Cancer treatment in rural areas

The inability to deliver cancer prevention and treatment to the rural population poses a significant barrier in the national effort to reduce cancer mortality. Since 25 percent of the U.S. population lives in rural areas and few rural areas are readily accessible to cancer centers or Community Clinical Oncology Programs (CCOPs), the prospects for accomplishing the National Cancer Institute (NCI) Goals for the Year 2000 are limited unless substantive changes occur in rural cancer care delivery. This article reviews the problem of cancer risk and care in rural areas and describes one effort to deliver state-of-the-art cancer treatment to rural patients in Virginia. It describes the needs and barriers to access in rural Virginia, the structural elements of the Rural Cancer Outreach Program, and the health policy issues that result when subspecialty care is exported to disadvantaged areas.     

Efficacy and cost-effectiveness of autologous bone marrow transplantation in metastatic breast cancer. Estimates using decision analysis while awaiting clinical trial results.

OBJECTIVE--To assess the efficacy and cost-effectiveness of standard chemotherapy and high-dose chemotherapy with autologous bone marrow transplantation (ABMT) in metastatic breast cancer. DESIGN--Decision analysis model using a Markov process. SETTING--Response and recurrence rates from the published literature for standard therapy and from case series of ABMT. Costs were based on local charges and on adjusted Medicare data. PATIENTS--Hypothetical cohorts of women with metastatic breast cancer who had no bone marrow involvement and no comorbid illness. INTERVENTION--The standard chemotherapy cohort received cyclophosphamide, doxorubicin, and fluorouracil. The ABMT cohort was treated with intense induction chemotherapy, then additional high-dose chemotherapy following a remission, with ABMT support. MAIN OUTCOME MEASURES--Anticipated survival, incremental cost per year of life, and incremental cost per quality-adjusted year of life gained using a 5-year time horizon. Rigorous sensitivity analyses were done, including assessing a benefit "tail" of normal life expectancy for those free of disease after 5 years. RESULTS--ABMT was the preferred approach under almost all assumptions, but the size of the benefit varied greatly. ABMT had a survival benefit of 6.0 months at 5 years at an incremental cost of $115,800 per year of life saved. If patients who were free of disease after 5 years had normal survival, the benefit was 18.1 months at an incremental cost of $28,600 per year. The benefit of ABMT was primarily dependent on whether the recurrence risk was constant or decreases after a finite period of time. CONCLUSION--Using reasonable assumptions, ABMT provided a substantial benefit but at a cost that may be untenable. Decision analysis highlights the limitations in the currently available data and the assumptions made for the emotional question of using ABMT in metastatic breast cancer. The model supports the need for randomized clinical trials.     

Collecting duct (Na+/K+)-ATPase activity is correlated with urinary sodium excretion in rat nephrotic syndromes

In puromycin aminonucleoside (PAN)-treated nephrotic rats, sodium retention is associated with increased (Na+/K+)-ATPase activity in the cortical collecting ducts (CCD). This study was undertaken to determine whether stimulation of (Na+/K+)-ATPase in the CCD is a feature of other experimental nephrotic syndromes, whether it might be responsible for renal sodium retention, and whether it is mediated by increased plasma vasopressin levels or activation of calcineurin. For this purpose, the time courses of urinary excretion of sodium and protein, sodium balance, ascites, and (Na+/K+)-ATPase activities in microdissected CCD were studied in rats with PAN or adriamycin nephrosis or HgCl2 nephropathy. The roles of vasopressin and calcineurin in PAN nephrosis were evaluated by measuring these parameters in Brattleboro rats and in rats treated with cyclosporin or tacrolimus. Despite different patterns of changes in urinary sodium and protein excretion in the three nephrotic syndrome models, there was a linear relationship between CCD (Na+/K+)-ATPase activities and sodium excretion in all three cases. The results also indicated that there was no correlation between proteinuria and sodium retention, but ascites was present only when proteinuria was associated with marked reduction of sodium excretion. Finally, the lack of vasopressin in Brattleboro rats or the inhibition of calcineurin by administration of either cyclosporin or tacrolimus did not prevent development of the nephrotic syndrome in PAN-treated rats or stimulation of CCD (Na+/K+)-ATPase. It is concluded that stimulation of Na(+/K+)-ATPase in the CCD of nephrotic rats might be responsible for sodium retention and that this phenomenon is independent of proteinuria and vasopressin and calcineurin activities.     

Talking About Sexuality in the Context of Rehabilitation Following Traumatic Brain Injury: An Integrative Review of Operational Aspects

Sexuality and Disability - An integrative review of the literature reporting operational aspects (how, when, who, with what) of rehabilitation professionals’ discussion of sexuality with...     

Darbepoetin, effective treatment of anaemia in paediatric patients with chronic renal failure

Darbepoetin alfa (DA) is a unique long-acting treatment for anaemia in patients with chronic renal failure (CRF). This study assessed the mean dose of DA to achieve and maintain haemoglobin (Hb) levels between 11 g/dl and 13 g/dl in CRF children aged 11 years to 18 years. This observational, prospective study was conducted in 39 patients treated with DA. Twenty-nine patients were switched from recombinant human erythropoietin (r-HuEPO), and ten patients were naive to r-HuEPO. Naive patients received initial doses of 0.45 μg/kg of DA. Switched patients received a dose adjusted to the prior dose of r-HuEPO (200 IU r-HuEPO:1 μg DA). Among the switched patients, 79.3% received dialysis. No naive patients underwent dialysis. Overall, 74% of patients showed increased Hb level, with a mean value of 11.6 ± 1.6 g/dl, using a mean DA dose of 0.63 ± 0.48 μg/kg per week, and 66.7% patients reached the target Hb level. Hb increased in naive patients from 9.5 (95% CI: 7.7, 11.4) to 11.7 (95% CI: 10.9, 12.6) g/dl and in switched patients from 11.1 (95% CI: 10.6, 11.5) to 11.5 (95% CI: 10.8, 12.2) g/dl). Higher doses of DA were needed in the “switched” than in the “naive” patients to maintain Hb levels over 11 g/dl, respectively 0.73 (95% CI: 0.54, 0.92) and 0.34 (95% CI: 0.16, 0.52) μg/kg per week. Our results indicate the doses of DA necessary to treat CRF patients aged 11 years to 18 years. DA was an effective treatment to stabilise CRF patients at extended dosing intervals. A prospective observational study, on behalf of the French Society for Pediatric Nephrology. Preliminary results of this study were published in part as an abstract and presented as a poster at the European Society of Pediatric Nephrology in Istanbul 11–13 September 2005 and at the ASN Renal Week in Philadelphia (Pennsylvania) 8–13 November 2005.     

Droperidol lengthens cardiac repolarization due to block of the rapid component of the delayed rectifier potassium current

INTRODUCTION: Torsades de pointes have been observed during treatment with droperidol, a butyrophenone neuroleptic agent. Our objectives were (1) to characterize the effects of droperidol on cardiac repolarization and (2) to evaluate effects of droperidol on a major time-dependent outward potassium current involved in cardiac repolarization (I(K)r). METHODS AND RESULTS: Isolated, buffer-perfused guinea pig hearts (n = 32) were stimulated at different pacing cycle lengths (150 to 250 msec) and exposed to droperidol in concentrations ranging from 10 to 300 nmol/L. Droperidol increased monophasic action potential duration measured at 90% repolarization (MAPD90) in a concentration-dependent manner by 9.8+/-2.3 msec (7.3%+/-0.7%) at 10 nmol/L but by 32.7+/-3.6 msec (25.7%+/-2.2%) at 300 nmol/L (250-msec cycle length). Increase in MAPD90 also was reverse frequency dependent. As noted previously, droperidol 300 nmol/L increased MAPD90 by 32.7+/-3.6 msec (25.7%+/-2.2%) at a pacing cycle length of 250 msec but by only 14.1+/-1.3 msec (13.6%+/-2.3%) at a pacing cycle length of 150 msec. Patch clamp experiments performed in isolated guinea pig ventricular myocytes demonstrated that droperidol decreases the time-dependent outward K+ current elicited by short depolarizations (250 msec; I(K)250) in a concentration-dependent manner. Estimated IC50 for I(K)250, which mostly underlies I(K)r, was 28 nmol/L. Finally, HERG K+ current elicited in HEK293 cells expressing high levels of HERG protein was decreased 50% by droperidol 32.2 nmol/L. CONCLUSION: Potent block of I(K)r by droperidol is likely to underlie QT prolongation observed in patients treated at therapeutic plasma concentrations (10 to 400 nmol/L) of the drug.     

Prevalence and predictors of sleep disturbance among liver diseases in long-term transplant survivors

BACKGROUND:

Patients with cirrhosis are known to experience sleep disturbance, which negatively impacts health-related quality of life.

OBJECTIVE:

To assess the prevalence and predictors of sleep disturbance before and after liver transplantation (LT).

METHODS:

Both pre- and post-LT patients were administered the Basic Nordic Sleep Questionnaire. The primary outcome was overall sleep satisfaction; the secondary outcomes were sleep latency and sleep duration.

RESULTS:

Eighty-three patients participated pre-LT and 273 post-LT. Overall, participants having completed both pre- and post-LT questionnaires reported satisfactory sleep 61% of the time before LT and 65% of the time after LT. However, on review of all questionnaires, patients with alcoholic liver disease (ETOH) experienced dramatically less sleep disturbance (OR 0.13 [95% CI 0.03 to 0.60]) post-LT, whereas those with hepatitis C remained without improvement (OR 0.90 [95% CI [0.38 to 2.15]). On logistic regression, patients with ETOH had statistically less sleep satisfaction pre-LT (OR 5.8 [95% CI 1.0 to 40.5]) and significantly better sleep satisfaction post-LT (OR 0.50 [95% CI 0.20 to 1.00]) compared with those with hepatitis C. In addition, both ETOH and other conditions had significantly better sleep latency than hepatitis C patients.

CONCLUSIONS:

Sleep parameters for patients who undergo LT for hepatitis C do not improve following LT as much as they do in patients transplanted for ETOH. Following LT, patients transplanted for ETOH are significantly more satisfied with their sleep than those transplanted for hepatitis C. Physicians should address and manage sleep quality after LT, so as to ultimately improve quality of life.     

Analysis of graft-versus-host disease (GVHD) and graft rejection using MHC class I-deficient mice

GVHD is a major complication in allogeneic bone marrow transplantation (BMT). MHC class I mismatching increases GVHD, but in MHC-matched BMT minor histocompatibility antigens (mH) presented by MHC class I result in significant GVHD. To examine the modification of GVHD in the absence of cell surface MHC class I molecules, β₂-microglobulin-deficient mice (β₂m-/-) were used as allogeneic BMT recipients in MHC- and mH-mismatched transplants. β₂m-/- mice accepted MHC class I-expressing BM grafts and developed significant GVHD. MHC (H-2)-mismatched recipients developed acute lethal GVHD. In contrast, animals transplanted across mH barriers developed indolent chronic disease that was eventually fatal. Engrafted splenic T cells in all β₂m-/- recipients were predominantly CD3⁺ αβ TCR⁺ CD4⁺ cells (15–20% of all splenocytes). In contrast, CD8⁺ cells engrafted in very small numbers (1–5%) irrespective of the degree of MHC mismatching. T cells proliferated against recipient strain antigens and recognized recipient strain targets in cytolytic assays. Cytolysis was blocked by anti-MHC class II but not anti-CD8 or anti-MHC class I monoclonal antibodies (MoAbs). Cytolytic CD4⁺ T cells induced and maintained GVHD in mH-mismatched β₂m-/- mice, supporting endogenous mH presentation solely by MHC class II. Conversely, haematopoietic β₂m-/- cells were unable to engraft in normal MHC-matched recipients, presumably due to natural killer (NK)-mediated rejection of class I-negative cells. Donor-derived lymphokine-activated killer cells (LAK) were unable to overcome graft rejection (GR) and support engraftment.