1.
An appraisal of the SDIR as an estimate of true individual differences in training responsiveness in parallel-arm exercise randomized controlled trials.
Bonafiglia, JT, Brennan, AM, Ross, R, Gurd, BJ
Physiological reports. 2019;(14):e14163
Abstract
Calculating the standard deviation of individual responses (SDIR ) is recommended for estimating the magnitude of individual differences in training responsiveness in parallel-arm exercise randomized controlled trials (RCTs). The purpose of this review article is to discuss potential limitations of parallel-arm exercise RCTs that may confound/complicate the interpretation of the SDIR . To provide context for this discussion, we define the sources of variation that contribute to variability in the observed responses to exercise training and review the assumptions that underlie the interpretation of SDIR as a reflection of true individual differences in training responsiveness. This review also contains two novel analyses: (1) we demonstrate differences in variability in changes in diet and physical activity habits across an intervention period in both exercise and control groups, and (2) we examined participant dropout data from six RCTs and found that significantly (P < 0.001) more participants in control groups (12.8%) dropped out due to dissatisfaction with group assignment compared to exercise groups (3.4%). These novel analyses raise the possibility that the magnitude of within-subject variability may not be equal between exercise and control groups. Overall, this review highlights that potential limitations of parallel-arm exercise RCTs can violate the underlying assumptions of the SDIR and suggests that these limitations should be considered when interpreting the SDIR as an estimate of true individual differences in training responsiveness.
2.
Clinical inquiries: what's the best way to manage upper extremity venous thrombosis?
Rabens, C, Goodemote, P, Jamieson, B
The Journal of family practice. 2010;(8):465-6
Abstract
Standard management is best: start with unfractionated heparin or low-molecular-weight heparin and follow with long-term therapy with a vitamin K antagonist. Some evidence supports thrombolytic therapy, placement of a superior vena cava filter, or surgical thrombectomy in selected patients. Whether to remove venous catheters during initial treatment for catheter-induced venous thrombosis remains unclear, because limited studies address this issue specifically.
3.
Craniosynostosis and related limb anomalies.
Wilkie, AO, Oldridge, M, Tang, Z, Maxson, RE
Novartis Foundation symposium. 2001;:122-33; discussion 133-43
Abstract
Many genetically determined craniosynostosis syndromes feature limb anomalies, implying that pathways of cranial suture and limb morphogenesis share some identical components. Identification of heterozygous mutations in FGFR1, FGFR2, FGFR3, TWIST and MSX2 in craniosynostosis has focused particular attention on these genes. Here we explore two themes: use of clinical/molecular analysis to provide new clues to pathophysiology and the contrasting effects of loss- and gain-of-function mutations. Apert syndrome is a severe craniosynostosis/syndactyly disorder usually caused by specific substitutions (Ser252Trp or Pro253Arg) in FGFR2. The relative severity of cranial and limb malformations varies in opposite directions for the two mutations, suggesting that these phenotypes arise by different mechanisms. Clinical and biochemical evidence supports a model in which alternative splice forms of FGFR2 mediate these distinct effects. Pro-->Arg substitutions equivalent the Pro253Arg/FGFR2 mutation occur in both FGFR1 and FGFR3, and are also associated with craniosynostosis. This suggests a common pathological mechanism, whereby enhanced affinity for a limited repertoire of tissue-specific ligand(s) excessively prolongs signalling in the cranial suture. The first MSX2 mutation in craniosynostosis was described in 1993 but this remains the only example. We have recently identified three MSX2 mutations associated with a different cranial phenotype, parietal foramina. DNA binding studies show that the craniosynostosis and parietal foramina arise from gain and loss of function, respectively.