Tag: pubmed

Arthritis Care Res (Hoboken). 2021 Aug 16. doi: 10.1002/acr.24768. Online ahead of print.

ABSTRACT

OBJECTIVES: Changes of routine disease management associated with COVID-19 lockdown might have potentially affected the clinical course of juvenile idiopathic arthritis (JIA). Aim of our study was to assess the rate of disease flare before and during COVID-19 lockdown to investigate its impact on disease course in JIA children.

METHODS: A single-center retrospective study was conducted, including patients presenting inactive JIA between September 1^st , 2018 and March 9^th , 2019 (group A) and between September 1^st , 2019 and March 9^th , 2020 (group B). For each patient, demographic and clinical data were collected. The rate of JIA flare from March 10^th , 2019 to June 30^th , 2019 for group A and from March 10^th , 2020 to June 30^th , 2020 for group B was compared.

RESULTS: Group A included 126 patients and group B 124 patients. Statistical analysis did not show significant differences among the two cohorts with respect to age, sex, age of JIA onset, JIA subtype, co-occurrence of uveitis, ANA positivity and past or ongoing medications. The rate of disease flare during lockdown at time of first COVID-19 pandemic wave, was significantly higher in comparison to the previous year (16.9% vs 6.3%, p=0.009).

CONCLUSION: Our study showed that COVID-19 lockdown was associated with a higher rate of joint inflammation in JIA children. This finding has a considerable clinical implication, since restrictive measures may be necessary in order to contain pandemics. Our data highlight the need for rearrangement in the home and healthcare management of JIA children during lockdowns.

PMID:34397168 | DOI:10.1002/acr.24768

Arthritis Care Res (Hoboken). 2021 Aug 16. doi: 10.1002/acr.24769. Online ahead of print.

ABSTRACT

OBJECTIVE: To quantify vehicle control as a metric of automobile driving performance in patients with rheumatoid arthritis (RA).

METHODS: Naturalistic driving assessments were completed in patients with active RA and controls without disease. Data were collected using in-car, sensor-based instrumentation installed in the participants’ own vehicles to observe typical driving habits. RA disease status, disease activity, and functional status were associated with vehicle control (lateral [steering] and longitudinal [braking/accelerating] acceleration variability [AV]) using mixed-effect linear regression models stratified by road type (defined by roadway speed limit).

RESULTS: Across 1,292 driving hours, RA drivers (n=33) demonstrated differences in vehicle control compared to controls (n=23) with evidence of significant statistical interaction between disease status and road type (p<0.001). On residential roads, participants with RA demonstrated overall lower braking/accelerating variability than controls (p≤0.004) and, when disease activity was low, lower steering variability (p=0.03). On interstates/highways, RA was associated with increased steering variability among those with moderate/high CDAI scores (p=0.04). In models limited to RA, increases in disease activity and physical disability over 12-weeks of observation were associated with a significant increase in braking/accelerating variability on interstate/highways (both p<0.05).

CONCLUSIONS: Using novel naturalistic assessments, we linked RA and worsening RA disease severity with aberrant vehicle control. These findings support the need for further research to map these observed patterns in vehicle control to metrics of driver risk, and, in turn, to link patterns of real-world driving behavior to diagnosis and disease activity.

PMID:34397172 | DOI:10.1002/acr.24769

J Neuroendocrinol. 2021 Jul 15:e13015. doi: 10.1111/jne.13015. Online ahead of print.

ABSTRACT

The quality and reporting of neuroendocrine tumour (NET) clinical trials has previously been found to be heterogeneous impairing trial interpretability. We aimed to perform an updated review of the quality of phase II/III clinical trials in NET to assess if trial design and reporting have improved since 2011. We performed a PubMed search for phase II/III trials evaluating systemic anticancer therapies or liver-directed therapies published between 2011 and 2018. Data collected comprised administrative data, study population characteristics, endpoints, reporting and statistical design parameters, and results. Sixty studies were included (5218 patients): 50 phase II and 10 phase III trials. Study populations were heterogeneous: 52% of trials allowed tumours from various primary sites, 28% allowed both well- and poorly-differentiated tumour morphology or did not specify, and 57% did not report proliferative indices and/or tumour grade in ≥80% of the study population. Only 36% of trials mandated radiological disease progression on participant enrolment using a validated measure. Statistical design and primary endpoint were clearly defined in 67% and 88% of trials, respectively. Toxicity (88%), radiological response rate (85%) and progression-free survival/time to progression (82%) were well reported in a majority of trials, but health-related quality of life was included in the minority. Of the randomised trials (n = 11), study populations were more homogeneous and study design was more often clearly defined; however, only 45% mandated radiological progression at baseline as measured per Response Evaluation Criteria In Solid Tumours, and reporting of health-related quality of life (55%) remained suboptimal. The design and reporting of NET clinical trials, predominantly of single-arm phase II trials, remains suboptimal and has not considerably improved over time despite the growth in our knowledge of the biology and unique characteristics of NETs. Higher quality is seen in randomised trials, although certain design and reporting elements remain inadequate in some studies. We must prioritise the design and conduct of NET clinical trials to effectively inform future research and guide practice change.

PMID:34397130 | DOI:10.1111/jne.13015

Can Rev Sociol. 2021 Aug;58(3):372-398. doi: 10.1111/cars.12348.

ABSTRACT

Young adults born at the end of the 20th century attend colleges and universities at much higher rates than did previous generations, which might give the impression of greater upward educational mobility and in turn, greater class mobility. This impression occurs, however, only because of structural expansion of the Canadian education system. In contrast to structural change, exchange mobility highlights the linkage between one’s social origins and destinations. This speaks more directly to questions of equality of educational opportunity and social fairness. Greater fairness or social progress occurs when, over time, destinations become less contingent on origins. We examine intergenerational exchange mobility in Canada by investigating how, if at all, the linkage between parents’ and their children’s education has changed over the past century. We construct a longitudinal dataset covering the 20th century by merging fifteen cross-sectional surveys from Statistics Canada’s General Social Survey (GSS) between 1986 and 2014. Comparing across synthetic birth cohorts we focus on transition probabilities, odds ratios, and logistic regression estimates to measure change. We contribute to a growing gap in the Canadian literature since social mobility has been largely neglected by sociologists as of late. We compare our results to recent findings of economists who examine intergenerational income mobility, another indicator of class mobility. Consistent with earlier sociological and economic research, our results show that despite the tremendous expansion of Canada’s education systems, intergenerational exchange mobility for both women and men has been stagnant in Canada over the past century.

PMID:34397157 | DOI:10.1111/cars.12348

Mov Disord. 2021 Aug 16. doi: 10.1002/mds.28749. Online ahead of print.

ABSTRACT

BACKGROUND: Spinocerebellar ataxia type 3 is a rare neurodegenerative disease caused by a CAG repeat expansion in the ataxin-3 gene. Although no curative therapy is yet available, preclinical gene-silencing approaches to reduce polyglutamine (polyQ) toxicity demonstrate promising results. In view of upcoming clinical trials, quantitative and easily accessible molecular markers are of critical importance as pharmacodynamic and particularly as target engagement markers.

OBJECTIVE: We aimed at developing an ultrasensitive immunoassay to measure specifically polyQ-expanded ataxin-3 in plasma and cerebrospinal fluid (CSF).

METHODS: Using the novel single molecule counting ataxin-3 immunoassay, we analyzed cross-sectional and longitudinal patient biomaterials.

RESULTS: Statistical analyses revealed a correlation with clinical parameters and a stability of polyQ-expanded ataxin-3 during conversion from the pre-ataxic to the ataxic phases.

CONCLUSIONS: The novel immunoassay is able to quantify polyQ-expanded ataxin-3 in plasma and CSF, whereas ataxin-3 levels in plasma correlate with disease severity. Longitudinal analyses demonstrated a high stability of polyQ-expanded ataxin-3 over a short period. © 2021 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

PMID:34397117 | DOI:10.1002/mds.28749

J Magn Reson Imaging. 2021 Aug 16. doi: 10.1002/jmri.27888. Online ahead of print.

ABSTRACT

BACKGROUND: Renal blood flow (RBF) can be measured with dynamic contrast enhanced-MRI (DCE-MRI) and arterial spin labeling (ASL). Unfortunately, individual estimates from both methods vary and reference-standard methods are not available. A potential solution is to include a third, arbitrating MRI method in the comparison.

PURPOSE: To compare RBF estimates between ASL, DCE, and phase contrast (PC)-MRI.

STUDY TYPE: Prospective.

POPULATION: Twenty-five patients with type-2 diabetes (36% female) and five healthy volunteers (HV, 80% female).

FIELD STRENGTH/SEQUENCES: A 3 T; gradient-echo 2D-DCE, pseudo-continuous ASL (pCASL) and cine 2D-PC.

ASSESSMENT: ASL, DCE, and PC were acquired once in all patients. ASL and PC were acquired four times in each HV. RBF was estimated and split-RBF was derived as (right kidney RBF)/total RBF. Repeatability error (RE) was calculated for each HV, RE = 1.96 × SD, where SD is the standard deviation of repeat scans.

STATISTICAL TESTS: Paired t-tests and one-way analysis of variance (ANOVA) were used for statistical analysis. The 95% confidence interval (CI) for difference between ASL/PC and DCE/PC was assessed using two-sample F-test for variances. Statistical significance level was P < 0.05. Influential outliers were assessed with Cook’s distance (D_i > 1) and results with outliers removed were presented.

RESULTS: In patients, the mean RBF (mL/min/1.73m² ) was 618 ± 62 (PC), 526 ± 91 (ASL), and 569 ± 110 (DCE). Differences between measurements were not significant (P = 0.28). Intrasubject agreement was poor for RBF with limits-of-agreement (mL/min/1.73m² ) [-687, 772] DCE-ASL, [-482, 580] PC-DCE, and [-277, 460] PC-ASL. The difference PC-ASL was significantly smaller than PC-DCE, but this was driven by a single-DCE outlier (P = 0.31, after removing outlier). The difference in split-RBF was comparatively small. In HVs, mean RE (±95% CI; mL/min/1.73 m² ) was significantly smaller for PC (79 ± 41) than for ASL (241 ± 85).

CONCLUSIONS: ASL, DCE, and PC RBF show poor agreement in individual subjects but agree well on average. Triangulation with PC suggests that the accuracy of ASL and DCE is comparable.

EVIDENCE LEVEL: 2 TECHNICAL EFFICACY: Stage 2.

PMID:34397124 | DOI:10.1002/jmri.27888

Cochrane Database Syst Rev. 2021 Aug 16;8:CD006822. doi: 10.1002/14651858.CD006822.pub6.

ABSTRACT

BACKGROUND: Croup is an acute viral respiratory infection with upper airway mucosal inflammation that may cause respiratory distress. Most cases are mild. Moderate to severe croup may require treatment with corticosteroids (the benefits of which are often delayed) and nebulised epinephrine (adrenaline) (the benefits of which may be short-lived and which can cause dose-related adverse effects including tachycardia, arrhythmias, and hypertension). Rarely, croup results in respiratory failure necessitating emergency intubation and ventilation. A mixture of helium and oxygen (heliox) may prevent morbidity and mortality in ventilated neonates by reducing the viscosity of the inhaled air. It is currently used during emergency transport of children with severe croup. Anecdotal evidence suggests that it relieves respiratory distress. This review updates versions published in 2010, 2013, and 2018.

OBJECTIVES: To examine the effect of heliox compared to oxygen or other active interventions, placebo, or no treatment on relieving signs and symptoms in children with croup as determined by a croup score and rates of admission and intubation.

SEARCH METHODS: We searched CENTRAL, which includes the Cochrane Acute Respiratory Infections Group Specialised Register, MEDLINE, Embase, CINAHL, Web of Science, and LILACS, on 15 April 2021. We also searched the World Health Organization International Clinical Trials Registry Platform (apps.who.int/trialsearch/) and ClinicalTrials.gov (clinicaltrials.gov) on 15 April 2021. We contacted the British Oxygen Company, a leading supplier of heliox.

SELECTION CRITERIA: Randomised controlled trials (RCTs) and quasi-RCTs comparing the effect of heliox in comparison with placebo, no treatment, or any active intervention(s) in children with croup.

DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane. Data that could not be pooled for statistical analysis were reported descriptively.

MAIN RESULTS: We included 3 RCTs involving a total of 91 children aged between 6 months and 4 years. Study duration was from 7 to 16 months, and all studies were conducted in emergency departments. Two studies were conducted in the USA and one in Spain. Heliox was administered as a mixture of 70% heliox and 30% oxygen. Risk of bias was low in two studies and high in one study because of its open-label design. We did not identify any new trials for this 2021 update. One study of 15 children with mild croup compared heliox with 30% humidified oxygen administered for 20 minutes. There may be no difference in croup score changes between groups at 20 minutes (mean difference (MD) -0.83, 95% confidence interval (CI) -2.36 to 0.70) (Westley croup score, scale range 0 to 16). The mean croup score at 20 minutes postintervention may not differ between groups (MD -0.57, 95% CI -1.46 to 0.32). There may be no difference between groups in mean respiratory rate (MD 6.40, 95% CI -1.38 to 14.18) and mean heart rate (MD 14.50, 95% CI -8.49 to 37.49) at 20 minutes. The evidence for all outcomes in this comparison was of low certainty, downgraded for serious imprecision. All children were discharged, but information on hospitalisation, intubation, or re-presenting to emergency departments was not reported. In another study, 47 children with moderate croup received one dose of oral dexamethasone (0.3 mg/kg) with either heliox for 60 minutes or no treatment. Heliox may slightly improve Taussig croup scores (scale range 0 to 15) at 60 minutes postintervention (MD -1.10, 95% CI -1.96 to -0.24), but there may be no difference between groups at 120 minutes (MD -0.70, 95% CI -1.56 to 0.16). Children treated with heliox may have lower mean Taussig croup scores at 60 minutes (MD -1.11, 95% CI -2.05 to -0.17) but not at 120 minutes (MD -0.71, 95% CI -1.72 to 0.30). Children treated with heliox may have lower mean respiratory rates at 60 minutes (MD -4.94, 95% CI -9.66 to -0.22), but there may be no difference at 120 minutes (MD -3.17, 95% CI -7.83 to 1.49). There may be a difference in hospitalisation rates between groups (odds ratio 0.46, 95% CI 0.04 to 5.41). We assessed the evidence for all outcomes in this comparison as of low certainty, downgraded due to imprecision and high risk of bias related to an open-label design. Information on heart rate and intubation was not reported. In the third study, 29 children with moderate to severe croup all received continuous cool mist and intramuscular dexamethasone (0.6 mg/kg). They were then randomised to receive either heliox (given as a mixture of 70% helium and 30% oxygen) plus one to two doses of nebulised saline or 100% oxygen plus nebulised epinephrine (adrenaline), with gas therapy administered continuously for three hours. Heliox may slightly improve croup scores at 90 minutes postintervention, but may result in little or no difference overall using repeated-measures analysis. We assessed the evidence for all outcomes in this comparison as of low certainty, downgraded due to high risk of bias related to inadequate reporting. Information on hospitalisation or re-presenting to the emergency department was not reported. The included studies did not report on adverse events, intensive care admissions, or parental anxiety. We could not pool the available data because each comparison included data from only one study.

AUTHORS’ CONCLUSIONS: Given the very limited available evidence, uncertainty remains regarding the effectiveness and safety of heliox. Heliox may not be more effective than 30% humidified oxygen for children with mild croup, but may be beneficial in the short term for children with moderate croup treated with dexamethasone. The effect of heliox may be similar to 100% oxygen given with one or two doses of adrenaline. Adverse events were not reported, and it is unclear if these were monitored in the included studies. Adequately powered RCTs comparing heliox with standard treatments are needed to further assess the role of heliox in the treatment of children with moderate to severe croup.

PMID:34397099 | DOI:10.1002/14651858.CD006822.pub6

J Clin Pharm Ther. 2021 Aug 16. doi: 10.1111/jcpt.13498. Online ahead of print.

ABSTRACT

WHAT IS KNOWN AND OBJECTIVE: The aim of this survey, conducted by the Gruppo Italiano per il Trapianto di Midollo Osseo (GITMO), was to evaluate the involvement of pharmacists in the haematopoietic stem cell transplant (HSCT) program in Italian adult and paediatric centres.

METHODS: A 63-item online questionnaire was developed and sent to the Italian Transplant Programs on behalf of GITMO.

RESULTS AND DISCUSSION: Overall, 54.7% of the Italian HSCT centres participated in the survey (88.5% adult, 7.7% paediatric, 3.8% mixed), of which 50% were in public hospitals and 50% affiliated with public universities. Just over 80% declared that a pharmacist is involved in the HSCT centre, and 86.5% reported the presence of a documentation system to signal of adverse events, accessible by physicians, nurses and pharmacists in 57.7%. Chemotherapy drugs were centralized in the pharmacy in 98.1% of HSCT centres, while parenteral nutrition was centralized in 55.8%. The use of off-label drugs was authorized by an internal committee and by the regional health authorities in 88.5% of the centres. On univariate analysis, few statistically significant differences were found on response frequencies between public hospitals and university centres or between HSCT centres performing only autologous stem cell transplantation versus other centres performing autologous and allogeneic stem cell transplantation.

WHAT IS NEW AND CONCLUSION: This survey suggests that there is good collaboration between pharmacists and physicians and nurses in Italian HSCT transplantation centres. The enhancement of pharmacists dedicated to HSCT programs could improve some problems, for example, the centralization of parenteral nutrition.

PMID:34397108 | DOI:10.1111/jcpt.13498

Eur J Orthod. 2021 Aug 16:cjab044. doi: 10.1093/ejo/cjab044. Online ahead of print.

ABSTRACT

OBJECTIVES: To identify the presence and characteristics of spin (using reporting strategies to distort study results and mislead readers) within randomized controlled trial (RCT) abstracts published in orthodontic journals, and to explore the association between spin and potentially related factors.

METHODS: A manual search was conducted to identify abstracts of RCTs with statistically non-significant primary outcomes published in five leading orthodontic journals between 2015 and 2020. Spin in the Results and Conclusions sections of each included abstract was evaluated and categorized according to pre-determined spin strategies. Logistic regression analyses were employed to explore the association between spin and relevant factors.

RESULTS: A total of 111 RCT abstracts were included, of which 69 (62.2 per cent) were identified with spin. In the Results section, 47 (42.3 per cent) abstracts had spin, and ‘focusing on significant within-group comparison for primary outcomes’ was the most frequent spin strategy. In the Conclusions section, 57 (51.4 per cent) abstracts presented spin, with the most common strategy being ‘claiming equivalence or non-inferiority for statistically nonsignificant results’. According to multivariable logistic regression analysis, a significantly lower presence of spin was found in studies with international collaboration (odds ratio [OR]: 0.331, 95 per cent confidence interval [CI]: 0.120-0.912, P = 0.033) and trial registration (OR: 0.336, 95 per cent CI: 0.117-0.962, P = 0.042).

CONCLUSION: The prevalence of spin is high among RCT abstracts in orthodontics. Clinicians need to be aware of the definition and presence of spin. Concerted efforts are needed from researchers and other stakeholders to address this issue.

PMID:34397084 | DOI:10.1093/ejo/cjab044

Ann Bot. 2021 Aug 16:mcab106. doi: 10.1093/aob/mcab106. Online ahead of print.

ABSTRACT

BACKGROUND AND AIMS: In hierarchically reticulate venation patterns, smaller orders of veins form areoles in which stomata are located. This study aimed to quantify the spatial relationship among stomata at the areole level.

METHODS: For each of 12 leaves of Michelia cavaleriei var. platypetala, we assumed that stomatal characteristics were symmetric on either side of the midrib, and divided the leaf surface on one side of the midrib into 6 layers equidistantly spaced along the apical-basal axis. We then further divided each layer into three positions equidistantly spaced from midrib to leaf margin, resulting in a total of 18 sampling locations. In addition, for 60 leaves, we sampled three positions from midrib to margin within only the widest layer of the leaf. Stomatal density (SD) and mean nearest neighbour distance (MNND) were calculated for each section. A replicated spatial point pattern approach quantified stomatal spatial relationships at different distances (0-300 μm).

KEY RESULTS: A tendency towards regular arrangement (inhibition as opposed to attraction or clustering) was observed between stomatal centres at distances smaller than ca. 100 μm. Leaf layer (leaf length dimension) had no significant effect on local SD, MNND or the spatial distribution characteristics of stomatal centres. In addition, we did not find greater inhibition at the center of areoles, and in positions farther from the midrib.

CONCLUSIONS: Spatial inhibition might be caused by the one-cell-spacing rule, resulting in more regular arrangement of stomata, and it was found to exist at distances up to ca. 100 μm. This work implies that leaf hydraulic architecture, consisting of both vascular and mesophyll properties, is sufficient to prevent important spatial variability in water supply at the areole level.

PMID:34397092 | DOI:10.1093/aob/mcab106