Objective
To provide recommendations for the management of juvenile idiopathic arthritis (JIA) with a focus on nonpharmacologic therapies, medication monitoring, immunizations, and imaging, ...irrespective of JIA phenotype.
Methods
We developed clinically relevant Patient/Population, Intervention, Comparison, and Outcomes questions. After conducting a systematic literature review, the Grading of Recommendations Assessment, Development and Evaluation approach was used to rate the quality of evidence (high, moderate, low, or very low). A Voting Panel including clinicians and patients/caregivers achieved consensus on the direction (for or against) and strength (strong or conditional) of recommendations.
Results
Recommendations in this guideline include the use of physical therapy and occupational therapy interventions; a healthy, well‐balanced, age‐appropriate diet; specific laboratory monitoring for medications; widespread use of immunizations; and shared decision‐making with patients/caregivers. Disease management for all patients with JIA is addressed with respect to nonpharmacologic therapies, medication monitoring, immunizations, and imaging. Evidence for all recommendations was graded as low or very low in quality. For that reason, more than half of the recommendations are conditional.
Conclusion
This clinical practice guideline complements the 2019 American College of Rheumatology JIA and uveitis guidelines, which addressed polyarthritis, sacroiliitis, enthesitis, and uveitis, and a concurrent 2021 guideline on oligoarthritis, temporomandibular arthritis, and systemic JIA. It serves as a tool to support clinicians, patients, and caregivers in decision‐making. The recommendations take into consideration the severity of both articular and nonarticular manifestations as well as patient quality of life. Although evidence is generally low quality and many recommendations are conditional, the inclusion of caregivers and patients in the decision‐making process strengthens the relevance and applicability of the guideline. It is important to remember that these are recommendations. Clinical decisions, as always, should be made by the treating clinician and patient/caregiver.
Objective
To provide recommendations for the management of juvenile idiopathic arthritis (JIA) with a focus on nonpharmacologic therapies, medication monitoring, immunizations, and imaging, ...irrespective of JIA phenotype.
Methods
We developed clinically relevant Patient/Population, Intervention, Comparison, and Outcomes questions. After conducting a systematic literature review, the Grading of Recommendations Assessment, Development and Evaluation approach was used to rate the quality of evidence (high, moderate, low, or very low). A Voting Panel including clinicians and patients/caregivers achieved consensus on the direction (for or against) and strength (strong or conditional) of recommendations.
Results
Recommendations in this guideline include the use of physical therapy and occupational therapy interventions; a healthy, well‐balanced, age‐appropriate diet; specific laboratory monitoring for medications; widespread use of immunizations; and shared decision‐making with patients/caregivers. Disease management for all patients with JIA is addressed with respect to nonpharmacologic therapies, medication monitoring, immunizations, and imaging. Evidence for all recommendations was graded as low or very low in quality. For that reason, more than half of the recommendations are conditional.
Conclusion
This clinical practice guideline complements the 2019 American College of Rheumatology JIA and uveitis guidelines, which addressed polyarthritis, sacroiliitis, enthesitis, and uveitis, and a concurrent 2021 guideline on oligoarthritis, temporomandibular arthritis, and systemic JIA. It serves as a tool to support clinicians, patients, and caregivers in decision‐making. The recommendations take into consideration the severity of both articular and nonarticular manifestations as well as patient quality of life. Although evidence is generally low quality and many recommendations are conditional, the inclusion of caregivers and patients in the decision‐making process strengthens the relevance and applicability of the guideline. It is important to remember that these are recommendations. Clinical decisions, as always, should be made by the treating clinician and patient/caregiver.
Treatment guidelines for Tourette's Disorder (TD) are based on patients' degree of tic severity and impairment. However, clear benchmarks for determining tic severity and impairment have not been ...established. This study examined benchmarks of tic severity and tic impairment using the Yale Global Tic Severity Scale (YGTSS) and the Clinical Global Impression of Severity (CGI-S).
Individuals with TD or another Tic Disorder (N = 519) recruited across nine sites were administered a diagnostic interview, the YGTSS, and the CGI-S. Correlations and trend analyses contrasted YGTSS scores across CGI-S ratings. A logistic regression model examined predictive benchmarks for tic severity, tic impairment, and global severity. Model classifications were compared against CGI-S ratings, and agreement was examined using kappa.
Spearman correlations between the CGI-S and YGTSS scores ranged from 0.54 to 0.63 (p < 0.001). Greater CGI-S ratings were associated with a linear stepwise increase in YGTSS Total Tic scores, Impairment scores, and Global Severity scores. Despite moderate-to-strong associations (ρ = 0.45–0.56, p < 0.001) between the CGI-S and predictive logistical regression models, only fair agreement was achieved when applying classification benchmarks (κ = 0.21–0.32, p < 0.001).
CGI-S ratings are useful to characterize benchmarks for tic severity, tic impairment, and global severity on the YGTSS. Logistic regression model benchmarks had only fair agreement with the CGI-S and underscore the heterogeneity of TD symptoms. Collectively, findings offer guidance on the delineation of tic severity categorizations to apply evidence-based treatment recommendations.
Pseudoloma neurophilia is a critical threat to the zebrafish (Danio rerio) model, as it is the most common infectious agent found in research facilities. In this study, our objectives were two‐fold: ...(1) compare the application of diagnostic tools for P. neurophilia and (2) track the progression of infection using PCR and histology. The first experiment showed that whole‐body analysis by qPCR (WB‐qPCR) can be a standardized process, providing a streamlined diagnostic protocol, without the need for extraction of specific tissues. Evaluating the course of infection in experimentally infected fish, we showed key dynamics in infection. Starting with a low dose exposure of 8000 spores/fish, the prevalence remained low until 92 days post‐exposure (dpe), followed by a 30%–40% prevalence by histology or 40%–90% by PCR until the end of the experiment at 334 dpe. WB‐qPCR positively detected infection in more fish than histology throughout the study, as WB‐qPCR detected the parasite as early as 4 dpe, whereas it was undetected by histology until 92 dpe. We also added a second slide for histologic analyses, showing an increase in detection rate from 24% to 26% when we combined all data from our experiments, but this increase was not statistically significant.
Trap and haul programmes are used to conserve fish populations by circumventing high mortality locations or events and enhancing population abundance by reintroducing fish to historical habitats and ...mitigating for fish passage limitations. Spring‐run Chinook salmon are transported in trucks upstream of barrier dams in Willamette River Tributaries as part of fish conservation efforts. Fish mortalities occurring during hauling minimize the utility of the effort because natural origin fish are targeted for theses outplanting efforts. The objectives of this study were to develop models predicting hauling mortality and identify optimal hauling densities that minimize mortality risk and effort. We used an information‐theoretic approach to evaluate multiple models predicting hauling mortality. Predictors identified varied between the two dams evaluated but were related to operations and annual or in‐river conditions. The amount of time loading fish and the density of fish in tank trucks were positively associated with hauling mortality. Instream flows and thermal exposure were also identified as factors predicting with hauling mortality. We used the results of model selection to predict mortality risk and calculate daily hauling effort. Risk and effort were combined into a utility to identify optimal hauling densities for varying numbers of fish to haul and transport truck volume. Optimal hauling densities varied between dams reflecting whether loading time or hauling density was associated with hauling mortality. This analysis provides managers a way to integrate research, monitoring, and management to improve understanding of factors associated with hauling mortality and adjust optimal hauling densities using adaptive management.
Mitochondrial disease diagnosis requires interrogation of both nuclear and mitochondrial (mtDNA) genomes for single-nucleotide variants (SNVs) and copy number alterations, both in the proband and ...often maternal relatives, together with careful phenotype correlation. We developed a comprehensive mtDNA sequencing test (‘MitoGenome’) using long-range PCR (LR-PCR) to amplify the full length of the mtDNA genome followed by next generation sequencing (NGS) to accurately detect SNVs and large-scale mtDNA deletions (LSMD), combined with droplet digital PCR (ddPCR) for LSMD heteroplasmy quantification. Overall, MitoGenome tests were performed on 428 samples from 394 patients with suspected or confirmed mitochondrial disease. The positive yield was 11% (43/394), including 34 patients with pathogenic or likely pathogenic SNVs (the most common being m.3243A > G in 8/34 (24%) patients), 8 patients with single LSMD, and 3 patients with multiple LSMD exceeding 10% heteroplasmy levels. Two patients with both LSMD and pathogenic SNV were detected. Overall, this LR-PCR/NGS assay provides a highly accurate and comprehensive diagnostic method for simultaneous mtDNA SNV detection at heteroplasmy levels as low as 1% and LSMD detection at heteroplasmy levels below 10%. Inclusion of maternal samples for variant classification and ddPCR to quantify LSMD heteroplasmy levels further enables accurate pathogenicity assessment and clinical correlation interpretation of mtDNA genome sequence variants and copy number alterations.
Stream fish managers often use fish sample data to inform management decisions affecting fish populations. Fish sample data, however, can be biased by the same factors affecting fish populations. To ...minimize the effect of sample biases on decision making, biologists need information on the effectiveness of fish sampling methods. We evaluated single‐pass backpack electrofishing and seining combined with electrofishing by following a dual‐gear, mark–recapture approach in 61 blocknetted sample units within first‐ to third‐order streams. We also estimated fish movement out of unblocked units during sampling. Capture efficiency and fish abundances were modeled for 50 fish species by use of conditional multinomial capture–recapture models. The best‐approximating models indicated that capture efficiencies were generally low and differed among species groups based on family or genus. Efficiencies of single‐pass electrofishing and seining combined with electrofishing were greatest for Catostomidae and lowest for Ictaluridae. Fish body length and stream habitat characteristics (mean cross‐sectional area, wood density, mean current velocity, and turbidity) also were related to capture efficiency of both methods, but the effects differed among species groups. We estimated that, on average, 23% of fish left the unblocked sample units, but net movement varied among species. Our results suggest that (1) common warmwater stream fish sampling methods have low capture efficiency and (2) failure to adjust for incomplete capture may bias estimates of fish abundance. We suggest that managers minimize bias from incomplete capture by adjusting data for site‐ and species‐specific capture efficiency and by choosing sampling gear that provide estimates with minimal bias and variance. Furthermore, if block nets are not used, we recommend that managers adjust the data based on unconditional capture efficiency.
The delta-toxin (δ-toxin) of
is the only hemolysin shown to cause mast cell degranulation and is linked to atopic dermatitis, a chronic inflammatory skin disease. We sought to characterize variation ...in δ-toxin production across
strains and identify genetic loci potentially associated with differences between strains.
A set of 124
strains was genome-sequenced and δ-toxin levels in stationary phase supernatants determined by high performance liquid chromatography (HPLC). SNPs and kmers were associated with differences in toxin production using four genome-wide association study (GWAS) methods. Transposon mutations in candidate genes were tested for their δ-toxin levels. We constructed XGBoost models to predict toxin production based on genetic loci discovered to be potentially associated with the phenotype.
The
strain set encompassed 40 sequence types (STs) in 23 clonal complexes (CCs). δ-toxin production ranged from barely detectable levels to >90,000 units, with a median of >8,000 units. CC30 had significantly lower levels of toxin production than average while CC45 and CC121 were higher. MSSA (methicillin sensitive) strains had higher δ-toxin production than MRSA (methicillin resistant) strains. Through multiple GWAS approaches, 45 genes were found to be potentially associated with toxicity. Machine learning models using loci discovered through GWAS as features were able to predict δ-toxin production (as a high/low binary phenotype) with a precision of .875 and specificity of .990 but recall of .333. We discovered that mutants in the
gene, encoding the small chain of carbamoyl phosphate synthase, completely abolished toxin production and toxicity in
.
The amount of stationary phase production of the toxin is a strain-specific phenotype likely affected by a complex interaction of number of genes with different levels of effect. We discovered new candidate genes that potentially play a role in modulating production. We report for the first time that the product of the
gene is necessary for δ-toxin production in USA300. This work lays a foundation for future work on understanding toxin regulation in
and prediction of phenotypes from genomic sequences.
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•Co-infection with Bolbophorus increased odds of Lernaea and Contracaecum infection.•A major marsh restoration project resulted in an increase in infections.•Declines in infections ...over about 25 days were attributed to parasite-induced host mortality.•Lernaea and Contracaecum might be directly lethal due to the small host sizes.•Recruitment was better in years without Lernaea infections.
We used odds ratios and a hurdle model to analyze parasite co-infections over 25 years on >20,000 young-of-the year of endangered Shortnose and Lost River Suckers. Host ecologies differed as did parasite infections. Shortnose Suckers were more likely to be caught inshore and 3–5 times more likely to have Bolbophorus spp. and Contracaecum sp. infections, and Lost River Suckers were more likely to be caught offshore and approximately three times more likely to have Lernaea cyprinacea infections. An observed peak shift seems likely to be due to a lower host size limit for Bolbophorus spp. (13.6 mm) compared with L. cyprinacea (23.4 mm). The large data set allowed us to generate strong hypotheses: (i) that a major marsh restoration project had unintended consequences that resulted in an increase in infections; (ii) that co-infection with Bolbophorus spp. increased the odds of infection by L. cyprinacea and Contracaecum sp.; (iii) that significant declines in the odds of infection over approximately 25 days were due to parasite-induced host mortality; (iv) that the fish’s small size relative to L. cyprinacea and Contracaecum sp. might be directly lethal; (v) that the absence of L. cyprinacea infections in the early 1990s was associated with good year-class production of the suckers; and (vi) that parasites might increase the odds of vagrancy from the nursery ground.
There is considerable uncertainty about the relative roles of stream habitat and landscape characteristics in structuring stream‐fish assemblages. We evaluated the relative importance of ...environmental characteristics on fish occupancy at the local and landscape scales within the upper Little Tennessee River basin of Georgia and North Carolina. Fishes were sampled using a quadrat sample design at 525 channel units within 48 study reaches during two consecutive years. We evaluated species–habitat relationships (local and landscape factors) by developing hierarchical, multispecies occupancy models. Modeling results suggested that fish occupancy within the Little Tennessee River basin was primarily influenced by stream topology and topography, urban land coverage, and channel unit types. Landscape scale factors (e.g., urban land coverage and elevation) largely controlled the fish assemblage structure at a stream‐reach level, and local‐scale factors (i.e., channel unit types) influenced fish distribution within stream reaches. Our study demonstrates the utility of a multi‐scaled approach and the need to account for hierarchy and the interscale interactions of factors influencing assemblage structure prior to monitoring fish assemblages, developing biological management plans, or allocating management resources throughout a stream system.
Received January 17, 2014; accepted June 4, 2014