Ultrasound pathology of the entheses in an age and gender stratified sample of healthy adult subjects: a prospective cross-sectional frequency study.

OBJECTIVES: Ultrasound (US) examination of the entheses is increasingly used. However, little is known about US findings in the entheses in asymptomatic persons. The aim of this study was to investigate the appearance of US signs in the enthuses of the lower limb in asymptomatic subjects. METHODS: We recruited 64 subjects, eight women and eight men whose ages covered four decades, from 20 to 60 years. None had tendon or joint disease in the lower limbs. Participants were examined by a rheumatologist and blood samples were collected to rule out enthesis pathology. The enthesis of the dominant leg were examined with grey-scale and Doppler US to evaluate increased thickness, changed structure, enthesophytes/calcifications, erosions, and colour Doppler signal. RESULTS: Ultrasound examination of 320 entheses was made. At enthesis level, elementary lesions were seen at 73 (22.8%) sites, at subject-level 47 (73.4%) persons showed elementary lesions, in 27 (57%) only one enthesis was affected. Doppler activity was seen in four sites, three at the quadriceps insertion. Most common US elementary lesion was enthesophytes at the Achilles and quadriceps tendon insertion. A tendency towards more elementary lesions was seen in men, and a slight increase was seen with increasing age, however, not statistically significance. CONCLUSIONS: Our findings suggest that US can be used to diagnose/examine subjects in adulthood for pathological changes in the entheses; however, caution should be taken regarding enthesophytes of the quadriceps and Achilles tendon.

Birth outcomes after exposure to mebendazole and pyrvinium during pregnancy - A Danish nationwide cohort study.

Mebendazole and pyrvinium are anthelmintics used to treat infections with pinworms, a common infection in children. Other indications for treatment with mebendazole are infections with soil-transmitted helminths. These infections are rare in Denmark, but affect more than 1.5 billion people worldwide. Limited safety data of anthelmintics during pregnancy exists and the purpose of this study was to investigate the association between exposure to mebendazole or pyrvinium during pregnancy and the adverse pregnancy outcomes: congenital malformations, stillbirths, neonatal mortality and small for gestational age. The Danish Fertility Database was used to identify all births in Denmark from 1997 to 2007. Maternal exposure to anthelmintics was identified through The Danish Prescription Registry. Of 713667 births, 2567 mothers redeemed a prescription for mebendazole; 1588 for pyrvinium. Logistic regression analysis adjusted for potential confounders. We found no association between exposure to mebendazole and major congenital malformations (OR = 0.7 (CI 95% 0.5-1.1)) or other negative birth outcomes and we found no association between exposure to pyrvinium and major congenital malformations (OR = 0.8 (CI 95% 0.4-1.5)) or other negative birth outcomes. No increased risk was found of having negative birth outcomes after exposure at any trimester during pregnancy.

Use of thyroid hormones in relation to pregnancy: a Danish nationwide cohort study.

OBJECTIVE: To determine the rate of exposure of pregnant women to levothyroxine and to assess changes in these rates before, during and after pregnancy. DESIGN: Register-based cohort study. SETTING: Danish nationwide registers. POPULATION: All women having a live birth in Denmark between 1 January 1997 and 31 December 2010 (n = 912 342). METHODS: All pregnant women in the study period were identified from the Danish Medical Birth Register. Exposed women were identified from the Danish National Prescription Register, based on redemption of levothyroxine prescriptions before, during or after pregnancy. MAIN OUTCOME MEASURES: The rate of pregnant women redeeming levothyroxine prescriptions and maternal characteristics. RESULTS: We identified a fourfold increase in levothyroxine prescription redemption during the study period, from 0.34% in 1997 to 1.39% by 2010. A mean of 0.79% of our cohort received levothyroxine. Most of the women who were using levothyroxine before pregnancy continued the therapy during their pregnancy, but 9.4% stopped redeeming their prescriptions. Overall, 0.28% of our cohort received a levothyroxine prescription for the first time within 9 months after pregnancy. CONCLUSIONS: Fewer women than expected received levothyroxine treatment during pregnancy even though a fourfold increase was observed during the study period. Furthermore, one of 10 discontinued treatments during pregnancy. These findings all indicate that too few women are treated for hypothyroidism during pregnancy. Further research is needed to determine whether hypothyroid pregnant women are suboptimally treated and the possible consequences for the mother and fetus.

Iron induced RNA-oxidation in the general population and in mouse tissue.

Iron promotes formation of hydroxyl radicals by the Fenton reaction, subsequently leading to potential oxidatively generated damage of nucleic acids. Oxidatively generated damage to RNA, measured as 8-oxo-7,8-dihydroguanosine (8-oxoGuo) in urine, is increased in patients with genetic iron overload, which have led us to test the hypothesis that high iron status, assessed by iron biomarkers and genetic disposition, increases urinary excretion of 8-oxoGuo. In a general Danish population study we used a Mendelian randomization design with HFE genotypes as a proxy for iron status and supplemented with ex vivo experiments in mice muscle tissue exposed to iron(II) sulfate to attempt to clarify this hypothesis. The biomarkers ferritin, transferrin, and transferrin saturation (TS) were associated with 8-oxoGuo (in linear univariable and multivariable regression analyses: P < 0.001). Mendelian randomization indicated a causal pathway between genetically elevated iron biomarkers (assessed by ferritin and TS) and high levels of 8-oxoGuo. The ex vivo experiments showed a monotonically increase in 8-oxoGuo with increased iron concentration (ANOVA: P = 0.0008) that was prevented with iron chelation (P = 0.01). Our results indicate a causal relationship between iron biomarkers and 8-oxoGuo. Furthermore, the ex vivo experiment shows a mechanistic link between iron and 8-oxoGuo formation. Both iron overload and the biomarker 8-oxoGuo have been linked to e.g. diabetes, which merits future studies to investigate if iron induced 8-oxoGuo is involved in disease development.

Risk of Adverse Pregnancy Outcome After Paternal Exposure to Methotrexate Within 90 Days Before Pregnancy.

OBJECTIVE: To study the association between paternal exposure to methotrexate within the 90-day period before pregnancy and congenital malformations and stillbirth in the offspring. METHODS: We conducted a nationwide register study. Our cohort consisted of all live births in Denmark between 1997 and 2011 identified from the Medical Birth Registry. Methotrexate-exposed fathers were identified from the National Prescription Registry. From the national Hospital Registry we identified paternity, live births, and stillbirths as well as discharge diagnoses on congenital malformations. RESULTS: We identified 849,676 live births with known paternity. There were 127 live births of methotrexate-exposed fathers. Of these, four (3.2%) had major malformations compared with 28,814 (3.4%) of the unexposed. The odds ratio (OR) for major congenital malformation among exposed fathers compared with unexposed was 0.93 (95% confidence interval [CI] 0.34-2.51) and when adjusted for year of birth, maternal age, educational length, household income, and parity, the adjusted OR was 1.01 (95% CI 0.37-2.74). There were no stillbirths in the methotrexate-exposed group compared with 2,541 (0.3%) in the unexposed group and no increased risk of preterm birth (adjusted OR 1.31, 95% CI 0.66-2.59) among the children from exposed fathers. CONCLUSION: We found no association between paternal exposure to methotrexate within 90 days before pregnancy and congenital malformations, stillbirths, or preterm birth. Available data suggest that prepregnancy paternal methotrexate exposure should not be of major concern. Multinational recommendations should be changed accordingly.

Power and color Doppler ultrasound settings for inflammatory flow: impact on scoring of disease activity in patients with rheumatoid arthritis.

OBJECTIVE: To determine how settings for power and color Doppler ultrasound sensitivity vary on different high- and intermediate-range ultrasound machines and to evaluate the impact of these changes on Doppler scoring of inflamed joints. METHODS: Six different types of ultrasound machines were used. On each machine, the factory setting for superficial musculoskeletal scanning was used unchanged for both color and power Doppler modalities. The settings were then adjusted for increased Doppler sensitivity, and these settings were designated study settings. Eleven patients with rheumatoid arthritis (RA) with wrist involvement were scanned on the 6 machines, each with 4 settings, generating 264 Doppler images for scoring and color quantification. Doppler sensitivity was measured with a quantitative assessment of Doppler activity: color fraction. Higher color fraction indicated higher sensitivity. RESULTS: Power Doppler was more sensitive on half of the machines, whereas color Doppler was more sensitive on the other half, using both factory settings and study settings. There was an average increase in Doppler sensitivity, despite modality, of 78% when study settings were applied. Over the 6 machines, 2 Doppler modalities, and 2 settings, the grades for each of 7 of the patients varied between 0 and 3, while the grades for each of the other 4 patients varied between 0 and 2. CONCLUSION: The effect of using different machines, Doppler modalities, and settings has a considerable influence on the quantification of inflammation by ultrasound in RA patients, and this must be taken into account in multicenter studies.