Use Of Practice Guidelines Research Articles

New horizons in clinical practice guidelines for use with older people.

Globally, more people are living into advanced old age, with age-associated frailty, disability and multimorbidity. Achieving equity for all ages necessitates adapting healthcare systems. Clinical practice guidelines (CPGs) have an important place in adapting evidence-based medicine and clinical care to reflect these changing needs. CPGs can facilitate better and more systematic care for older people. But they can also present a challenge to patient-centred care and shared decision-making when clinical and/or socioeconomic heterogeneity or personal priorities are not reflected in recommendations or in their application. Indeed, evidence is often lacking to enable this variability to be reflected in guidance. Evidence is more likely to be lacking about some sections of the population. Many older adults are at the intersection of many factors associated with exclusion from traditional clinical evidence sources with higher incidence of multimorbidity and disability compounded by poorer healthcare access and ultimately worse outcomes. We describe these challenges and illustrate how they can adversely affect CPG scope, the evidence available and its summation, the content of CPG recommendations and their patient-centred implementation. In all of this, we take older adults as our focus, but much of what we say will be applicable to other marginalised groups. Then, using the established process of formulating a CPG as a framework, we consider how these challenges can be mitigated, with particular attention to applicability and implementation. We consider why CPG recommendations on the same clinical areas may be inconsistent and describe approaches to ensuring that CPGs remain up to date.

LIKELIHOOD AND DEPTH-BASED CRITERIA FOR COMPARING SIMULATION RESULTS WITH EXPERIMENTAL DATA, IN SUPPORT OF VALIDATION OF NUMERICAL SIMULATORS

Within the framework of best-estimate-plus-uncertainty approaches, the assessment of model parameter uncertainties, associated with numerical simulators, is a key element in safety analysis. The results (or outputs) of the simulation must be compared and validated against experimental values, when such data are available. This validation step, as part of the broader verification, validation, and uncertainty quantification process, is required to ensure a reliable use of the simulator for modeling and prediction. This work aims to define quantitative criteria to support this validation for multivariate outputs, while taking into account modeling uncertainties (uncertain input parameters) and experimental uncertainties (measurement uncertainties). For this purpose, different statistical indicators, based on likelihood or statistical depths, are investigated and extended to the multidimensional case. First, the properties of the criteria are studied, either analytically or by simulation, for some specific cases (Gaussian distribution for experimental uncertainties, identical distributions of experiments and simulations, particular discrepancies). Then, some natural extensions to multivariate outputs are proposed, with guidelines for practical use depending on the objectives of the validation (strict/hard or average validation). From this, transformed criteria are proposed to make them more comparable and less sensitive to the dimension of the output. It is shown that these transformations allow for a fairer and more relevant comparison and interpretation of the different criteria. Finally, these criteria are applied to a code dedicated to nuclear material behavior simulation. The need to reduce the uncertainty of the model parameters is thus highlighted, as well as the outputs on which to focus.

Pediatric resident use, perceptions, and desires for improvement of a clinical secure messaging application

BackgroundHospitals are transitioning away from traditional pagers to secure text messaging (STM) applications. STM is perceived to improve efficiency and accessibility. There is limited research on user's impressions of how STM impacts patient safety, provider wellness, and quality of patient care. ObjectivesTo understand the use and perceptions of a clinical STM by pediatric residents at a free-standing quaternary care children's hospital. MethodsA survey was conducted of pediatric residents regarding their experience with Diagnotes®. Demographic data were obtained along with use patterns, ability to perform tasks, and perceptions of intended purpose. Further questions evaluated agreement with communication strategies and satisfaction with features. Three open-ended questions asked about experience where STM impacted (1) patient care coordination and (2) patient safety. A final question asked for any additional STM feedback. ResultsOf 169 surveys, there were 112 respondents (66.3 % response rate). Respondents unanimously endorsed daily STM use on their personal mobile devices with good knowledge of basic features. Respondents were overall satisfied with Diagnotes® (73.9 %) including the ability to communicate efficiently (84.8 %) and effectively (79.5 %). Yet only 32.1 % were satisfied with Diagnotes® training. Only 59.5 % believed Diagnotes® was appropriate for urgent patient care needs and only 43.2 % believed its purpose was to inform the team of patient emergencies. Key qualitative themes included improved coordination of patient care tasks through STM, but there were concerns raised around sending and receiving messages, the additional cognitive burden placed by STM, and differences in culture of use that created conflict. ConclusionsDiagnotes® is viewed positively including use for effective coordination of patient care and familiarity of functions of Diagnotes®. Barriers included unclear interprofessional expectations for use. Future research should incorporate a broad range of healthcare professionals' perceptions and co-creation of STM best practice guidelines for use, including around urgent or emergent patient care issues.

Splicing Polymorphism rs12459419 Modulates Antibody-Bound Internalization of CD33 Isoforms

Background: While the standard regimen for AML has been intense chemotherapy followed by stem-cell transplantation (SCT), addition of immunotherapeutics such as gemtuzumab ozogamicin (GO) to this has shown to improve outcomes in multiple clinical trials. Since these trials, GO has been added to the National Comprehensive Cancer Network (NCCN) practice guidelines for use in AML therapy (NCCN., 2018). GO is a humanized monoclonal antibody conjugated to calicheamicin and targets the cell surface antigen CD33, observed on most AML blasts. Upon binding to GO, CD33 is internalized and the subsequent release of calicheamicin mediates cytotoxicity. CD33 contains two extracellular domains: IgV and IgC, the IgV domain is coded by CD33 exon 2 and is the binding site for GO. A splicing SNP, rs12459419 (C>T; A14V) in exon 2 results in a shorter isoform (CD33-D2) and has been previously associated with CD33 abundance on cell surface as well as clinical benefit from GO addition to standard chemotherapy. Patients with CC genotype (~50% of the cohort) expressed full length CD33 (CD33-FL) and benefited significantly from GO. However, heterozygous CT and homozygous TT genotype groups did not derive the same benefit. These results were perplexing as CT genotype group had intermediate levels of CD33-FL and CD33-D2 isoforms (Lamba et al., 2017). It is hypothesized that lack of IgV domain in CD33-D2 and putative CD33-FL/CD33-D2 dimerization prevents GO binding and subsequent internalization in rs12459419 CT/TT genotype cells, however this has never been tested. We have generated novel antibodies directed against the IgC domain that recognizes CD33-D2 in AML cell lines as well as primary AML cells (Gbadamosi et al., 2021) thus facilitating testing the above indicated hypothesis. Objective: In this study, we first tested the ability of antibody-bound CD33-D2 to internalize, followed by impact of the internalization status of CD33-FL and CD33-D2 in cells co-expressing both isoforms along with the concomitant impact on GO induced cytotoxicity. Methods: Using pMXs retroviral particles encoding CD33-FL or CD33-D2, we engineered CRISPR/Cas9 mediated CD33 KO in AML cell lines to overexpress either one or both CD33 isoforms to mimic cells expression varying proportions of CD33-FL/CD33-D2. Internalization of either CD33-FL or CD33-D2 over a duration of 4 hours in the presence of antibodies recognizing either of the two isoforms was performed. Cells were labeled with unconjugated mouse anti-CD33-FL P67.6 or anti-CD33-D2 HL2541 antibody on ice and incubated at 37°C for 0-4 hours, followed by staining with mouse anti-mouse IgG antibody conjugated with biotin. Surface CD33-FL or CD33-D2 was then detected using streptavidin-FITC conjugate. Percentage antibody-bound CD33-FL or CD33-D2 internalization was expressed as change in FITC MFI between each time point incubated and cells kept at 0°C post CD33 antibody labeling. Results: While P67.6-bound-CD33-FL internalized as expected in AML cell lines expressing CD33-FL only (Fig. 1A), we show for the first time that HL2541-bound-CD33-D2 also internalizes upon antibody binding in cell lines expressing CD33-D2 isoform only (Fig. 1B). In AML cell lines co-expressing both CD33-FL and CD33-D2 isoforms, a >2.5-3 fold decrease in this antibody-bound internalization was observed for each isoform (Figs. 1C and D). In response to GO exposure for 48 hours, cells co-expressing both CD33-FL and CD33-D2 isoforms had 7-9.5-fold higher IC50 values (233 nmol and 277 nmol) compared to cells expressing only CD33-FL (33.19 nmol and 29 nmol) (Figs. 1E and F). As expected, cells expressing CD33-D2 only did respond to GO. Discussion: Our finding that antibody-bound CD33-D2 internalizes like CD33-FL adds a novel piece of evidence in understanding the biology of this variant isoform and opens opportunities to develop antibody drug conjugate (ADC) such as GO using CD33-D2 antibody. This new CD33-D2 targeting ADC will provide a treatment option in patients with TT genotypes. Our results also provide a mechanistic insight on the previous clinical observation showing lack of benefit from GO in patients heterozygous for the splicing SNP. Our ongoing studies are focused on validating this result using live cell imaging and efforts towards design of new ADC or T cell engagers using CD33-D2 antibody. The study was supported by Leukemia Lymphoma Society, UFHealth Cancer Center, and the Frank A. Duckworth Endowment.

Deconstructing Social Work Exam Bias: Advocacy Practice Guidelines to Close the Gap

ABSTRACT Introduction The social work profession is in a precarious situation regarding licensure. Test takers of color are struggling to pass social work licensure exams at rates comparable to their White counterparts, per data released by the Association of Social Work Boards (ASWB). As a nation, we are required to meet the needs of our increasingly diverse population. Yet the recruitment and retention of a diverse body of social workers is unlikely to be actualized if disparities persist in these exams. Given ASWB’s monopoly on social work exams and the likelihood that many states will continue to require the exams for licensure, we sought to explore public responses to the data released, using the National Association of Social Work (NASW) as our starting point. As the nation’s largest association of social workers, having local chapters within each state, NASW serves as an area of connection between social workers nationwide. Methods We utilized content analysis to explore emerging themes and conduct a review of the state chapter’s public responses to exam pass rate data. Results A variety of state chapter’s responses, with few states engaging in advocacy efforts or taking action to facilitate change. Discussion Advocacy efforts play a pivotal role in the restructuring of fragmented systems. This study revisits seemingly ignored disparities diverse test takers may face, while also serving as a call-to-action in advocacy engagement. We conclude with a set of advocacy practice guidelines for use in the promotion of equitable licensing opportunities for all test takers.

Online Monitoring of Test‐Taking Behavior Based on Item Responses and Response Times

AbstractThe study presents multivariate sequential monitoring procedures for examining test‐taking behaviors online. The procedures monitor examinee's responses and response times and signal aberrancy as soon as significant change is identifieddetected in the test‐taking behavior. The study in particular proposes three schemes to track different indicators of a test‐taking mode—the observable manifest variables, latent trait variables, and measurement likelihood. For each procedure, sequential sampling strategies are presented to implement online monitoring. Numerical experimentation based on simulated data suggests that the proposed procedures demonstrate adequate performance. The procedures identified examinees with aberrant behaviors with high detection power and timeliness, while maintaining error rates reasonably small. Experimental application to real data also suggested that the procedures have practical relevance to real assessments. Based on the observations from the experiential analysis, the study discusses implications and guidelines for practical use.

Variation in clinical practice guidelines for use of palivizumab in preventing severe respiratory syncytial viral (RSV) disease in high-risk infants.

Uniformity and compliance with clinical practice guidelines (CPGs) for use of palivizumab in preventing severe respiratory syncytial viral infection in Australian high-risk infants remain unclear. An online survey was conducted across the Australian and New Zealand Neonatal Network (ANZNN) to determine clinical practices around palivizumab. A literature search was also performed to identify and compare national and international guidelines. A total of 65 of 422 ANZNN members completed the survey. Respondents included 61 senior medical staff of consultants/staff specialists (78%) and four nursing staff (6%). According to the survey, infants most likely to be recommended palivizumab included preterm infants born <29 weeks gestational age (GA) (30%), children with chronic lung diseases (CLDs) born <32 weeks GA (40%), and with hemodynamically significant heart disease (35%). Many of the respondents (53%) stated that CPGs for palivizumab were developed locally. Literature search identified 20 guidelines (10 international and 10 domestic); 16 (80%) recommended palivizumab use in preterm infants, 16 (80%) recommended use in infants with CLD, 17 (85%) in congenital heart disease and 6 (30%) in bronchopulmonary dysplasia (BPD). Eight (40%) guidelines provided specific recommendations for immunocompromised infants. Canada, Western Australia, and American Academy of Paediatrics provided recommendations for Indigenous children. Frequency and dosage of palivizumab was universal across all CPGs. None of the international guidelines obtained were from low- or middle-income countries. Standardization of CPGs may improve clinical decision making around use of palivizumab in high-risk infants.

The Role of Nutrients and Diet Characteristics in the Management of Diabetic Foot Ulcers: A Systematic Review.

Diabetic foot ulcers (DFUs) are common complications of diabetes mellitus that affect patients' quality of life and pose a burden on the healthcare system. Although malnutrition and specific nutritional deficiencies can seriously impact wound healing in patients with chronic nonhealing wounds, the role of nutrition in the prevention and management of DFUs is still not clear. This review discusses the significance of frequent diet assessment and nutritional education of patients with DFUs with individualized correction of deficiencies and emphasis on adequate protein intake along with correction of vitamins D, C, E, and selenium status. Future research should clarify the impact of nutritional interventions, potentially involving the use of probiotics, zinc, and omega-3 fatty acids, and successfully translating the findings into practical guidelines for use in everyday clinical practice.

O016 Actigraphy: A review of practice down under

Abstract Background In 2018, the American Academy of Sleep Medicine (AASM) published practice guidelines for use of actigraphy in evaluating adult and paediatric patients with suspected sleep disorders. Whilst there is significant evidence of actigraphy use in research, this study aims to evaluate current and future intended use of actigraphy in paediatric clinical cohorts across Australia and New Zealand (NZ). Methods A 16-item survey was electronically distributed to medical leads from Australian and NZ paediatric sleep centres. Questions enquired on sleep centre logistics, current actigraphy practice behaviours and qualitative assessments on future use. Progress to date The survey was distributed on July 22nd. Thus far, 8 responses have been returned, representing a range of locales, centre types and actigraphy practices. Findings will be collated and presented. Intended outcome and impact This study will provide an understanding for the contemporary trends in actigraphy use through Australia and NZ. This is particularly relevant given changes across recent years with both an increase in commercial prevalence for consumer sleep health devices as well as a surge in ambulatory medical services following the COVID-19 pandemic. It will identify barriers limiting its universal utility and explore clinician preferences for future practice. Such findings can guide actions around improving clinical services, product design and government funding advocacy.

Consensus Delphi study on guidelines for the assessment of anterior cruciate ligament injuries in children.

Background: Knee examination guidelines in minors are intended to aid decision-making in the management of knee instability. Clinical question: A Delphi study was conducted with a formal consensus process using a validated methodology with sufficient scientific evidence. A group consensus meeting was held to develop recommendations and practical guidelines for use in the assessment of instability injuries in children. Key findings: there is a lack of evidence to analyse anterior cruciate ligament injuries in children and their subsequent surgical management if necessary. Diagnostic guidelines and clinical assessment of the patient based on a thorough examination of the knee are performed and a guide to anterior cruciate ligament exploration in children is developed. Clinical application: In the absence of a strong evidence base, these established guidelines are intended to assist in that decision-making process to help the clinician decide on the most optimal treatment with the aim of benefiting the patient as much as possible. Following this expert consensus, surgical treatment is advised when the patient has a subjective sensation of instability accompanied by a pivot shift test ++, and may include an anterior drawer test + and a Lachman test +. If these conditions are not present, the conservative approach should be chosen, as the anatomical and functional development of children, together with a physiotherapy programme, may improve the evolution of the injury.

Transparency in Non-Technical Project Summaries to Promote the Three Rs in Respiratory Disease Research.

Non-Technical Project Summaries (NTS) are legal documents that were first introduced by the Directive 2010/63/EU to enhance transparency within scientific animal experimentation. Researchers intending to conduct biological research on animal models must fulfil the NTS requirements by outlining their proposed use of animals and how they plan to implement the Three Rs (replacement, reduction and refinement of animal use) in their experiments. This study outlines a novel systematic analysis approach that enables the assessment of NTS transparency based on the accuracy of reporting of certain Three Rs-specific information. This potentially customisable strategy could help toward the development of practical guidelines for use by Animal Welfare and Ethical Review Bodies (AWERBs) in establishments conducting animal research, in the process of scrutinising NTS during their pre-submission review of proposed licence applications. This could help to identify gaps in reporting of Three Rs-specific information relating to the planned animal experiments, which represents a remarkable step toward achieving greater openness in scientific communication. This study supports the concept that NTS transparency can promote the implementation of non-animal alternatives in fields where this is currently lacking, such as respiratory disease research. Although NTS were originally conceived as informative documents for a lay audience, we can conclude that data in NTS can be successfully used as a basis for systematic analysis. By reviewing the NTS, the experimental limitations of the currently available replacement strategies can also be highlighted, potentially pinpointing where there is a need for future method development.

Recent Advances Regarding Precious Metal-Based Electrocatalysts for Acidic Water Splitting

Electrochemical water splitting has wide applicability in preparing high-density green energy. The Proton exchange membrane (PEM) water electrolysis system is a promising technique for the generation of hydrogen due to its high electrolytic efficiency, safety and reliability, compactness, and quick response to renewable energy sources. However, the instability of catalysts for electrochemical water splitting under operating conditions limits their practical applications. Until now, only precious metal-based materials have met the requirements for rigorous long-term stability and high catalytic activity under acid conditions. In this review, the recent progress made in this regard is presented and analyzed to clarify the role of precious metals in the promotion of the electrolytic decomposition of water. Reducing precious metal loading, enhancing catalytic activity, and improving catalytic lifetime are crucial directions for developing a new generation of PEM water electrolysis catalysts. A summary of the synthesis of high-performance catalysts based on precious metals and an analysis of the factors affecting catalytic performance were derived from a recent investigation. Finally, we present the remaining challenges and future perspectives as guidelines for practical use.

Weighted Average Conditional Mean Spectrum (WACMS): A bridge between common CMS and Uniform Hazard Spectrum (UHS)

In order to accurately predict structural response subject to ground motion excitation in the hazard level of interest, it is necessary to determine appropriate target spectrum. Conditional Mean Spectrum (CMS) conditioned on occurrence of a target spectral acceleration (Sa) at a single period is an alternative of the overly conservative Uniform Hazard Spectrum (UHS). The first-mode period is usually advised as conditioned period to create CMS, but it is not always appropriate. A Weighted Average Conditional Mean Spectrum (WACMS) is newly introduced as a more suitable target spectrum to long-period structures and practical guidelines for use are presented. WACMS is the weighted average of CMS suite conditioned on occurrence of target Sa at first several periods, the sum of whose mass participation factors exceeding 90%. The significant advantage is that it can consider hazard levels at multiple periods and use mass participation factor as the weight. CMS and UHS can be integrated with WACMS. WACMS is equivalent to CMS when one period is considered while almost overlaps UHS when all periods are considered. That is, WACMS bridges the gap between CMS and UHS. In this paper, three different structures designed by Chinese code are utilized as examples to verify this method. Results show that WACMS is more appropriate as a target spectrum to predict mean inter-storey drift ratio (IDR) consistent with Chinese code, compared to CMS conditioned on occurrence of Sa at the first-mode period. Meanwhile, WACMS increases the rate of exceeding IDR limit and IDR dispersion.

Unraveling Subcellular Localization of CD33 Splicing Polymorphism Variant

Acute myeloid leukemia (AML) is a heterogeneous disease with poor outcome. The standard AML therapy has been intense chemotherapy and stem-cell transplantation (SCT). However, the addition of targeted immunotherapeutic agents such as gemtuzumab ozogamicin (GO) to this regimen has shown promise in trials, such as AAML03P1 (NCT00070174) and AAML0531 (NCT00372593) (Cooper et al., 2012; Gamis et al., 2014). Since these trials, GO has been added to the National Comprehensive Cancer Network (NCCN) practice guidelines for use in AML therapy for newly diagnosed and relapse patients, both in combination with chemotherapy and as monotherapy (NCCN., 2018). GO is a humanized monoclonal antibody conjugated to calicheamicin and targets the cell surface antigen CD33, observed on most AML blasts (Bernstein, 2002; Walter et al., 2012). Upon binding to GO, CD33 is internalized and the subsequent release of calicheamicin mediates cytotoxicity. CD33 is a member of the SIGLEC family containing two extracellular domains: IgV and IgC (Andrews et al., 1983). The IgV domain is coded by CD33 exon 2 and is the binding site for GO. A modulatory splicing single nucleotide polymorphism (SNP) rs12459419 (C>T; A14V) in exon 2 results in a shorter isoform (CD33-D2) and has been previously reported to be significantly associated with CD33 abundance on cell surface as well as clinical benefit from GO addition to standard chemotherapy. Patients with CC genotype (~50% of the study cohort) expressed full length CD33 (CD33-FL) and benefitted significantly from GO. However, heterozygous CT patients did not derive the same benefit and were shown to have intermediate CD33 levels (Lamba et al., 2017). The biological rationale for this discrepancy is poorly understood, with a major barrier being the lack of antibodies binding the IgC domain, and by extension the only extracellular domain of CD33-D2. To address this, we generated novel antibodies directed against the IgC domain and have recently shown that CD33-D2 is variably expressed on the surface of AML cell lines as well as primary cells (Gbadamosi et al., 2021). In this study, we have further explored the subcellular localization of both CD33-D2 and CD33-FL. Using pMXs retroviral particles encoding CD33-FL or CD33-D2, we engineered CRSIPR/Cas mediated CD33 KO AML cell lines to overexpress either of the two CD33 isoforms. Cells were then screened and confirmed for expression using either P67.6 or HL2541, which recognizes CD33-D2 (Fig. 1). We used immunofluorescence microscopy to determine subcellular localization of CD33 isoforms in these cell lines with the following organelles and their specific markers: endoplasmic reticulum (calreticulin), peroxisomes (PMP70), or lysosomes (LAMP1). Maximum projections from Z-stacks show that both CD33-FL and CD33-D2 localize only to peroxisomes in AML cells under normal, unperturbed conditions (Fig. 2). With this, our group has shown the cell surface and subcellular localization of CD33-D2 for the first time in AML cells. Ongoing studies are focused on determining the differences in CD33 glycosylation patterns as well cytokine signaling in AML cells expressing these variants. Our finding adds to the growing knowledge of CD33-D2 biology and sets the platform for further functional studies to gain mechanistic insights into its role in response to AML immunotherapy. The study was supported by Leukemia Lymphoma Society and St Baldrick's Foundation. [Display omitted] DisclosuresHylkema: Quest Diagnostics Inc: Current equity holder in publicly-traded company; Moderna: Current equity holder in publicly-traded company.

Effect of Treatment With Sacubitril/Valsartan in Patients With Advanced Heart Failure and Reduced Ejection Fraction

The use of sacubitril/valsartan is not endorsed by practice guidelines for use in patients with New York Heart Association class IV heart failure with a reduced ejection fraction because of limited clinical experience in this population. To compare treatment with sacubitril/valsartan treatment with valsartan in patients with advanced heart failure and a reduced ejection fraction and recent New York Heart Association class IV symptoms. A double-blind randomized clinical trial was conducted; a total of 335 patients with advanced heart failure were included. The trial began on March 2, 2017, and was stopped early on March 23, 2020, owing to COVID-19 risk. Patients were randomized to receive sacubitril/valsartan (target dose, 200 mg twice daily) or valsartan (target dose, 160 mg twice daily) in addition to recommended therapy. The area under the curve (AUC) for the ratio of N-terminal pro-brain natriuretic peptide (NT-proBNP) compared with baseline measured through 24 weeks of therapy. Of the 335 patients included in the analysis, 245 were men (73%); mean (SD) age was 59.4 (13.5) years. Seventy-two eligible patients (18%) were not able to tolerate sacubitril/valsartan, 100 mg/d, during the short run-in period, and 49 patients (29%) discontinued sacubitril/valsartan during the 24 weeks of the trial. The median NT-proBNP AUC for the valsartan treatment arm (n = 168) was 1.19 (IQR, 0.91-1.64), whereas the AUC for the sacubitril/valsartan treatment arm (n = 167) was 1.08 (IQR, 0.75-1.60). The estimated ratio of change in the NT-proBNP AUC was 0.95 (95% CI 0.84-1.08; P = .45). Compared with valsartan, treatment with sacubitril/valsartan did not improve the clinical composite of number of days alive, out of hospital, and free from heart failure events. Aside from a statistically significant increase in non-life-threatening hyperkalemia in the sacubitril/valsartan arm (28 [17%] vs 15 [9%]; P = .04), there were no observed safety concerns. The findings of this trial showed that, in patients with chronic advanced heart failure with a reduced ejection fraction, there was no statistically significant difference between sacubitril/valsartan and valsartan with respect to reducing NT-proBNP levels. ClinicalTrials.gov Identifier: NCT02816736.

A framework for quantifying deviations from dynamic equilibrium theory

AbstractAimIn an age of increased anthropogenic changes, it is crucially important to understand how and why ecological communities change. Community assembly is governed by colonization and extinction processes, and the simplest model describing it is dynamic equilibrium (DE), which assumes that communities are shaped solely by stochastic colonization and extinction events. Deviations from this model can point to the role of species life histories, niches or human stressors acting on communities. Despite its potential to serve as a null model for community dynamics, there is currently no accepted methodology for identifying and measuring such deviations.InnovationHere we propose a new, easily applicable methodology for testing and quantifying deviations of empirically observed time series of community dynamics from the predictions and assumptions of the classical DE model, in which assemblages of independent species undergo stochastic colonization–extinction dynamics with constant rates. The methodology consists of a novel randomization‐based null model to generate synthetic time series (PARIS) and a set of statistics that quantify and test how different facets of community dynamics deviate from DE. These statistics are designed to test the assumptions of the theory, namely species independence and constancy of colonization and extinction rates, and the predictions of the theory regarding the magnitude of changes in species richness and composition.Main conclusionsTested against simulated data and a case study, the proposed methodology is shown to have good statistical properties: acceptable type I error rates, good statistical power and robustness against errors in the data. We discuss alternative methods and present guidelines for practical use of the methodology, hoping it will enhance the applicability of DE as a reference for studying changes in ecological communities.

Nonparametric estimation of the survival distribution under covariate-induced dependent truncation.

There is often delayed entry into observational studies, which results in left truncation. In the estimation of the distribution of time-to-event from left-truncated data, standard survival analysis methods require quasi-independence between the truncation time and event time. Incorrectly assuming quasi-independence may lead to biased estimation. We address the problem of estimation of the survival distribution when dependence between the event time and its left truncation time is induced by shared covariates. We introduce propensity scores for truncated data and propose two inverse probability weighting methods that adjust for both truncation and dependence, if all of the shared covariates are measured. The proposed methods additionally allow for right censoring. We evaluate the proposed methods in simulations, conduct sensitivity analyses, and provide guidelines for use in practice. We illustrate our approach in application to data from a central nervous system lymphoma study. The proposed methods are implemented in the R package, depLT.

The European Paediatric Rare Tumours Network - European Registry (PARTNER) project for very rare tumors in children.

The PARTNER project (Paediatric Rare Tumours Network - European Registry) was launched in 2016. PARTNER aims to create a European Registry dedicated to children and adolescents with very rare tumors (VRT). It links existing national registries and provides a registry for those countries in which a VRT registry has not yet been created. This consortium is composed of the various national cooperative groups and their respective member institutions. The strategic value of this project is based on the Europe-wide data collection concerning the treatment of VRTs. These data are provided to experts and constitute the basis for new clinical practice guidelines for use by ERN (European Reference Network) and non-ERN institutions. The proposed tasks and milestones will increase collaboration in the field of pediatric oncology among member states and will also facilitate the inclusion of low health expenditure average rate (LHEAR) countries in this process. In addition, this project creates a platform for VRTs that may represent a model on how to elaborate a comprehensive approach (case registration, international case consultation and treatment recommendations, and website to provide information for parents/patients) for rare diseases.

Topical Antiseptic Formulations for Skin and Soft Tissue Infections.

Skin and soft tissue infections (SSTIs) are usually acute conditions of inflammatory microbial occupation of the skin layers and underlying soft tissues. SSTIs are one of the most frequent types of infection, typically requiring medical intervention and contribute to morbidity and mortality in both primary care and hospitalised patients. Due to the dramatic rise of antibiotic resistance, antiseptic agents can be potential alternatives for the prevention and treatment of SSTIs. Notably, they are commonly recommended in many global practical guidelines for use in per- and post- operative procedures. A range of antiseptics, including chlorhexidine, triclosan, alcohol, and povidone-iodine, are used and are mainly formulated as traditional, simple dosage forms such as solutions and semi-solids. However, in recent years, there have been studies reporting the potential for nanotechnology in the delivery of antiseptics. In this review, we have collated the scientific literature that focuses on topical antiseptic formulations for prevention and treatment of SSTIs, and have divided findings into traditional and advanced formulations. We conclude that although nanotechnological formulations have demonstrated potential advantages for delivering drugs; nevertheless, there is still scope for traditional formulations and further development of optimised topical formulations to address the rise of antimicrobial resistance.

Combining stimulants with antipsychotics for foster children and adolescents: Do prescribers adhere to guidelines?

ObjectiveConsistent with federal requirements for states to monitor psychotropic medication use in foster children and adolescents, we assessed prescribers’ adherence to best practice guidelines. Specifically, we identified the prevalence and patterns of combined use of stimulants and antipsychotics among a sample of foster children and adolescents that received additional non-pharmacological interventions from a state-funded team. A secondary purpose of this paper was to demonstrate a method for monitoring psychotropic medication use for this vulnerable population. MethodsUsing data from a state Medicaid database and a state-funded team, we tracked medication use among a sample of 128 foster children and adolescents aged 5–19 years with varying diagnoses who received behavioral and medication review services. We extracted data for children and adolescents who received the combination of stimulants and antipsychotics, and then we visually depicted the data to show changes in medication use before, during, and after our services. ResultsOut of the larger sample, twenty-one foster children and adolescents (16%) simultaneously received stimulants and antipsychotics. Visual depictions of data show that less than 50% received stimulants alone before combined use. In addition, participants experienced limited changes in medication regimens even after receiving non-pharmacological services. ConclusionsThese findings suggest that prescribers may not adhere to practice guidelines for use of stimulants and antipsychotics, even for clients who receive other services, and highlight the need for relevant stakeholders to monitor unsafe prescribing practices.