME/CFS, CFS, and SEID) and broadly characterized according to primary disorder (ME-viral, CFS-unknown, ME/CFS-inflammatory, SEID-multisystemic), compulsory symptoms (ME and ME/CFS-neuroinflammatory, CFS and SEID-fatigue and/or malaise), and required conditions (ME-infective agent, ME/CFS, CFS, SEID-symptoms associated with fatigue, e.g., duration of illness). ME and ME/CFS widely cover all symptom categories, while CFS mainly covers neurologic and neurocognitive symptoms. Fatigue, cognitive impairment, PEM, sleep disorder, and orthostatic intolerance were the overlapping symptoms of the 4 categories, which were included as SEID criteria.Conclusions: This study comprehensively described the journey of the development of case definitions and compared the symptom criteria. This review provides broader insights and explanations to understand the complexity of ME/CFS for clinicians and researchers. [ABSTRACT FROM AUTHOR]

Background: Critical stakeholder-identified gaps in current health research engagement strategies include the exclusion of voices traditionally less heard and a lack of consideration for the role of trauma in lived experience. Previous work has advocated for a trauma-informed, intersectional, and critical reflexive approach to patient and public involvement in health research. The Valuing All Voices Framework embodies these theoretical concepts through four key components: trust, self-awareness, empathy, and relationship building. The goal of this framework is to provide the context for research teams to conduct patient engagement through the use of a social justice and health equity lens, to improve safety and inclusivity in health research. The aim of this study was to revise the proposed Valuing All Voices Framework with members of groups whose voices are traditionally less heard in health research. Methods: A qualitative descriptive approach was used to conduct a thematic analysis of participant input on the proposed framework. Methods were co-developed with a patient co-researcher and community organizations. Results: Group and individual interviews were held with 18 participants identifying as Inuit; refugee, immigrant, and/or newcomer; and/or as a person with lived experience of a mental health condition. Participants supported the proposed framework and underlying theory. Participant definitions of framework components included characterizations, behaviours, feelings, motivations, and ways to put components into action during engagement. Emphasis was placed on the need for a holistic approach to engagement; focusing on open and honest communication; building trusting relationships that extend beyond the research process; and capacity development for both researchers and patient partners. Participants suggested changes that incorporated some of their definitions; simplified and contextualized proposed component definitions; added a component of "education and communication"; and added a 'how to' section for each component. The framework was revised according to participant suggestions and validated through member checking. Conclusions: The revised Valuing All Voices Framework provides guidance for teams looking to employ trauma-informed approaches, intersectional analysis, and critical reflexive practice in the co-development of meaningful, inclusive, and safe engagement strategies. Plain English Summary: Patient engagement in health research continues to exclude many people who face challenges in accessing healthcare, including (but not limited to) First Nations, Inuit, and Metis people; immigrants, refugees, and newcomers; and people with lived experience of a mental health condition. We proposed a new guide to help researchers engage with patients and members of the public in research decision-making in a meaningful, inclusive, and safe way. We called this the Valuing All Voices Framework, and met with people who identify as members of some of these groups to help define the key parts of the framework (trust; self-awareness; empathy; and relationship building), to tell us what they liked and disliked about the proposed framework, and what needed to be changed. Input from participants was used to change the framework, including clarifying definitions of the key parts, adding another key part called "education and communication", and providing action items so teams can put these key parts into practice. [ABSTRACT FROM AUTHOR]

Background: The interest in patient and public involvement (PPI) in health research is increasing. However, the experience and knowledge of PPI throughout the entire research process and especially in the analysis are limited. We explored ways to embrace the perspectives of patients in a research process, and the impact and challenges our collaboration has had on patients, researchers, and the research outcomes. Methods: This is an explorative single case study of a Danish, clinical, controlled intervention trial and a nested intervention fidelity study included herein. Five patient representatives with metastatic melanoma were part of designing, undertaking and disseminating the trial where the effect of using patient-reported outcome (PRO)-measures as a dialogue tool in the patient-physician consultation was tested. In the fidelity study, audio-recorded consultations were analyzed after training in the Verona Coding Definitions of Emotional Sequences (VR-CoDES). Results were jointly disseminated at an international scientific conference. The outcomes, impact, and challenges were explored through a workshop. Results: In the design phase, we selected PRO-measures and validated the dialogue tool. The information sheet was adjusted according to the patients' suggestions. The analysis of the fidelity study showed that patients and researchers had a high consensus on the coding of emotional cues and concerns. The patients contributed with a new vocabulary and perspective on the dialogue, and they validated the results. PPI caused considerations related to emotional (sadness/sorrow and existential thoughts), administrative (e.g. arranging meetings, balancing work and small talk) and intellectual (e.g. avoiding information harm, continuing activities despite the death of patients) investments. A limitation of the study was the lack of use of a solid evaluation tool to determine the impact of PPI. Conclusion: PPI throughout the process and co-creation in the analysis was feasible and beneficial. The case is unique in the degree of workable details, sustainability, and transparency. Moreover, the co-creation provides ideas of ways to operationalize PPI. An evaluation workshop revealed considerations about emotional, administrative and intellectual investments – best described as tacit, yet important 'work'. This knowledge and experience can be applied to other studies where patients are partners in the research. Trial registration: ClinicalTrials.gov ID: NCT03163433, registration date: 8th May 2017. [ABSTRACT FROM AUTHOR]

Background: Although phylogenomic analyses are increasingly used to reveal evolutionary relationships among ciliates, relatively few nuclear protein-coding gene markers have been tested for their suitability as candidates for inferring phylogenies within this group. In this study, we investigate the utility of the heat-shock protein 90 gene (Hsp90) as a marker for inferring phylogenetic relationships among hypotrich ciliates. Results: A total of 87 novel Hsp90 gene sequences of 10 hypotrich species were generated. Of these, 85 were distinct sequences. Phylogenetic analyses based on these data showed that: (1) the Hsp90 gene amino acid trees are comparable to the small subunit rDNA tree for recovering phylogenetic relationships at the rank of class, but lack sufficient phylogenetic signal for inferring evolutionary relationships at the genus level; (2) Hsp90 gene paralogs are recent and therefore unlikely to pose a significant problem for recovering hypotrich clades; (3) definitions of some hypotrich orders and families need to be revised as their monophylies are not supported by various gene markers; (4) The order Sporadotrichida is paraphyletic, but the monophyly of the "core" Urostylida is supported; (5) both the subfamily Oxytrichinae and the genus Urosoma seem to be non-monophyletic, but monophyly of Urosoma is not rejected by AU tests. Conclusions: Our results for the first time demonstrate that the Hsp90 gene is comparable to SSU rDNA for recovering phylogenetic relationships at the rank of class, and its paralogs are unlikely to pose a significant problem for recovering hypotrich clades. This study shows the value of careful gene marker selection for phylogenomic analyses of ciliates. [ABSTRACT FROM AUTHOR]

Background: As the COVID-19 (coronavirus) pandemic develops, healthcare professionals are looking for support with, and guidance to inform, the difficult decisions they face. In the (current) absence of an authoritative national steer in England, professional bodies and local organisations have been developing and disseminating their own ethical guidance. Questions inevitably arise, some of which are particularly pressing during the pandemic, as events are unfolding quickly and the field is becoming crowded. My central question here is: which professional ethical guidance should the professional follow?Main Body: Adopting a working definition of "professional ethical guidance", I offer three domains for a healthcare professional to consider, and some associated questions to ask, when determining whether - in relation to any guidance document - they should "bin it or pin it". First, the professional should consider the source of the guidance: is the issuing body authoritative or, if not, at least sufficiently influential that its guidance should be followed? Second, the professional should consider the applicability of the guidance, ascertaining whether the guidance is available and, if so, whether it is pertinent. Pertinence has various dimensions, including whether the guidance applies to this professional, this patient and/or this setting, whether it is up-to-date, and whether the guidance addresses the situation the professional is facing. Third, the professional should consider the methodology and methods by which the guidance was produced. Although the substantive quality of the guidance is important, so too are the methods by which it was produced. Here, the professional should ask whether the guidance is sufficiently inclusive - in terms of who has prepared it and who contributed to its development - and whether it was rigorously developed, and thus utilised appropriate processes, principles and evidence.Conclusion: Asking and answering such questions may be challenging, particularly during a pandemic. Furthermore, guidance will not do all the work: professionals will still need to exercise their judgment in deciding what is best in the individual case, whether or not this concerns COVID-19. But such judgments can and should be informed (and constrained) by guidance, and hopefully these preliminary observations will provide some useful pointers for time-pressed professionals. [ABSTRACT FROM AUTHOR]