ABSTRACT
OBJECTIVES: The plethora of self-administered questionnaires to assess positive psychosocial factors complicates questionnaire selection. This study aimed to identify and reach consensus on the most suitable self-administered questionnaires to assess resilience, optimism, pain acceptance and social support in people with pain. DESIGN: A three-round modified Delphi study. PARTICIPANTS: Forty international experts. METHODS: In Round 1, the experts suggested questionnaires deemed appropriate to assess resilience, optimism, pain acceptance and/or social support. In Round 2, experts indicated whether they considered the suggested questionnaires to be suitable (Yes/No/Don't know) to assess these psychosocial factors, taking into consideration content, feasibility, personal experience and the measurement properties which we provided for each questionnaire. Questionnaires that were considered suitable by the majority of experts (≥60%) were retained for Round 3. In Round 3, the suitability of each questionnaire was rated on a 0-10 Likert scale. Consensus was reached if ≥75% of experts rated the questionnaire ≥7. RESULTS: From the 67 questionnaires suggested in Round 1, one questionnaire could be recommended per domain. For resilience: Pain Resilience Scale; for optimism: Revised Version of the Life Orientation Test; for pain acceptance: 8-item and Revised Versions of the Chronic Pain Acceptance Questionnaire; for social support: Emotional Support Item Bank of the PROMIS tool. Consensus for these questionnaires was also reached in a sensitivity analysis which excluded the ratings of experts involved in the development, translation and/or validation of relevant questionnaires. CONCLUSION: We advocate the use of these recommended questionnaires so data can be compared and pooled more easily.
Subject(s)
Chronic Pain , Social Support , Humans , Delphi Technique , Surveys and Questionnaires , Pain MeasurementABSTRACT
The treatment of transformed indolent lymphoma (TRIL) often includes salvage chemotherapy (SC) and autologous stem cell transplant (ASCT). NCIC CTG LY12 is a randomized phase 3 trial comparing gemcitabine, dexamethasone, and cisplatin (GDP) with dexamethasone, cytarabine, and cisplatin (DHAP) before ASCT. This analysis compares the results of SC and ASCT for TRIL with de novo diffuse large B-cell lymphoma (DLBCL). Six-hundred nineteen patients with relapsed/refractory aggressive non-Hodgkin lymphoma were randomized to GDP or DHAP; 87 patients (14%) had TRIL and 429 (69%) had DLBCL. The response rate to SC was 47% in TRIL and 45% in DL (P = .81). Transplantation rates were similar: TRIL 53% and DL 52% (P = 1.0). With a median follow-up of 53 months, 4 year overall survival was 39% for TRIL and 41% for DL (P = .78); 4 year event-free survival (EFS) was 27% for TRIL and 27% for DL (P = .83). Post-ASCT, 4-year EFS was 45% for TRIL and 46% for DL. Histology (TRIL or DL) was not a predictor of any outcome in multivariate models. Patients with relapsed or refractory TRIL and DLBCL have similar outcomes with SC and ASCT; this therapy should be considered the standard of care for patients with TRIL who have received prior systemic chemotherapy. NCIC CTG LY12 is registered at ClinicalTrials.gov as #NCT00078949.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols , Hematopoietic Stem Cell Transplantation , Lymphoma, Large B-Cell, Diffuse/therapy , Lymphoma, Non-Hodgkin/therapy , Salvage Therapy/methods , Adult , Aged , Cisplatin/administration & dosage , Cytarabine/administration & dosage , Deoxycytidine/administration & dosage , Deoxycytidine/analogs & derivatives , Dexamethasone/administration & dosage , Etoposide/administration & dosage , Female , Follow-Up Studies , Humans , Lymphoma, Large B-Cell, Diffuse/pathology , Lymphoma, Non-Hodgkin/pathology , Male , Middle Aged , Multivariate Analysis , Prognosis , Recurrence , Survival Analysis , Time Factors , Transplantation, Autologous , GemcitabineABSTRACT
Non-Hodgkin lymphoma (NHL) frequently manifests in extranodal structures in the chest, often in the form of secondary involvement but occasionally as primary disease. Because staging and treatment are affected by the presence of extranodal disease at imaging, radiologists' interpretation and management of suspicious findings are critical to patient care. Unfortunately, owing to considerable imaging overlap with other diseases, primary extranodal lymphoma is difficult to diagnose with imaging alone. Radiologists should have a heightened degree of suspicion in patients at risk (including patients with immune compromise, autoimmune diseases, or a history of stem cell or solid organ transplant) or with particular imaging appearances (including the vertebral wraparound sign, nonresolving consolidation, an infiltrative soft-tissue mass, and lesions demonstrating vascular encasement without invasion). For patients with known NHL, positron emission tomography/computed tomography (PET/CT) using fluorine 18 (18F)-labeled fluorodeoxyglucose (FDG) is now preferred for routine staging in most cases. CT remains heavily used, and identification of subtle extranodal involvement with CT can be improved with use of intravenous contrast material and careful review of multiplanar images. Pericardial effusion, pleural soft tissue (even when mild), mass-like consolidation, perilymphatic nodularity, and new lytic bone lesions are particularly suggestive of secondary involvement in a patient with known NHL. Magnetic resonance imaging is a helpful problem-solving tool when equivocal findings would change staging and treatment. This comprehensive review illustrates the spectrum of CT manifestations of extranodal NHL in the chest, including the pleura, lung, airways, heart, pericardium, esophagus, chest wall, and breast. ©RSNA, 2017.
Subject(s)
Lymphoma, Non-Hodgkin/diagnostic imaging , Thoracic Neoplasms/diagnostic imaging , Tomography, X-Ray Computed , Contrast Media , Diagnosis, Differential , Humans , Lymphoma, Non-Hodgkin/pathology , Thoracic Neoplasms/pathologyABSTRACT
BACKGROUND: Falls are a major public health concern globally. While falls are associated with osteoarthritis and persistent pain at the hip and knee, falls have not been investigated in people with chronic ankle symptoms. This study aimed to compare self-reported history of falls between adults with and without chronic ankle symptoms. Secondary aims were to compare concern about falling and balance confidence between groups, and to identify factors associated with falling. METHODS: A total of 226 participants (134 with chronic ankle pain and/or stiffness and 92 controls) participated in this cross-sectional case-control study. Participants completed an online questionnaire about falls in the past 12 months, injuries associated with falling, concern about falling, balance confidence, function, pain and multimorbidity. RESULTS: Eighty-six (64%) participants with chronic ankle symptoms and 24 (26%) controls reported at least one fall in the last 12 months (p < 0.001). Participants with chronic ankle symptoms reported more falls, more injurious falls, and more hospitalisations because of a fall than controls (p > 0.002). There was a small effect for lower balance confidence and higher concern about falling in symptomatic participants (standardised mean difference: 0.39-0.49; p > 0.017). Logistic regression analysis identified that falling was associated with the presence of ankle symptoms (3.08 (1.20, 7.92); p = 0.02) and concern about falling (odds ratio (95% confidence intervals): 1.13 (1.05, 1.23); p = 0.002). CONCLUSIONS: Falls and falls-related injuries are a problem in individuals with chronic ankle symptoms. The high falls occurrence and concern about falling in individuals with chronic ankle symptoms suggest the need for clinicians to assess these factors in this population.
Subject(s)
Ankle , Chronic Pain , Adult , Humans , Cross-Sectional Studies , Case-Control Studies , Self ReportABSTRACT
STUDY DESIGN: Cross-sectional design. OBJECTIVES: To investigate lumbar multifidus (LM) thickness differences, using ultrasound imaging in people during remission from recurrent low back pain (LBP) and healthy participants, during the following lower extremity movements: (1) active straight leg raise (ASLR), (2) crook-lying active leg raise (CLR), and (3) prone straight leg raise (PSLR). BACKGROUND: ASLR, CLR, and PSLR are used clinically to challenge the ability of the trunk muscles to control spinal motion in people with LBP, and it is believed that decreased LM activity is related to altered spinal control in this population. However, it is unclear whether LM behavior differs between healthy individuals and people with recurrent LBP during symptom remission in such tasks. METHODS: The present study used ultrasound imaging to measure LM percentage thickness change parasagitally at the L4-5 and L5-S1 levels in people with recurrent LBP during symptom remission and in healthy participants, during the ASLR, CLR, and PSLR tasks. RESULTS: LM percentage thickness change was greater in the recurrent LBP group than in healthy participants during the PSLR task (P<.01) and greater in both groups during the PSLR than the ASLR and CLR tasks (P<.01). LM percentage thickness change was greatest at L4-5 in both groups (P<.01) and during all tasks (P≤.02). No difference was found in LM percentage thickness change between groups in either the ASLR (P = .70) or CLR (P = .69) task. CONCLUSIONS: These data suggest that, during symptom remission, individuals with recurrent LBP, compared to healthy individuals, may have greater activity in at least some parts of the LM. Further investigation is required to determine whether the LM percentage thickness change observed in this study may be explained by differential changes in deep and/or superficial fibers of LM activity. This observation may have implications for clinical practice, but requires further investigation.
Subject(s)
Low Back Pain/physiopathology , Low Back Pain/rehabilitation , Lower Extremity/physiopathology , Lumbosacral Region/physiopathology , Movement/physiology , Muscle, Skeletal/physiopathology , Analysis of Variance , Case-Control Studies , Cross-Sectional Studies , Female , Humans , Low Back Pain/diagnostic imaging , Lower Extremity/diagnostic imaging , Lumbosacral Region/diagnostic imaging , Male , Muscle, Skeletal/diagnostic imaging , Reproducibility of Results , Ultrasonography , Young AdultABSTRACT
BACKGROUND: Ankle osteoarthritis (OA) is associated with several physical impairments but investigations into balance impairments in this population are limited. Understanding balance impairments in ankle OA may help inform the management of this condition. RESEARCH QUESTION: Does balance overall performance differ between individuals with symptomatic radiographic ankle OA, asymptomatic radiographic ankle OA and healthy controls? Are there any differences in mediolateral or anteroposterior balance, or confidence to perform balance tasks between these groups? METHODS: Ninety-six volunteers (31 symptomatic radiographic ankle OA, 41 asymptomatic radiographic ankle OA and 24 healthy controls) completed six static balance tasks: bilateral stance on a firm surface, bilateral stance on foam, and tandem stance, all performed with eyes open and closed. Centre of pressure (COP) data were collected using force plates. Confidence to perform each balance task was collected using an 11-point numerical rating scale. RESULTS: Compared to controls, participants with symptomatic radiographic ankle OA had greater COP area when standing on a firm surface, foam and in tandem with eyes closed (all p < 0.05) and greater total COP sway in both firm surface and tandem stance conditions (p < 0.04). Participants with symptomatic ankle OA had greater COP area (p < 0.04) and total COP sway (p = 0.01) than those with asymptomatic ankle OA during tandem stance. Total COP sway and area were similar between asymptomatic ankle OA and control participants. Some differences in mediolateral and anteroposterior balance were identified between groups. Individuals with symptomatic ankle OA had lower confidence to perform the tandem stance eyes closed task compared to controls. SIGNIFICANCE: Balance impairments and decreased balance confidence were identified in those with symptomatic radiographic ankle OA compared to asymptomatic individuals with and without radiographic ankle OA. This suggests that balance deficits in ankle OA may be related to symptoms, rather than radiographic evidence of disease.
Subject(s)
Ankle , Osteoarthritis , Cross-Sectional Studies , Gravitation , Humans , Postural BalanceABSTRACT
OBJECTIVE: To compare physical and patient-reported outcomes between (1) individuals with symptomatic radiographic ankle osteoarthritis (OA) and asymptomatic individuals, and (2) asymptomatic individuals with and without radiographic ankle OA. DESIGN: Cross-sectional study. METHODS: Ninety-six volunteers (31 symptomatic individuals with radiographic ankle OA, 41 asymptomatic individuals with radiographic ankle OA, and 24 asymptomatic individuals without radiographic ankle OA) completed a survey on quality of life (QoL), function, pain, disability, kinesiophobia, ankle instability, and physical activity, and undertook physical assessments of ankle muscle strength, heel-raise endurance, dorsiflexion range of motion (ROM), and ambulatory function. RESULTS: Symptomatic individuals with radiographic ankle OA reported greater pain (standardized mean difference [SMD], 1.70; 95% confidence interval [CI]: 1.18, 2.23), disability (SMD, 1.44; 95% CI: 0.93, 1.95), and instability (SMD, -3.92; 95% CI: -4.68, -3.17), and lower patient-reported function (SMD, -2.10; 95% CI: -2.66, -1.54) and QoL (SMD, -0.98; 95% CI: -1.47, -0.50), than asymptomatic individuals. Muscle strength (all SMDs, -0.73 or greater), heel-raise endurance (SMD, -0.71; 95% CI: -1.16, -0.25), dorsiflexion ROM (SMD, -1.54; 95% CI: -2.02, -1.06), and ambulatory function (all SMDs, 0.57 or greater) were significantly impaired in symptomatic individuals with radiographic ankle OA compared to asymptomatic individuals. Most patient-reported and physical outcomes were similar between asymptomatic individuals with and without radiographic ankle OA. CONCLUSION: Individuals with symptomatic radiographic ankle OA had poorer physical outcomes, function, and QoL compared to asymptomatic individuals with and without radiographic ankle OA. This suggests that disability in ankle OA is related to symptoms rather than to radiographic evidence of degeneration. J Orthop Sports Phys Ther 2020;50(12):711-722. doi:10.2519/jospt.2020.9376.
Subject(s)
Ankle/physiopathology , Osteoarthritis/physiopathology , Physical Functional Performance , Quality of Life , Adult , Aged , Ankle/diagnostic imaging , Asymptomatic Diseases , Cross-Sectional Studies , Exercise , Female , Humans , Joint Instability/physiopathology , Male , Middle Aged , Muscle Strength , Osteoarthritis/diagnostic imaging , Osteoarthritis/psychology , Patient Reported Outcome Measures , Radiography , Range of Motion, Articular , Self Report , Stair Climbing , Walking Speed , Young AdultABSTRACT
INTRODUCTION: Intramuscular electromyography electrodes targeting flexor digitorum profundus (FDP) are inserted via the anterior or medial aspect of the forearm. These two methods pose different risks to neurovascular structures which overly FDP. This study aimed to compare the insertion depth and consider advantages and limitations of two different techniques to insert intramuscular electrodes into FDP. METHODS: Using ultrasound imaging, neurovascular structures were identified along the path of FDP electrode insertion at the junction of the proximal and middle third of the ulna, bilaterally, in ten healthy individuals. Insertion depth was compared between the anterior and medial approaches for the mid muscle belly and targeted insertion to the index finger fascicle of FDP. RESULTS: In our sample the ulnar artery was superficial to the FDP muscle when viewed anteriorly and was beyond the furthest border of FDP when viewed medially. Compared to the anterior approach, the medial insertion depth was 1.5â¯cm (95%CI 1.4-1.7, pâ¯<â¯0.001) less to the mid-belly of FDP and 0.6â¯cm (95%CI 0.4-0.7, pâ¯<â¯0.001) less to the index finger fascicle of FDP. DISCUSSION: The medial approach involves less depth and lower risk for perforation of neurovascular structures when inserting intramuscular electrodes into the FDP muscle.
Subject(s)
Electromyography/methods , Fingers/physiology , Muscle, Skeletal/physiology , Adult , Electrodes, Implanted , Female , Humans , Male , Middle AgedABSTRACT
The treatment of early or limited-stage Hodgkin's lymphoma continues to evolve. With the likelihood of cure of the lymphoma approaching 95% it has become increasingly necessary to balance improved effectiveness of treatment with minimization of troublesome late toxicity. Carefully crafted treatment strategies based on optimal combinations of brief chemotherapy and involved-field radiation or even reliance on brief chemotherapy alone for carefully selected patients have emerged as the most attractive approaches to achieve this important balance.
Subject(s)
Hodgkin Disease/drug therapy , Hodgkin Disease/radiotherapy , Antineoplastic Combined Chemotherapy Protocols , Chemotherapy, Adjuvant , Clinical Trials as Topic , Combined Modality Therapy , Drug Administration Schedule , Hodgkin Disease/pathology , Humans , Neoplasm Staging , Radiotherapy, AdjuvantABSTRACT
This review draws from leading research on pain neuroscience and control of posture and movement to help inform rehabilitation approaches and when it may or may not be prudent to "dance through" pain. Control of posture and movement is frequently distorted by pain perception, and that may not be altered even when the pain is resolved. It is important to exclude serious systemic disease or major tissue injury with severe, unremitting, or persistent symptoms before focusing on movement-based rehabilitation. Both specific exercises (contraction of specific muscles and use of movement techniques) and general exercises which promote strength, power, endurance, and flexibility) can help to manage individuals with persistent pain problems. Training control of posture and movement can improve motor skills and tissue integrity and also normalize perception of sensory stimuli from the peripheral nervous system. A framework for planning such training can be considered in terms of progression of load, complexity, and context.
Subject(s)
Athletic Injuries/diagnosis , Athletic Injuries/prevention & control , Dancing/injuries , Pain/etiology , Pain/prevention & control , Athletic Injuries/complications , Humans , Muscle Strength/physiology , Pain Management , Range of Motion, Articular/physiologyABSTRACT
BACKGROUND: Perceived task complexity can impact participation in an exercise programme and the level of skill acquisition resulting from participation. Although trunk stability exercises are commonly included in the management of people with low back pain, potential differences in perceived task complexity between those exercises have not been investigated previously. OBJECTIVE: To investigate the perceived task complexity following first time instruction of two common stability exercises: the abdominal brace and abdominal hollow. DESIGN: Cross-sectional. METHODS: Twenty-four naïve healthy participants received instruction in the performance of an abdominal brace and an abdominal hollow with feedback. Participants rated their perceived task complexity (mental, physical, and temporal demand, performance, effort, frustration) for each exercise on the NASA-Task Load Index. RESULTS: The abdominal hollow was associated with higher perceived mental demand than the abdominal brace (p = 0.01), and required more time to learn (p < 0.01). The abdominal brace was associated with greater mental demand and frustration when performed after the abdominal hollow than before. CONCLUSIONS: This study has provided the first evidence for differences in perceived task complexity between two commonly used trunk stability exercises. Those differences in perceived task complexity may influence the selection of exercises intended to enhance the robustness of spinal stability.
Subject(s)
Exercise Therapy/methods , Exercise Therapy/psychology , Healthy Volunteers/psychology , Low Back Pain/therapy , Posture/physiology , Task Performance and Analysis , Torso/physiopathology , Adult , Cross-Sectional Studies , Female , Humans , Male , Young AdultABSTRACT
Objective: To evaluate safety, tolerability, and preliminary activity of inotuzumab ozogamicin (InO) plus rituximab, gemcitabine, dexamethasone, and cisplatin (R-GDP) in patients with relapsed/refractory CD22+ B-cell non-Hodgkin lymphoma (NHL). Methods: Patients received InO plus R-GDP (21-day cycle; six-cycle maximum) using up-and-down dose-escalation schema for gemcitabine and cisplatin to define the highest dosage regimen(s) with acceptable toxicity (Part 1; n = 27). Part 2 (n = 10) confirmed safety and tolerability; Part 3 (n = 18) evaluated preliminary efficacy. Results: Among 55 patients enrolled, 42% were refractory at baseline (median 2 [range, 1-6] prior therapies); 38% had diffuse large B-cell lymphoma (DLBCL). The highest dosage regimen with acceptable toxicity was InO 0.8 mg/m2, rituximab 375 mg/m2, cisplatin 50 mg/m2, gemcitabine 500 mg/m2 (day 1 only) and dexamethasone 40 mg (days 1-4); this was confirmed in Part 2, in which three patients had dose-limiting toxicities (grade 4 thrombocytopenia [n = 2], febrile neutropenia [n = 2]). Most frequent treatment-related adverse events were thrombocytopenia (any grade, 85%; grade ≥3, 75%) and neutropenia (69%; 62%). Overall (objective) response rate (ORR) was 53% (11 complete, 18 partial responses); ORR was 71%, 33%, and 62% in patients with follicular lymphoma (n = 14), DLBCL (n = 21), and mantle cell lymphoma (n = 13), respectively. Conclusions: InO 0.8 mg/m2 plus R-GDP was associated with manageable toxicity, although gemcitabine and cisplatin doses were lower than in the standard R-GDP regimen due to hematologic toxicity. Evidence of antitumor activity was observed; however, these exploratory data should be interpreted with caution due to the small sample size and short follow-up duration (Clinicaltrials.gov number: NCT01055496).
ABSTRACT
The contribution of the trunk muscles to spinal stability is well established. There is convincing evidence for the role of multifidus in spinal stability. Recently, emphasis has shifted to the deep fibres of this muscle (DM) and five key clinical beliefs have arisen: (i) that DM stabilizes the lumbar spine whereas the superficial fibres of lumbar multifidus (SM) and the erector spinae (ES) extend and/or rotate the lumbar spine, (ii) that DM has a greater percentage of type I (slow twitch) muscle fibres than SM and ES, (iii) that DM is tonically active during movements of the trunk and gait, whereas SM and ES are phasically active, (iv) that DM and the transversus abdominis (TrA) co-contract during function, and (v) that changes in the lumbar paraspinal muscles associated with LBP affect DM more than SM or ES. This paper reviews the biomechanical, electromyographic, histochemical and morphological data that underpin these beliefs. Although there is support for the importance of the lumbar multifidus and the specific contribution of this muscle to intervertebral control, several of the clinical beliefs have little or no support and require further evaluation. These findings have implications for clinical practice.
Subject(s)
Exercise Therapy , Low Back Pain/therapy , Lumbosacral Region/anatomy & histology , Muscle Fibers, Skeletal/physiology , Muscle, Skeletal/physiology , Adolescent , Adult , Biomechanical Phenomena , Electromyography , Female , Humans , Male , Middle Aged , Muscle, Skeletal/anatomy & histologyABSTRACT
We report the management and outcome of 4 patients with 5 knee dislocations associated with ipsilateral femoral shaft fractures. All patients were managed by immediate reduction of the knee dislocation, intramedullary nailing of the femur, and angiography, followed by postoperative immobilization of the knee (brace or external fixation) for a minimum of 6 weeks. Four of the 5 dislocations underwent a secondary ligament reconstruction. At the 2-year follow up, the mean Knee Society Score was 133 (range 99-170).
Subject(s)
Femoral Fractures/complications , Fracture Fixation, Intramedullary/methods , Knee Dislocation/complications , Adult , Female , Femoral Fractures/classification , Femoral Fractures/surgery , Humans , Injury Severity Score , Knee Dislocation/diagnostic imaging , Male , Postoperative Period , RadiographyABSTRACT
PURPOSE: Bendamustine is used in chronic lymphocytic leukemia (first-line) and indolent B-cell non-Hodgkin lymphoma (NHL) that progressed during/within 6 months of treatment with rituximab or a rituximab-containing regimen. This study was a postapproval commitment to investigate bendamustine's effect on cardiac repolarization in treatment-naïve adults with advanced indolent NHL/mantle cell lymphoma (MCL). METHODS: In this multicenter, open-label, phase 3 study, patients received 6-8 28-day cycles of bendamustine (90 mg/m(2), days 1 and 2) and rituximab (375 mg/m(2), day 1). Exclusions included a history of cardiac conditions with potential for QT prolongation. The primary endpoint was change in Fridericia-corrected QT (QTcF; 3 electrocardiograms per time point) on day 2 of cycle 1, from just before infusion to end of infusion (immediately postinfusion, coinciding with maximum plasma concentration of bendamustine). Change 1 h postinfusion was also measured. Exploratory assessments included specific QTcF outlier analyses (new QTcF >500 ms, change >60 ms) and morphological changes. RESULTS: Of the 54 enrolled patients (mean age, 62.9 years), 53 received ≥1 dose; 49 completed ≥6 cycles. Mean QTcF change from baseline was 6.7 ms at end of infusion; no mean changes >20 ms were detected ≤1 h postinfusion. No patients met specific outlier criteria at end of infusion or 1 h postinfusion. No morphological changes were detected. CONCLUSIONS: In this small treatment-naïve population with advanced NHL/MCL, bendamustine did not produce a clinically relevant increase in mean QTcF on the second infusion day. The potential for delayed effects on QT interval after 1 h was not evaluated.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Heart Rate/drug effects , Lymphoma, Mantle-Cell/drug therapy , Lymphoma, Non-Hodgkin/drug therapy , Antibodies, Monoclonal, Murine-Derived/administration & dosage , Antibodies, Monoclonal, Murine-Derived/pharmacology , Antineoplastic Combined Chemotherapy Protocols/pharmacology , Bendamustine Hydrochloride , Electrocardiography/drug effects , Female , Humans , Lymphoma, Mantle-Cell/physiopathology , Lymphoma, Non-Hodgkin/physiopathology , Male , Middle Aged , Nitrogen Mustard Compounds/administration & dosage , Nitrogen Mustard Compounds/pharmacology , RituximabABSTRACT
UNLABELLED: Genetic factors may influence implant failure caused by osteolysis after THA. In an association study of 481 subjects after THA, we found that carriage of the TNF-238A allele was associated with an increased incidence of osteolysis versus noncarriage (odds ratio, 1.7) and was independent of other risk factors. Genetic and environmental factors influence implant survival after THA. INTRODUCTION: Tumor necrosis factor (TNF) is thought to play a role in osteolysis, the major cause of implant failure after total hip arthroplasty (THA). Natural sequence variations at -238 and -308 in the TNF gene promoter are associated with differences in susceptibility to several TNF-mediated diseases. We tested whether these polymorphisms are associated with osteolysis after THA. MATERIALS AND METHODS: A total of 481 whites (214 with failed versus 267 with intact implants) were recruited 11.7 +/- 4 years after cemented THA. Genomic DNA was extracted from peripheral blood and genotyped for the -238 and -308 polymorphisms using the Taqman 5' nuclease method. Healthy controls (n = 500) from the background population were also genotyped to establish the local prevalence of these alleles. RESULTS: The carriage of -238A was 8.8% in the background population and 10.9% in the THA controls (p > 0.05). Carriage of -238A in the osteolysis group was 17.3% (odds ratio, 1.7; 95% CI, 1.0-2.9). Carriage was highest (20.5%) in patients with more widespread osteolysis (OR, 2.1; 1.2-3.8). The association of -238A with osteolysis was independent of other risk factors for osteolysis (logistic regression analysis: OR, 1.8; 1.0-3.2). Carriage of -308A was not associated with osteolysis. CONCLUSION: Genetic, as well as environmental factors, influence implant failure after THA. Whether the TNF-238 polymorphism causes a biological change that predisposes to loosening or is in linkage disequilibrium with such a locus is not yet known.
Subject(s)
Arthroplasty, Replacement, Hip/adverse effects , Genetic Variation/genetics , Graft Survival/genetics , Osteolysis/genetics , Promoter Regions, Genetic/genetics , Tumor Necrosis Factor-alpha/genetics , Aged , Environment , Female , Gene Frequency , Genotype , Humans , Male , Middle Aged , Odds Ratio , Osteolysis/etiology , Risk FactorsABSTRACT
PURPOSE: For patients with relapsed or refractory aggressive lymphoma, we hypothesized that gemcitabine-based therapy before autologous stem-cell transplantation (ASCT) is as effective as and less toxic than standard treatment. PATIENTS AND METHODS: We randomly assigned 619 patients with relapsed/refractory aggressive lymphoma to treatment with gemcitabine, dexamethasone, and cisplatin (GDP) or to dexamethasone, cytarabine, and cisplatin (DHAP). Patients with B-cell lymphoma also received rituximab. Responding patients proceeded to stem-cell collection and ASCT. Coprimary end points were response rate after two treatment cycles and transplantation rate. The noninferiority margin for the response rate to GDP relative to DHAP was set at 10%. Secondary end points included event-free and overall survival, treatment toxicity, and quality of life. RESULTS: For the intention-to-treat population, the response rate with GDP was 45.2%; with DHAP the response rate was 44.0% (95% CI for difference, -9.0% to 6.7%), meeting protocol-defined criteria for noninferiority of GDP (P = .005). Similar results were obtained in a per-protocol analysis. The transplantation rates were 52.1% with GDP and 49.3% with DHAP (P = .44). At a median follow-up of 53 months, no differences were detected in event-free survival (HR, 0.99; stratified log-rank P = .95) or overall survival (HR, 1.03; P = .78) between GDP and DHAP. Treatment with GDP was associated with less toxicity (P < .001) and need for hospitalization (P < .001), and preserved quality of life (P = .04). CONCLUSION: For patients with relapsed or refractory aggressive lymphoma, in comparison with DHAP, treatment with GDP is associated with a noninferior response rate, similar transplantation rate, event-free survival, and overall survival, less toxicity and hospitalization, and superior quality of life.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Hematopoietic Stem Cell Transplantation , Lymphoma/drug therapy , Adolescent , Adult , Aged , Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Cisplatin/administration & dosage , Cytarabine/administration & dosage , Deoxycytidine/administration & dosage , Deoxycytidine/analogs & derivatives , Dexamethasone/administration & dosage , Female , Humans , Male , Middle Aged , Quality of Life , Survival Rate , Transplantation, Autologous , Treatment OutcomeABSTRACT
Sorafenib is active in patients with acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). The National Cancer Institute of Canada (NCIC) Clinical Trials Group initiated a phase I/II study of the combination of sorafenib with cytarabine in older patients with AML or high-risk MDS who were unsuitable for intensive chemotherapy. FLT3 mutational status was determined in all patients. Twenty-one patients were enrolled (four MDS, 17 AML) with a median age of 77 years. The recommended phase II dose (RP2D) was cytarabine 10 mg bid days 1-10 and sorafenib 600 mg/day days 2-28. Dose-limiting toxicities were fatigue, sepsis and skin rash. Of 15 evaluable patients treated at the RP2D, two patients responded. The overall response rate for eligible patients was 10%. FLT3 mutations were found in only three patients. We conclude that this combination of sorafenib and cytarabine has limited activity in this unselected cohort of elderly patients with AML/MDS in which FLT3 mutations seemed underrepresented.