Colchicine is not effective for reducing osteoarthritic hand pain compared to placebo: a randomised, placebo-controlled trial (COLAH).

BACKGROUND: Colchicine may offer relief in osteoarthritis. This has never been investigated for hand osteoarthritis. OBJECTIVES: To investigate the effect of 1 mg daily colchicine vs placebo on hand pain and function over 12 weeks in older adults with hand osteoarthritis. METHODS: Community-dwelling adults with diagnosed osteoarthritis of the hand aged 40-80 years were randomised to receive colchicine (0.5 mg twice daily) or matching placebo. Primary outcome measure was VAS hand pain score (0-100 mm). Secondary outcome measures included tender and swollen joint count, grip strength, C-reactive protein, and Michigan Hand Questionnaire total, function and pain scores. In an exploratory assessment, we compared synovial grade and power Doppler. All outcome measures were obtained at baseline and week 12. Stata v16 was used to perform constrained longitudinal data analysis models. RESULTS: 64 adults (54 females, 10 males) aged 48-79 years of age were enrolled. 59 participants completed the study (N = 28 colchicine, N = 31 placebo) (withdrawal rate 8%). Adverse reactions to the study medication occurred in nine patients. VAS score was not significantly different at baseline (61 ± 17 mm in the colchicine, 64 ± 17 mm in the placebo group). Between-group difference for VAS score at week 12 was 7.6 mm (95% CI -3.5-18.7, p-value 0.18). There were no significant differences between groups for any secondary outcomes at baseline or week 12. CONCLUSIONS: 1 mg colchicine daily for 12 weeks was not effective for reducing pain, tender and swollen joint count or increasing grip strength in symptomatic hand osteoarthritis. Our results do not support the use of colchicine in hand osteoarthritis.

Study protocol: families and childhood transitions study (FACTS) - a longitudinal investigation of the role of the family environment in brain development and risk for mental health disorders in community based children.

BACKGROUND: Extant research has demonstrated that parenting behaviour can be a significant contributor to the development of brain structure and mental health during adolescence. Nonetheless, there is limited research examining these relationships during late childhood, and particularly in the critical period of brain development occurring between 8 and 10 years of age. The effects of the family environment on the brain during late childhood may have significant implications for later functioning, and particularly mental health. The Families and Childhood Transitions Study (FACTS) is a multidisciplinary longitudinal cohort study of brain development and mental health, with two waves of data collection currently funded, occurring 18-months apart, when child participants are aged approximately 8- and 10-years old. METHODS/DESIGN: Participants are 163 children (M age [SD] = 8.44 [0.34] years, 76 males) and their mothers (M age [SD] = 40.34 [5.43] years). Of the 163 families who consented to participate, 156 completed a video-recorded and observer-coded dyadic interaction task and 153 completed a child magnetic resonance imaging brain scan at baseline. Families were recruited from lower socioeconomic status (SES) areas to maximise rates of social disadvantage and variation in parenting behaviours. All experimental measures and tasks completed at baseline are repeated at an 18-month follow-up, excluding the observer coded family interaction tasks. The baseline assessment was completed in October 2015, and the 18-month follow up will be completed May 2017. DISCUSSION: This study, by examining the neurobiological and mental health consequences of variations in parenting, has the potential to significantly advance our understanding of child development and risk processes. Recruitment of lower SES families will also allow assessment of resilience factors given the poorer outcomes often associated with this population.

Dispositional mindfulness is predicted by structural development of the insula during late adolescence.

Adolescence is a critical period of development, in which the increasing social and cognitive demands of independence need to be met by enhanced self-regulatory abilities. The cultivation of mindfulness has been associated with improved self-regulation in adult populations, and it is theorized that one neurodevelopmental mechanism that supports this capacity is the development of the prefrontal cortex. The current study examined the neurodevelopmental mechanisms associated with dispositional mindfulness in adolescence. Using a longitudinal within-persons design, 82 participants underwent structural magnetic resonance imaging (MRI) assessments at approximately ages 16 and 19, and also completed self-reported measurements of mindfulness at age 19. It was hypothesized that adolescents who demonstrated greater thinning of frontal cortical regions between the age of 16 and 19 would exhibit higher dispositional mindfulness levels at age 19. Results indicated that, contrary to predictions, adolescents with higher levels of mindfulness demonstrated less thinning in the left anterior insula. By contrast, higher IQ was associated with greater thinning of the right caudal middle frontal and right superior frontal regions. The involvement of insula development in mindfulness is consistent with a direct role for this structure in managing self-regulation, and in doing so concords with recent models of self-referential interoceptive awareness.

The accuracy of methods for urate crystal detection in synovial fluid and the effect of sample handling: a systematic review.

This study aims to compare different methods of monosodium urate crystal (MSU) detection in synovial fluid (SF) and the effect of sample storage and handling on crystal detection. A systematic literature search was performed in MEDLINE, EMBASE, the Cochrane Library and the American College of Rheumatology/European League Against Rheumatism conference abstracts of 2010 and 2011. Studies that compared a method for detecting MSU crystals in SF with polarised light microscopy (PLM) or compared various SF storage and handling factors with the detection of MSU crystals as an outcome were included. Twelve studies out of 247 identified references were included in the review. Seven studies compared different methods of MSU crystal detection in SF with PLM. Due to study heterogeneity, methodological limitations and risk of bias, no firm conclusions could be drawn from the available data. Five studies examining SF storage and handling factors were identified. A reduction in MSU crystal concentration was observed over time at room temperature that was not seen in refrigerated samples. The use of anticoagulation as a storage medium provided no benefit. Dried cytospin preparations appeared to be a suitable medium for long-term storage and delayed crystal analysis for at least 12 months. The existing data do not provide a compelling argument for the replacement of PLM as the current standard. SF sample storage and handling have an effect on MSU crystals and may impact on the reliability of analysis.

Folate supplementation and methotrexate treatment in rheumatoid arthritis: a review.

OBJECTIVES: The folate antagonist methotrexate (MTX) has become established as the most commonly used disease-modifying anti-rheumatic drug (DMARD) in the treatment of rheumatoid arthritis (RA) but is commonly discontinued due to adverse effects. Adverse effects are thought to be mediated via folate antagonism. In this paper we summarize the current data on the use of folates as a supplement to MTX use in RA for the prevention of adverse effects and as a potential modulator of cardiovascular risk, and propose guidelines for standard practice. METHODS: A Medline search was performed using the search terms "methotrexate", "folic acid", "folinic acid", "folate" and "homocysteine". Literature relevant to the use of folates as a supplement to MTX in the treatment of RA was reviewed and other papers referred to as references were explored. RESULTS: The use of supplemental folates, including folic and folinic acid, in RA patients treated with MTX has been shown to improve continuation rates by reducing the incidence of liver function test abnormalities and gastrointestinal intolerance. Folate supplements do not appear to significantly reduce the effectiveness of MTX in the treatment of RA. Furthermore, supplemental folic acid offsets the elevation in plasma homocysteine associated with the use of MTX. This may in turn reduce the risk of cardiovascular disease, which is over-represented amongst patients with RA, and for which hyperhomocysteinaemia is now recognized as an independent risk factor. CONCLUSIONS: We propose that folic acid supplements be prescribed routinely to all patients receiving MTX for the treatment of RA. We recommend a pragmatic dosing schedule of 5 mg of oral folic acid given on the morning following the day of MTX administration.

Radiographic changes in the knee after meniscal transplantation. An experimental study in a sheep model.

Meniscal transplantation has been suggested as an alternative to total meniscectomy, which is now known to lead to long-term osteoarthritic degeneration of the knee joint. To evaluate the success of meniscal transplantation, we divided 28 sheep knees into 4 groups: total meniscectomy, allograft, autograft, and control. After a mean postoperative time of 21.4 months, we radiographed the excised knee joints in a loaded state and graded the radiographs for osteoarthritic changes. The knees with meniscectomies, allografts, and autografts showed significantly more degenerative changes than the control knees. However, there were no statistically significant differences between these three groups. The results of this study suggest that meniscal allograft transplantation does not protect the knee against degenerative changes.