Autoimmune disease in mothers with the FMR1 premutation is associated with seizures in their children with fragile X syndrome

An increased prevalence of autoimmune diseases in family members of children with autism spectrum disorders (ASD) has been previously reported. ASD is also a common problem co-occurring in children with fragile X syndrome (FXS). Why ASD occurs in some individuals with FXS, but not all, is largely unknown. Furthermore, in premutation carrier mothers, there is an increased risk for autoimmune diseases. This study compared the rate of ASD and other neurodevelopmental/behavioral problems in 61 children with FXS born to 41 carrier mothers who had autoimmune disease and in 97 children with FXS of 78 carrier mothers who did not have autoimmune disease. There were no significant differences in the mean age (9.61 ± 5.59 vs. 9.41 ± 6.31, P = 0.836), cognitive and adaptive functioning in children of mothers with and without autoimmune disease. Among children whose mothers had autoimmune disease, the odds ratio (OR) for ASD was 1.27 (95% CI 0.62–2.61, P = 0.5115). Interestingly, the OR for seizures and tics was 3.81 (95% CI 1.13–12.86, P = 0.031) and 2.94 (95% CI 1.19–7.24, P = 0.019), respectively, in children of mothers with autoimmune disease compared to children of mothers without autoimmune disease. In conclusion, autoimmune disease in carrier mothers was not associated with the presence of ASD in their children. However, seizures and tics were significantly increased in children of mothers with autoimmune disease. This suggests a potential new mechanism of seizure and tic exacerbation in FXS related to an intergenerational influence from autoimmunity in the carrier mother

Colchicine twice daily for hand osteoarthritis: results from the double-blind, randomised, placebo-controlled COLOR trial

Background: Colchicine has been suggested for osteoarthritis treatment, but evidence is contradictory. We aimed to investigate colchicine's efficacy and safety compared with placebo in people with hand osteoarthritis. Methods: In this single-centre, double-blind, randomised, placebo-controlled trial we recruited adults with symptomatic hand osteoarthritis and finger pain of at least 40 mm on a 100 mm visual analogue scale from an outpatient clinic in Denmark. The hand with the most severe finger pain at inclusion was the target hand. Participants were randomly assigned (1:1) to 0 center dot 5 mg colchicine or placebo taken orally twice a day for 12 weeks, stratified by BMI (>= 30 kg/m2), sex, and age (>= 75 years). Participants, outcome assessors, and data analysts were masked to treatment allocation. The primary endpoint was change from baseline to week 12 in target hand finger pain, assessed on a 100 mm visual analogue scale with a pre-specified minimal clinically important difference of 15 mm, in the intention-to-treat population. Safety was assessed at week 12 in the intention-to-treat population. The study was registered with ClinicalTrials.gov, NCT04601883, and with EudraCT, 2020-002803-20. Findings: Between Jan 15, 2021, and March 3, 2022, 186 people were screened for eligibility, and 100 were randomly assigned to receive colchicine (n=50) or placebo (n=50). Participants had a mean age of 70 center dot 9 (SD 7 center dot 5) years, 69 (69%) of 100 were women and 31 (31%) were men. All participants completed the study. The mean change from baseline to week 12 in finger pain were -13 center dot 9 mm (SE 2 center dot 8) in the colchicine group and -13 center dot 5 mm (2 center dot 8) in the placebo group, with a between-group difference (colchicine vs placebo) of -0 center dot 4 mm (95% CI -7 center dot 6 to 6 center dot 7; p=0 center dot 90). In the colchicine group, there were 76 adverse events in 36 (72%) of 50 participants and one serious adverse advent (migraine attack leading to hospital admission). In the placebo group, there were 42 adverse events in 22 (44%) of 50 participants and two serious adverse events (cholecystitis and elevated alanine aminotransferase concentrations, in the same patient). Interpretation: In people with painful hand osteoarthritis, treatment with 0 center dot 5 mg of colchicine twice day for 12 weeks did not effectively relieve pain, and treatment with colchicine was associated with more adverse events.Pathophysiology and treatment of rheumatic disease

Tests of the empirical classification of horizontal and vertical intra-industry trade

F14,