Defining remission in childhood-onset lupus: PReS-endorsed consensus definitions by an international task force.

OBJECTIVE: To derive childhood-onset SLE (cSLE) specific remission definitions for future treat-to-target (T2T) trials, observational studies, and clinical practice. METHODS: The cSLE International T2T Task Force conducted Delphi surveys exploring paediatric perspectives on adult-onset SLE remission targets. A modified nominal group technique was used to discuss, refine, and agree on the cSLE remission target criteria. RESULTS: The Task Force proposed two definitions of remission: 'cSLE clinical remission on steroids (cCR)' and 'cSLE clinical remission off steroids (cCR-0)'. The common criteria are: (1) Clinical-SLEDAI-2 K = 0; (2) PGA score < 0.5 (0-3 scale); (4) stable antimalarials, immunosuppressive, and biologic therapy (changes due to side-effects, adherence, weight, or when building up to target dose allowed). Criterion (3) in cCR is the prednisolone dose ≤0.1 mg/kg/day (maximum 5 mg/day), whereas in cCR-0 it is zero. CONCLUSIONS: cSLE definitions of remission have been proposed, maintaining sufficient alignment with the adult-SLE definition to facilitate life-course research.

PReS-endorsed international childhood lupus T2T task force definition of childhood lupus low disease activity state (cLLDAS).

OBJECTIVE: To achieve a consensus-based definition of Low Disease Activity (LDA) for use in cSLE trials. METHODS: The International cSLE T2T Task Force, comprising of paediatric rheumatologists/nephrologists, and adult rheumatologists undertook a series of Delphi surveys/consensus meetings to discuss, refine, and vote upon cSLE LDA criteria. RESULTS: The Task Force agreed that LDA should be based upon the adult-SLE Lupus Low Disease Activity State definition (LLDAS), with modifications to make it applicable to cSLE (cLLDAS). They agreed upon five cLLDAS criteria: (1) SLE Disease Activity Index (SLEDAI)-2 K ≤4, with no activity in major organ systems; (2) no new features of lupus disease activity compared with the last assessment; (3) Physician Global Assessment score of ≤1 (0-3 scale); (4) prednisolone dose of ≤0.15 mg/kg/day, 7.5 mg/day/maximum; while on (5) stable antimalarials, immunosuppressives, and biologics. CONCLUSIONS: A cSLE-appropriate definition of cLLDAS has been generated, maintaining alignment with the adult-SLE definition to promote life-course research.

Influence of environmental temperature and heatwaves on surgical site infection after hip and knee arthroplasty: a nationwide study.

BACKGROUND: Previous studies reported higher incidence of surgical site infection (SSI) after procedures performed in summer or with high temperatures. However, no study used detailed climate data to assess this risk after hip and knee arthroplasty, and no study specifically investigated the role of heatwaves. AIM: To assess the impact of higher environmental temperatures and heatwaves on SSI rates after hip and knee arthroplasty. METHODS: Data on hip and knee arthroplasty procedures performed between January 2013 and September 2019 in hospitals participating in the Swiss SSI surveillance were linked to climate data extracted from weather stations located in their vicinity. The association between temperature, heatwaves and SSI was studied using mixed effects logistic regression models fitted at the patient level. Poisson mixed models were fitted for both calendar year and month of the year to investigate the SSI incidence trajectory over time. RESULTS: We included 116,981 procedures performed in 122 hospitals. Significantly higher SSI rates were observed for procedures performed in the summertime (incidence rate ratio 1.39, 95% CI (1.20-1.60), P<0.001; reference: autumn) or in calendar months in which the mean temperature was above 20 °C (reference 5-10 °C; odds ratio 1.59, 95% CI (1.27, 1.98), P<0.001). We observed a slight but non-significant increase in the rate of SSI during heatwaves (1.44% versus 1.01%, P=0.2). CONCLUSION: SSI rates after hip and knee replacement appear to increase with higher environmental temperature. To establish whether, and to what extent, heatwaves increase the risk of SSI, studies involving geographical areas with larger variability in temperature are needed.

Risk factors for hospital-acquired infection during the SARS-CoV-2 pandemic.

OBJECTIVE: To evaluate risk factors for hospital-acquired infection (HAI) in patients during the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) pandemic, including historical and concurrent cohorts. DESIGN: Retrospective cohort. SETTING: Three Missouri hospitals, data from 1st January 2017 to 30th September 2020. PARTICIPANTS: Patients aged ≥18 years and admitted for ≥48 h. METHODS: Univariate and multi-variate Cox proportional hazards models incorporating the competing risk of death were used to determine risk factors for HAI. A-priori sensitivity analyses were performed to assess the robustness of the urine-, blood- and respiratory-culture-based HAI definition. RESULTS: The cohort included 254,792 admissions, with 7147 (2.8%) HAIs (1661 blood, 3407 urine, 2626 respiratory). Patients with SARS-CoV-2 had increased risk of HAI (adjusted hazards ratio 1.65, 95% confidence interval 1.38-1.96), and SARS-CoV-2 infection was one of the strongest risk factors for development of HAI. Other risk factors for HAI included certain admitting services, chronic comorbidities, intensive care unit stay during index admission, extremes of body mass index, hospital, and selected medications. Factors associated with lower risk of HAI included year of admission (declined over the course of the study), admitting service and medications. Risk factors for HAI were similar in sensitivity analyses restricted to patients with diagnostic codes for pneumonia/upper respiratory infection and urinary tract infection. CONCLUSIONS: SARS-CoV-2 was associated with significantly increased risk of HAI.

Utility of strain typing of Propionibacterium acnes in central nervous system and prosthetic joint infections to differentiate contamination from infection: a retrospective cohort.

The study aimed to retrospectively assess if strain typing of Propionibacterium acnes could help to distinguish between infection and contamination in isolates recovered from the central nervous system (CNS) and prosthetic joints (PJs). This was a retrospective cohort of all Propionibacterium species isolates from the Barnes-Jewish Hospital (St Louis, MO, USA) clinical microbiology laboratory from 2011 to 2014. Available frozen isolates were recovered, and strain type (IA-1, IA-2, IB, II, III, or nontypeable class A or B) was determined via polymerase chain reaction (PCR)-based methods. For CNS isolates, P. acnes was considered pathogenic if treating physicians administered ≥7 days of directed antibiotic therapy against P. acnes. During the study period, Propionibacterium species was isolated from clinical cultures 411 times. 152 isolates were available for analysis. Of the 152 isolates, 140 were confirmed to be P. acnes, 61 of which were from the CNS (45 contaminants, 16 infections). Strain type IA-1 was more common (50.0%, 8 out of 16) among CNS infections than among contaminants (22.2%, 10 out of 45). For PJ isolates 61.3% (19 out of 31) met the criteria for infection. The predominant strain type for CNS infection was IA-1 and for PJ isolates, IB. Strain type IA-1 was isolated more often in patients with CNS infections, which may indicate a predilection of this strain type to cause CNS infection. Future research should prospectively evaluate strain typing as a means of assisting in the diagnosis of CNS infections and confirm our findings.

Predictors of arthritis in pediatric patients with lupus.

BACKGROUND: Arthritis is one of the most common manifestations of systemic lupus erythematosus (SLE). Although typically non-erosive and non-deforming, children with SLE arthritis can have significant morbidity with decreased quality of life. Our goal was to identify potential clinical and laboratory predictors of arthritis in a cohort of pediatric patients with SLE. METHODS: We performed a cohort study of incident and prevalent patients with SLE aged ≤ 19 years. In cross sectional analysis, we compared demographic and clinical characteristics at initial clinic presentation between patients with arthritis noted at any time during follow-up and those without arthritis. We performed time to event analysis using Cox proportional hazard ratios to identify predictors of arthritis, clustering for repeated measures. RESULTS: Forty seven children and adolescents with SLE were followed in the cohort, 91 % female and 68 % Black. In cross-sectional analyses, presence of malar rash was associated with arthritis. In longitudinal analyses, controlling for gender and race, increased age (HR: 1.4, 95 % CI: 1.1-1.7), malar rash (HR: 2.1, 95 % CI: 1.1-3.6), and presence of RNP antibodies (HR: 1.9, 95 % CI: 1.1-3.4) were predictive of arthritis. When controlling for gender, race, and medication use, anemia (HR: 8.5, 95 % CI: 2.9-24.2) and thrombocytopenia (HR: 6.1, 95 % CI: 2.4-15.6) were associated with increased risk of arthritis. CONCLUSIONS: We identified markers predictive of arthritis in a longitudinal cohort of children with SLE. The recognition of these markers may help clinicians identify patients at risk for arthritis before its onset thus improving quality of life in children with SLE.

Predictors of kidney disease in a cohort of pediatric patients with lupus.

INTRODUCTION: Children with systemic lupus erythematosus (SLE) have an increased prevalence of kidney disease compared to their adult counterparts. Our goal was to identify potential clinical and laboratory predictors of renal disease. METHODS: We performed a cohort study of incident and prevalent patients with SLE aged ≤19 years. Retrospective data from initial presentation until study enrollment was also collected. Laboratory and clinic data were recorded from each clinic visit including disease activity indices, autoantibodies, urinalyses, blood counts, and metabolic profile. Kidney disease was defined as the presence of abnormal renal biopsy or by American College of Rheumatology case definition for lupus nephritis. Logistic regression analyses were used to determine the association between clinical and laboratory data with kidney disease in those who had renal involvement within 30 days of SLE diagnosis. We also performed a time to event analysis to identify antecedents of renal disease. RESULTS: Forty-seven children and adolescents with SLE were followed in the cohort, 91% female and 68% black. All of the males in the cohort developed renal disease, and all within one month of the diagnosis of SLE. In logistic regression, low serum albumin (odds ratio (OR): 4.8, 95% CI: 1.9-12.5) and positive dsDNA antibodies (OR: 3.2, 95% CI: 1.7-5.9) were associated with kidney disease. In longitudinal analyses, isolated sterile pyuria (hazard ratio (HR): 3, 95% CI: 1.1-6.4) and low serum albumin (HR: 3.4, 95% CI: 1.7-6.9) were predictors of future kidney disease. The presence of antibodies against Ro were protective against renal disease (HR: 0.2, 95% CI: 0.05-0.5). CONCLUSION: We identified variables associated with kidney disease, both at initial diagnosis of SLE and in longitudinal follow-up in a cohort of children with SLE. The recognition of these abnormal laboratory values may help clinicians identify patients at risk for kidney disease before its onset thus preventing long-term complications.

Changes in trabecular bone density in incident pediatric Crohn's disease: a comparison of imaging methods.

UNLABELLED: This study of changes in dual energy x-ray absorptiometry (DXA) spine BMD following diagnosis and treatment for childhood Crohn's disease demonstrated that changes in conventional posteroanterior BMD results were confounded by impaired growth, and suggested that lateral spine measurements and strategies to estimate volumetric BMD were more sensitive to disease and treatment effects. INTRODUCTION: We previously reported significant increases in peripheral quantitative CT (pQCT) measures of trabecular volumetric bone mineral density (vBMD) following diagnosis and treatment of pediatric Crohn's disease (CD). The objective of this study was to compare pQCT trabecular vBMD and three DXA measures of spine BMD in this cohort: (1) conventional posteroanterior BMD (PA-BMD), (2) PA-BMD adjusted for height Z (PA-BMDHtZ), and (3) width-adjusted volumetric BMD (WA-BMD) estimated from PA and lateral scans. METHODS: Spine DXA [lumbar (L1-4) for posteroanterior and L3 for lateral] and tibia pQCT scans were obtained in 65 CD subjects (ages 7-18 years) at diagnosis and 12 months later. BMD results were converted to sex, race, and age-specific Z-scores based on reference data in >650 children (ages 5-21 years). Multivariable linear regression models identified factors associated with BMD Z-scores. RESULTS: At CD diagnosis, all BMD Z-scores were lower compared with the reference children (all p values <0.01). The pQCT vBMD Z-scores (-1.46 ± 1.30) were lower compared with DXA PA-BMD (-0.75 ± 0.98), PA-BMDHtZ (-0.53 ± 0.87), and WA-BMD (-0.61 ± 1.10) among CD participants. Only PA-BMD Z-scores were correlated with height Z-scores at baseline (R = 0.47, p < 0.0001). pQCT and WA-BMD Z-scores increased significantly over 12 months to -1.04 ± 1.26 and -0.20 ± 1.14, respectively. Changes in all four BMD Z-scores were positively associated with changes in height Z-scores (p < 0.05). Glucocorticoid doses were inversely associated with changes in WA-BMD (p < 0.01) only. CONCLUSIONS: Conventional and height Z-score-adjusted PA DXA methods did not demonstrate the significant increases in trabecular vBMD noted on pQCT and WA-BMD scans. WA-BMD captured glucocorticoid effects, potentially due to isolation of the vertebral body on the lateral projection. Future studies are needed to identify the BMD measure that provides greatest fracture discrimination in CD.

Usage of intra-articular corticosteroid injections for the treatment of juvenile idiopathic arthritis: a survey of pediatric rheumatologists in the United States and Canada.

OBJECTIVE: To characterize the current usage of intra-articular corticosteroid injections (IACI) by pediatric rheumatologists and the perceived disadvantages of and obstacles to IACI therapy. METHODS: We mailed a 32-item questionnaire to pediatric rheumatologists in the United States and Canada (n=201) to assess treatment strategies for the initial treatment of monoarthritis of the knee in juvenile idiopathic arthritis (JIA). Information regarding the usage of IACI for all patients with JIA and physicians' perceptions of IACI therapy was obtained. Respondents were dichotomized into those who performed frequent pediatric IACI (greater than 50 IACI in the last 12 months) and those who did not. RESULTS: One hundred and twenty-nine (64%) completed questionnaires were returned. IACI were recommended as one therapy for JIA by 99% of respondents, and 90% personally perform IACI. Frequent IACI were performed by 22%, and 15% had performed greater than 10 IACI in a single pediatric patient at one time. Those who did not perform frequent IACI were more likely to report concern about the pain of the procedure, the availability of nursing support, and their own comfort with performing the procedure; they were less likely to have performed greater than 20 pediatric IACI during fellowship training and evaluated fewer clinic patients per week. CONCLUSION: IACI are essentially universally recommended in the treatment regimen for JIA. However, there are differences in the usage of IACI among pediatric rheumatologists. The frequency of IACI use is associated with different perceptions of and training received in IACI therapy.

Childhood onset arthritis is associated with an increased risk of fracture: a population based study using the General Practice Research Database.

BACKGROUND: Childhood onset arthritis is associated with low bone mass and strength. OBJECTIVE: To determine whether childhood onset arthritis is associated with greater fracture risk. METHODS: In a retrospective cohort study all subjects with onset of arthritis between 1 and 19 years of age in the United Kingdom General Practice Research Database were identified. As controls, all sex and age matched subjects from a practice that included a subject with arthritis were included. Incidence rate ratios (IRRs) for first fracture were generated using Mantel-Haenszel methods and Poisson regression. RESULTS: 1939 subjects with arthritis (51% female) and 207 072 controls (53% female) were identified. The median age at arthritis diagnosis was 10.9 years. A total of 129 (6.7%) first fractures were noted in subjects with arthritis compared with 6910 (3.3%) in controls over a median follow up of 3.90 and 3.95 years in the subjects with arthritis and controls, respectively. The IRR (95% confidence interval) for first fracture among subjects with arthritis, compared with controls, according to the age at the start of follow up were 1.49 (0.91 to 2.31) for age <10 years, 3.13 (2.21 to 4.33) at 10-15 years, 1.75 (1.18 to 2.51) at 15-20 years, 1.40 (0.91 to 2.08) at 20-45 years, and 3.97 (2.23 to 6.59) at >45 years. CONCLUSIONS: Childhood onset arthritis is associated with a clinically significant increased risk of fracture in children, adolescents and, possibly, adults. Studies are urgently needed to characterise the determinants of structural bone abnormalities in childhood arthritis and devise prevention and treatment strategies.

Empirical fear profiles among American youth.

Fears among children can range from relatively innocuous fears of simple objects to significant phobias that affect youths' everyday functioning in the home, school, or community environments. This study investigated empirically derived fear profiles among American youth ages 7-19 (N=556). Based upon youths' scores on the 5 factors of the Fear Survey Schedule for Children-II (FSSC-II; Burnham & Gullone (Behav Res Ther, 35, 1997)), multistage Euclidean grouping was applied and produced 5 replicable fear cluster profiles with unique contours. Logistic regression odds ratios revealed specific associations of profile group membership with demographic characteristics such as child age, sex, and ethnicity.

Age and TP53 mutation frequency in childhood malignant gliomas: results in a multi-institutional cohort.

Malignant astrocytoma is one of the most deadly primary central nervous system tumors. Although significant progress has been made in understanding the molecular pathways that lead to the development of these tumors in adults, comparatively little analysis has been done in childhood astrocytomas, which are less common and have a more favorable prognosis. Our previous studies of an institutional cohort of children with malignant gliomas suggested the existence of distinct molecular pathways of tumorigenesis in younger versus older children, based on the finding of a high frequency of TP53 mutations in tumors from children >3 years of age at diagnosis, compared with those from younger children. In the current study, the association between TP53 mutations and age was examined in greater detail using the multi-institutional group of children enrolled in Children's Cancer Group Study 945, the largest cohort of childhood high-grade gliomas analyzed to date. Seventy-seven tumors with centrally reviewed diagnoses of anaplastic astrocytoma or glioblastoma multiforme had sufficient archival histopathological material for microdissection-based genotyping. Sections were examined histologically, and topographic targets that contained malignant tissue were isolated by microdissection and subjected to PCR-based amplification and sequencing of TP53 exons 5-8. Twenty-six tumors (33.8%) had mutations in those exons. Mutations were observed in 2 of 17 tumors (11.8%) from children <3 years of age at diagnosis versus 24 of 60 tumors (40%) from older children, a difference that was statistically significant (P = 0.04), in agreement with our previous results. Whereas malignant gliomas in older children have a frequency of mutations comparable to tumors that arise in young adults, those from children <3 years old do not. The association between age and frequency of TP53 mutations among pediatric malignant gliomas indicates the probable existence of two distinct pathways of molecular tumorigenesis in younger versus older children.

Ascorbic acid enhances destruction of Escherichia coli O157:H7 during home-type drying of apple slices.

Destruction of Escherichia coli O157:H7 was evaluated on inoculated apple slices dehydrated at two temperatures with and without application of predrying treatments. Half-ring slices (0.6 cm thick) of peeled and cored Gala apples were inoculated by immersion for 30 min in a four-strain composite inoculum of E. coli O157:H7. The inoculated slices (8.7 to 9.4 log CFU/g) either received no predrying treatment (control), were soaked for 15 min in a 3.4% ascorbic acid solution, or were steam blanched for 3 min at 88 degrees C immediately prior to drying at 57.2 or 62.8 degrees C for up to 6 h. Samples were plated on tryptic soy (TSA) and sorbitol MacConkey (SMAC) agar media for direct enumeration of surviving bacterial populations. Steam blanching changed initial inoculation levels by +0.3 to -0.7 log CFU/g, while immersion in the ascorbic acid solution reduced the inoculation levels by 1.4 to 1.6 log CFU/g. Dehydration of control samples for 6 h reduced mean bacterial populations by 2.9 log CFU/g (TSA or SMAC) at 57.2 degrees C and by 3.3 (SMAC) and 3.5 (TSA) log CFU/g at 62.8 degrees C. Mean decreases from initial inoculum levels for steam-blanched slices after 6 h of drying were 2.1 (SMAC) and 2.0 (TSA) log CFU/g at 57.2 degrees C, and 3.6 (TSA or SMAC) log CFU/g at 62.8 degrees C. In contrast, initial bacterial populations on ascorbic acid-pretreated apple slices declined by 5.0 (SMAC) and 5.1 (TSA) log CFU/g after 3 h of dehydration at 57.2 degrees C, and by 7.3 (SMAC) and 6.9 (TSA) log CFU/g after 3 h at 62.8 degrees C. Reductions on slices treated with ascorbic acid were in the range of 8.0 to 8.3 log CFU/g after 6 h of drying, irrespective of drying temperature or agar medium used. The results of immersing apple slices in a 3.4% ascorbic acid solution for 15 min prior to drying indicate that a predrying treatment enhances the destruction of E. coli O157:H7 on home-dried apple products.

The perceptual consequences of within-talker variability in fricative production.

The effect of talker and token variability on speech perception has engendered a great deal of research. However, most of this research has compared listener performance in multiple-talker (or variable) situations to performance in single-talker conditions. It remains unclear to what extent listeners are affected by the degree of variability within a talker, rather than simply the existence of variability (being in a multitalker environment). The present study has two goals: First, the degree of variability among speakers in their /s/ and /S/ productions was measured. Even among a relatively small pool of talkers, there was a range of speech variability: some talkers had /s/ and /S/ categories that were quite distinct from one another in terms of frication centroid and skewness, while other speakers had categories that actually overlapped one another. The second goal was to examine whether this degree of variability within a talker influenced perception. Listeners were presented with natural /s/ and /S/ tokens for identification, under ideal listening conditions, and slower response times were found for speakers whose productions were more variable than for speakers with more internal consistency in their speech. This suggests that the degree of variability, not just the existence of it, may be the more critical factor in perception.