Sjoerd P.F.T. Nota

Measurement of Upper Extremity Disability Using the Patient-Reported Outcomes Measurement Information System

PURPOSE Current questionnaires used to measure upper extremity-specific disability can be time-consuming and subject to ceiling effects. The National Institutes of Health developed Patient-Reported Outcomes Measurement Information System (PROMIS) measures based on computer adaptive testing (CAT), a technique that is more efficient and less subject to floor and ceiling effects than traditional questionnaires with a fixed number of questions. This study tested the correlation of the Physical Function-Upper Extremity CAT with the Quick-Disabilities of the Arm, Shoulder, and Hand (QuickDASH) questionnaire. METHODS Patients presenting to our orthopedic outpatient clinic were invited to participate in this observational cross-sectional study between August and October 2013. A study sample of 84 patients completed the QuickDASH and PROMIS Physical Function-Upper Extremity CAT, and 3 other PROMIS measures, as well as the 2-question Pain Self-efficacy Questionnaire and the 2-question Patient Health Questionnaire. RESULTS A strong correlation was found between QuickDASH and PROMIS Physical Function-Upper Extremity CAT, with a significantly shorter completion time for the latter. CONCLUSIONS We recommend the PROMIS Upper Extremity CAT because it is valid, reliable, and easy to use, and it provides easy reference to population norms (a score of 50 represents the norm in the United States population, and every 10 points represents a standard deviation from the norm). TYPE OF STUDY/LEVEL OF EVIDENCE Prognostic I.

PD-L1 and HLA Class I Antigen Expression and Clinical Course of the Disease in Intrahepatic Cholangiocarcinoma

Purpose: More effective therapy is needed for intrahepatic cholangiocarcinoma (ICC). The encouraging clinical results obtained with checkpoint molecule-specific monoclonal antibodies (mAb) have prompted us to investigate whether this type of immunotherapy may be applicable to ICC. The aims of this study were to determine whether (i) patients mount a T-cell immune response to their ICC, (ii) checkpoint molecules are expressed on both T cells and tumor cells, and (iii) tumor cells are susceptible to recognition by cognate T cells. Experimental Design: Twenty-seven ICC tumors were analyzed for (i) lymphocyte infiltrate, (ii) HLA class I and HLA class II expression, and (iii) PD-1 and PD-L1 expression by T cells and ICC cells, respectively. The results of this analysis were correlated with the clinicopathologic characteristics of the patients investigated. Results: Lymphocyte infiltrates were identified in all tumors. PD-L1 expression and HLA class I antigen expression by ICC cells was observed in 8 and 11, respectively, of the 27 tumors analyzed. HLA class I antigen expression correlated with CD8+ T-cell infiltrate. Furthermore, positive HLA class I antigen expression in combination with negative/rare PD-L1 expression was associated with favorable clinical course of the disease. Conclusions: ICC patients are likely to mount a T-cell immune response against their own tumors. Defects in HLA class I antigen expression in combination with PD-L1 expression by ICC cells provide them with an immune escape mechanism. This mechanism justifies the implementation of immunotherapy with checkpoint molecule-specific mAbs in patients bearing ICC tumors without defects in HLA class I antigen expression. Clin Cancer Res; 22(2); 470–8. ©2015 AACR.

The PROMIS Physical Function Correlates With the QuickDASH in Patients With Upper Extremity Illness

BackgroundTo assess disability more efficiently with less burden on the patient, the National Institutes of Health has developed the Patient Reported Outcomes Measurement Information System (PROMIS) Physical Function—an instrument based on item response theory and using computer adaptive testing (CAT). Initially, upper and lower extremity disabilities were not separated and we were curious if the PROMIS Physical Function CAT could measure upper extremity disability and the Quick Disability of Arm, Shoulder and Hand (QuickDASH).Questions/purposesWe aimed to find correlation between the PROMIS Physical Function and the QuickDASH questionnaires in patients with upper extremity illness. Secondarily, we addressed whether the PROMIS Physical Function and QuickDASH correlate with the PROMIS Depression CAT and PROMIS Pain Interference CAT instruments. Finally, we assessed factors associated with QuickDASH and PROMIS Physical Function in multivariable analysis.MethodsA cohort of 93 outpatients with upper extremity illnesses completed the QuickDASH and three PROMIS CAT questionnaires: Physical Function, Pain Interference, and Depression. Pain intensity was measured with an 11-point ordinal measure (0–10 numeric rating scale). Correlation between PROMIS Physical Function and the QuickDASH was assessed. Factors that correlated with the PROMIS Physical Function and QuickDASH were assessed in multivariable regression analysis after initial bivariate analysis.ResultsThere was a moderate correlation between the PROMIS Physical Function and the QuickDASH questionnaire (r = −0.55, p < 0.001). Greater disability as measured with the PROMIS and QuickDASH correlated most strongly with PROMIS Depression (r = −0.35, p < 0.001 and r = 0.34, p < 0.001 respectively) and Pain Interference (r = −0.51, p < 0.001 and r = 0.74, p < 0.001 respectively). The factors accounting for the variability in PROMIS scores are comparable to those for the QuickDASH except that the PROMIS Physical Function is influenced by other pain conditions while the QuickDASH is not.ConclusionsThe PROMIS Physical Function instrument may be used as an upper extremity disability measure, as it correlates with the QuickDASH questionnaire, and both instruments are influenced most strongly by the degree to which pain interferes with achieving goals.Level of Evidence Level III, diagnostic study. See the Instructions for Authors for a complete description of levels of evidence.

Disability and depression after orthopaedic trauma

INTRODUCTION Musculoskeletal injury is a common cause of impairment (pathophysiology), but the correlation of impairment with pain intensity and magnitude of disability is limited. Psychosocial factors explain a large proportion of the variance in disability for various orthopaedic pathologies. The aim of this study is to prospectively assess the relationship between psychological factors and magnitude of disability in a sample of orthopaedic trauma patients in The Netherlands. MATERIAL AND METHODS One hundred and one adult patients between 1 and 2 months after one or more fractures, tendon or ligament injuries were enrolled. Four eligible patients refused to participate. Thirty-five women and 30 men with an average age of 50 years (range, 22-92 years) completed the follow-up evaluation between 5 and 8 months after their injury and their data was analyzed. The patients completed a measure of disability (the Short Musculoskeletal Function Assessment-Netherlands, SMFA-NL), the Dutch Centre for Epidemiologic Study of Depression-scale (CES-D), the Dutch Impact of Event Scale (SVL), and the Dutch Pain Catastrophizing Scale (PCS) at the time of enrollment and again 5-8 months after injury. RESULTS There were moderate correlations between symptoms of depression (CES-D, r=0.48, p<0.001) and symptoms of PTSD (SVL, r=0.35, p=0.004) at enrollment and magnitude of disability 5-8 months after trauma. Catastrophic thinking (PCS) at enrollment and magnitude of disability 5-8 months after trauma showed a small correlation (PCS, r=0.26, p=0.034). The Pain Catastrophizing Scale (Beta=0.29; p=0.049), surgery (Beta=0.26; p=0.034), additional surgery (Beta=0.26; p=0.019) and other pain conditions (Beta=0.31; p=0.009) were the significant predictors in the final model (adjusted R-squared=0.35; p<0.001) for greater disability 5-8 months after trauma. DISCUSSION AND CONCLUSIONS In The Netherlands, symptoms of depression measured 1-2 months after musculoskeletal trauma correlate with disability 5-8 months after this trauma. The psychological aspects of recovery from musculoskeletal injury merit greater attention. LEVEL OF EVIDENCE Level II, Prognostic study.

Opioid Use, Satisfaction, and Pain Intensity After Orthopedic Surgery

BACKGROUND Patients in other countries use fewer opioids than patients in the United States with satisfactory pain relief. OBJECTIVE This study tested the null hypothesis that opioid intake after orthopedic surgery does not influence satisfaction with pain management. METHODS A total of 232 orthopedic surgical inpatients completed measures of pain self-efficacy and symptoms of depression at enrollment and commonly used measures of pain intensity, satisfaction with pain relief, and satisfaction with hospital staff attention to pain approximately 14 days after surgery. Inpatient opioid intake per 24-hour period was quantified. RESULTS At a phone evaluation approximately 2 weeks after discharge from the hospital, patients who were always satisfied with their pain relief in hospital and always satisfied with staff attention to pain used significantly less opioids on day 1 compared with patients who were not always satisfied. There were no differences in satisfaction by type of surgery. The final multivariable model for not always satisfied with pain relief included greater opioid use on day 1 (odds ratio = 1.2), and preadmission diagnosis of depression (odds ratio = 2.6). Greater opioid use on day 1 was the only factor associated with less than always satisfied with the staff attention to pain relief (odds ratio = 1.3). CONCLUSIONS Patients who take more opioids report less satisfaction with pain relief and greater pain intensity. Evidence-based interventions to increase self-efficacy merit additional study for the management of postoperative pain. LEVEL OF EVIDENCE Prognostic, Level 1.

The Identification of Prognostic Factors and Survival Statistics of Conventional Central Chondrosarcoma

Introduction. Chondrosarcomas are malignant bone tumors that are characterized by the production of chondroid tissue. Since radiation therapy and chemotherapy have limited effect on chondrosarcoma, treatment of most patients depends on surgical resection. We conducted this study to identify independent predictive factors and survival characteristics for conventional central chondrosarcoma and dedifferentiated central chondrosarcoma. Methods. A systematic literature review was performed in September 2014 using the Pubmed, Embase, and Cochrane databases. Subsequent to a beforehand-composed selection procedure we included 13 studies, comprising a total of 1114 patients. Results. The prognosis of central chondrosarcoma is generally good for the histologically low-grade tumors. Prognosis for the high-grade chondrosarcoma and the dedifferentiated chondrosarcoma is poor with lower survival rates. Poor prognostic factors in conventional chondrosarcoma for overall survival are high-grade tumors and axial/pelvic tumor location. In dedifferentiated chondrosarcoma the percentage of dedifferentiated component has significant influence on disease-free survival. Conclusion. Despite the fact that there are multiple prognostic factors identified, as shown in this study, there is a need for prospective and comparative studies. The resulting knowledge about prognostic factors and survival can give direction in the development of better therapies. This could eventually lead to an evidence-based foundation for treating chondrosarcoma patients.

The Creation of an Abbreviated Version of the PSEQ: The PSEQ-2

BACKGROUND Self-efficacy is an effective coping strategy associated with less pain and disability. The Pain Self-Efficacy Questionnaire (PSEQ) is a valid and reliable tool to measure this strategy, but could be inconvenient to implement in a busy surgical practice owing to its length. OBJECTIVE The purpose of this study was to develop a shorter version of the 10-item PSEQ. METHODS A total of 316 patients (53% men, mean age of 46 y) with a variety of upper extremity diagnosis were enrolled in this study. In addition to demographic information, patients completed the PSEQ measure of self-efficacy, the QuickDASH measure of disability, and an ordinal measure of pain intensity. We conducted inter-item correlation analyses for the PSEQ and selected questions based on the magnitude of their correlation. RESULTS Questions 8 and 9 were selected to form the PSEQ-2. The PSEQ-2 showed good internal consistency (α = 0.90) and had a large correlation with the original PSEQ (r = 0.76). Both the PSEQ-2 and the original PSEQ correlated significantly with QuickDASH and pain intensity. CONCLUSIONS This study provides preliminary evidence that a shortened version of the PSEQ might be useful as a screening instrument to identify patients with hand and upper extremity conditions who have low self-efficacy and might benefit from cognitive behavioral therapy. LEVEL OF EVIDENCE Diagnostic level III.

Antitumor Activity of BRAF Inhibitor and IFNα Combination in BRAF-Mutant Melanoma

BACKGROUND BRAF(V600E)-mediated MAPK pathway activation is associated in melanoma cells with IFNAR1 downregulation. IFNAR1 regulates melanoma cell sensitivity to IFNα, a cytokine used for the adjuvant treatment of melanoma. These findings and the limited therapeutic efficacy of BRAF-I prompted us to examine whether the efficacy of IFNα therapy of BRAF(V600E) melanoma can be increased by its combination with BRAF-I. METHODS BRAF/NRAS genotype, ERK activation, IFNAR1, and HLA class I expression were tested in 60 primary melanoma tumors from treatment-naive patients. The effect of BRAF-I on IFNAR1 expression was assessed in three melanoma cell lines and in four biopsies of BRAF(V600E) metastases. The antiproliferative, pro-apoptotic and immunomodulatory activity of BRAF-I and IFNα combination was tested in vitro and in vivo utilizing three melanoma cell lines, HLA class I-MA peptide complex-specific T-cells and immunodeficient mice (5 per group for survival and 10 per group for tumor growth inhibition). All statistical tests were two-sided. Differences were considered statistically significant when the P value was less than .05. RESULTS The IFNAR1 level was statistically significantly (P < .001) lower in BRAF(V600E) primary melanoma tumors than in BRAF wild-type tumors. IFNAR1 downregulation was reversed by BRAF-I treatment in the three melanoma cell lines (P ≤ .02) and in three out of four metastases. The IFNAR1 level in the melanoma tumors analyzed was increased as early as 10 to 14 days following the beginning of the treatment. These changes were associated with: 1) an increased susceptibility in vitro of melanoma cells to the antiproliferative (P ≤ .04), pro-apoptotic (P ≤ .009) and immunomodulatory activity, including upregulation of HLA class I antigen APM component (P ≤ .04) and MA expression as well as recognition by cognate T-cells (P < .001), of BRAF-I and IFNα combination and 2) an increased survival (P < .001) and inhibition of tumor growth of melanoma cells (P < .001) in vivo by BRAF-I and IFNα combination. CONCLUSIONS The described results provide a strong rationale for the clinical trials implemented in BRAF(V600E) melanoma patients with BRAF-I and IFNα combination.

Does Verbal and Nonverbal Communication of Pain Correlate With Disability

BACKGROUND Illness (symptoms and disability) consistently correlates more with coping strategies and symptoms of depression than with pathophysiology or impairment. OBJECTIVE This study tested the primary null hypothesis that there is no correlation between verbal and nonverbal communication of pain (pain behavior) and upper extremity-specific disability in patients with hand and upper extremity illness. METHODS A total of 139 new and followed up adult patients completed the QuickDASH, an ordinal rating of pain, and 4 Patient-Reported Outcomes Measurement Information System (PROMIS) Computer Adaptive Testing instruments: (1) PROMIS pain behavior, (2) PROMIS pain interference (measuring the degree to which pain interferes with achieving ones physical goals), (3) PROMIS physical function, and (4) PROMIS depression. RESULTS Factors associated with a higher QuickDASH score in bivariate analysis included a higher PROMIS pain behavior score, not working, being separated/divorced or widowed, having sought treatment before, having other pain conditions, a higher PROMIS pain interference score, a higher PROMIS depression score, and lower education level. The final multivariable model of factors associated with QuickDASH included PROMIS pain interference, having other pain conditions, and being separated/divorced or widowed, and it explained 64% of the variability. CONCLUSION PROMIS pain behavior (verbal and nonverbal communication of pain) correlates with upper extremity disability, but PROMIS pain interference (the degree to which pain interferes with activity) is a more important factor. LEVEL OF EVIDENCE Level IV, cross-sectional study.

Is Social Support Associated With Upper Extremity Disability

BackgroundPain intensity and disability correlate with psychosocial factors such as depression and pain interference (the degree to which pain interferes with activities of daily living) as much or more than pathophysiology in upper extremity illness. However, other factors like emotional support (perception of being cared for and valued as a person), instrumental support (perception of availability of tangible assistance when needed), positive psychosocial impact (perception and focus on the positive side of a difficult situation, sometimes characterized as posttraumatic growth, benefit-finding, or meaning making), also might be associated with disability in patients with upper extremity orthopaedic illness. This is the first published study, to our knowledge, addressing the potential association of emotional support, instrumental support, and positive psychosocial illness impact with disability in patients with upper extremity illness.Questions/PurposesWe asked: (1) Is there a correlation between the QuickDASH and the Patient-reported Outcomes Measurement Information System (PROMIS®) emotional support Computer Adaptive Testing (CAT)? (2) Is there a correlation between the QuickDASH and PROMIS® instrumental support CAT? (3) Is there a correlation between the QuickDASH and PROMIS® positive psychosocial illness impact CAT? (4) Among the PROMIS® measures of depression, emotional support, instrumental support, positive illness impact, and pain interference, which accounts for the most variance in QuickDASH scores?MethodsOne hundred ninety-three patients with upper extremity illness (55% women; average age, 51 ± 18 years) of 213 approached (91% recruitment rate) completed the QuickDASH, and five different PROMIS® CATs: pain interference (the degree to which pain interferes with accomplishing one’s goals), depression, emotional support, psychosocial illness impact, and instrumental support. We recruited patients from the practice of three surgeons in hand service of the department of orthopaedic surgery at a major urban university hospital.ResultsPearson Product Moment Correlations showed that emotional support (r = −0.18; p = 0.014) and instrumental support (r = −0.19; p = 0.008) were weakly and inversely associated with the QuickDASH), while positive psychosocial illness impact was moderately and inversely associated with the QuickDASH (r = −0.36; p < 0.001). In multivariable analyses, pain interference, but not the social support measures, was the only psychosocial factor associated with the QuickDASH and alone explained 66% of variance.ConclusionsEmotional support, instrumental support and positive psychosocial illness impact are all individually associated with disability to a small degree, but pain interference (the degree to which pain interferes with accomplishing one’s goals) has the strongest influence on magnitude of disability.Level of EvidenceLevel 1, prognostic study.