Pulmonary adaptations to swim and inspiratory muscle training

Because the anomalous respiratory characteristics of competitive swimmers have been suggested to be due to inspiratory muscle work, the respiratory muscle and pulmonary function of 30 competitively trained swimmers was assessed at the beginning and end of an intensive 12-week swim training (ST) program. Swimmers (n = 10) combined ST with either inspiratory muscle training (IMT) set at 80% sustained maximal inspiratory pressure (SMIP) with progressively increased work–rest ratios until task failure for 3-days per week (ST + IMT) or ST with sham-IMT (ST + SHAM-IMT, n = 10), or acted as controls (ST only, ST, n = 10). Measures of respiratory and pulmonary function were assessed at the beginning and end of the 12 week study period. There were no significant differences (P > 0.05) in respiratory and pulmonary function between groups (ST + IMT, ST + SHAM-IMT and ST) at baseline and at the end of the 12 week study period. However, within all groups significant increases (P < 0.05) were observed in a number of respiratory and pulmonary function variables at the end of the 12 week study, such as maximal inspiratory and expiratory pressure, inspiratory power output, forced vital capacity, forced expiratory and inspiratory volume in 1-s, total lung capacity and diffusion capacity of the lung. This study has demonstrated that there are no appreciable differences in terms of respiratory changes between elite swimmers undergoing a competitive ST program and those undergoing respiratory muscle training using the flow-resistive IMT device employed in the present study; as yet, the causal mechanisms involved are undefined

Cerebral blood flow predicts differential neurotransmitter activity

Application of metabolic magnetic resonance imaging measures such as cerebral blood flow in translational medicine is limited by the unknown link of observed alterations to specific neurophysiological processes. In particular, the sensitivity of cerebral blood flow to activity changes in specific neurotransmitter systems remains unclear. We address this question by probing cerebral blood flow in healthy volunteers using seven established drugs with known dopaminergic, serotonergic, glutamatergic and GABAergic mechanisms of action. We use a novel framework aimed at disentangling the observed effects to contribution from underlying neurotransmitter systems. We find for all evaluated compounds a reliable spatial link of respective cerebral blood flow changes with underlying neurotransmitter receptor densities corresponding to their primary mechanisms of action. The strength of these associations with receptor density is mediated by respective drug affinities. These findings suggest that cerebral blood flow is a sensitive brain-wide in-vivo assay of metabolic demands across a variety of neurotransmitter systems in humans

AB1059 A RANDOMIZED, PLACEBO-CONTROLLED STUDY OF ANAKINRA IN PATIENTS WITH STILL´S DISEASE

Background:Adult-onset Still's disease (AOSD) and systemic juvenile idiopathic arthritis (SJIA) are rare autoinflammatory disorders associated with an activated IL-1 pathway, characterized by spiking fever, rash, arthritis, lymphadenopathy, hepatosplenomegaly and serositis. There is a growing understanding that SJIA and AOSD are one disease with different ages of onset, i.e. Still's disease. The anaSTILLs study (anakinra inStill´sdisease) was designed to further evaluate efficacy and safety of anakinra in patients with Still´s disease across all age groups.Objectives:The primary objective was to demonstrate efficacy of anakinra versus placebo as assessed by ACR30 response with absence of fever at Week 2. Secondary objectives included: early onset of efficacy, sustained efficacy, time to study drug discontinuation, safety, pharmacokinetics, clinical signs and biomarkers.Methods:'anaSTILLs' was a randomized, double-blind, placebo-controlled, 12-week study including patients with active and newly diagnosed (6 months) Still´s disease according to adapted ILAR criteria if <16, or Yamaguchi criteria, if ≥16 years of age at disease onset. Patients were randomized to anakinra 2 mg/kg (max 100 mg/day), 4 mg/kg (max 200 mg/day) or placebo.Results:12 patients were randomized and received study drug: 6 anakinra (2 mg/kg n=2, 4 mg/kg n=4) and 6 placebo, the study was terminated early due to slow recruitment. 1 patient on placebo had lymphoma, not Still's disease, and was excluded; thus in total 11 patients were analyzed for efficacy, 8 were children [median (range) age=4.0 (1-11) years] and 3 were adults [median (range) age=32.0 (25-51) years]. 55% were male and the mean symptom duration was 74.2 days. All patients on anakinra but none on placebo achieved ACR30 response with absence of fever at Week 2 (p-value=0.0022). The efficacy of anakinra was further demonstrated by superiority to placebo in ACR50/70/90 responses with absence of fever at Week 2. All placebo patients discontinued the study within 6 weeks, 2 due to progressive disease, 2 due to lack of efficacy and 1 due to withdrawal by patient. There was a numerically higher proportion with early onset of efficacy (Week 1) in the anakinra group compared to placebo. The ACR30/50/70/90 responses in the anakinra group were sustained throughout the study period. Patients in the anakinra group had a prompt and persistent decrease in CRP and ferritin levels at Week 1, which was not observed in the placebo group. There were no unexpected safety findings. All anakinra patients developed anti-drug antibodies (ADAs) at some timepoint during the study. ADAs were persistent throughout the treatment period, except in one patient. Titers were low to moderate. One placebo patient had low ADA titers at one occasion. No neutralizing antibodies were observed and the ADAs did not appear to impact clinical efficacy or safety.Conclusion:Anakinra is superior to placebo in the treatment of Still's disease. ADAs occur frequently but do not appear to adversely impact efficacy or safety. These results confirm the benefits of anakinra treatment in patients with active, newly diagnosed Still´s disease across ages.Disclosure of Interests:Laura Schanberg Grant/research support from: Sobi, BMS, Consultant of: Aurinia, UCB, Sanofi, Peter Nigrovic Grant/research support from: Novartis, BMS, Pfizer, Consultant of: Novartis, BMS, Pfizer, Sobi, Miach Orthopedics, Simcere, XBiotech, Quench Bio, Ashley Cooper: None declared, Winn Chatham Grant/research support from: Sobi, Consultant of: Sobi, Shoghik Akoghlanian: None declared, Namrata Singh: None declared, Egla Rabinovich Grant/research support from: AbbVie, UCB Pharma, Janssen Research & Development, Akaluck Thatayatikom: None declared, Alysha Taxter: None declared, Jonathan Hausmann Consultant of: Novartis, Milan Zdravkovic Shareholder of: Sobi, Employee of: Sobi, Sven Ohlman Shareholder of: Sobi, Employee of: Former employee of Sobi, Henrik Andersson Employee of: Sobi, Susanna Cederholm Shareholder of: Sobi, Employee of: Sobi, Margareta Wikén Shareholder of: Sobi, Employee of: Former employee of Sobi, Rayfel Schneider Grant/research support from: Roche, Novartis, Sobi, Pfizer, Consultant of: Sobi, Novartis, Novimmune, Fabrizio De Benedetti Grant/research support from: AbbVie, Pfizer, Novartis, Novimmune, Sobi, Sanofi, Roche, Speakers bureau: AbbVie, Novartis, Roche, Sob

Individualized decision aid for diverse women with lupus nephritis (IDEA-WON): A randomized controlled trial.

BackgroundTreatment decision-making regarding immunosuppressive therapy is challenging for individuals with lupus. We assessed the effectiveness of a decision aid for immunosuppressive therapy in lupus nephritis.Methods and findingsIn a United States multicenter, open-label, randomized controlled trial (RCT), adult women with lupus nephritis, mostly from racial/ethnic minority backgrounds with low socioeconomic status (SES), seen in in- or outpatient settings, were randomized to an individualized, culturally tailored, computerized decision aid versus American College of Rheumatology (ACR) lupus pamphlet (1:1 ratio), using computer-generated randomization. We hypothesized that the co-primary outcomes of decisional conflict and informed choice regarding immunosuppressive medications would improve more in the decision aid group. Of 301 randomized women, 298 were analyzed; 47% were African-American, 26% Hispanic, and 15% white. Mean age (standard deviation [SD]) was 37 (12) years, 57% had annual income of &lt;$40,000, and 36% had a high school education or less. Compared with the provision of the ACR lupus pamphlet (n = 147), participants randomized to the decision aid (n = 151) had (1) a clinically meaningful and statistically significant reduction in decisional conflict, 21.8 (standard error [SE], 2.5) versus 12.7 (SE, 2.0; p = 0.005) and (2) no difference in informed choice in the main analysis, 41% versus 31% (p = 0.08), but clinically meaningful and statistically significant difference in sensitivity analysis (net values for immunosuppressives positive [in favor] versus negative [against]), 50% versus 35% (p = 0.006). Unresolved decisional conflict was lower in the decision aid versus pamphlet groups, 22% versus 44% (p &lt; 0.001). Significantly more patients in the decision aid versus pamphlet group rated information to be excellent for understanding lupus nephritis (49% versus 33%), risk factors (43% versus 27%), medication options (50% versus 33%; p ≤ 0.003 for all); and the ease of use of materials was higher in the decision aid versus pamphlet groups (51% versus 38%; p = 0.006). Key study limitations were the exclusion of men, short follow-up, and the lack of clinical outcomes, including medication adherence.ConclusionsAn individualized decision aid was more effective than usual care in reducing decisional conflict for choice of immunosuppressive medications in women with lupus nephritis.Trial registrationClinicaltrials.gov, NCT02319525

Between feminism and anorexia: An autoethnography

Critical feminist work on eating disorders has grown substantially since its establishment in the 1980s, and has increasingly incorporated the use of anorexic stories, voices and experiences. Yet rarely do such accounts offer the anorexic a space to respond to the now established feminist conceptions of the problem which structure the books or articles in which they appear. Anorexic, or recovered anorexic, voices are used by the researcher to interpret the role played by gender, even whilst the subjects are invited to respond to and critique, medical and popular discourses on the disorder. This lack of dialogue is all the more striking in the context of the feminist aim to fight ‘back against the tendency to silence anorexic women’s’ own interpretations of their starving, treatment and construction (Saukko, 2008: 34). As someone who suffered from anorexia for 20 years, this article offers an autoethnographic account of my experience of encountering the feminist literature on anorexia in a bid to speak back, or enter into a dialogue between feminist politics and eating disorder experience

Being and doing anorexia nervosa: An autoethnography of diagnostic identity and performance of illness

This autoethnography examines my experience of the diagnosis and treatment of anorexia nervosa. Drawing on memory and personal and medical documents relating to inpatient admissions in an adult specialist eating disorder unit, I narrate and analyse my experience in terms of my relationship to the diagnosis of anorexia and the constructions of it I encountered. I show how I came to value an identity based on anorexia and how I learned ways of ‘doing’ the diagnosis in treatment. This involved me valuing medical markers of illness, including signs of poor health, which became crucial to how I performed my diagnosis and retained the diagnostically-informed sense of self that I valued. I suggest that, ultimately, these diagnostic-dynamics, alongside other effects of long-term inpatient treatment such as detachment from ‘normal life’, prolonged my struggles with self-starvation. The insights from this autoethnography shed light on potential iatrogenic impacts of diagnosis and treatment for anorexia