Reappraisal of the diagnostic and prognostic value of morning stiffness in arthralgia and early arthritis: results from the Groningen EARC,Leiden EARC,ESPOIR, Leiden EAC and REACH

IntroductionMorning stiffness is assessed daily in the diagnostic process of arthralgia and arthritis, but large-scale studies on the discriminative ability are absent. This study explored the diagnostic value of morning stiffness in 5,202 arthralgia and arthritis patients and the prognostic value in early rheumatoid arthritis (RA).MethodsIn arthralgia patients referred to the Early Arthritis Recognition Clinics (EARC) of Leiden (n = 807) and Groningen (n = 481) or included in the Rotterdam Early Arthritis Cohort (REACH) study (n = 353), the associations (cross-sectional analyses) between morning stiffness and presence of arthritis at physical examination were studied. In early arthritis patients, included in the Leiden Early Arthritis Clinic (EAC) (n = 2,748) and Evaluation et Suivi de POlyarthrites Indifférenciées Récentes (ESPOIR) (n = 813), associations with fulfilling the 2010-RA criteria after one year were assessed. In 2010-RA patients included in the EAC (n = 1,140) and ESPOIR (n = 677), association with the long-term outcomes of disease-modifying antirheumatic drug (DMARD)-free sustained remission and radiological progression were determined. Morning stiffness was defined as a duration ≥60 minutes; sensitivity analyses were performed for other definitions.ResultsIn arthralgia, morning stiffness (≥60 minutes) associated with the presence of arthritis; Leiden EARC odds ratio (OR) 1.49 (95% CI 1.001 to 2.20), Groningen EARC OR 2.21 (1.33 to 3.69) and REACH OR 1.55 (0.97 to 2.47) but the areas under the receiver operating characteristic curve (AUCs) were low (0.52, 0.57, 0.54). In early arthritis, morning stiffness was associated with 2010-RA independent of other predictors (Leiden EAC OR 1.72 (95% CI 1.31 to 2.25, AUC 0.68), ESPOIR OR 1.68 (1.03 to 2.74, AUC 0.64)). Duration of ≥30 minutes provided optimal discrimination for RA in early arthritis. Morning stiffness was not associated with radiological progression or DMARD-free sustained remission.ConclusionsMorning stiffness in arthralgia and early arthritis is associated with arthritis and RA respectively. This supports the incorporation of morning stiffness in the diagnostic process.

Electronic supplementary material

The online version of this article (doi:10.1186/s13075-015-0616-3) contains supplementary material, which is available to authorized users.     

Principal stratification and attribution prohibition: good ideas taken too far

Pearl's article provides a useful springboard for discussing further the benefits and drawbacks of principal stratification and the associated discomfort with attributing effects to post-treatment variables. The basic insights of the approach are important: pay close attention to modification of treatment effects by variables not observable before treatment decisions are made, and be careful in attributing effects to variables when counterfactuals are ill-defined. These insights have often been taken too far in many areas of application of the approach, including instrumental variables, censoring by death, and surrogate outcomes. A novel finding is that the usual principal stratification estimand in the setting of censoring by death is by itself of little practical value in estimating intervention effects.     

Atypical and complicated Kawasaki disease in infants. Do we need criteria?

Case reports suggest that infants with Kawasaki disease have atypical presentations and a high complication rate, likely related to delayed diagnosis and treatment. To date, no study of consecutive cases has compared infants with older children who have both atypical and typical Kawasaki disease. We retrospectively reviewed 44 cases of Kawasaki disease treated at our hospital from March 1980 to 1990: 11 (25%) were infants; 9 (20%) had atypical Kawasaki disease, of which 5 (56%) were infants; the male to female ratio was 1.7:1. Infants had a higher incidence of atypical Kawasaki disease (5 [45%] versus 4 [12%]; P = .007) and of coronary artery complications (7 [64%] versus 3 [9%]; P = .002), and coronary artery complications developed in all of the infants with atypical Kawasaki disease (5 [100%] versus 0 [0%]; P < .01). Yet, the other manifestations and laboratory changes were at least as common as in the older children. Coronary artery complications did not develop in any patient who received early intravenous immune globulin therapy. We suggest that in infants with Kawasaki disease, accepted criteria are too restrictive to allow early diagnosis and effective treatment. Until a definitive test is available, clinical judgment is required in the diagnosis of atypical Kawasaki disease. Intravenous immune globulin is known to be safe, and its early use in patients with suspected atypical Kawasaki disease is appropriate.     

Dual‐energy X‐ray Absorptiometry and Anthropometric Estimates of Visceral Fat in Black and White South African Women

Visceral adipose tissue (VAT) is associated with increased risk for cardiovascular disease, and therefore, accurate methods to estimate VAT have been investigated. Computerized tomography (CT) is the gold standard measure of VAT, but its use is limited. We therefore compared waist measures and two dual‐energy X‐ray absorptiometry (DXA) methods (Ley and Lunar) that quantify abdominal regions of interest (ROIs) to CT‐derived VAT in 166 black and 143 white South African women. Anthropometry, DXA ROI, and VAT (CT at L4–L5) were measured. Black women were younger (P < 0.001), shorter (P < 0.001), and had higher body fat (P < 0.05) than white women. There were no ethnic differences in waist (89.7 ± 18.2 cm vs. 90.1 ± 15.6 cm), waist:height ratio (WHtR, 0.56 ± 0.12 vs. 0.54 ± 0.09), or DXA ROI (Ley: 2.2 ± 1.5 vs. 2.1 ± 1.4; Lunar: 2.3 ± 1.4 vs. 2.3 ± 1.5), but black women had less VAT, after adjusting for age, height, weight, and fat mass (76 ± 34 cm² vs. 98 ± 35 cm²; P < 0.001). Ley ROI and Lunar ROI were correlated in black (r = 0.983) and white (r = 0.988) women. VAT correlated with DXA ROI (Ley: r = 0.729 and r = 0.838, P < 0.01; Lunar: r = 0.739 and r = 0.847, P < 0.01) in black and white women, but with increasing ROI android fatness, black women had less VAT. Similarly, VAT was associated with waist (r = 0.732 and r = 0.836, P < 0.01) and WHtR (r = 0.721 and r = 0.824, P < 0.01) in black and white women. In conclusion, although DXA‐derived ROIs correlate well with VAT as measured by CT, they are no better than waist or WHtR. Neither DXA nor anthropometric measures are able to accurately distinguish between high and low levels of VAT between population groups.     

Effects of crop sequence and soil types on the mycoflora of groundnut kernels

Summary In Israel, the effects of crop sequence and soil types on the mycoflora of groundnut kernels has been investigated over 3 years in 81 fields, of those some previously fallowed, others continuously cropped with or without groundnuts. The general mycoflora of kernels was richest in fields previously sown with groundnuts. In the cropped fields, whether groundnuts were included in the previous crops or not,Aspergillus niger made up 50–60 per cent of the total mycoflora.Penicillium funiculosum andP. rubrum were considerably more prevalent on previously fallowed fields. Prevalence ofA. flavus was always low and not influenced by crop sequences. Total kernel mycofloras were constantly higher on medium and heavy than on other soils. This research was supported by Grant Number PG-Is-161 of the United States Department of Agriculture to whom the authors are indebted.     

Effects of Light, Temperature, and pH Value on Aflatoxin Production In Vitro

In the complete absence of light, an isolate of Aspergillus flavus produced up to 170,000 pg aflatoxin per g, whereas the incubation of the fungus in light caused a reduction (35,000 pg/g) of the toxin synthesis.     

Relationships betweenAspergillus flavus,A. niger and some other fungi in the mycoflora of groundnut kernels

Summary The relationships betweenAspergillus flavus, A. niger, Penicillium funiculosum, P. rubrum, andFusarium solani have been studied in 234 samples and 5850 plates from fresh and stored kernels derived from 2 years' groundnut crops in Israel.Numerical relations between these fungi, as obtained by totalling the number of colonies developing in all the 25 platings made for each sample, did not always give reliable indications of potential antagonism between the species. But consideration of the number of colonies developing in individual plates showed pronounced antagonism betweenA. flavus andA. niger, and slightly less but still marked antagonism between each of these species andP. funiculosum, P. rubrum andF. solani.This research is supported by Grant Number FG-Is-161 of the United States Department of Agriculture to whom the author is indebted.     

The effect of maternal and fetal corticosteroids on the development of function of the pituitary-adrenocortical system.

The pituitary-adrenocortical system of rat fetuses was stimulated (larger adrenals at birth) by maternal adrenalectomy, or suppressed (smaller adrenals at birth) by implantation of an ACTH secreting pituitary tumor (MtTF4). Offspring were delivered by caesarean section and fostered to untreated females. Offspring of intact females delivered by caesarean section and normally delivered offspring of intact mothers both fostered to untreated lactating females served as controls. Body growth in the first three weeks of life was delayed in offspring of tumor bearing mothers in Control-fostered subjects as compared to the 2 other groups. At 70 days of age female offspring of the tumor implanted and adrenalectomized mothers, as well as the Control-caesarean females, had smaller adrenals than Control-fostered animals of the same sex. The adrenal size of males was not significantly affected. No significant differences were found in resting concentrations of corticosterone in plasma, although offspring of adrenalectomized mothers had high values. Suppressed adrenal response to ether stress was found in offspring of tumor bearing mothers. The supposition is that interference with maternal pituitary-adrenocortical activity during pregnancy has a long lasting effect on fetal hypothalamo-pituitary-adrenocortical system.