IDH-mutant myeloid neoplasms are associated with seronegative rheumatoid arthritis and innate immune activation.

ABSTRACT: High prevalence of IDH mutations in seronegative rheumatoid arthritis (RA) with myeloid neoplasm, elevated 2-hydroxyglutarate, dysregulated innate immunity, and proinflammatory microenvironment suggests causative association between IDH mutations and seronegative RA. Our findings merit investigation of IDH inhibitors as therapeutics for seronegative IDH-mutated RA.

Comparison of catheters or new arteriovenous fistulas for commencement of haemodialysis in pregnant women with chronic kidney disease: an international observational study.

BACKGROUND: Evidence surrounding vascular access options for commencing dialysis in pregnancy complicated by chronic kidney disease (CKD) is limited. Creation of new arteriovenous fistulas (AVFs) in pregnant women is rare. METHODS: Retrospective cohort study of approaches to vascular access in pregnancy in centres in Australia, the United Kingdom (UK) and Canada (2002-2018). RESULTS: Twenty-three women with advanced CKD commenced dialysis in pregnancy (n = 20) or planned to commence (n = 3). Access at dialysis start was a tunnelled catheter (n = 13), temporary catheter (n = 1), AVF created pre-conception but used in pregnancy (n = 3) and AVF created during pregnancy (n = 3). No women commencing dialysis with an AVF required a catheter. No differences in perinatal outcomes were observed comparing AVFs and catheters at dialysis commencement. No AVFs were created in pregnancy in Canadian women. From Australia and the UK, 10 women had a new AVF created in pregnancy, at median gestation 14.5 weeks (IQR 12.5, 20.75). Four women still needed a catheter for dialysis initiation and 3 eventually used the new AVF. Six AVFs were successfully used in pregnancy at median gestation 24 weeks (IQR 22.5, 28.5), 2 were successfully created but not used and 2 had primary failure. No catheter-associated complications were identified except one episode of catheter-related sepsis. CONCLUSIONS: Catheter-related complications were minimal. In selected women, with sufficient pre-planning, an AVF can be created and successfully used during pregnancy to minimise catheter use if preferred. Pre-conception counselling in advanced CKD should include discussing vascular access options reflecting local expertise and patient preferences.

Association of Musculoskeletal Joint Pain With Obstructive Sleep Apnea, Daytime Sleepiness, and Poor Sleep Quality in Men.

OBJECTIVE: To investigate the association of musculoskeletal pain with objectively determined obstructive sleep apnea (OSA) and subjective sleep measures in a population-based sample. METHODS: Participants were community-dwelling men (n = 360) age ≥35 years from the Men Androgen Inflammation Lifestyle Environment and Stress (MAILES) study. Shoulder, back, hip, knee, hand, and foot pain were assessed by computer-assisted telephone interview or self-completed questionnaire. OSA was determined with full in-home unattended polysomnography (Embletta X100) scored by 2007 American Academy of Sleep Medicine alternative criteria. The Epworth Sleepiness Scale assessed daytime sleepiness and the Pittsburgh Sleep Quality Index assessed sleep quality. RESULTS: OSA was not associated with the presence of any joint pain (adjusted odds ratio [OR] 1.03 [95% confidence interval (95% CI) 0.61-1.76]). There was no association between OSA and pain in any specific joint (shoulder, back, hip, knee, hand, or foot), nor was the number of joints in pain associated with OSA. There was, similarly, no association between pain variables and excessive daytime sleepiness, except for hand pain (OR 3.10 [95% CI 1.50-6.39]). However, pain was associated with poor sleep quality: any pain (OR 2.19 [95% CI 1.25-3.82]), shoulder pain (OR 2.16 [95% CI 1.25-3.75]), back pain (OR 2.24 [95% CI 1.41-3.55]), and foot pain (OR 2.47 [95% CI 1.43-4.26]). The number of painful joints was also associated with poor sleep quality (5-6 joints versus no joints OR 7.34 [95% CI 2.30-23.42]). CONCLUSION: No association between OSA and pain or between daytime sleepiness and pain was found. Consistent with previous reports, poor sleep quality was associated with musculoskeletal pain in this population sample. The etiologic differences between OSA-related sleep disruption and poor subjective sleep quality require further investigation.

Muscle grip strength predicts incident type 2 diabetes: Population-based cohort study.

OBJECTIVES: To determine the longitudinal relationship of muscle mass and strength with incident type 2 diabetes, and previously unstudied mediating effects of testosterone and inflammation. METHODS: Community-dwelling male participants (aged ≥35years) of the Men Androgen Inflammation Lifestyle Environment and Stress (MAILES) Study underwent biomedical assessment in 2002-2006 and 2007-2010, including hand grip strength (dynamometer), testosterone and inflammatory markers. Body composition (dual-energy X-ray absorptiometry) was assessed at baseline only. Incident type 2 diabetes was defined as a self-reported doctor diagnosis, diabetes medication use, fasting plasma glucose ≥7.0mmol/L, or glycated haemoglobin ≥6.5% (48mmol/mol) at follow-up, that was not present at baseline. RESULTS: Of n=1632 men, incident type 2 diabetes occurred in 146 (8.9%). Muscle mass was not associated with incident type 2 diabetes. Grip strength was inversely associated with incident type 2 diabetes [unadjusted odds ratio (OR) per 5kg: 0.87, 95% confidence interval (CI): 0.80-0.95; adjusted OR, 95% CI: 0.87, 0.78-0.97]. Arm muscle quality (grip strength divided by arm lean mass) was similarly associated with incident type 2 diabetes. Testosterone, IL-6 and TNF-α did not significantly mediate the associations. The population attributable fraction of type 2 diabetes from low grip strength was 27% (13-40%), assuming intervention could increase strength by 25%. CONCLUSIONS: Reduced muscle strength, but not reduced muscle mass, is a risk factor for incident type 2 diabetes in men. This is not mediated by testosterone or inflammation. Intervention could prevent a substantial proportion of disease.

Developing the future Indigenous health workforce: The feasibility and impact of a student-led placement programme in remote Indigenous communities.

OBJECTIVE: To describe and evaluate a programme where medical students designed and implemented Indigenous health placements for students with an interest in rural/Indigenous health. DESIGN, SETTING AND PARTICIPANTS: In 2011, a student-led programme at the University of Adelaide was set up to give medical students the opportunity to undertake outreach trips and clinical placements in remote Indigenous communities. Twenty-four medical students attended trips to remote communities between 2012 and 2014. Here we evaluate our programme using a single-arm experimental design. MAIN OUTCOME MEASURES: Responses to questionnaire items before and after attending an outreach placement, scored on 6-point Likert scales. RESULTS: Following their remote Indigenous health placement, participants expressed a significantly higher mean likelihood of working in an Indigenous community in the future (3.17 (2.69-3.64) versus 4.00 (3.65-4.35); P < 0.007). Furthermore, after their placement participants felt better prepared to work in Indigenous communities (mean 1.79 (1.44-2.14) versus 3.21 (2.88-3.54); P < 0.001). CONCLUSIONS: A placement programme initiated and run by medical students can provide meaningful exposure to Indigenous health. Implementation of this student-led model in other medical schools may encourage nationwide development of the Indigenous health workforce.

The relationship between functional health literacy and obstructive sleep apnea and its related risk factors and comorbidities in a population cohort of men.

STUDY OBJECTIVES: To examine the relationship between functional health literacy (FHL) and obstructive sleep apnea (OSA), its diagnosis, related risk factors, and comorbidities. DESIGN: Population cohort study. SETTING: Adelaide, South Australia, 2011-12. PARTICIPANTS: 1,021 Men Androgen Inflammation Lifestyle Environment and Stress Study participants aged ≥ 40 years, of whom 627 were identified with OSA by self-report (n = 184 previously diagnosed) or with in-home polysomnography in 837 randomly selected participants without self-reported OSA (n = 443 previously undiagnosed). INTERVENTIONS: The Newest Vital Sign assessed FHL in 88% of participants. Full in-home unattended polysomnography (Embletta X100) was scored by 2007 AASM (alternative) criteria. MEASUREMENTS AND RESULTS: FHL was adequate in 75.3% (n = 122) of previously diagnosed and 68.3% (n = 261) of previously undiagnosed OSA. Not having a previous diagnosis was independently associated with inadequate FHL (odds ratio [OR]:2.84, 95% confidence interval [CI]:1.25-6.45) and workforce participation (OR = 2.04, 95% CI = 1.01-4.00), and inversely associated with previous snoring (OR = 0.48, 95% CI = 0.29-0.81), obesity (OR = 0.35, 95% CI = 0.15-0.81), and cardiovascular disease (OR = 0.45, 95% CI = 0.24-0.85). In polysomnography participants, inadequate FHL was independently associated with previously undiagnosed OSA (OR = 2.43, 95% CI = 1.40-4.20). In undiagnosed men, less than adequate FHL was independently associated with sedentary lifestyle (OR = 2.42, 95% CI = 1.36-4.29), and depression (OR = 2.50, 95% CI = 1.23-5.09) and inadequate FHL was associated with current smoking (OR = 2.87, 95% CI = 1.21-6.84). The depression association was attenuated after additional adjustment for comorbidities and general health (OR = 2.04, 95% CI = 0.93-4.49, P = 0.076). In previously diagnosed OSA, less than adequate FHL was independently associated with cardiovascular disease (OR = 2.76, 95% CI = 1.09-7.01). CONCLUSIONS: Limited functional health literacy was independently associated with obstructive sleep apnea (OSA), OSA diagnosis, lifestyle factors and comorbidities, highlighting the importance of developing and promoting national disease-specific health literacy policies.