Objective Forced vital capacity (FVC) and carbon monoxide diffusion (DLCO) are used for systemic sclerosis-associated interstitial lung disease (SSc-ILD) screening. The study purpose was to determine the sensitivity, specificity, and negative predictive value (NPV) (proportion of true negative screening tests) of FVC and DLCO thresholds for SSc-ILD on chest high-resolution computed tomography (HRCT) scans. Methods Patients fulfilling American College of Rheumatology 2013 SSc criteria with a chest HRCT scan and pulmonary function tests (PFT) were studied. A thoracic radiologist quantified radiographic ILD. Optimal FVC and DLCO % predicted thresholds for ILD were identified using receiver operating characteristic curves. The FVC and DLCO combinations with greatest sensitivity and specificity were also determined. Sub-analysis was performed in patients with positive Scl-70 autoantibodies. Results 265 patients were studied. Of 188 (71%) with radiographic ILD, 59 out of 188 (31%) had “normal” FVC (≥80% predicted), and 65 out of 151 (43%) had “normal” DLCO (≥60% predicted). FVC <80% (sensitivity 0.69, specificity 0.74), and DLCO <62% (sensitivity 0.60, specificity 0.70) were optimal thresholds for radiographic SSc-ILD. All FVC and DLCO threshold combinations evaluated had NPV <0.70. The NPV for radiographic ILD for FVC <80% was lower in patients with positive Scl-70 autoantibody (NPV=0.05) compared to negative Scl-70 autoantibody (NPV=0.57). Conclusions Radiographic ILD is prevalent in SSc despite “normal” PFTs. No % predicted FVC or DLCO threshold combinations yielded high NPV for SSc-ILD screening. “Normal” FVC and DLCO in SSc patients, especially those with positive Scl-70 autoantibodies, should not obviate consideration of HRCT for ILD evaluation.

The positive association of AC C2 and AC C4-DC/Ci4-DC levels with leptin may reflect excess fat stores, higher fatty acid oxidation rate, and mitochondrial dysfunction leading to accumulation of acylcarnitine intermediates. Principal component analysis revealed a positive association between branched chain amino acid and ketone body metabolites and adiposity, confirming prior findings in adults. Cord blood acylcarnitine profiles may identify at-risk children before obesity or insulin resistance develops.

Background In cluster-randomized controlled trials (C-RCTs), covariate-constrained randomization (CCR) methods efficiently control imbalance in multiple baseline cluster-level variables, but the choice of imbalance metric to define the subset of “adequately balanced” possible allocation schemes for C-RCTs involving more than two arms and continuous variables is unclear. In an ongoing three-armed C-RCT, we chose the min(three Kruskal–Wallis [KW] test P values) > 0.30 as our metric. We use simulation studies to explore the performance of this and other metrics of baseline variable imbalance in CCR. Methods We simulated three continuous variables across three arms under varying allocation ratios and assumptions. We compared the performance of min(analysis of variance [ANOVA] P value) > 0.30, min(KW P value) > 0.30, multivariate analysis of variance (MANOVA) P value > 0.30, min(nine possible t test P values) > 0.30, and min(Wilcoxon rank-sum [WRS] P values) > 0.30. Results Pairwise comparison metrics ( t test and WRS) tended to be the most conservative, providing the smallest subset of allocation schemes (10%–13%) meeting criteria for acceptable balance. Sensitivity of the min( t test P values) > 0.30 for detecting non-trivial imbalance was 100% for both hypothetical and resampled simulation scenarios. The KW criterion maintained higher sensitivity than both the MANOVA and ANOVA criteria (89% to over 99%) but was not as sensitive as pairwise criteria. Conclusions Our criterion, the KW P value > 0.30, to signify “acceptable” balance was not the most conservative, but it appropriately identified imbalance in the majority of simulations. Since all are related, CCR algorithms involving any of these imbalance metrics for continuous baseline variables will ensure robust simultaneous control over multiple continuous baseline variables, but we recommend care in determining the threshold of “acceptable” levels of (im)balance. Trial registration This trial is registered on ClinicalTrials.gov (initial post: December 1, 2016; identifier: NCT02979444 ). Electronic supplementary material The online version of this article (10.1186/s13063-019-3324-5) contains supplementary material, which is available to authorized users.

A positive family history of HD appears to be associated with an earlier onset of depression and overall disease manifestations. Implications regarding the role of genetic versus environmental contributions to symptom onset in HD are discussed.

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