Abstract Aims The aims of the present study were: (i) to evaluate the effects of a Dutch translation and adaptation of Blood Glucose Awareness Training (BGAT‐III) on blood glucose (bg) perception, glycaemic control, and decisions not to drive or to raise the bg during hypoglycaemia; (ii) to compare the effects of individual and group BGAT. Methods Fifty‐nine patients with Type 1 diabetes participated in BGAT in either a group or an individual setting. Before and after BGAT, 39 (66%) of them completed 30–70 measurements on a hand‐held computer (hhc). During every measurement, they estimated their bg, indicated whether they would drive or raise their bg on the basis of their estimation, and then measured their bg. Results Individual and group BGAT did not have significantly different effects ( P = 0.35–0.98). Overall, BGAT did not significantly affect bg perception ( P = 0.11–0.65). Before BGAT patients recognized a mean of 32% of their hypoglycaemic episodes, after BGAT a mean of 39% ( P = 0.12). After BGAT, patients more often decided not to drive when their bg was low ( P = 0.03). They tended to decide more often to raise their bg during hypoglycaemia ( P = 0.09). Conclusions The effects of BGAT were smaller than expected. Possible reasons for this negative outcome may be the adapted version of BGAT (shorter in duration), a lack of statistical power, or a difference between American and European samples in their reaction to BGAT.
We have shown that 14q32 microRNAs are highly involved in vascular remodelling and cardiovascular disease. However, the 14q32 locus also encodes 41 'orphan' small nucleolar RNAs (snoRNAs). We aimed to gather evidence for an independent role for 14q32 snoRNAs in human cardiovascular disease.We performed a lookup of the 14q32 region within the dataset of a genome wide association scan in 5244 participants of the PROspective Study of Pravastatin in the Elderly at Risk (PROSPER). Single nucleotide polymorphisms (SNPs) in the snoRNA-cluster were significantly associated with heart failure. These snoRNA-cluster SNPs were not linked to SNPs in the microRNA-cluster or in MEG3, indicating that snoRNAs modify the risk of cardiovascular disease independently. We looked at expression of 14q32 snoRNAs throughout the human cardio-vasculature. Expression profiles of the 14q32 snoRNAs appeared highly vessel specific. When we compared expression levels of 14q32 snoRNAs in human vena saphena magna (VSM) with those in failed VSM-coronary bypasses, we found that 14q32 snoRNAs were up-regulated. SNORD113.2, which showed a 17-fold up-regulation in failed bypasses, was also up-regulated two-fold in plasma samples drawn from patients with ST-elevation myocardial infarction directly after hospitalization compared with 30 days after start of treatment. However, fitting with the genomic associations, 14q32 snoRNA expression was highest in failing human hearts. In vitro studies show that the 14q32 snoRNAs bind predominantly to methyl-transferase Fibrillarin, indicating that they act through canonical mechanisms, but on non-canonical RNA targets. The canonical C/D-box snoRNA seed sequences were highly conserved between humans and mice.14q32 snoRNAs appear to play an independent role in cardiovascular pathology. 14q32 snoRNAs are specifically regulated throughout the human vasculature and their expression is up-regulated during cardiovascular disease. Our data demonstrate that snoRNAs merit increased effort and attention in future basic and clinical cardiovascular research.
Atypical naevi are potential precursors of melanoma and markers of increased melanoma risk. To examine the possibility of chemoprevention of melanoma by retinoids, we studied the effect of topical tretinoin 0.1% (all-transretinoic acid; vitamin A acid) and tretinoin 0.1% with hydrocortisone on atypical naevi. Thirty patients with atypical naevi were enrolled in a prospective randomized double blind study. For each patient three comparable naevi were selected and randomized to receive tretinoin 0.1% (T), tretinoin 0.1% with hydrocortisone 1% (C) or a placebo cream (P) once a week under Actiderm occlusion for 4 months. Baseline views of the naevi, taken with a videomicroscope (magnification 20 x), were assessed for morphological changes compared with views taken 2 months after the beginning of treatment, 1 week after completion of treatment and 6 months later. After completion of the study all naevi in the T and C groups and six naevi in the P group were removed and evaluated histologically for the presence of atypia. The number of naevi that had changed in colour or size was significantly higher in the T and C groups compared with the placebo group. A size reduction took place in 42.9% (T) and 40.0% (C) of the naevi and the colour changed in 75.0% (T) and 66.7% (C). The effect of treatment, in general subtle, did not differ significantly between groups T and C, but naevi treated with C became significantly less irritated. Histologically, 75.0% of the naevi treated with T and 69.6% of the naevi treated with C were atypical. Therefore, no major change was seen in the clinical aspect of atypical naevi after treatment with tretinoin 0.1% or tretinoin with hydrocortisone 1%, and most of the treated naevi still met the histological criteria for atypia after the treatment period. The current management of follow-up of atypical naevi and excision when change to melanoma is suspected is therefore still recommended. Nevertheless, some response was seen, which may justify a further exploration of tretinoin and hydrocortisone 1% therapy for a longer treatment period in combination with research to clarify its mechanism.
MRI sensitively detects inflammation, but the clinical relevance of MRI-detected inflammation is undetermined in early arthritis. Therefore, this cross-sectional study investigated the association between MRI-detected inflammation of hands and feet and functional disability in early arthritis.
Methods
514 early arthritis patients, consecutively included in the Leiden Early Arthritis Clinic, were studied. At baseline, unilateral 1.5T MRI of the wrist, metacarpophalangeal (MCP) and metatarsophalangeal-joints was made and functional disability was measured using the Health Assessment Questionnaire (HAQ). MRIs were scored for bone marrow oedema (BME), tenosynovitis and synovitis by two readers. The sum of these three features yielded the total MRI-inflammation score. Linear and non-linear regression analyses were performed with HAQ as dependent variable.
Results
The total MRI-inflammation score was associated with the HAQ-score (β=0.014, p<0.001), as were BME (β=0.015, p<0.001), tenosynovitis (β=0.046, p<0.001) and synovitis (β=0.039, p<0.001) separately. Analysing these three MRI-features in one multivariable model, revealed that only tenosynovitis was independently associated with HAQ-score (β=0.039, p<0.001). Also when correcting for age, gender, joint counts, acute phase reactants and auto-antibodies this association remained (β=0.034, p<0.001). MRI-detected inflammation at wrists or MCP-joints associated significantly with impairments in hand functioning (e.g. difficulties with opening milk cartons or jars). Exploring the relation between MRI-detected inflammation and HAQ-scores non-linear, suggested the presence of a ceiling effect, because after a certain inflammation-level, more inflammation was not associated with higher HAQ-scores.
Conclusions
MRI-detected inflammation, and tenosynovitis in particular, is associated with functional disability. This demonstrates the functional relevance of MRI-detected inflammation in early arthritis patients.
References
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Acknowledgement
This work was supported by a Vidi-grant of the Netherlands Organisation for Scientific Research and the Dutch Arthritis Foundation
<i>Background:</i> Deletions and mutations in the NSD1 gene are the major cause of Sotos syndrome. We wanted to evaluate the genotype-phenotype correlation in patients suspected of having Sotos syndrome and determine the best discriminating parameters for the presence of a NSD1 gene alteration. <i>Methods:</i> Mutation and fluorescence in situ hybridization analysis was performed on blood samples of 59 patients who were clinically scored into 3 groups. Clinical data were compared between patients with and without NSD1 alterations. With logistic regression analysis the best combination of predictive variables was obtained. <i>Results:</i> In the groups of typical, dubious and atypical Sotos syndrome, 81, 36 and 0% of the patients, respectively, showed NSD1 gene alterations. Four deletions were detected. In 23 patients (2 families) 19 mutations were detected (1 splicing defect, 3 non-sense, 7 frameshift and 8 missense mutations). The best predictive parameters for a NSD1 gene alteration were frontal bossing, down-slanted palpebral fissures, pointed chin and overgrowth. Higher incidences of feeding problems and cardiac anomalies were found. The parameters, delayed development and advanced bone age, did not differ between the 2 subgroups. <i>Conclusions:</i> In our patients suspected of having Sotos syndrome, facial features and overgrowth were highly predictive of a NSD1 gene aberration, whereas developmental delay and advanced bone age were not.
Early diagnosis and treatment of rheumatoid arthritis (RA) is advocated. However, in part of the RA-patients a classifiable diagnosis cannot be made at first presentation; these patients present with unclassified arthritis (UA). The use of MRI for early diagnosis of RA is recommended, yet the evidence is limited.
Objectives
To assess the performance of hand and foot MRI for early diagnosis of RA.
Methods
Unilateral contrast-enhanced 1.5T MRI of the hand and foot was performed in 589 early arthritis patients included in the Leiden Early Arthritis Clinic, of whom 229 presented with RA, 159 with other arthritides and 201 with UA. MRI-findings observed in symptom-free controls served as reference to define an abnormal MRI. In preliminary investigations, patients that presented with RA were compared with symptom-free controls and with patients that presented with other arthritides. Thereafter, the accuracy of MRI was determined in UA-patients that were followed for 1-year on fulfilling the 1987-RA-criteria (primary outcome); the secondary outcome was start of disease-modifying drugs.
Results
The results of the preliminary investigations were promising and showed that MRI-detected tenosynovitis was more discriminative than other types of MRI-inflammation. Of all UA-patients, 29 (14%) developed RA and 75 (37%) started disease-modifying treatment. MRI-detected tenosynovitis was associated with RA-development independent of other types of MRI-inflammation (odds ratio (OR) 7.5 95%CI 2.4–23) and also independent of age and commonly used measures of inflammation (number of swollen joints and C-reactive protein) (OR 4.2 95%CI 1.4–12.9). Within UA-patients, the negative predictive value (NPV) of abnormal tenosynovitis was 95% and the positive predictive value (PPV) 25%. The performance was best in the subgroup UA-patients presenting with oligo-arthritis (18% developed RA): PPV was 36%, NPV 98%, sensitivity 93%, and specificity 63%. Decision curve analysis revealed a higher net benefit for a model including MRI-detected tenosynovitis.
Conclusions
MRI-detected inflammation, MRI-detected tenosynovitis in particular, contributes to identification of the UA-patient that will develop RA.
Hypertensive disorders, i.e. pregnancy induced hypertension and preeclampsia, complicate 10 to15% of all pregnancies at term and are a major cause of maternal and perinatal morbidity and mortality. The only causal treatment is delivery. In case of preterm pregnancies conservative management is advocated if the risks for mother and child remain acceptable. In contrast, there is no consensus on how to manage mild hypertensive disease in pregnancies at term. Induction of labour might prevent maternal and neonatal complications at the expense of increased instrumental vaginal delivery rates and caesarean section rates. Women with a pregnancy complicated by pregnancy induced hypertension or mild preeclampsia at a gestational age between 36+0 and 41+0 weeks will be asked to participate in a multi-centre randomised controlled trial. Women will be randomised to either induction of labour or expectant management for spontaneous delivery. The primary outcome of this study is severe maternal morbidity, which can be complicated by maternal mortality in rare cases. Secondary outcome measures are neonatal mortality and morbidity, caesarean and vaginal instrumental delivery rates, maternal quality of life and costs. Analysis will be by intention to treat. In total, 720 pregnant women have to be randomised to show a reduction in severe maternal complications of hypertensive disease from 12 to 6%. This trial will provide evidence as to whether or not induction of labour in women with pregnancy induced hypertension or mild preeclampsia (nearly) at term is an effective treatment to prevent severe maternal complications. The protocol is registered in the clinical trial register number ISRCTN08132825.
