The effect of race on access and outcome in transplantation.
Explore the source record for details and available documents.
Biomedical subjects
Publications and source records attributed to S R Alexander.
Explore the source record for details and available documents.
OBJECTIVE: To compare outcomes from pediatric intensive care in hospitals with different levels of resources. DESIGN: Prospective, blinded comparison of outcome and care. SETTING: Tertiary (n = 3) and nontertiary (n = 71) hospitals in Oregon and southwestern Washington. PATIENTS: All critically ill children admitted with respiratory failure and head trauma for 6 months. MEASUREMENTS AND MAIN RESULTS: Severity of illness adjusted mortality rates were determined using admission day, physiologic profiles (Pediatric Risk of Mortality score) and care modalities were assessed daily. The crude mortality rate of the tertiary patients was four times higher than for the nontertiary patients (23.4% vs. 6.0%, p less than .0001). In the tertiary patients, the numbers of outcomes were accurately predicted by physiologic profiles (observed: 30 deaths and 98 survivors; predicted: 29.3 deaths and 98.7 survivors, z = -.25, p greater than .4). However, for the nontertiary patients, the number of the deaths were significantly different than predicted (observed: 20 deaths and 315 survivors; predicted: 14.4 deaths and 320.6 survivors, z = -2.08, p less than .05). The odds ratios of dying in a nontertiary vs. a tertiary facility were about 1.1, 2.3, and 8 (p less than .05) for mortality risk groups of less than 5%, 5% to 30%, and greater than 30%. Patients in tertiary facilities received more (p less than .05) invasive (e.g., arterial catheters) and complex (e.g., mechanical ventilation) care, whereas patients in nontertiary facilities received more (p less than .05) labor-intensive care (e.g., hourly vital signs). CONCLUSIONS: Care of the most seriously ill children in tertiary pediatric ICUs could improve their chances of survival.
Data from the North American Pediatric Renal Transplant Cooperative Study were analyzed to determine the incidence and possible causes of graft thrombosis in pediatric renal transplant recipients. Between January 1987, and November 1989, 1045 renal transplants in recipients less than 18 years of age were registered in the study, including 484 living-related donor and 561 cadaver donor transplants. There were 213 graft failures (67 LRD, 146 CAD), and of these 27 were caused by thrombosis (8 LRD, 19 CAD). Thrombosis occurred in 2.6% of all transplants and accounted for 22.5% (27/120) of all graft failures that occurred in the first 60 days following transplantation. Among the LRD recipients, there were 24 graft failures in those less than 6 years of age, and 7 of these were due to thrombosis, compared to 1 thrombosis in 43 graft losses in recipients greater than 6 years (P less than 0.01). In recipients less than 6 years old, the thrombosis rate for those who received transplants without prior dialysis was 4/32 (12.5%) versus 3/109 (2.8%) with prior dialysis. Among the CAD recipients, age of the recipient did not influence graft thrombosis. Donor age, however, was strongly associated with the risk of thrombosis, as was cold storage time. Donor age and cold storage time were not independently distributed within the population, with longer cold storage times required for younger donors. Both factors, however, independently affected outcome. Other factors, including prior nephrectomy, prior transplant, center size, and use of cyclosporine were not associated with increased risk of thrombosis in LRD or CAD recipients. We conclude that graft thrombosis is an important cause of renal graft loss in children. In LRD transplants the risk of graft thrombosis is increased in recipients less than 6 years old, and preliminary data suggest that the lack of prior dialysis may be associated with thrombotic risk in these patients. CAD transplant recipients who receive grafts from young donors, particularly those with long cold storage time, are at increased risk for graft failure due to thrombosis.
Between 1985 and 1988, there were 3,393 children (Medicare insured) under age 20 who began treatment for chronic ESRD. Patterns of modality use, modality switch, mortality rates, and various aspects of transplantation were analyzed for different age and incident groups of this pediatric cohort. The pediatric cohort as a whole exhibited a distinct pattern of modality use when compared to adults in general, a point evidenced most clearly by their substantially higher rates of transplantation. Furthermore, notable differences were found within the pediatric cohort when the younger than 5, 5-9, 10-14, and 15- to 19-year-old age groups were analyzed separately. Younger pediatric patients, particularly those younger than 5 years, received peritoneal dialysis as initial ESRD therapy more frequently than their older pediatric counterparts. This result would be expected given vascular access problems often associated with very young patients. In addition, those patients younger than 5 years who began RRT with some form of hemodialysis had the highest likelihood of switching to CAPD/CCPD within the first year of therapy. Conversely, older pediatric patients were most likely to begin RRT therapy with some form of hemodialysis. By day 91, slightly over half of the 15- to 19-year-old age group was utilizing center hemodialysis; the CAPD/CCPD, other peritoneal, and functioning transplant modalities each contained about 10% of the patients with the remainder falling into the death and unknown dialysis categories. The overall pattern of switching to transplantation during the first year of RRT was similar for pediatric patients initiating RRT with center hemodialysis versus peritoneal dialysis (CAPD/CCPD), but differed by age group within each dialysis type. Pediatric patients on peritoneal dialysis were somewhat more likely to receive a transplant during the first year of ESRD compared to hemodialysis, although the difference was small. Mortality rates during the first year for patients who began treatment with center hemodialysis versus CAPD/CCPD were similar. The well-documented dominance of transplantation as a method of RRT for pediatric patients was further verified by this study. Results show that transplantation was implemented rapidly during the initial months of ESRD. Nearly 50% of surviving pediatric patients had a functioning transplant at 1 year following onset and 64% at 3 years. These percentages were exceeded for the 5- to 9-year-old age group, of which 74% had a functioning graft 3 years following onset.(ABSTRACT TRUNCATED AT 400 WORDS)
Extensive clinical studies have documented the effectiveness of recombinant human erythropoietin (rHuEPO) in correcting the anemia of adult dialysis patients, but the safety and efficacy of rHuEPO in children with renal anemia cannot yet be confirmed, due to the relative deficiency of reported studies involving pediatric subjects. To date, published experience with rHuEPO therapy in children has totaled 257 patients, although the majority of these reports have appeared only as abstracts. Overall experience has been favorable, with renal anemia and transfusion dependency successfully resolved in almost all pediatric patients reported. However, controlled clinical trials have not been performed, so it is not yet possible to clearly define the risks associated with rHuEPO therapy in children. Hypertension appears to occur or become worse in up to one third of treated children, but it is unclear to what extent rHuEPO therapy is accompanied by an increased risk of seizures, thrombosis of vascular access, hyperkalemia, hyperphosphatemia, or peritonitis (when administered via the intraperitoneal route). Only preliminary and somewhat conjectural recommendations can be offered regarding pediatric rHuEPO dosing, route of administration, special precautions, and adjunctive monitoring and therapy. Fortunately, a multicenter controlled clinical trial is underway that is designed to address these issues. Because the harmful effects of renal anemia are typically more profound for children than they are for adults, the benefits of rHuEPO promise to be even greater among pediatric patients. Whether rHuEPO therapy will substantially improve growth and neurologic and psychosocial development remains to be seen, but the potential is there for rHuEPO to dramatically improve the lives of children who suffer from the effects of the anemia of chronic renal failure. Other non-renal anemias that afflict pediatric patients, such as the anemia of prematurity, also may be amenable to rHuEPO therapy.
This report of the North American Pediatric Transplant Cooperative Study summarizes data contributed by 57 participating centers on 754 children with 761 transplants from 1 January 1989 to 16 February 1989. Data collection was initiated in October 1987 and follow-up of all patients is ongoing. Transplant frequency increased with age; 24% of the patients were less than 5 years, with 7% being under 2 years. Common frequent diagnoses were: aplastic/dysplastic kidneys (18%), obstructive uropathy (16%), and focal segmental glomerulosclerosis (12%). Preemptive transplant, i.e., transplantation without prior maintenance dialysis, was performed in 21% of the patients. Dialytic modalities pretransplant were peritoneal dialysis in 42% and hemodialysis in 25%. Bilateral nephrectomy was reported in 29%. Live-donor sources accounted for 42% of the transplants. Among cadaveric donors, 41% of the donors were under 11 years old. During the first post-transplant month, maintenance therapy was used similarly for live-donor and cadaver source transplants, with prednisone, cyclosporine, and azathioprine used in 93%, 83%, and 81%, respectively. Triple therapy with prednisone, cyclosporine, and azathioprine was used in 78%, 75%, and 75% of functioning cadaver source transplants at 6 months, 12 months, and 18 months as opposed to 60%, 63%, and 54% for live-donor procedures, with single-drug therapy being uncommon. Rehospitalization during months 1-5 occurred in 62% of the patients, with treatment of rejection and infection being the main causes. Additionally, 9% were hospitalized for hypertension. During months 6-12 and 12-17, 30% and 28% of the patients with functioning grafts were rehospitalized. Times to first rejection differed significantly for cadaver and live-donor transplants. The median time to the first rejection was 36 days for cadaver transplants and 156 days for live-donor transplants. Overall, 57% of treated rejections were completely reversible although the complete reversal rate decreased to 37% for four or more rejections. One hundred and fifty-two graft failures had occurred at the time of writing, with a 1-year graft survival estimate of 0.88 for live-donor and 0.71 for cadaver source transplants. In addition to donor source, recipient age is a significant prognostic factor for graft survival. Among cadaver donors, decreasing donor age is associated with a decreasing probability of graft survival. Thirty-five deaths have occurred; 16 attributed to infection and 19 to other causes. The current 1-year survival estimate is 0.94. There have been 9 malignancies.
Between 1981 and 1986, 89 patients with advanced head and neck squamous cancer were treated with a continuous accelerated fractionation radiotherapy (AFRT) regimen. Three fractions of 1.80 Gy, 4 h apart, were given on three treatment days per week (Monday, Wednesday, Friday), and the tumour dose was taken to 59.40 Gy in 33 fractions in 24-25 days. Acute mucosal reactions were generally quite severe, but a split was avoided by providing the patient with intensive support, often as an in-patient, until the reactions settled. Late radiation effects have been comparable to those obtained with conventional fractionation. The probability of local-regional control was 47% at 3 years for 69 previously untreated patients, whereas it was only 12% at one year for 20 patients treated for recurrence after radical surgery. Fifty-eight previously untreated patients with tumours arising in the upper aero-digestive tract were analysed in greater detail. The probability of local-regional control at 3 years was 78% for 17 Stage III patients and 15% for 31 Stage IV patients. This schedule of continuous AFRT is feasible and merits further investigation.
Thirty-one pediatric patients with acute renal allograft rejection were treated with the monoclonal antibody OKT3. In 24 cases, increased doses of steroids followed by a polyclonal antithymocyte globulin were ineffective in reversing the rejection episode. Twenty-eight patients completed the prescribed minimum 10-day treatment course, with effective rejection reversal in 22. Three patients failed to complete the course of therapy: one because of leukopenia that developed after the first dose, one because of a clotted graft, and another because of symptomatic cytomegalovirus infection. The overall success rate of OKT3 for rejection reversal was 74%; however, 55% of recipients had rebound rejection, and 85% of patients had detectable anti-OKT3 antibodies after completion of the course of therapy. Ten patients were treated with a second course of OKT3, and in eight of these patients, rejection was at least temporarily reversed. The starting dose of OKT3 for second-course therapy was the same as that used during first-course therapy, but in five cases the dose was increased during the course because of inadequate therapeutic response. Seven of these patients lost their grafts a mean of 6.5 months after completion of second-course therapy. We looked for anti-OKT3 antibody in nine recipients after completion of a second treatment course and found it in all nine. Our observations regarding a second treatment course with this monoclonal antibody preparation suggest that although rejection reversal may be observed, ultimate graft survival is poor and anti-OKT3 antibody formation is enhanced.
We analyzed the results obtained with protocols for immunosuppression of pediatric recipients of haploidentical living-related renal transplants. In the donor-specific transfusion group transfusion of blood products obtained from the prospective organ donor was performed before transplantation, and at transplantation maintenance immunosuppression of azathioprine and prednisone was begun. In the cyclosporine group donor-specific transfusion was not used, and maintenance immuno-suppression of cyclosporine and azathioprine was begun 1 week before transplantation, with the addition of prednisone at transplantation. Of 24 donor-specific transfusion recipients 3 had circulating cytotoxic antibodies to the prospective donor for an incidence of 12%. There was no significant difference between groups with respect to 1-year actual patient and graft survival (100 and 89 versus 100 and 86%, respectively), 1-year mean serum creatinine level (1.1 versus 1.2 mg./dl.), rejection treatments per patient (2.5 versus 2.6) and total days hospitalized during year 1 after transplantation (27 versus 18), with donor-specific transfusion data presented first. Initial hospitalization was significantly shorter (10 versus 16 days, p less than 0.05) and the incidence of rejection crises within 3 months was significantly less (68 versus 94%, p less than 0.05) in the cyclosporine group. We believe that cyclosporine and azathioprine pre-treatment of pediatric recipients of haploidentical living-related renal transplants with the addition of prednisone at transplantation is preferable to a donor-specific transfusion protocol because there is no risk of recipient sensitization to the prospective donor, and patient and graft survival is not adversely affected.
Patients receiving hemodialysis therapy risk exposure to disinfectants used to reduce bacterial burdens in hemodialysis equipment and to reprocess hemodialyzers. From April 29 through May 9, 1988, 3 patients undergoing hemodialysis treatments at a single center were exposed to dialysis fluid that was inadvertently contaminated with hydrogen peroxide (HP). All patients showed a significant decline in blood hemoglobin level and required packed red blood cell transfusions during the 11-day exposure to HP. Contamination of dialysis fluid may have been due to the inadequate rinsing of HP from the water treatment system (WTS) following its disinfection on April 27-28, 1988. The failure to check water at point-of-use stations with a sensitive enough test kit after the disinfection for HP permitted patient exposure to contaminated dialysis fluid. To prevent similar occurrences, we recommend that after each disinfection (or other modifications of the WTS), the WTS be adequately rinsed to remove potentially toxic chemicals. Dialysis center personnel need to be aware of the potential effects that each modification or disinfection of the WTS may have on the product water used.
Twelve pediatric patients, aged 28 months to 17 years, received OKT3 to reverse renal allograft rejection. In 11 patients, the rejection crisis was resistant to conventional antirejection therapy with high doses of prednisone or polyclonal antithymocyte globulin. Reversal of rejection was successful in 10 patients who completed a treatment course. Because of recurring resistant rejection, five patients received a second course of OKT3, which was successful in reversing the rejection crisis in two. Among these patients, the persistence or the appearance of high levels of circulating T3 lymphocytes after initiating the second treatment course correlated with treatment failure. The immediate side effects associated with OKT3 therapy were transient and medically manageable. We conclude that this monoclonal antibody preparation is a safe and effective treatment for pediatric renal allograft in recipients experiencing rejection crisis resistant to conventional therapy. However, the potential impact of this immunosuppressive medication on long-term renal allograft survival in this patient population remains to be determined.
Explore the source record for details and available documents.
The authors conducted a retrospective hospital-based chart review of cases of hemolytic-uremic syndrome among children less than or equal to 18 years of age, hospitalized in Oregon during the four-year period from January 1979 to December 1982. Thirty children with hemolytic-uremic syndrome living in Oregon were hospitalized during this period, for an average annual incidence of 0.97 cases per 100,000 children. Seventy per cent of cases occurred in children under five years of age, for an incidence of 2.65 cases per 100,000 children. Twenty-seven (90%) of the 30 children were white, and 17 (57%) were female. Twenty-four (80%) had a diarrheal prodromal illness including 20 who had bloody diarrhea. Twelve children (40%) acutely required peritoneal dialysis, and two (7%) developed chronic renal failure. Three children died, for a case fatality ratio of 10%. Sixty per cent of the 30 cases occurred during the summer and early fall months. Geographic clustering was also evident. Hemolytic-uremic syndrome is a rare but endemic disease in Oregon and may occur in small clusters. Although descriptions of several large series of patients have been published, this study describes the first statewide population-based study of this syndrome.
The applicability of continuous arteriovenous hemofiltration (CAVH) for renal replacement therapy was evaluated in three infants and two young children with catastrophic medical and surgical illnesses. In the first four patients, CAVH was used in conjunction with either peritoneal or hemodialysis. In the fifth patient, CAVH was the sole renal replacement therapy employed; in this critically ill anuric infant, we were best able to evaluate the ability of CAVH to continuously control fluid, electrolyte, and acid-base balance, and allow the administration of adequate parenteral nutrition. The difficulties encountered were related to anticoagulation, establishment of adequate vascular access, and selection of an appropriate hemofilter for the performance of the technique. Despite the application of suction-assistance, we were unable to effectively employ a prototype pediatric hemofilter to attain a level of plasma ultrafiltration consistent with the objectives of therapy. However, we were able to effectively and safely employ an adult hemofilter for these purposes; modifications were made in the adult hemofilter system before its application in the smallest pediatric patients. Our experience suggests that, even in critically ill infants, CAVH can be successfully applied as an effective renal replacement therapy. However, further experience is required before its potential impact on patient survival can be assessed.
Explore the source record for details and available documents.
We report two patients undergoing continuous ambulatory peritoneal dialysis (CAPD) in whom peritonitis developed and nontuberculous mycobacteria were isolated from peritoneal fluid. In one, Mycobacterium avium-intracellularis was the only organism isolated. Despite a three-month course of antibiotics to which the organism showed in vitro sensitivity, there was no apparent response. The patient died, and an autopsy showed disseminated mycobacterial disease. In the second case, Mycobacterium fortuitum and diphtheroids were isolated from the peritoneal fluid. Although it was not clear that the mycobacterium was solely responsible for the peritonitis in the second case, the infection failed to resolve with antibiotic therapy appropriate for diphtheroids. This patient also died. Both patients had indolent, chronic infections, although there was granulocyte predominance in the peritoneal fluid. Both had involvement of the catheter exit site. To our knowledge, these are the first reported cases of nontuberculous mycobacterial peritonitis in CAPD patients. We recommend evaluation for mycobacteria, including cultures and stains of dialysate specimens, in all cases of CAPD-associated peritonitis where no organism is identified, or where no improvement is noted after 48 hours of therapy. Repeated cultures for mycobacteria are appropriate for suggestive cases. Since these infections are difficult to treat, it may be prudent to remove the dialysis catheter if they are isolated.
A mother and daughter with Campylobacter jejuni-associated hemolytic-uremic syndrome (HUS) are discussed. The mother was hospitalized with bloody diarrhea and HUS; C jejuni was isolated from her stool. The 2-year-old daughter had been admitted five days prior to her mother with HUS following a three-day prodrome of vomiting and diarrhea. Multiple stool cultures were negative for enteric pathogens; however, cultures were not obtained until the eighth hospital day and after antibiotic therapy. Extensive investigation failed to identify another cause for the diarrheal illness or HUS in our patients. Indirect immunofluorescent antibody titers for C jejuni were 1:32 and 1:16 for the mother and daughter, respectively. An asymptomatic 9-month-old son had C jejuni isolated from his stool and had an immunofluorescent antibody titer of 1:64. Three other family members were asymptomatic, stool-culture negative, and had immunofluorescent antibody titers less than or equal to 1:4. The susceptibility to develop HUS following an enteric antigenic stimulus is illustrated by the patients presented. The need for systematic investigation of all HUS cases for potential susceptibility markers, as well as an exhaustive etiologic search, is emphasized.
We report 3 cases of cystine calculi. The stones were dissolved by pelviocaliceal irrigation with tromethamine-E, performed either through a percutaneous nephrostomy tube or ureteral catheters. The 25, 27 and 37-day courses of irrigation were well tolerated by all patients. Complications included a single asymptomatic urinary tract infection that required antibiotic therapy and transient hematuria due to catheter irritation. Our experience demonstrates that cystine calculi, including staghorn, can be dissolved by tromethamine-E irrigation, thereby obviating the need for surgical intervention.