Determinants of patient and surgeon perspectives on maximum acceptable waiting times for hip and knee arthroplasty

OBJECTIVES: Lengthy waiting times for hip and knee arthroplasty have raised concerns about equitable and timely access to care. The Western Canada Waiting List project has developed priority criteria scores linked to maximum acceptable waiting times (MAWT) for different levels of priority. Our study purpose was to assess the determinants of patient- and surgeon-rated MAWT, and to test whether the anticipated waiting time has an independent influence after adjusting for age, sex and patient urgency. A second aim was to compare MAWT, waiting time and anticipated waiting time for different levels of urgency assessed using the priority criteria score. METHODS: Orthopaedic surgeons assessed 233 consecutive patients waiting for arthroplasty in terms of their urgency (assessed using the priority criteria score and a visual analogue scale), MAWT and anticipated waiting time. Patient data included urgency (assessed by a visual analogue scale), MAWT and the Western Ontario McMaster Osteoarthritis index. We used hierarchical linear regression to test the models. RESULTS: After adjusting for age and sex, urgency (assessed by priority criteria score and visual analogue scale) and anticipated waiting time accounted for 40% of the variance in surgeon MAWT. The patient model accounted for 30% of the variance in patient MAWT. Older patients preferred signficantly shorter MAWTs (P <0.05). Anticipated waiting time added significantly to both the surgeon and patient MAWT models (R(2) change 0.11 and 0.07, respectively). Actual waiting time was weakly correlated with urgency assessed using the priority criteria score (r = -0.25, P <0.0001). CONCLUSIONS: Patients' and surgeons' views are critical to a fair process of establishing MAWT for elective procedures. Anticipated waiting time may influence the perspectives on MAWT and must be considered in their interpretation.     

Engraftment of acute myeloid leukemia in NOD/SCID mice is independent of CXCR4 and predicts poor patient survival

The aim of this study was to investigate factors influencing the engraftment potential of acute myeloid leukemia (AML) CD34+ cells in nonobese diabetic/severe combined immunodeficiency (NOD/SCID) mice. We examined the relationship between engraftment, CXCR4 expression on CD34+ and CD34+CD38- cells, and patient (Pt) clinical/laboratory characteristics in 44 samples from 11 Pts. Engraftment, evaluated by Southern blot and CD45 flow cytometric analyses, was observed in murine bone marrow of 6 of 11 Pt samples, ranging from 0.1% to 73.9% by Southern blot and from 0.1%-36.8% by flow cytometry. Poor Pt prognosis was inversely correlated with engraftment; the median overall survival was 95.9 weeks for Pts whose cells did not engraft and 26.1 weeks for those whose cells did engraft (p = 0.012, log-rank test). No other clinical/laboratory variable predicted engraftment. No correlation between the level of CXCR4 expression on AML cells and engraftment was observed. Cells with virtually absent CXCR4 expression were able to engraft, and cells from two Pts with high expression levels of CXCR4 did not engraft. Furthermore, anti-CXCR4 antibody failed to block the engraftment of AML cells into NOD/SCID mice. In conclusion, we demonstrated that CXCR4 is not critical for the engraftment of AML CD34+ cells in NOD/SCID mice. The model may, however, reflect the clinical course of the disease.     

Intravenous itraconazole for prophylaxis of systemic fungal infections in patients with acute myelogenous leukemia and high-risk myelodysplastic syndrome undergoing induction chemotherapy

BACKGROUND: Systemic fungal infections remain the leading cause of mortality in patients with newly diagnosed acute myelogenous leukemia (AML) and high-risk myelodysplastic syndrome (MDS). The objective of the current study was to determine whether intravenous itraconazole (i.v. ITRA) reduced the incidence of probable/proven fungal infections in this group of patients, and compare the results with those of a historic control group treated with fluconazole plus itraconazole capsules (F+I). METHODS: Patients with AML and high-risk MDS who underwent induction chemotherapy received 200 mg of i.v. itraconazole over 60 minutes every 12 hours during the first 2 days followed by 200 mg given i.v. once daily. RESULTS: One hundred patients were enrolled, 96 of whom were evaluable. Approximately 48% of the patients in the group of patients treated with i.v. ITRA as well as in the F+I group completed prophylaxis. Nine patients (9%) in the study group developed either proven/probable fungal infections (Candida glabrata in 5 patients, C. tropicalis in 1 patient, C krusei in 1 patient, and Fusarium in 2 patients) compared with 3 patients (4%) with proven fungal infection in the historic control group (C. tropicalis in 1 patient and Aspergillus in 2 patients). There were no significant differences noted between the two groups with regard to the percentage of patients who developed proven/probable or possible fungal infection as well as with regard to survival. These results also were obtained after adjusting for relevant prognostic factors (creatinine and bilirubin). The most common toxicity encountered with the use of i.v. ITRA was NCI Grade 3-4 hyperbilirubinemia (6%). CONCLUSIONS: Despite its theoretic advantages, the authors found no evidence that i.v. ITRA is superior to itraconazole capsules, at least when the latter is combined with fluconazole.     

Gemtuzumab ozogamicin,fludarabine, cytarabine and cyclosporine combination regimen in patients with CD33+ primary resistant or relapsed acute myeloid leukemia

Clinical resistance to gemtuzumab ozogamicin (Mylotarg) in acute myeloid leukemia (AML) is associated with blast multidrug resistance (MDR) phenotype. A Phase II study of Mylotarg, fludarabine, ara-C and the MDR-modifier, cyclosporine (CSA) (MFAC) was conducted in 32 patients with primary resistant (11, 34%) or relapsed (21, 66%) AML. Nine (28%) patients obtained complete remission (CR), two (6%) CR with incomplete platelet recovery. Overall median survival was 5.3 months, 12-month survival rate 19%. Fourteen patients (44%) developed grade 3/4 hyperbilirubinemia; six (18%) grade 3/4 hepatic transaminitis; three (9%) hepatic veno-occlusive disease (VOD). CSA inclusion in gemtuzumab ozogamicin-based regimens is feasible. MFAC is an effective regimen for refractory AML.     

Telomerase activity is prognostic in pediatric patients with acute myeloid leukemia: comparison with adult acute myeloid leukemia

BACKGROUND: Significantly elevated telomerase activity (TA) has been found in samples from patients with almost all malignant hematologic diseases. The impact of elevated TA on the course of pediatric patients with acute myeloid leukemia (P-AML) is unknown. METHODS: Using a modified polymerase chain reaction-based, telomeric repeat-amplification protocol assay, the authors measured TA in bone marrow samples from 40 patients with P-AML and, for comparison, in 65 adult patients with AML (A-AML), excluding patients with French-American-British M3 disease. The results were correlated with patient characteristics and survival. RESULTS: TA in patients with P-AML was significantly lower compared with TA in patients with A-AML (P = 0.005). Patients who had P-AML with low TA had a projected 5-year survival rate of 88%, whereas patients who had P-AML with high TA had a projected 5-year survival rate of 43% (P = 0.009). Conversely, patients who had A-AML with very high TA (upper quartile) had significantly longer survival compared with patients who had A-AML with lower TA (P = 0.03). There was no correlation between complete remission rate or disease free survival and TA in P-AML or A-AML. In the A-AML group, when patients were separated by cytogenetic findings (poor prognosis vs. others), it was found that TA was significantly lower in patients with a poor prognosis, but the prognostic value of TA was not independent of cytogenetic status. CONCLUSIONS: The current results suggest, that for patients with P-AML, bone marrow TA is a highly significant prognostic factor.     

Adaptive randomization in a treatment study of patients with adverse karyotype acute myeloid leukemia

Conclusions Neither troxacitabine combination is likely to be better than IA in this particular group of patients.     

Do physicians correctly estimate radiation risks from medical imaging?

Proper use of medical imaging tools requires knowledge of their associated radiation risks, as well as their possible benefits. The authors assessed physicians' knowledge of the radiation risks associated with bone scintigraphy (bone scan) during an annual meeting of the Israeli Orthopedic Society. The mortality risk of radiation-induced carcinoma from bone scan was identified correctly by less than 5% of respondents. The most frequent answer (38.4%) was the option that was least correct. Senior orthopedists estimated lower risks than did residents. Overall, respondents grossly underestimated the potential radiation risk from bone scan.     

Creatine phosphate kinase elevations signaling muscle damage following exposures to anticholinesterases: 2 sentinel patients

In this study, the authors describe 2 patients who experienced confirmed exposures to anticholinesterases that commenced in the 1970s. Subsequently, elevations in creatine phosphate kinase (CPK) were initially detected more than a decade following the first acute exposure. Beginning in the early 1980s, the patients suffered from progressive generalized muscle weakness, chronic fatigue, myopathy, neuropathy, and severe neurobehavioral impairments. Previous occupational exposures included pyridostigmine, as well as isopropyl methylphosphonofluoridate (percutaneous lethal dose [LD50] < 28 mg/kg body weight), and 1 patient had exposure to agricultural organophosphates. The authors hypothesize that the workers' CPK elevations, first detected more than a decade following acute exposures to anticholinesterases, were sentinel events for impending muscle damage and necrosis. Many Gulf War veterans with Gulf War disease who reported exposures to anticholinesterases 1 decade earlier currently suffer from vague neuromuscular and cognitive impairments. Therefore, medical programs for Gulf War veterans with Gulf War Syndrome should include surveillance for elevated CPK, abnormalities of neuromuscular conduction, and genetic susceptibility, and they should promote therapeutic trials for palliation.