Psychometric evaluation of the Disabilities of the Arm, Shoulder and Hand (DASH) with Dupuytren's contracture: validity evidence using Rasch modeling

Background Dupuytren’s contracture is a progressive, fibroproliferative disorder that causes fixed finger contractures and can lead to disability. With the advances of new therapeutic interventions, the necessity to assess the functional repercussions of this condition using valid, reliable and sensitive outcome measures is of growing interest. The Disabilities of the Arm, Shoulder and Hand (DASH) is one frequently used patient-reported outcome measure but its reliability and validity have never been demonstrated specifically for a population affected with Dupuytren’s contracture. The objective of this study was to evaluate the psychometric properties of the DASH, with focus on validity evidence using the Rasch measurement model. Methods Secondary analysis was performed on data collected as part of a randomised clinical trial. One hundred fifty-three participants diagnosed with Dupuytren’s contracture completed the DASH at four time points (pre-op, 3, 6 and 12 months post-op). Baseline data were analysed using traditional analysis and to test whether they adhered to the expectations of the Rasch model. Post-intervention data were subsequently included and analyzed to determine the effect of the intervention on the items. Results DASH scores demonstrated large ceiling effects at all time points. Initial fit to the Rasch model revealed that the DASH did not adhere to the expectations of the Rasch partial credit model (χ2 = 119.92; p < 0.05). Multiple items displayed inadequate response categories and two items displayed differential item functioning by gender. Items were transformed and one item deleted leading to an adequate fit. Remaining items fit the Rasch model but still do not target well the population under study. Conclusions The original version of the 30-item DASH did not display adequate validity evidence for use in a population with Dupuytren’s contracture. Further development is required to improve the DASH for this population

14-3-3 Proteins Interact with a Hybrid Prenyl-Phosphorylation Motif to Inhibit G Proteins

Signaling through G proteins normally involves conformational switching between GTP- and GDP-bound states. Several Rho GTPases are also regulated by RhoGDI binding and sequestering in the cytosol. Rnd proteins are atypical constitutively GTP-bound Rho proteins, whose regulation remains elusive. Here, we report a high-affinity 14-3-3-binding site at the C terminus of Rnd3 consisting of both the Cys241-farnesyl moiety and a Rho-associated coiled coil containing protein kinase (ROCK)-dependent Ser240 phosphorylation site. 14-3-3 binding to Rnd3 also involves phosphorylation of Ser218 by ROCK and/or Ser210 by protein kinase C (PKC). The crystal structure of a phosphorylated, farnesylated Rnd3 peptide with 14-3-3 reveals a hydrophobic groove in 14-3-3 proteins accommodating the farnesyl moiety. Functionally, 14-3-3 inhibits Rnd3-induced cell rounding by translocating it from the plasma membrane to the cytosol. Rnd1, Rnd2, and geranylgeranylated Rap1A interact similarly with 14-3-3. In contrast to the canonical GTP/GDP switch that regulates most Ras superfamily members, our results reveal an unprecedented mechanism for G protein inhibition by 14-3-3 proteins

Prospective observational cohort study on grading the severity of postoperative complications in global surgery research

Background The Clavien–Dindo classification is perhaps the most widely used approach for reporting postoperative complications in clinical trials. This system classifies complication severity by the treatment provided. However, it is unclear whether the Clavien–Dindo system can be used internationally in studies across differing healthcare systems in high- (HICs) and low- and middle-income countries (LMICs). Methods This was a secondary analysis of the International Surgical Outcomes Study (ISOS), a prospective observational cohort study of elective surgery in adults. Data collection occurred over a 7-day period. Severity of complications was graded using Clavien–Dindo and the simpler ISOS grading (mild, moderate or severe, based on guided investigator judgement). Severity grading was compared using the intraclass correlation coefficient (ICC). Data are presented as frequencies and ICC values (with 95 per cent c.i.). The analysis was stratified by income status of the country, comparing HICs with LMICs. Results A total of 44 814 patients were recruited from 474 hospitals in 27 countries (19 HICs and 8 LMICs). Some 7508 patients (16·8 per cent) experienced at least one postoperative complication, equivalent to 11 664 complications in total. Using the ISOS classification, 5504 of 11 664 complications (47·2 per cent) were graded as mild, 4244 (36·4 per cent) as moderate and 1916 (16·4 per cent) as severe. Using Clavien–Dindo, 6781 of 11 664 complications (58·1 per cent) were graded as I or II, 1740 (14·9 per cent) as III, 2408 (20·6 per cent) as IV and 735 (6·3 per cent) as V. Agreement between classification systems was poor overall (ICC 0·41, 95 per cent c.i. 0·20 to 0·55), and in LMICs (ICC 0·23, 0·05 to 0·38) and HICs (ICC 0·46, 0·25 to 0·59). Conclusion Caution is recommended when using a treatment approach to grade complications in global surgery studies, as this may introduce bias unintentionally