Kidney paired donation: a payer perspective.

Kidney transplantation is the most cost-effective and clinically effective form of renal replacement therapy. Due to long wait times for deceased donors, kidney transplantation is not available to many patients with incompatible living donors. Increased access to kidney transplantation is a shared goal that can be achieved through kidney paired donation (KPD). A single, national system of KPD administered to a set of clinical and ethical standards determined by a consensus of stakeholders including recipients, donors, providers, payers and the United States federal government will provide the best opportunity to offer kidney transplantation to the most people and particularly to those currently unlikely to receive a transplant. We propose that this system will use uniform tissue typing algorithms and a computerized donor and recipient matching program using a national pool of willing donors. The proposed system can be managed best through a single administrative structure that takes advantage of uniform donor evaluation and management with a standardized organ acquisition charge that recognizes that the current lack of standardization contributes to delays in transplantation and payment to programs. This program will use the existing Organ Procurement Organization infrastructure to manage the logistics of organ acquisition, transportation and billing.

Call to develop a standard acquisition charge model for kidney paired donation.

We propose a Medicare Demonstration Project to develop a standard acquisition charge for kidney paired donation. A new payment strategy is required because Medicare and commercial insurance companies may not directly pay living donor costs intended to lead to transplantation of a beneficiary of a different insurance provider. Until the 1970s, when organ procurement organizations were empowered to serve as financial intermediaries to pay the upfront recovery expenses for deceased donor kidneys before knowing the identity of the recipient, there existed similar limitations in the recovery and placement of deceased donor organs. Analogous to the recovery of deceased donor kidneys, kidney paired donation requires the evaluation of living donors before identifying their recipient. Tissue typing, crossmatching and transportation of living donors or their kidneys represent additional financial barriers. Finally, the administrative expenses of the organizations that identify and coordinate kidney paired donation transplantation require reimbursement akin to that necessary for organ procurement organizations. To expand access to kidney paired donation for more patients, we propose a model to reimburse paired donation expenses analogous to the proven strategy used for over 30 years to pay for deceased donor solid organ transplantation in America.

Allogeneic, syngeneic, and autologous marrow transplantation for Hodgkin's disease: the 21-year Seattle experience.

PURPOSE: To analyze results of 127 patients undergoing myeloablative therapy followed by marrow transplantation for relapsed or refractory Hodgkin's disease. PATIENTS AND METHODS: Twenty-three patients had primary refractory disease, 34 were in early first relapse or second complete remission (CR), and 70 had refractory first relapse or disease beyond second CR. Preparative regimens included total-body irradiation (TBI) and chemotherapy (n = 61) or chemotherapy only (n = 66). Sixty-eight patients received autologous marrow, six syngeneic marrow, and 53 allogeneic marrow. RESULTS: The 5-year actuarial probabilities of survival, event-free survival (EFS), relapse, and nonrelapse mortality for the entire group were 21%, 18%, 65%, and 49%, respectively. HLA-identical allogeneic marrow recipients had a statistically lower relapse rate compared with recipients of autologous marrow, but survival, EFS, and nonrelapse mortality rates were not significantly different. In the multivariate analysis, higher performance status and absence of bulky disease predicted for improved EFS and lower relapse rates, while fewer prior treatment regimens predicted for improved EFS and lower nonrelapse mortality rates. Additionally, the univariate analysis showed that patients who underwent transplantation with disease refractory to chemotherapy or beyond second CR had a worse outcome compared with those who had less advanced disease. CONCLUSION: Outcome with transplantation for patients with Hodgkin's disease is improved if transplantation is performed early after relapse when disease burden is less, tumor chemosensitivity is greater, and the patient is likely to have a better performance status. The use of HLA-matched sibling marrow results in a lower relapse rate and, thus, for some individuals, may be preferable to the use of autologous marrow.

Biopsy diagnosis and clinical outcome of persistent focal pulmonary lesions after marrow transplantation.

We reviewed the results of all percutaneous fine needle aspirations (FNA) and open lung biopsies (OLB) after bone marrow transplantation at our center (1984-1987) for the evaluation of focal lung lesions that developed or persisted despite antibiotic administration. We sought to determine the prevalence and types of infections, the yield of diagnostic procedures, and the clinical outcome of these focal lesions. Infection was documented in 78% (18/23) of all lesions and was fungal in each case. FNA detected fungal lung infection with a sensitivity of 67% (10/15) but had a negative predictive value of only 50% (5/10). Complications occurred in 15% of FNA. OLB without prior FNA was performed in 6 cases and demonstrated fungal infections in 5. Overall, seven of the 18 patients with localized invasive fungal lung disease recovered after antifungal therapy. This study demonstrates that focal lung lesions that develop or persist despite antibiotics after BMT are most often fungal. FNA may safely identify these localized infections in selected patients and with appropriate treatment recovery may be achieved.

Idiopathic pneumonia syndrome: changing spectrum of lung injury after marrow transplantation.

BACKGROUND: The aim of our study was to describe the incidence, clinical course, and risk factors for the idiopathic pneumonia syndrome (IPS), compared with those previously described for "idiopathic pneumonia," after bone marrow transplantation (BMT). METHODS: Our study design was a case-series review with determination of risk by comparison with unaffected controls by log-rank or Fisher's exact (two-tailed) test and logistic regression analyses. The study group comprised 1165 consecutive marrow recipients at a single center from 1988 to 1991. RESULTS: IPS was documented in 85 BMT recipients (7.3%) by bronchoalveolar lavage (n=68), open lung biopsy (n=3), or autopsy (n=14). The calculated actuarial incidence for IPS within 120 days after BMT was 7.7%. Median time to onset was 21 days (mean 34+/-30). Hospital mortality was 74%, and 53 BMT recipients (62%) died with progressive respiratory failure. IPS resolved in 22 patients (26%); 18 patients (21%) survived to discharge. Mechanical ventilation was required by 59 BMT recipients (69%), within a median of 2 days of onset of infiltrates. Two of these 59 recipients (3%) survived to discharge. Pulmonary infection (predominantly fungal) was noted in 7 of 25 (28%) BMT recipients who had an autopsy. Potential risk factors for IPS were assessed in univariate and multivariate logistic regression analyses. Although the incidence was not significantly different between autologous (5.7%) and allogeneic marrow recipients (7.6%), risks were identified only for the latter: malignancy other than leukemia (odds ratio=6.5 compared with aplastic anemia), and grade 4 graft-versus-host disease (odds ratio=5.4 compared with lower grades). No factors were associated with recovery. CONCLUSIONS: The incidence of idiopathic lung injury seems lower, the onset earlier, and the risk factors different from those previously reported. The major risks seem to be regimen-related toxicity and multi-organ dysfunction associated with alloreactive processes.

Predictive value of pulmonary function tests before marrow transplantation.

OBJECTIVE: To evaluate association between pulmonary function tests (PFT) performed before marrow transplantation and mortality after transplant. SETTING: A single marrow transplantation research center. DESIGN: Case-series review. PATIENTS: All patients between January 1986 and July 1990 who performed PFT before a first marrow transplant for the treatment of malignancy (n = 1297) were included in study. Six hundred twenty-eight (48 percent) patients had morphologically or cytologically active malignant neoplasms at the time of transplant. Allogeneic marrow transplants were performed in 1,056 (82 percent) and autologous transplants were performed in 235 (18 percent). Three hundred seventy-two (29 percent) patients received HLA-nonidentical donor marrow. Graft-vs-host disease prophylaxis was methotrexate and cyclosporine in 901 (85 percent) of the allogeneic recipients. Most patients were prepared for transplant with total body irradiation in addition to cyclophosphamide (n = 1,059, 82 percent), while 230 (18 percent) were conditioned with busulfan and cyclophosphamide. MEASUREMENTS AND MAIN RESULTS: The overall mortality during the first six months of follow-up was 44 percent. Respiratory failure requiring assisted mechanical ventilation occurred in 23 percent (n = 298) of patients. A proportional hazards regression analysis was used to evaluate the predictive value of PFT results: (1) FEV1/FVC; (2) P(A-a)O2 gradient; (3) TLC; and (4) Dcosb (the latter two presented a percent of predicted). Abnormalities in TLC, Dcosb, and P(A-a)O2 were found to be significantly associated with death in univariate analysis. Next, the value of PFT for prediction above and beyond other baseline covariates was evaluated by first using the step-up stepwise proportional hazards model to select predictive variables other than the PFT variables. Then each of the PFT variables was tested in the presence of these other variables. The factors of age, primary diagnosis, relapse status, and donor-recipient HLA nonidentity were found to be risks for death and were entered as covariates. Each of the variables of PFT were entered stepwise into the model. Dcosb (RR = 1.43 for a value 80 percent of predicted) and P(A-a)O2 (RR = 1.28 for a value of 20 mm Hg) were found to be independent risk factors for death. The use of assisted mechanical ventilation appeared to increase proportionately with the increase in mortality among patients with abnormal Dcosb or P(A-a)O2. CONCLUSIONS: Decreased Dcosb and increased P(A-a)O2 gradient before marrow transplant carry significantly increased risk of death after marrow transplant. The risk associated with abnormal PFT is less than that associated with other recognized risk factors, such as relapse status and donor-recipient HLA nonidentity. Respiratory failure does not appear to account entirely for the increased mortality associated with abnormal pretransplant PFT. PFT should be used in assessing fully the risks to recipients of marrow transplants for malignancy, but should not be used as absolute exclusion criteria for transplantation.

Virtual reality bronchoscopy simulation: a revolution in procedural training.

BACKGROUND: In the airline industry, training is costly and operator error must be avoided. Therefore, virtual reality (VR) is routinely used to learn manual and technical skills through simulation before pilots assume flight responsibilities. In the field of medicine, manual and technical skills must also be acquired to competently perform invasive procedures such as flexible fiberoptic bronchoscopy (FFB). Until recently, training in FFB and other endoscopic procedures has occurred on the job in real patients. We hypothesized that novice trainees using a VR skill center could rapidly acquire basic skills, and that results would compare favorably with those of senior trainees trained in the conventional manner. METHODS: We prospectively studied five novice bronchoscopists entering a pulmonary and critical care medicine training program. They were taught to perform inspection flexible bronchoscopy using a VR bronchoscopy skill center; dexterity, speed, and accuracy were tested using the skill center and an inanimate airway model before and after 4 h of group instruction and 4 h of individual unsupervised practice. Results were compared to those of a control group of four skilled physicians who had performed at least 200 bronchoscopies during 2 years of training. Student's t tests were used to compare mean scores of study and control groups for the inanimate model and VR bronchoscopy simulator. Before-training and after-training test scores were compared using paired t tests. For comparisons between after-training novice and skilled physician scores, unpaired two-sample t tests were used. RESULTS: Novices significantly improved their dexterity and accuracy in both models. They missed fewer segments after training than before training, and had fewer contacts with the bronchial wall. There was no statistically significant improvement in speed or total time spent not visualizing airway anatomy. After training, novice performance equaled or surpassed that of the skilled physicians. Novices performed more thorough examinations and missed significantly fewer segments in both the inanimate and virtual simulation models. CONCLUSION: A short, focused course of instruction and unsupervised practice using a virtual bronchoscopy simulator enabled novice trainees to attain a level of manual and technical skill at performing diagnostic bronchoscopic inspection similar to those of colleagues with several years of experience. These skills were readily reproducible in a conventional inanimate airway-training model, suggesting they would also be translatable to direct patient care.

Open lung biopsy diagnosis of diffuse pulmonary infiltrates after marrow transplantation.

The results were reviewed of 111 open lung biopsies (OLB) performed on 109 marrow transplantation recipients with diffuse pulmonary infiltrates between January 1983 and July 1987. We determined the frequency and types of infections identified, and the relationship to time after transplantation. Infection was found in 70 of the 111 cases (63 percent) and cytomegalovirus (CMV) was present in 90 percent of all cases with infection. Infection was identified in only five of 26 (19 percent) cases within the first 30 days after transplant, and when present, was viral. The prevalence of infection after 30 days (over 75 percent of 85 cases) was significantly higher (chi 2 = 26.2, p = 0.00001). Bacterial or yeast infections were found in only four cases (4 percent) (two cases each), and Pneumocystis carinii in six cases (6 percent). Simultaneous infection with two or more organisms was found in four cases (4 percent). Four of 25 autopsies performed within ten days after OLB revealed fungal infections with Aspergillus not detected at OLB. Thus, the prevalence of infection detected by OLB is low within the first 30 days after marrow transplantation among patients receiving broad spectrum antibiotics. CMV infection is found in most transplantation recipients who undergo OLB with diffuse infiltrates between days 30 and 180.

Complications of fiberoptic bronchoscopy in thrombocytopenic patients.

STUDY OBJECTIVE: To determine the risk of epistaxis and pulmonary hemorrhage due to fiberoptic bronchoscopy (FOB) and bronchoalveolar lavage (BAL) in the presence of thrombocytopenia. DESIGN: Prospective study of all patients undergoing FOB with BAL with a 4.9-mm-diameter bronchoscope after bone marrow transplantation (BMT) during a 6-month period. SETTING: A single BMT center. PATIENTS: Forty-seven BMT recipients undergoing 66 FOB with BAL. Thrombocytopenia (platelets < 100,000/ml) was present in 58 (88 percent). Platelets were < 50,000/ml in 44 (67 percent) and < 20,000/ml in 13 (20 percent). In the thrombocytopenic patients, FOB with BAL was transnasal in 37 (64 percent), transoral in 5 (9 percent), and via endotracheal tube in 16 (28 percent). INTERVENTIONS: Fiberoptic bronchoscopy with BAL using a bronchoscope (Pentax FB-15H) (4.9-mm diameter). In one case, a pediatric bronchoscope (Pentax FB-10H; 3.5-mm diameter) was used in a 7-year-old patient. MEASUREMENTS AND RESULTS: The BAL was diagnostic in 22 of 47 patients studied (47 percent). Complications occurred in 7 of 58 (12 percent) thrombocytopenic patients (epistaxis and/or hemoptysis, 4; bradycardia, 2; bronchospasm, 1) of which all but 1 were minor and self-limiting. One life-threatening complication of severe epistaxis occurred during a transoral FOB in a patient with prior epistaxis (platelet count, 18,000/ml). One of 8 (13 percent) nonthrombocytopenic patients had hemoptysis. No patient had worsening fever or oxygenation at 4 h and no patient displayed worsening radiographic infiltrates suggestive of pulmonary hemorrhage attributable to the BAL at 24 h. CONCLUSIONS: We conclude that transnasal FOB in thrombocytopenic patients was safe, being associated with minor airway bleeding in 3 of 37 patients (8 percent). In conclusion, FOB with BAL, even via the transnasal route, may be performed with relative safety despite the presence of significant thrombocytopenia.

Acute graft-versus-host disease and the risks for idiopathic pneumonia after marrow transplantation for severe aplastic anemia.

The risks for the development of idiopathic pneumonia after allogeneic BMT were assessed in a case-series review at a single marrow transplantation center. All allogeneic marrow recipients (n = 299) (age range 1-60 years) with severe aplastic anemia (SAA) transplanted from family member donors after conditioning with CY were evaluated. Post-grafting immunosuppression consisted of MTX alone in 205 patients (69%), CY alone in 16 (5%) and a combination of the two in 78 (26%). The incidence estimate for any pneumonia within the first 200 days after transplant was 18% (95% confidence interval = 14-24%). Of 48 cases of pneumonia, CMV infection was documented in 44%, 21% were idiopathic and the remainder were either due to other infections or were not evaluated. The effect of acute GVHD on the incidence of pneumonia was examined using multivariate Cox proportional hazards models which included covariates for potential confounding factors. Consistent with previous reports, acute GVHD was associated with an increased incidence of any pneumonia (relative risk (RR) = 3.5, 95% Cl = 1.9-6.9; p < 0.001). Specifically, acute GVHD also was associated with the largest risk of idiopathic pneumonia (RR = 5.0, 95% Cl = 1.1-22; p = 0.04). In conclusion, recognition of acute GVHD as a risk factor for idiopathic pneumonia suggests that mechanisms in addition to chemoradiation damage are responsible for non-infectious lung injury after BMT.

Acute acquired demyelinating polyneuropathy with respiratory failure following high-dose systemic cytosine arabinoside and marrow transplantation.

Reversible ventilatory failure secondary to acute, acquired polyneuropathy developed in a patient undergoing marrow transplantation for chronic myelogenous leukemia. The onset of the neuropathy was temporally related to the conditioning regimen of high-dose, systemic cytosine arabinoside (Ara-C). The clinical features and course were consistent with the Guillain-Barré syndrome and no other conditions causally associated with the syndrome were noted. Although central nervous system toxicity is a well recognized complication of high-dose Ara-C, peripheral neuropathy is infrequently reported. Possible mechanisms of peripheral polyneuropathy in this marrow transplant recipient are discussed.

Association of pulmonary function testing abnormalities and severe veno-occlusive disease of the liver after marrow transplantation.

We investigated an association between pulmonary function testing (PFT) before bone marrow transplantation and the development of severe veno-occlusive disease (VOD) of the liver. We previously noted that reductions in diffusing capacity of the lung for carbon monoxide (corrected for hemoglobin) (D(L)COc) were associated with mortality after transplantation, but this was not caused by respiratory failure. We performed a case-series review of prospectively collected data from 307 marrow recipients who underwent PFT within 2 weeks of transplantation. Of these, 170 (56%) developed VOD; 39 (13%) mild, 81 (26%) moderate, and 50 (16%) severe or fatal. Both total lung capacity (TLC) and D(L)COc were associated with severe VOD in univariate analysis (P = 0.006 for each). However, D(L)COc entered logistic regression models that contained variables for all known risk factors for severe VOD, while TLC did not contribute additional predictive information. The odds ratio (OR) associated with a D(L)COc below the lower limits of normal (70% of predicted) was 2.4 (95 % CI, 1.0 to 5.4; P = 0.04). We conclude that reduced diffusion capacity of the lung measured before marrow transplantation is an independent risk for severe hepatic VOD. We speculate that the decreased D(l)COc indicates pre-existing systemic endothelial cell damage and a susceptibility to severe hepatic injury from chemotherapy.

Bronchiolitis associated with bone marrow transplantation.

New onset airflow obstruction after BMT is a relatively common complication and may be seen in as many as 11% of long-term survivors of allogeneic BMT with chronic GVHD. Bronchiolitis and, occasionally, obliterative bronchiolitis is seen in the majority of cases in which histopathology is available. The primary risk factors recognized are the presence of clinical chronic GVHD, administration of methotrexate as an immunosuppressive, and older recipient age. Improved control of chronic GVHD with effective agents such as cyclosporine likely will decrease the incidence of this airway disorder. The causes probably are multifactorial and donor cytotoxic T-lymphocyte interaction with host cells is a likely contributor in many cases. The clinical course is variable, but the process usually is fatal in cases with rapidly progressive or severe obstruction. Interventions are directed at immune suppression and at diagnosing and treating infections that frequently occur in association with the airflow obstruction.

Translating the Dietary Approaches to Stop Hypertension diet from research to practice: dietary and behavior change techniques. DASH Collaborative Research Group.

The Dietary Approaches to Stop Hypertension (DASH) clinical trial demonstrated that a diet that emphasizes fruits, vegetables, and low-fat dairy products, includes whole grains, nuts, fish, and poultry, and is reduced in fats, red meats, sweets, and sugar-containing beverages can be highly effective in lowering blood pressure. The National High Blood Pressure Education Program now suggests the DASH diet for preventing and managing hypertension. For persons modifying their diets, the DASH diet offers varied choices. However, simultaneously modifying several dimensions of a diet can be challenging, even for knowledgeable and motivated persons. Persons who are uncertain about modifying their diet may become overwhelmed by the needed dietary changes. Dietitians and other health care practitioners can help patients adopt the DASH diet by exploring possible ambivalence, increasing motivation, and strengthening commitment to change; encouraging patients to select dietary modifications that will fit their lifestyle; and, finally, offering information about how to change their eating behavior. In this article, we offer dietary advice and counseling suggestions for tailoring interventions to match patients' readiness for adopting the DASH diet.

Respiratory infections following organ transplantation.

Successful organ transplantation often is limited by infection. The early transplant period is predominated by bacterial and fungal infections related to surgery and neutropenia, whereas opportunistic infections occur later due to long-term immunosuppression therapy. Despite technical differences between various types of organ transplants, the diagnostic approaches to lung disease are similar and rely largely on fiberoptic bronchoscopy. Whereas better antibacterial prophylaxis is available, fungal infections are emerging as significant problems. Lipid suspension formulations of amphotericin B and itraconazole offer new treatment options for fungal pulmonary infection. These formulations appear to have improved pharmacologic safety, but relative efficacy is unclear. Cytomegalovirus infections continue to plague transplant recipients. Improved understanding of the risk factors (especially the role of screened blood products) and improved prophylactic strategies with ganciclovir and immunoglobulin are decreasing the incidence of fatal infection. Surveillance for viremia and antigenemia now permit early identification of patients at significant risk for clinical disease, and responses to prompt administration of ganciclovir are encouraging, especially among solid organ recipients.

Decision making in critically ill patients with hematologic malignancy.

Hematologic neoplasms that were previously considered fatal are now potentially curable with techniques such as bone marrow transplantation. Such therapies also carry significant morbidity and mortality. With the increasing application of these therapies, a growing number of physicians are using medical decision making regarding critical care for these patients. The process by which ethical decisions are reached for these critically ill patients may be baffling because of several factors: rapidly evolving treatments, uncertain probabilities of the cure of the malignant disorder, the relatively young age of many of these patients, and the poor prognosis with critical illness. I discuss a process to reach acceptable decisions, providing a case example of the application of the process. This process is derived from the ethical principles that drive decision making in general medicine and attempts to maximize patients' autonomy. It involves a consideration of accurate information regarding the disease process and the prognosis, a clear delineation of the goals of the medical care, and communication with patients. Appropriate, ethical, and consistent decisions regarding the critical care of patients with hematologic malignancy can be reached when these considerations are addressed.

Bone-marrow transplantation and related infections.

The utility of bone-marrow transplantation (BMT) in the treatment of malignant and hematopoietic diseases is increasing. Additionally, refinements in the use of peripheral stem cells, unrelated marrow donors, and management of immunological complications of graft-versus-host reactions have contributed to the increase in the number of BMT performed each year. At the same time, the spectrum of infections associated with BMT are evolving. Improved prophylactic measures are decreasing the severity and frequency of bacterial, yeast and cytomegalovirus and Herpes simplex viral infections. However, other viruses are now emerging as pathogens. Common community-acquired respiratory viruses have caused significant morbidity and reports of human herpes virus-6 (HHV-6) infections in diffuse pneumonia raise the specter of additional previously unrecognized viral pathogens. Most alarming however, is the apparent increase in infections caused by filamentous fungi, which appear to develop despite anti-fungal prophylaxis. Improvement in preventive and treatment options for fungal disease is crucial to continued improvement in the outcome of BMT recipients.