Racial variability in immune responses only partially explains differential systemic sclerosis disease severity.

OBJECTIVE: To understand if autoantibodies account for racial variation in disease severity, we compared autoantibody distribution and associated phenotype between self-identified black and white systemic sclerosis (SSc) patients. METHODS: 803 black and 2178 white SSc patients had systematic testing for autoantibodies using Euroimmun (centromere (ACA), RNA-polymerase III (POLR3), Scl70, PM/Scl, NOR90, Th/To, Ku, U3RNP and Ro52) and commercial ELISA (U1RNP). In this observational study, logistic regression was performed to assess the association between self-identified race and outcomes, adjusting for autoantibodies. To estimate whether the effect of race was mediated by autoantibody status, race coefficients from multivariate models including and excluding autoantibodies were compared. RESULTS: Anti-Scl70, anti-U1RNP, anti-U3RNP, anti-Th/To, anti-Ku and anti-NOR90 were more common in the black cohort than in the white cohort, which was enriched for ACA, anti-POLR3 and anti-PM/Scl. Black individuals had a higher prevalence of severe Raynaud's, skin, lung, gastrointestinal and renal disease whereas white individuals had a higher prevalence of severe heart and muscle disease. Adjusting for autoantibodies decreased the effect of race on outcome for telangiectasias, forced vital capacity <70%, pulmonary hypertension and severe lung, heart, muscle and gastrointestinal disease by 11%-44% and increased the association between race and renal crisis and severe kidney disease by 37%-52%. CONCLUSIONS: This study is the largest systematic analysis of autoantibody responses in a geographically diverse population of black SSc patients. Black and white individuals with SSc have distinct autoantibody profiles. Autoantibodies explain only a fraction of the effect of race on clinical outcomes, suggesting other factors contribute to disparate outcomes between these groups.

Single-case design emphasis in American Psychological Association-accredited school psychology programs.

Single-case design (SCD) is an underutilized research methodology in school psychology literature. Despite its relevance to practitioners and applied intervention researchers alike, the majority of intervention research disseminated in school psychology journals tends to involve group designs, such as the randomized controlled trial. Group designs are useful for answering a wide variety of research questions but may not always be relevant to practitioners seeking procedures that work for their students or researchers seeking for the optimal design to answer their research questions. In comparison, the relative dearth of SCD studies in school psychology literature, in conjunction with common values among the field regarding data-based decision making and the scientist-practitioner model to training, raises questions about the cause of this gap. The present study sought to review doctoral training programs in school psychology and evaluate their relative emphasis on SCD in training. Seventy-six American Psychological Association-accredited school psychology programs were reviewed, and results indicated that roughly two thirds of programs do not emphasize SCD during training. Implications regarding school psychology training and research are discussed and recommendations are provided on future directions for school psychology trainers and researchers. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Examining effects of a novel estrogenic perfluoro-alcohol, 1H,1H,8H,8H-Perfluorooctane-1,8-diol (FC8-diol), using the fathead minnow EcoToxChip.

In a previous in vivo study, adult male fathead minnows (Pimephales promelas) were exposed via water for 4 days to 1H,1H,8H,8H-perfluorooctane-1,8-diol (FC8-diol). The present study expands on the evaluation of molecular responses to this perfluoro-alcohol by analyzing 26 male fathead minnow liver RNA samples from that study (five from each test concentration: 0, 0.018, 0.051, 0.171, and 0.463 mg FC8-diol/L) using fathead minnow EcoToxChips Ver. 1.0. EcoToxChips are a quantitative polymerase chain reaction array that allows for simultaneous measurement of >375 species-specific genes of toxicological interest. Data were analyzed with the online tool EcoToxXplorer. Among the genes analyzed, 62 and 96 were significantly up- and downregulated, respectively, by one or more FC8-diol treatments. Gene expression results from the previous study were validated, showing an upregulation of vitellogenin mRNA (vtg) and downregulation of insulin-like growth factor 1 mRNA (igf1). Additional genes related to estrogen receptor activation including esr2a (estrogen receptor 2a) and esrrb (estrogen related receptor beta) were also affected, providing further confirmation of the estrogenic nature of FC8-diol. Furthermore, genes involved in biological pathways related to lipid and carbohydrate metabolism, innate immune response, endocrine reproduction, and endocrine thyroid were significantly affected. These results both add confidence in the use of the EcoToxChip tool for inferring chemical mode(s) of action and provide further insights into the possible biological effects of FC8-diol. Environ Toxicol Chem 2024;00:1-9. © 2024 SETAC. This article has been contributed to by U.S. Government employees and their work is in the public domain in the USA.

Reconstruction of Palatal Defects Using a Composite Chondromucosal Nasoseptal Flap and Comparative Analysis.

OBJECTIVE: The use of composite chondromucosal nasal septal flaps (ccNSF) has been demonstrated to be effective in cadaveric studies for the anterior skull base and the orbit. However, their application in the clinical setting remains unexplored. Our study aims to introduce a new method for treating palatal defects using ccNSF. Additionally, we studied the average NSF area and compared it to the average palate area. METHODS: We collected 108 CT scans from the medical records of patients without head and neck pathologies from a tertiary medical institution. We quantified the quadrangular (septal) cartilage and palate areas. Furthermore, we included a clinical case in which we used the ccNSF for the palatal defect reconstruction. This was to compare the mean area between the palate and the septal cartilage. RESULTS: The ccNSF covered the palatal defect without any significant complications for the first 9 months of follow-up. A total of 102 CT scans met the inclusion criteria and were measured. We found that the mean quadrangular cartilage had a length of 2.50 (±0.52) cm, a width of 2.28 (±0.51) cm, and an area of 5.43 (±1.68) cm2. The mean palate length was 2.73 (±0.44) cm, with a width of 3.13 (±0.34) cm, and area of 7.87 (±1.43) cm2. CONCLUSIONS: The ccNSF proved successful in palatal defect reconstruction, resulting in positive outcomes and no major complications until the 9-month follow-up. The ccNSF is a useful flap that avoids the use of free flap transfer and its associated morbidities. LEVEL OF EVIDENCE: 4 Laryngoscope, 2024.

Targeting neuroinflammation in distal symmetrical polyneuropathy in diabetes.

Diabetic distal symmetric polyneuropathy is the most common type of peripheral neuropathy complication of diabetes mellitus. Neuroinflammation is emerging as an important contributor to diabetes-induced neuropathy. Long-term hyperglycemia results in increased production of advanced glycation end products (AGEs). AGEs interact with their receptors to activate intracellular signaling, leading to the release of various inflammatory cytokines. Increased release of inflammatory cytokines is associated with diabetes, diabetic neuropathy and neuropathic pain. Thus, anti-inflammatory intervention is a potential therapy for diabetic distal symmetric polyneuropathy. Further characterization of inflammatory mechanisms might identify novel therapeutic targets to mitigate diabetic neuropathy.

An ordinal clinical score predicts seizure freedom after minimally invasive epilepsy surgery.

OBJECTIVE: To predict one-year seizure freedom, using a combination of relevant clinical variables, following stereotactic laser amygdalohippocampotomy for mesial temporal lobe epilepsy in a series of 101 patients. METHODS: Eight predictors of seizure freedom were selected based on their association with medial temporal lobe epilepsy: (1) MRI evidence of mesial temporal sclerosis (MTS); (2) unitemporal interictal epileptiform discharges; (3) absence of generalized tonic-clonic seizures; (4) history of febrile seizures; (5) onset of epilepsy ≤16 years; (6) absence of an auditory, visual, or vertiginous aura; and (7) unitemporal ictal onset; (8) unitemporal PET hypometabolism. We compared four multivariate models: "MTS," using just evidence of MTS; "FULL," using all eight binary predictors; "AIC" using backwards selection of variables; and "SCORE," using a 0-to-8-point ordinal score awarding one point for each binary predictor. RESULTS: In univariate analysis, significant predictors for seizure freedom were evidence of mesial temporal sclerosis (p = 0.011, Fisher exact) and unitemporal interictal discharges (p = 0.005). For multivariate prediction (using leave one-out cross-validation), the ordinal SCORE model had a significantly higher area under the curve (AUC 0.70) than the other three models: MTS (AUC 0.54, p = 0.002, Delong's test), FULL (AUC 0.62, p = 0.003), or AIC (AUC 0.53, p < 0.001). INTERPRETATION: An ordinal score incorporating eight independent binary clinical variables predicted seizure freedom better on novel data than a model using MTS alone, a full multivariate model, or a backwards selected model. The ordinal score model represents a simple clinical heuristic to identify which patients should be offered minimally invasive laser surgery.

Two decades of molecular surveillance in Senegal reveal rapid changes in known drug resistance mutations over time.

BACKGROUND: Drug resistance in Plasmodium falciparum is a major threat to malaria control efforts. Pathogen genomic surveillance could be invaluable for monitoring current and emerging parasite drug resistance. METHODS: Data from two decades (2000-2020) of continuous molecular surveillance of P. falciparum parasites from Senegal were retrospectively examined to assess historical changes in malaria drug resistance mutations. Several known drug resistance markers and their surrounding haplotypes were profiled using a combination of single nucleotide polymorphism (SNP) molecular surveillance and whole genome sequence based population genomics. RESULTS: This dataset was used to track temporal changes in drug resistance markers whose timing correspond to historically significant events such as the withdrawal of chloroquine (CQ) and the introduction of sulfadoxine-pyrimethamine (SP) in 2003. Changes in the mutation frequency at Pfcrt K76T and Pfdhps A437G coinciding with the 2014 introduction of seasonal malaria chemoprevention (SMC) in Senegal were observed. In 2014, the frequency of Pfcrt K76T increased while the frequency of Pfdhps A437G declined. Haplotype-based analyses of Pfcrt K76T showed that this rapid increase was due to a recent selective sweep that started after 2014. DISCUSSION (CONCLUSION): The rapid increase in Pfcrt K76T is troubling and could be a sign of emerging amodiaquine (AQ) resistance in Senegal. Emerging AQ resistance may threaten the future clinical efficacy of artesunate-amodiaquine (ASAQ) and AQ-dependent SMC chemoprevention. These results highlight the potential of molecular surveillance for detecting rapid changes in parasite populations and stress the need to monitor the effectiveness of AQ as a partner drug for artemisinin-based combination therapy (ACT) and for chemoprevention.

Developing a Multi-Spectral NIR LED-Based Instrument for the Detection of Pesticide Residues Containing Chlorpyrifos-Methyl in Rough, Brown, and Milled Rice.

A recent study showed the potential of the DA Perten 7200 NIR Spectrometer in detecting chlorpyrifos-methyl pesticide residue in rough, brown, and milled rice. However, this instrument is still lab-based and generally suited for point-of-sale testing. To provide a field-deployable version of this technique, an existing light emitting diode (LED)-based instrument that provides discrete NIR wavelength illumination and reflectance spectra over the range of 850-1550 nm was tested. Spectra were collected from rough, brown, and milled rice at different pesticide concentrations and analyzed for quantitative and qualitative measurement using partial least squares regression (PLS) and discriminant analysis (DA). Simulations for two LED-based instruments were also evaluated using corresponding segments of spectra from the DA7200 to represent LED illumination. For the simulation of the existing LED-based instrument (LEDPrototype1) fitted with 850, 910, 940, 970, 1070, 1200, 1300, 1450, and 1550 nm LED wavelengths, resulting R2 ranged from 0.52 to 0.71, and the correct classification was 70.4% to 100%. The simulation of a second LED instrument (LEDPrototype2) fitted with 980, 1050, 1200, 1300, 1450, 1550, 1600, and 1650 nm LED wavelengths showed R2 of 0.59 to 0.82 and correct classifications of 66% to 100%. These LED wavelengths were selected based on the significant wavelength regions from the PLS regression coefficients of DA7200 and the commercial availability of LED wavelengths. Results showed that it is possible to use a multi-spectral LED-based instrument to detect varying levels of chlorpyrifos-methyl pesticide residue in rough, brown, and milled rice.

Utility of Targeted Sequencing Compared to FISH for Detection of Chronic Lymphocytic Leukemia Copy Number Alterations.

Chronic lymphocytic leukemia (CLL) is characterized by multiple copy number alterations (CNAs) and somatic mutations that are central to disease prognosis, risk stratification, and mechanisms of therapy resistance. Fluorescence in situ hybridization (FISH) panels are widely used in clinical applications as the gold standard for screening prognostic chromosomal abnormalities in CLL. DNA sequencing is an alternative approach to identifying CNAs but is not an established method for clinical CNA screening. We sequenced DNA from 509 individuals with CLL or monoclonal B-cell lymphocytosis (MBL), the precursor to CLL, using a targeted sequencing panel of 59 recurrently mutated genes in CLL and additional amplicons across regions affected by clinically relevant CNAs [i.e., del(17p), del(11q), del(13q), and trisomy 12]. We used the PatternCNV algorithm to call CNA and compared the concordance of calling clinically relevant CNAs by targeted sequencing to that of FISH. We found a high accuracy of calling CNAs via sequencing compared to FISH. With FISH as the gold standard, the specificity of targeted sequencing was >95%, sensitivity was >86%, positive predictive value was >90%, and negative predictive value was >84% across the clinically relevant CNAs. Using targeted sequencing, we were also able to identify other common CLL-associated CNAs, including del(6q), del(14q), and gain 8q, as well as complex karyotype, defined as the presence of 3 or more chromosomal abnormalities, in 26 patients. In a single and cost-effective assay that can be performed on stored DNA samples, targeted sequencing can simultaneously detect CNAs, somatic mutations, and complex karyotypes, which are all important prognostic features in CLL.

G Protein-Coupled Receptor-Ligand Pose and Functional Class Prediction.

G protein-coupled receptor (GPCR) transmembrane protein family members play essential roles in physiology. Numerous pharmaceuticals target GPCRs, and many drug discovery programs utilize virtual screening (VS) against GPCR targets. Improvements in the accuracy of predicting new molecules that bind to and either activate or inhibit GPCR function would accelerate such drug discovery programs. This work addresses two significant research questions. First, do ligand interaction fingerprints provide a substantial advantage over automated methods of binding site selection for classical docking? Second, can the functional status of prospective screening candidates be predicted from ligand interaction fingerprints using a random forest classifier? Ligand interaction fingerprints were found to offer modest advantages in sampling accurate poses, but no substantial advantage in the final set of top-ranked poses after scoring, and, thus, were not used in the generation of the ligand-receptor complexes used to train and test the random forest classifier. A binary classifier which treated agonists, antagonists, and inverse agonists as active and all other ligands as inactive proved highly effective in ligand function prediction in an external test set of GPR31 and TAAR2 candidate ligands with a hit rate of 82.6% actual actives within the set of predicted actives.

A unified metric of human immune health.

Immunological health has been challenging to characterize but could be defined as the absence of immune pathology. While shared features of some immune diseases and the concept of immunologic resilience based on age-independent adaptation to antigenic stimulation have been developed, general metrics of immune health and its utility for assessing clinically healthy individuals remain ill defined. Here we integrated transcriptomics, serum protein, peripheral immune cell frequency and clinical data from 228 patients with 22 monogenic conditions impacting key immunological pathways together with 42 age- and sex-matched healthy controls. Despite the high penetrance of monogenic lesions, differences between individuals in diverse immune parameters tended to dominate over those attributable to disease conditions or medication use. Unsupervised or supervised machine learning independently identified a score that distinguished healthy participants from patients with monogenic diseases, thus suggesting a quantitative immune health metric (IHM). In ten independent datasets, the IHM discriminated healthy from polygenic autoimmune and inflammatory disease states, marked aging in clinically healthy individuals, tracked disease activities and treatment responses in both immunological and nonimmunological diseases, and predicted age-dependent antibody responses to immunizations with different vaccines. This discriminatory power goes beyond that of the classical inflammatory biomarkers C-reactive protein and interleukin-6. Thus, deviations from health in diverse conditions, including aging, have shared systemic immune consequences, and we provide a web platform for calculating the IHM for other datasets, which could empower precision medicine.

AI-based differential diagnosis of dementia etiologies on multimodal data.

Differential diagnosis of dementia remains a challenge in neurology due to symptom overlap across etiologies, yet it is crucial for formulating early, personalized management strategies. Here, we present an artificial intelligence (AI) model that harnesses a broad array of data, including demographics, individual and family medical history, medication use, neuropsychological assessments, functional evaluations and multimodal neuroimaging, to identify the etiologies contributing to dementia in individuals. The study, drawing on 51,269 participants across 9 independent, geographically diverse datasets, facilitated the identification of 10 distinct dementia etiologies. It aligns diagnoses with similar management strategies, ensuring robust predictions even with incomplete data. Our model achieved a microaveraged area under the receiver operating characteristic curve (AUROC) of 0.94 in classifying individuals with normal cognition, mild cognitive impairment and dementia. Also, the microaveraged AUROC was 0.96 in differentiating the dementia etiologies. Our model demonstrated proficiency in addressing mixed dementia cases, with a mean AUROC of 0.78 for two co-occurring pathologies. In a randomly selected subset of 100 cases, the AUROC of neurologist assessments augmented by our AI model exceeded neurologist-only evaluations by 26.25%. Furthermore, our model predictions aligned with biomarker evidence and its associations with different proteinopathies were substantiated through postmortem findings. Our framework has the potential to be integrated as a screening tool for dementia in clinical settings and drug trials. Further prospective studies are needed to confirm its ability to improve patient care.

Reported Incidence of Infections Caused by Pathogens Transmitted Commonly Through Food: Impact of Increased Use of Culture-Independent Diagnostic Tests - Foodborne Diseases Active Surveillance Network, 1996-2023.

Reducing foodborne disease incidence is a public health priority. This report summarizes preliminary 2023 Foodborne Diseases Active Surveillance Network (FoodNet) data and highlights efforts to increase the representativeness of FoodNet. During 2023, incidences of domestically acquired campylobacteriosis, Shiga toxin-producing Escherichia coli infection, yersiniosis, vibriosis, and cyclosporiasis increased, whereas those of listeriosis, salmonellosis, and shigellosis remained stable compared with incidences during 2016-2018, the baseline used for tracking progress towards federal disease reduction goals. During 2023, the incidence and percentage of infections diagnosed by culture-independent diagnostic tests (CIDTs) reported to FoodNet continued to increase, and the percentage of cases that yielded an isolate decreased, affecting observed trends in incidence. Because CIDTs allow for diagnosis of infections that previously would have gone undetected, lack of progress toward disease reduction goals might reflect changing diagnostic practices rather than an actual increase in incidence. Continued surveillance is needed to monitor the impact of changing diagnostic practices on disease trends, and targeted prevention efforts are needed to meet disease reduction goals. During 2023, FoodNet expanded its catchment area for the first time since 2004. This expansion improved the representativeness of the FoodNet catchment area, the ability of FoodNet to monitor trends in disease incidence, and the generalizability of FoodNet data.

Epidemiology of Travel-Associated Dengue from 2007 to 2022: A GeoSentinel Analysis.

BACKGROUND: Dengue is a leading cause of febrile illness among international travellers. We aimed to describe the epidemiology and clinical characteristics of imported dengue in returning travellers evaluated at GeoSentinel sites from 2007-2022. METHODS: We retrieved GeoSentinel records of dengue among travellers residing in non-endemic countries. We considered dengue confirmed when diagnosed by a positive DENV-specific RT-PCR, positive NS-1 antigen, and/or anti-DENV IgG seroconversion, and probable when diagnosed by single anti-DENV IgM or high titre anti-DENV IgG detection. Severe dengue was defined as evidence of clinically significant plasma leakage or bleeding, organ failure, or shock, according to the 2009 WHO guidance. Complicated dengue was defined as either severe dengue or dengue with presence of any warning sign. Analyses were descriptive. RESULTS: This analysis included 5958 travellers with confirmed (n = 4859; 81.6%) or probable (n = 1099; 18.4%) dengue. The median age was 33 years (range: < 1-91); 3007 (50.5%) travellers were female. The median travel duration was 21 days (interquartile range [IQR]: 15-32). The median time between illness onset and GeoSentinel site visit was 7 days (IQR: 4-15). The most frequent reasons for travel were tourism (67.3%), visiting friends or relatives (12.2%), and business (11.0%). The most frequent regions of acquisition were Southeast Asia (50.4%), South-Central Asia (14.9%), the Caribbean (10.9%), and South America (9.2%). Ninety-five (1.6%) travellers had complicated dengue, of whom 27 (0.5%) had severe dengue, and one died. Of 2710 travellers with data available, 724 (26.7%) were hospitalized. The largest number of cases (n = 835) was reported in 2019. CONCLUSIONS: A broad range of international travellers should be aware of the risk of acquiring dengue and receive appropriate pretravel counselling regarding preventive measures. Prospective cohort studies are needed to further elucidate dengue risk by destination and over time, as well as severe outcomes and prolonged morbidity (long-dengue) due to travel-related dengue.

Suillus hypogaeus: First record of a truffle Suillus.

Suillus (order Boletales) is a diverse genus of epigeous, mushroom-forming fungi native to temperate forests across the Northern Hemisphere; however, some species are also present in areas where Pinaceae has been introduced in the Southern Hemisphere. Unlike the closely related genus Rhizopogon, there are no described hypogeous, sequestrate species of Suillus. Here, we describe Suillus hypogaeus, the first known species of the genus with hypogeous, sequestrate sporocarps. Collections were made on Marys Peak in Benton County, Oregon, USA, at an elevation of 800 m in forests dominated by Pseudotsuga menziesii var. menziesii. The peridium is white, quickly staining pink to purple-reddish where bruised or cut. The gleba is pale yellow when young, becoming purple with maturity, and the basidiospores are obovoid, light yellow in KOH, and amyloid in Melzer's reagent. Multilocus molecular phylogenetic analyses support the placement of S. hypogaeus among the Larix specialists in the spectabilis group of Suillus. Although Larix and Pseudotsuga are sister genera, Larix does not occur on Marys Peak or elsewhere in western Oregon. Suillus hypogaeus, therefore, represents both an independent origin of the hypogeous, sequestrate sporocarp within the Boletales and an independent host shift between Larix and Pseudotsuga within the genus Suillus.

Molecular patterns and mechanisms of tumorigenesis in HPV-associated and HPV-independent sinonasal squamous cell carcinoma.

Mechanisms of tumorigenesis in sinonasal squamous cell carcinoma (SNSCC) remain poorly described due to its rare nature. A subset of SNSCC are associated with the human papillomavirus (HPV); however, it is unknown whether HPV is a driver of HPV-associated SNSCC tumorigenesis or merely a neutral bystander. We hypothesized that performing the first large high-throughput sequencing study of SNSCC would reveal molecular mechanisms of tumorigenesis driving HPV-associated and HPV-independent SNSCC and identify targetable pathways. High-throughput sequencing was performed on 64 patients with HPV-associated and HPV-independent sinonasal carcinomas. Mutation annotation, viral integration, copy number, and pathway-based analyses were performed. Analysis of HPV-associated SNSCC revealed similar mutational patterns observed in HPV-associated cervical and head and neck squamous cell carcinoma, including lack of TP53 mutations and the presence of known hotspot mutations in PI3K and FGFR3. Further similarities included enrichment of APOBEC mutational signature, viral integration at known hotspot locations, and frequent mutations in epigenetic regulators. HPV-associated SNSCC-specific recurrent mutations were also identified including KMT2C , UBXN11 , AP3S1 , MT-ND4 , and MT-ND5 . Mutations in KMT2D and FGFR3 were associated with decreased overall survival. We developed the first known HPV-associated SNSCC cell line and combinatorial small molecule inhibition of YAP/TAZ and PI3K pathways synergistically inhibited tumor cell clonogenicity. In conclusion, HPV-associated SNSCC and HPV-independent SNSCC are driven by molecularly distinct mechanisms of tumorigenesis. Combinatorial blockade of YAP/TAZ and vertical inhibition of the PI3K pathway may be useful in targeting HPV-associated SNSCC whereas targeting MYC and horizontal inhibition of RAS/PI3K pathways for HPV-independent SNSCC. One Sentence Summary: This study solidifies HPV as a driver of HPV-associated SNSCC tumorigenesis, identifies molecular mechanisms distinguishing HPV-associated and HPV-independent SNSCC, and elucidates YAP/TAZ and PI3K blockade as key targets for HPV-associated SNSCC.

Capturing patient mobility levels in the hospital: An examination of nursing charting and behavioural mapping.

AIMS: Our study aimed to (1) validate the accuracy of nursing mobility documentation and (2) identify the most effective timings for behavioural mapping. DESIGN: We monitored the mobility of 55 inpatients using behavioural mapping throughout a nursing day shift, comparing the observed mobility levels with the nursing charting in the electronic health record during the same period. RESULTS: Our results showed a high level of agreement between nursing records and observed mobility, with improved accuracy observed particularly when documentation was at 12 PM or later. Behavioural mapping observations revealed that the most effective timeframe to observe the highest levels of patient mobility was between 10 AM AND 2 PM. CONCLUSION: To truly understand patient mobility, comparing nursing charting with methods like behavioural mapping is beneficial. This comparison helps evaluate how well nursing records reflect actual patient mobility and offers insights into the best times for charting to capture peak mobility. While behavioural mapping is a valuable tool for auditing patient mobility, its high resource demands limit its regular use. Thus, determining the most effective times and durations for observations is key for practical implementation in hospital mobility audits. IMPLICATION FOR THE PROFESSION AND/OR PATIENT CARE: Nurses are pivotal in ensuring patient mobility in hospitals, an essential element of quality care. Their role involves safely mobilizing patients and accurately charting their mobility levels during each shift. For nursing practice, this research underscores that nurse charting can accurately reflect patient mobility, and highlights that recording the patient's highest level of mobility later in the shift offers a more precise representation of their actual mobility. REPORTING METHOD: Strobe. PATIENT OR PUBLIC CONTRIBUTION: No Patient or Public Contribution.

Strategies for DPYD testing prior to fluoropyrimidine chemotherapy in the US.

PURPOSE: Patients with dihydropyrimidine dehydrogenase (DPD) deficiency are at high risk for severe and fatal toxicity from fluoropyrimidine (FP) chemotherapy. Pre-treatment DPYD testing is standard of care in many countries, but not the United States (US). This survey assessed pre-treatment DPYD testing approaches in the US to identify best practices for broader adoption. METHODS: From August to October 2023, a 22-item QualtricsXM survey was sent to institutions and clinicians known to conduct pre-treatment DPYD testing and broadly distributed through relevant organizations and social networks. Responses were analyzed using descriptive analysis. RESULTS: Responses from 24 unique US sites that have implemented pre-treatment DPYD testing or have a detailed implementation plan in place were analyzed. Only 33% of sites ordered DPYD testing for all FP-treated patients; at the remaining sites, patients were tested depending on disease characteristics or clinician preference. Almost 50% of sites depend on individual clinicians to remember to order testing without the assistance of electronic alerts or workflow reminders. DPYD testing was most often conducted by commercial laboratories that tested for at least the four or five DPYD variants considered clinically actionable. Approximately 90% of sites reported receiving results within 10 days of ordering. CONCLUSION: Implementing DPYD testing into routine clinical practice is feasible and requires a coordinated effort among the healthcare team. These results will be used to develop best practices for the clinical adoption of DPYD testing to prevent severe and fatal toxicity in cancer patients receiving FP chemotherapy.