RESULTS OF EXTERNAL BEAM RADIOTHERAPY IN 448 PATIENTS WITH CLINICALLY LOCALIZED ADENOCARCINOMA OF THE PROSTATE

The results of external beam radiotherapy for clinically localized adenocarcinorna of the prostate in 448 patients treated in the period 1980–90 were reviewed. The average follow up was 4.9 years. The patients were aged 44–87 years (median 69 years) and all had histopathological evidence of adenocarcinoma by needle biopsy or transurethral resection of prostate. The histopathological grading was: 127 G₁; 154 G₂; 127 G₃; 12 G₄; 28 G_x. Clinical staging according to TNM (American Urological Association) was: 29 T₀ (A2); 4 T₁ (B1); 173 T₂ (B2); 176 T₃ (C1); 63 T₄ (C2); 3 T_x. Routine surgical pelvic lymph node staging was not performed but patients had radiological (computerized tomography scan or lymphogram) nodal staging: 350 N₀; 22 N₁; 12 N₂; 64 N_x. High energy linear accelerator external beam radiotherapy was given by multiple fields to total doses of 50–70 Gy (median 60 Gy). The majority of patients (307, 69%) was treated by a uniform policy under the care of one radiation oncologist (HM). The rates of local and distant failure at 5 years were 10% (s.e. = 2%) and 42% (s.e. = 3%), respectively. The late complication rate at 5 years was 25% (s.e. = 2%), comprising mild 16%, moderate 7% and severe 1.3%. The 5 year overall survival rate was 64% (s.e. = 2%) and the cancer-specific survival rate was 74% (s.e. = 3%). Both histological grade and clinical stage were strongly predictive of overall survival and distant failure. Only histological grade was predictive of local failure. Treatment with external beam radiotherapy for this common cancer resulted in survival and disease control rates that compare favourably with other published radiotherapy series and has been accompanied by acceptably low morbidity.     

Identifying potential indicators of the quality of end-of-life cancer care from administrative data.

PURPOSE: To explore potential indicators of the quality of end-of-life services for cancer patients that could be monitored using existing administrative data. METHODS: Quality indicators were identified and assessed by literature review for proposed indicators, focus groups with cancer patients and family members to assess candidate indicators and generate new ideas, and an expert panel ranking the meaningfulness and importance of each potential indicator using a modified Delphi approach. RESULTS: There were three major concepts of poor quality of end-of-life cancer care that could be examined using currently-available administrative data (such as Medicare claims): institution of new anticancer therapies or continuation of ongoing treatments very near death; a high number of emergency room visits, inpatient hospital admissions, or intensive care unit days near the end of life; and a high proportion of patients never enrolled in hospice, only admitted in the last few days of life, or dying in an acute-care setting. Concepts such as access to psychosocial and other multidisciplinary services and pain and symptom control are important and may eventually be feasible, but they cannot currently be applied in most data systems. Indicators based on limiting the use of treatments with low probability of benefit or indicators based on economic efficiency were not acceptable to patients, family members, or physicians. CONCLUSION: Several promising claims-based quality indicators were identified that, if found to be valid and reliable within data systems, could be useful in identifying health-care systems in need of improving end-of-life services.     

Heart failure survival score continues to predict clinical outcomes in patients with heart failure receiving β-blockers

BACKGROUND: The Heart Failure Survival Score (HFSS) has been previously shown to effectively risk-stratify patients under evaluation for heart transplantation. However, this model was developed before broad use of beta blockade. We hypothesized that the prognostic tool would retain its ability to risk stratify patients treated with beta-blockers. METHODS: We collected clinical data on 524 consecutive patients referred for heart transplantation from 1994 to 2001. Kaplan-Meier survival analysis and multivariable Cox regression analysis were performed with events defined as death, left ventricular assist device placement, or United Network of Organ Sharing 1 heart transplantation. RESULTS: Kaplan-Meier analysis of the patient population revealed effective discrimination by the survival score both for beta-blocker treated and untreated patients (both p <0.0001). Two-year event-free survival was 94% +/- 2% and 84% +/- 4% for beta-blocker and no beta-blocker patients in the low-risk HFSS strata. Cox proportional hazard modeling showed that HFSS strata (medium risk: HR 2.65, 95% CI 1.75-4.02, p <0.001; high risk: HR 5.51, 95% CI 3.64-8.33, p <0.001) and beta-blocker treatment (HR 0.45, 95% CI 0.31-0.64, p <0.001) were significant predictors of event-free survival. Receiver operating curves (area under the curve) for HFSS strata used to predict 2-year events were similar for beta-blocker treated (0.78 +/- 0.04) and untreated (0.80 +/- 0.03) patients. CONCLUSIONS: The HFSS provides effective risk stratification with or without beta-blocker therapy. Consideration of beta-blocker therapy with survival score strata improves outcome prediction in patients evaluated for heart transplantation.     

The art of rewarding and retaining staff - part 1

As the nursing shortage escalates, nurse managers will continue to grapple with how to retain their most valuable asset—the talented staff they are charged to lead. Survival in the current market makes both recruitment and retention efforts critical. One primary concern is an aging workforce. The American Nursing Association projects that 65% of current nurses will retire within this decade and predicts that the supply will no longer meet the demand by the year 2010.¹ In fact, by 2020, the health care industry will need 1.7 million nurses—yet only 600,000 will be available.¹ The key for success is retention of your current staff.     

Breaking down barriers to treat a patient with a germinoma: a case study.

Germinomas are the most common type of germ cell tumor occurring commonly before the second decade of life. Because of the radiosensitivity of germinomas, traditional treatment following diagnosis has been conventional radiotherapy. The desire to defer radiotherapy to avoid the delayed neurocognitive effects has led researchers to investigate the use of up front chemotherapy. A major limitation in using chemotherapy for brain tumors has been the inability to deliver drugs across the blood brain barrier. The blood brain barrier consortium has developed chemotherapy protocols for patients with malignant brain tumors through the use of reversible osmotic opening of the blood brain barrier. While the patient is under general anesthesia, osmotic opening or disruption is achieved by a 30-second intracarotid infusion of mannitol. The mannitol infusion is followed by both intraarterial and intravenous chemotherapy. By administering chemotherapy in conjunction with blood brain barrier disruption, drug delivery to the tumor and the brain around tumor is increased.     

Diagnosing osteoporosis by using dental panoramic radiographs: the OSTEODENT project.

OBJECTIVES: Measurement of cortical thickness and subjective assessment of cortical porosity on panoramic radiographs are methods previously reported for diagnosing osteoporosis. The aims of this study were to determine the relative efficacy of the mandibular cortical index and cortical width in detecting osteoporosis, both alone and in combination, and to determine the optimal cortical width threshold for referral for additional osteoporosis investigation. STUDY DESIGN: Six hundred seventy-one postmenopausal women 45 to 70 years of age were recruited for this study. They received dual energy x-ray absorptiometry (DXA) scans of the left hip and lumbar spine (L1 to L4), and dental panoramic radiographic examinations of the teeth and jaws. Three observers separately assessed the mandibular cortical width and porosity in the mental foramen region of the mandible. Cortical width was corrected for magnification errors. Chi-squared automatic interaction detection analysis (CHAID) software was used (SPSS AnswerTree, version 3.1, SPSS Inc., Chicago, IL). RESULTS: Chi-squared automatic interaction detection analysis showed that the cortical porosity was a poorer predictor of osteoporosis than mandibular cortical width. For the 3 observers, a mandibular cortical width of <3 mm provided diagnostic odds ratios of 6.51, 6.09, and 8.04. The test is therefore only recommended in triage screening of individuals by using radiographs made for purposes other than osteoporosis. CONCLUSION: When evaluating panoramic radiographs, only those patients with the thinnest mandibular cortices (i.e., <3 mm) should be referred for further osteoporosis investigation.     

Endotoxin preconditioning protects against the cytotoxic effects of TNFalpha after stroke: a novel role for TNFalpha in LPS-ischemic tolerance.

Lipopolysaccharide (LPS) preconditioning provides neuroprotection against subsequent cerebral ischemic injury. Tumor necrosis factor-alpha (TNFalpha) is protective in LPS-induced preconditioning yet exacerbates neuronal injury in ischemia. Here, we define dual roles of TNFalpha in LPS-induced ischemic tolerance in a murine model of stroke and in primary neuronal cultures in vitro, and show that the cytotoxic effects of TNFalpha are attenuated by LPS preconditioning. We show that LPS preconditioning significantly increases circulating levels of TNFalpha before middle cerebral artery occlusion in mice and show that TNFalpha is required to establish subsequent neuroprotection against ischemia, as mice lacking TNFalpha are not protected from ischemic injury by LPS preconditioning. After stroke, LPS preconditioned mice have a significant reduction in the levels of TNFalpha (approximately threefold) and the proximal TNFalpha signaling molecules, neuronal TNF-receptor 1 (TNFR1), and TNFR-associated death domain (TRADD). Soluble TNFR1 (s-TNFR1) levels were significantly increased after stroke in LPS-preconditioned mice (approximately 2.5-fold), which may neutralize the effect of TNFalpha and reduce TNFalpha-mediated injury in ischemia. Importantly, LPS-preconditioned mice show marked resistance to brain injury caused by intracerebral administration of exogenous TNFalpha after stroke. We establish an in vitro model of LPS preconditioning in primary cortical neuronal cultures and show that LPS preconditioning causes significant protection against injurious TNFalpha in the setting of ischemia. Our studies suggest that TNFalpha is a twin-edged sword in the setting of stroke: TNFalpha upregulation is needed to establish LPS-induced tolerance before ischemia, whereas suppression of TNFalpha signaling during ischemia confers neuroprotection after LPS preconditioning.