Validation of Patient-Reported Outcomes Measurement Information System Computerized Adaptive Tests Against the Foot and Ankle Outcome Score for 6 Common Foot and Ankle Pathologies.

BACKGROUND: The field of foot and ankle surgery lacks a widely accepted gold-standard patient-reported outcome instrument. With the changing infrastructure of the medical profession, more efficient patient-reported outcome tools are needed to reduce respondent burden and increase participation while providing consistent and reliable measurement across multiple pathologies and disciplines. The primary purpose of the present study was to validate 3 Patient-Reported Outcomes Measurement Information System computer adaptive tests (CATs) most relevant to the foot and ankle discipline against the Foot and Ankle Outcome Score (FAOS) and the Short Form 12 general health status survey in patients with 6 common foot and ankle pathologies. METHODS: Patients (n = 240) indicated for operative treatment for 1 of 6 common foot and ankle pathologies completed the CATs, FAOS, and Short Form 12 at their preoperative surgical visits, 1 week subsequently (before surgery), and at 6 months postoperatively. The psychometric properties of the instruments were assessed and compared. RESULTS: The Patient-Reported Outcomes Measurement Information System CATs each took less than 1 minute to complete, whereas the FAOS took 6.5 minutes, and the Short Form 12 took 3 minutes. CAT scores were more normally distributed and had fewer floor and ceiling effects than those on the FAOS, which reached as high as 24%. The CATs were more precise than the FAOS and had similar responsiveness and test-retest reliability. The physical function and mobility CATs correlated strongly with the activities subscale of the FAOS, and the pain interference CAT correlated strongly with the pain subscale of the FAOS. The CATs and FAOS were responsive to changes with operative treatment for 6 common foot and ankle pathologies. CONCLUSIONS: The CATs performed as well as or better than the FAOS in all aspects of psychometric validity. The Patient-Reported Outcomes Measurement Information System CATs show tremendous potential for improving the study of patient outcomes in foot and ankle research through improved precision and reduced respondent burden. LEVEL OF EVIDENCE: Level II, prospective comparative study.

Contribution of Lateral Column Lengthening to Correction of Forefoot Abduction in Stage IIb Adult Acquired Flatfoot Deformity Reconstruction.

BACKGROUND: Correction of forefoot abduction in stage IIb adult acquired flatfoot likely depends on the amount of lateral column lengthening (LCL) performed, although this represents only one aspect of a successful reconstruction. The purpose of this study was to evaluate the correlation between common reconstructive variables and the observed change in forefoot abduction. METHODS: Forty-one patients who underwent flatfoot reconstruction involving an Evans-type LCL were assessed retrospectively. Preoperative and postoperative anteroposterior (AP) radiographs of the foot at a minimum of 40 weeks (mean, 2 years) after surgery were reviewed to determine correction in forefoot abduction as measured by talonavicular coverage (TNC) angle, talonavicular uncoverage percent, talus-first metatarsal (T-1MT) angle, and lateral incongruency angle. Fourteen demographic and intraoperative variables were evaluated for association with change in forefoot abduction including age, gender, height, weight, body mass index, as well as the amount of LCL and medializing calcaneal osteotomy performed, LCL graft type, Cotton osteotomy, first tarsometatarsal fusion, flexor digitorum longus transfer, spring ligament repair, gastrocnemius recession and any one of the modified McBride/Akin/Silver procedures. RESULTS: Two variables significantly affected the change in lateral incongruency angle. These were weight (P = .04) and the amount of LCL performed (P < .001). No variables were associated with the change in TNC angle, talonavicular uncoverage percent, or T-1MT angle. Multivariate regression analysis revealed that LCL was the only significant predictor of the change in lateral incongruency angle. The final regression model for LCL showed a good fit (R2 = 0.70, P < .001). Each millimeter of LCL corresponded to a 6.8-degree change in lateral incongruency angle. CONCLUSION: Correction of forefoot abduction in flatfoot reconstruction was primarily determined by the LCL procedure and could be modeled linearly. We believe that the lateral incongruency angle can serve as a valuable preoperative measurement to help surgeons titrate the proper amount of correction performed intraoperatively.

Toxicogenomic studies of the rat brain at an early time point following acute sarin exposure.

We have studied sarin-induced global gene expression patterns at an early time point (2 h: 0.5 x LD50) using Affymetrix Rat Neurobiology U34 chips and male Sprague-Dawley rats. A total of 46 genes showed statistically significant alterations from control levels. Three gene categories contained more of the altered genes than any other groups: ion channel (8 genes) and calcium channel and binding proteins (6 genes). Alterations were also found in the following gene groups: ATPases and ATP-based transporters (4), growth factors (4), G-protein-coupled receptor pathway-related molecules (3), neurotransmission and neurotransmitter transporters (3), cytoskeletal and cell adhesion molecules (2), hormones (2), mitochondria-associated proteins (2), myelin proteins (2), stress-activated molecules (2), cytokine (1), caspase (1), GABAnergic (1), glutamergic (1), immediate early gene (1), prostaglandin (1), transcription factor (1), and tyrosine phosphorylation molecule (1). Persistent alteration of the following genes also were noted: Arrb1, CaMKIIa, CaMKIId, Clcn5, IL-10, c-Kit, and Plp1, suggesting altered GPCR, kinase, channel, and cytokine pathways. Selected genes from the microarray data were further validated using relative RT-PCR. Some of those genes (GFAP, NF-H, CaMKIIa, Calm, and MBP) have been shown by other laboratories and ours, to be involved in the pathogenesis of sarin-induced pathology and organophosphate-induced delayed neurotoxicity (OPIDN). Induction of both proapoptotic (Bcl2l11, Casp6) and antiapoptotic (Bcl-X) genes, besides suppression of p21, suggest complex cell death/protection-related mechanisms operating early on. Principal component analysis (PCA) of the expression data confirmed that the changes in gene expression are a function of sarin exposure, since the control and treatment groups separated clearly. Our model (based on current and previous studies) indicates that both degenerative and regenerative pathways are activated early and contribute to the level of neurodegeneration at a later time, leading to neuro-pathological alterations.

Gene expression profiles of the rat brain both immediately and 3 months following acute sarin exposure.

We have studied sarin-induced global gene expression patterns at an early time point (15 min; 0.5xLD50) and a later time point (3 months; 1xLD50) using Affymetrix: Rat Neurobiology U34 chips in male, Sprague-Dawley rats and have identified a total of 65 (early) and 38 (late) genes showing statistically significant alterations from control levels at 15 min and 3 months, respectively. At the early time point, those that are classified as ion channel, cytoskeletal and cell adhesion molecules, in addition to neuropeptides and their receptors predominated over all other groups. The other groups included: cholinergic signaling, calcium channel and binding proteins, transporters, chemokines, GABAnergic, glutamatergic, aspartate, catecholaminergic, nitric oxide synthase, purinergic, and serotonergic signaling molecules. At the late time point, genes that are classified as calcium channel and binding proteins, cytoskeletal and cell adhesion molecules and GABAnergic signaling molecules were most prominent. Seven molecules (Ania-9, Arrb-1, CX-3C, Gabab-1d, Nos-2a, Nrxn-1b, PDE2) were identified that showed altered persistent expression in both time points. Selected genes from each of these time points were further validated using semi quantitative RT-PCR approaches. Some of the genes that were identified in the present study have been shown to be involved in organophosphate-induced neurotoxicity by both other groups as well as ours. Principal component analysis (PCA) of the expression data from both time points was used for comparative analysis of the gene expression, which indicated that the changes in gene expression were a function of dose and time of euthanasia after the treatment. Our model also predicts that besides dose and duration of post-treatment period, age and possibly other factors may be playing important roles in the regulation of pathways, leading to the neurotoxicity.