Knowledge gaps and confidence in counseling about aneuploidy screening and testing: A survey of prenatal care clinicians.

OBJECTIVES: Comprehensive counseling on prenatal genetic screening and diagnostic testing is challenging for clinicians. We sought to identify baseline clinician knowledge of prenatal genetic screening and diagnostic testing and needs to promote counseling aligned with ACOG recommendations. METHODS: We performed an anonymous, cross-sectional survey of clinicians at two unaffiliated, tertiary academic institutions to assess the knowledge of, confidence in, and time spent counseling on prenatal genetic screening and diagnostic testing. Stata (Version 17, College Station, TX) was used to perform descriptive statistics. Deductive and inductive coding was used to analyze responses regarding ideal education resources. RESULTS: The survey response rate was 78% (100/129). Only 36% of respondents correctly answered knowledge questions about prenatal genetic screening and diagnostic testing. A majority, 59% (16/39), of those confident or extremely confident in counseling were unable to answer all questions accurately. Respondents reported a median of 5.6 min (95% CI 4.9-6.4 min) spent counseling. Thematic analysis of free responses revealed desire for visual tools that discuss financial costs and patient values. CONCLUSIONS: Surveyed clinicians demonstrated deficiencies in knowledge about prenatal genetic counseling. To provide better and more comprehensive care, we noted a desire for the development of formalized resources for clinician and patient education.

Prediction of long-term dependence on vitamin D analogues following total thyroidectomy for Graves' disease.

INTRODUCTION: This study aimed to identify patients at risk of long-term hypocalcaemia following total thyroidectomy for Graves' disease, and to determine the thresholds of postoperative day 1 serum calcium and parathyroid hormone (PTH) at which long-term activated vitamin D treatment can be safely excluded. METHODS: This study was a retrospective analysis of 115 consecutive patients undergoing total thyroidectomy for Graves' disease at a university referral centre between 2010 and 2018. Outcome measures were the day 1 postoperative adjusted calcium and PTH results, and vitamin D analogue need at 6 months postoperatively. Logistic receiver operating curves were used to identify optimal cut-off values for adjusted serum calcium and serum PTH, and sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) were calculated. RESULTS: Temporary hypocalcaemia was observed in 20.9% of patients (mean day 1 serum adjusted calcium 2.2±0.14mmol/l and PTH 4.15±2.42pmol/l). Long-term (>6 months) activated vitamin D analogue therapy was required in five patients (4.3%), four of whom had normal serum PTH and one with undetectable PTH at 6 weeks post surgery. No patient with a day 1 postoperative calcium >2.05mmol/l and detectable PTH required vitamin D supplementation at 6 months post surgery (100% sensitivity, PPV 50%, NPV 100%). CONCLUSIONS: The biochemical postoperative day 1 thresholds identified in this paper have a 100% NPV in the identification of patients who are likely to require either no or only temporary activated vitamin D supplementation. We were able to identify all patients requiring activated vitamin D supplementation 6 months postoperatively from the day 1 postoperative serum calcium and PTH values, while excluding those that may only need temporary calcium supplementation. These threshold levels could be used for targeted follow-up and management of this subset of patients most at risk of long-term hypocalcaemia.

Clinical validation of dual-source dual-energy computed tomography (DECT) for coronary and valve imaging in patients undergoing trans-catheter aortic valve implantation (TAVI).

AIM: To assess the validity of virtual non-contrast (VNC) reconstructions for coronary artery calcium (CACS) and aortic valve calcium scoring (AVCS) in patients undergoing trans-catheter aortic valve implantation (TAVI). MATERIALS AND METHODS: Twenty-three consecutive TAVI patients underwent a three-step computed tomography (CCT) acquisition: (1) traditional CACS; (2) dual-energy (DE) CT coronary angiogram (CTCA); and (3) DE whole-body angiogram. Linear regression was used to model calcium scores generated from VNC images with traditional scores to derive a conversion factor [2.2 (95% CI: 1.97-2.58)]. The effective radiation dose for the TAVI protocol was compared to a standard control group. Bland-Altman analysis and weighted k-statistic were used to assess inter-method agreement for absolute score and risk centiles. RESULTS: CACS and AVCS from VNC reconstructions correlated well with traditional scores (r = 0.94 and r = 0.86; both p < 0.0001). There was excellent agreement between VNC and non-contrast coronary calcium scores [mean difference -71.8 (95% limits of agreement -588.7 to 445.1)], with excellent risk stratification into risk centiles (k = 0.99). However, the agreement was weaker for the aortic valve [mean difference -210.6 (95% limits of agreement -1233.2 to 812)]. Interobserver variability was excellent for VNC CACS [mean difference of 6 (95% limits of agreement 134.1-122.1)], and AVCS [mean difference of -16.4 (95% limits of agreement 576 to -608.7)]. The effective doses for the DE TAVI protocol was 16.4% higher than standard TAVI protocol (22.7 versus 19.5 mSv, respectively) accounted for by the DE CTCA dose being 47.8% higher than that for a standard CTCA [9.9 (5.6-14.35) versus 6.7 (1.17-13.72) mSv; p < 0.01). CONCLUSIONS: CACS and AVCS can be accurately quantified, and patients can be risk stratified using DECT VNC reconstructions. However, the dose from DE CTCA is significantly greater than the standard single-energy CTCA precluding the use of this technology in routine clinical practice.

Cost of production of live attenuated dengue vaccines: a case study of the Instituto Butantan, Sao Paulo, Brazil.

BACKGROUND: A vaccine to prevent dengue disease is urgently needed. Fortunately, a few tetravalent candidate vaccines are in the later stages of development and show promise. But, if the cost of these candidates is too high, their beneficial potential will not be realized. The price of a vaccine is one of the most important factors affecting its ultimate application in developing countries. In recent years, new vaccines such as those for human papilloma virus and pneumococcal disease (conjugate vaccine) have been introduced with prices in developed countries exceeding $50 per dose. These prices are above the level affordable by developing countries. In contrast, other vaccines such as those against Japanese encephalitis (SA14-14-2 strain vaccine) and meningitis type A have prices in developing countries below one dollar per dose, and it is expected that their introduction and use will proceed more rapidly. Because dengue disease is caused by four related viruses, vaccines must be able to protect against all four. Although there are several live attenuated dengue vaccine candidates under clinical evaluation, there remains uncertainty about the cost of production of these tetravalent vaccines, and this uncertainty is an impediment to rapid progress in planning for the introduction and distribution of dengue vaccines once they are licensed. METHOD: We have undertaken a detailed economic analysis, using standard industrial methodologies and applying generally accepted accounting practices, of the cost of production of a live attenuated vaccine, originally developed at the US National Institutes of Health (National Institute of Allergy and Infectious Diseases), to be produced at the Instituto Butantan in Sao Paulo, Brazil. We determined direct costs of materials, direct costs of personnel and labor, indirect costs, and depreciation. These were analyzed assuming a steady-state production of 60 million doses per year. RESULTS: Although this study does not seek to compute the price of the final licensed vaccine, the cost of production estimate produced here leads to the conclusion that the vaccine can be made available at a price that most ministries of health in developing countries could afford. This conclusion provides strong encouragement for supporting the development of the vaccine so that, if it proves to be safe and effective, licensure can be achieved soon and the burden of dengue disease can be reduced.

Safety of an amino-acetonitrile derivative (AAD), monepantel, in ewes and their offspring following repeated oral administration.

AIM: To demonstrate the clinical and reproductive safety in ewes and their offspring of repetitive oral doses of monepantel, an amino-acetonitrile derivative (AAD), when administered at three times the proposed maximum recommended dose (MRD) over an entire reproductive cycle. METHODS: A randomised controlled blinded study design was used. One hundred and twelve primi- or multi-parous ewes and 28 rams were randomly allocated into control and treated groups (n=56 for groups of ewes, n=14 for groups of rams). Two control ewes and two treated ewes were randomly selected to form 28 subgroups. A control or treated ram was then randomly allocated to each subgroup, to form control ram/treated ewe, control ram/control ewe, treated ram/treated ewe, and treated ram/control ewe 'treatment/mating' units. Control animals were treated with saline, and treated animals given three times the MRD (11.25 mg/kg) of monepantel. Treatments were administered orally every 5 days during an entire reproductive cycle, including oestrus and mating, gestation, and post-lambing to weaning. Detailed recording at multiple time points were made of veterinary examinations; observations for adverse events; bodyweight measurements; faecal scores; and haematology, clinical chemistry and coagulation variables. Reproductive indices determined included percent pregnant, number of failed embryos, abortion percentage, number of lambs with teratogenic defects, length of gestation, percentage of stillbirths, number of ewes experiencing reproductive problems, lambing percentage, and pre-weaning mortality. Post-mortem examination, including measurement of organ weights, was performed on randomly selected ewes (n=40) and lambs (n=40) at the completion of the study. RESULTS: All ewes treated with monepantel and those in the control group thrived and behaved normally to the end of the study. No treatment-related, toxicologically relevant adverse events, clinical observations or gross post-mortem changes were observed. Furthermore, there were no significant differences in bodyweight or organ weights, and haematological, clinical chemistry or coagulation variables between ewes treated with monepantel and control ewes. No significant differences were observed in any of the reproductive indices measured. No significant clinical differences were noted between lambs born from treated ewes and those from controls. CONCLUSIONS AND CLINICAL RELEVANCE: Repeated oral administration of monepantel at three times the MRD every 5 days over an entire reproductive cycle was not associated with any treatment-related adverse effects on the reproductive performance of ewes nor on the viability of their offspring, and was systemically very well tolerated. This study demonstrated that this population of ewes could tolerate accidental overdoses of up to three times the MRD of monepantel or prolonged repetitive administration of overdoses. Thus, those so treated entering a breeding programme would have normal reproductive indices, mating behaviour, and health, and their lambs would suffer no ill effects.

Reproductive safety of an amino-acetonitrile derivative (AAD), monepantel, in rams following repeated oral administration.

AIM: To demonstrate the clinical and reproductive safety in rams of repetitive oral doses of monepantel, an amino-acetonitrile derivative (AAD), when administered at three times the proposed maximum recommended dose (MRD) over an entire spermatogenic cycle and during mating with ewes. METHODS: A randomised controlled blinded study design was used with 28 rams randomly divided into two groups. The control group was treated with saline, and the other group was given three times the MRD (11.25 mg/kg) of monepantel. Treatments were administered orally every 5 days, for 100 days, during an entire spermatogenic cycle and subsequent mating period. Detailed recording at multiple time points were made of veterinary examinations; observations for adverse events; bodyweight measurements; faecal scores; haematology, clinical chemistry and coagulation variables; semen indices; evaluation of serving capacity; and gross pathology (including measurement of organ weights) performed on 10 rams from each group at the completion of the study. RESULTS: All rams treated with monepantel and those in the control group thrived and behaved normally to the end of the study. No treatment-related, toxicologically relevant adverse events, clinical observations or macroscopic changes were observed. Furthermore, there were no significant differences in bodyweight or organ weights, and haematological, clinical chemistry or coagulation variables between rams treated with monepantel and control rams. No significant changes were observed in any semen variable measured in any rams, and the serving capacity of rams mated to ewes was unaffected. CONCLUSIONS AND CLINICAL RELEVANCE: Repeated oral administration of monepantel at three times the MRD every 5 days over an entire spermatogenic cycle and during mating was not associated with any treatment-related adverse effects on the reproductive performance of rams and was systemically very well tolerated. This study demonstrated that this population of rams could tolerate accidental overdoses of up to three times the MRD of monepantel or prolonged repetitive administration at overdoses. Thus, those so treated entering a breeding programme would have normal sperm indices, mating behaviour, and health.

The Caregivers for Alzheimer's disease Problems Scale (CAPS): development of a new scale within the LASER-AD study.

BACKGROUND: we developed the Caregivers for Alzheimer's disease Problems Scale (CAPS) comprising common risk factors for anxiety and depression for family carers of people with dementia. OBJECTIVE: to calculate the sensitivity and specificity of the CAPS in order to measure its usefulness in identifying dementia caregivers at risk of anxiety and depression and therefore whether it identifies clinically relevant areas for intervention or highlights the need for support if the problem could not be changed. METHOD: 153 family caregivers were interviewed as part of a larger epidemiologically representative study of people with Alzheimer's disease and their caregivers. Caregiver anxiety and depression were measured using the Hospital Anxiety and Depression Scale (HADS). RESULTS: the CAPS had high sensitivity and specificity in detecting caregivers with screen positive anxiety and depression. Five areas were indicated: neuropsychiatric symptoms and depression in the care-recipient, co-residence and relationships with the care-recipient, and physical health of the caregiver. CONCLUSIONS: awareness of these problems can help clinicians identify those carers most likely to be anxious or depressed and indicate appropriate intervention and support. We recommend that this instrument be used as part of routine assessments of people with dementia and their families.

The efficacy of formulations of triclabendazole and ivermectin in combination against liver fluke (Fasciola hepatica) and gastro-intestinal nematodes in cattle and sheep and sucking lice species in cattle.

OBJECTIVE: To assess the efficacy of two formulations of triclabendazole and ivermectin in combination against liver fluke (Fasciola hepatica), gastro-intestinal nematodes and sucking louse species in cattle and sheep. PROCEDURE: A study of 540 cattle and 428 sheep at 18 sites throughout Victoria and New South Wales was undertaken. At each site, one group of cattle or sheep was treated with a combined formulation (Fasimec Cattle or Fasimec Sheep), another received ivermectin and triclabendazole separately. In trials on lice infestation, an additional group remained untreated. Samples for faecal egg counts were collected on days -7, 0 (treatment day), +7, +14 and +21 after treatment. Lice assessments were carried out on days -7, 0, +7, +14, +28, +42 and +56. RESULTS: Both treatments were highly efficacious (> 98% efficacy) against liver fluke in cattle and sheep, against three sucking lice species of cattle and against gastro-intestinal nematodes in sheep. There was also no significant difference between treatments in efficacy. Against gastro-intestinal nematodes, Fasimec Cattle was significantly (P < 0.01) more effective than the separately applied ivermectin and triclabendazole treatment. Mean efficacy for the Fasimec Cattle and Ivomec/Fasinex 120 groups respectively, was 97.6% and 94.2% on Day +7, 98.9% and 91% on Day +14 and 98.5% and 92.6% on Day +21. CONCLUSION: The efficacy of Fasimec' Cattle and Fasimec Sheep was at least equal to that of currently registered products (with the same active ingredients) used to control these parasites.

Cost of immunization with a locally produced, oral cholera vaccine in Viet Nam.

Policy decisions regarding whether to incorporate new vaccines into routine public health practice in developing countries will depend in part on the costs of vaccine purchase and of vaccine delivery. In March, 1997, a large-scale effectiveness trial of a locally produced, orally administered bivalent vaccine against Vibrio cholerae 01 and 0139 began in Viet Nam. Empirical data obtained from the trial was used to determine the costs of the immunization campaign from the government perspective. The study population, including the children less than one year of age and pregnant women who were ineligible for immunization, was 353926. A total of 289041 persons received two doses of vaccine, and 13340 persons received one dose of vaccine. Two-dose vaccine coverage was 83.4%. The total cost of vaccine delivery during the immunization campaign was $66527. The cost of each dose of vaccine was $0.31. Therefore, the total cost of the immunization campaign was $0.44 per dose administered, and $0.91 per fully immunized person. Attempts to reduce the cost per dose of vaccine (e.g. the use of a monovalent vaccine against serogroup 01) are likely to have a large impact on the cost of future similar immunization campaigns.

Assessing human-robotic performance for vocational placement.

This paper describes the results of an exploratory study of the use of standard occupational therapy assessment tests to measure the effective manipulation ability of individuals with disabilities using a robotic aid. Robotic manipulators have been explored for use as a vocational accommodation to support the job placement of individuals with severe manipulation disabilities. One of the factors that has impeded the transfer of this work is the lack of practical information that is relevant to the vocational placement process. The preliminary performance data presented in this paper provides an indication of robot-assisted manipulation skill that rehabilitation professionals may use to better understand the potential for use of this technology in providing greater job opportunities for people with severe manipulation impairment. Three different assessment tests were administered to nine different subjects with severe physical disabilities using a computer-controlled robotic workstation to perform the manipulation requirements of the tests. In all cases, the subjects, who were otherwise unable to physically perform the tasks without the robot, were able to perform manipulation tasks a factor of 20-700 times less than that of the performance indicated in published norms. Although these performance levels are modest in terms of nondisabled populations, supporting data is also provided that suggests that individuals with severe manipulation deficits could have access to a much wider range of vocational opportunities with an appropriate implementation of robot technology.

The introduction of new vaccines into developing countries II. Vaccine financing.

The development of new vaccines for important childhood diseases presents an unparalleled opportunity for disease control but also a significant problem for developing countries: how to pay for them. To help address this problem, the William H. Gates Foundation has established a Global Fund for Children's Vaccine. In this paper, we discuss the allocation of this and other similar funds, which we call Global Funds. We propose that allocation of the Global Funds to individual countries be guided in part by a Vaccine Procurement Baseline (VPB). The VPB would set a minimum of 0.01% of gross national product (GNP) as an amount each developing country would devote to its own vaccine procurement. When this amount is not sufficient to procure the vaccines needed by a developing country, the Global Funds would meet the shortfall. The amount required of donors to maintain the Global Funds would be about $403 million per year for both existing EPI vaccines as well as for a hypothetical group of five new vaccines costing $0.50 per dose and requiring three doses per child. Including program costs, poor developing countries currently spend about 0.13% of GNP on EPI immunizations. In contrast, the United States, as one example donor country, spends about 0.035% of GNP for childhood immunization including several new vaccines. This paper analyzes the Global Funds requirements for hepatitis B and Haemophilus influenzae type b (Hib) vaccines. After a ramp-up period, needier countries would eventually require about $62 million for hepatitis B and $282 million for Hib at current prices. Various additional criteria could be used to qualify countries for participation in the Global Funds.

HLA-DMA allele polymorphism: no impact on kidney allograft outcome.

The purpose of this study was to analyze the association of HLA-DMA alleles with rejection episodes and early graft loss (EGL) in renal transplant recipients. One hundred and eighty four HLA-DMA alleles were retrospectively analyzed by DNA sequence analysis in 92 kidney transplant recipients. The gene frequencies of HLA-DMA *0101, *0102, *0103 and *0104 were found to be similar in all recipients, regardless of rejection vs non rejection episodes and EGL incidence. In conclusion, HLA-DMA allele polymorphism did not impact renal allograft outcome.

Multimodal chronic pain rehabilitation program: its effect on immune function, depression, and health behaviors.

This pilot study examined the effects of a multimodal pain rehabilitation program on the immune function, self-reported pain, depression levels, and health behaviors of patients with chronic back pain. It also estimated the relationships between self-reported pain levels, immune function, depression, and health behaviors. Data were collected at week 1 (baseline) and at week 4 (last week of treatment program) on a convenience sample of 23 patients. In general, the patients' mean T lymphocyte proliferation levels showed a decline from baseline to week 4, while natural killer cell activity showed a slight increase in cell lysis. None of the findings were statistically significant. Failure to detect significant differences may be attributed to a small effect size due to the relatively small sample size. The depression levels dropped significantly during the treatment program (p = .001). Reported levels of pain and health behaviors did not significantly change. More research is needed to determine treatment effects on immune function as well as relationships between pain levels, immune function, depression, and health behaviors in this patient population.

Powered feeding devices: an evaluation of three models.

OBJECTIVE: To evaluate and compare three powered feeding devices (Beeson, Handy 1, Winsford) as perceived by disabled individuals who require assistance with eating. DESIGN: Subjects and assistants were surveyed after using each device and serving their own controls. The order in which the devices were used was balanced. SETTING: Place of subjects' residence. SUBJECTS: Twelve subjects, ages 11 to 42 years, and their feeding assistants. INTERVENTION: Each device trial covered a 4-day period. Day 1 focused on training to use the device, Days 2 and 3 focused on using the device at home, and on Day 4 subjects returned to the laboratory for debriefing, completing questionnaires, and videotaping. MAIN OUTCOME MEASURE: Subjects and assistants answered questionnaires including Likert-like rankings and yes/no responses regarding functional and esthetic characteristics of each feeding device. RESULTS: Significant differences were found among three powered feeding devices regarding specific design characteristic. Great percentages of both subjects and their feeding assistants responded that the devices were an improvement over how they were currently being fed and that they would use such a device on a daily basis. CONCLUSION: Individuals dependent on others for feeding may benefit from the use of a powered feeding device.

Long-lasting prevention against blowfly strike using the insect growth regulator dicyclanil.

OBJECTIVE: To assess a ready-to-use formulation of dicyclanil to prevent blowfly strike on Merino sheep under Australian conditions. DESIGN: Randomised clinical trials conducted in an environment house and in the field. PROCEDURE: Two environment house trials were used to measure the protection against flystrike provide by a jetting or a ready-to-use 5% spray-on formulation of dicyclanil over 22 and 31 weeks respectively. Oviposition and strikes were recorded weekly for each sheep. In two field trials the occurrence of strike in Merino sheep treated off-shears or in long wool with dicyclanil or with cyromazine was compared for up to 38 weeks after treatment. Efficacy was assessed by calculating the cumulative percentage of sheep struck. RESULTS: Under environment house conditions, sheep jetted with dicyclanil at 1.50, 0.75 and 0.30 g per sheep developed 0, 8 and 9 strikes respectively during the 22 weeks of the trial, whereas there were 358 strikes present in the placebo group. Sheep sprayed with dicyclanil at 2.25, 1.50 and 0.75 g per sheep developed 5, 11 and 29 strikes respectively between weeks 15 and 31 after treatment, whereas there were 185 strikes present in the untreated controls. In field trials the cumulative percentage of sheep struck reached 1% between weeks 12 to 13 after sheep had been treated with cyromazine. Sheep treated with dicyclanil reached the 1% limit at week 21 after treatment. CONCLUSION: Under Australian field conditions, a ready-to-use 5% spray-on formulation of dicyclanil applied off-shears or to long wool protected Merino sheep from blowfly strike for a period of at least 20 weeks.

Inhibition of HLA antibody cytotoxicity by intravenous immunoglobulin G F(ab')2 dimers, monomers, and monovalent F(ab).

IVIgG preparations are clinically relevant to sensitized transplant candidates because they inhibit HLA alloantibody in vitro and in vivo. We hypothesized that IVIgG F(ab')2 idiotypic-antiidiotypic dimers may possess a greater immunomodulatory capacity when remonomerized than non-dimerizable F(ab')2 monomers in IVIgG. We reasoned that when 60-75% of potential antiidiotypic IVIgG monomers fail to bind to IVIgG molecules in a large pool of plasma donors (>10,000), IVIgG monomers may fail to inhibit HLA idiotypic antibodies of sensitized transplant candidates. In the first series of AHG T cell crossmatches, non-fractionated IVIgG F(ab')2 was found to inhibit titered HLA antibodies in 13 out of 29 (45%) crossmatch combinations. Crossmatch inhibition was incomplete, i.e., a particular titered HLA antibody specificity was not always inhibited by IVIgG F(ab')2 in every HLA antigen-matched target cell crossmatch. Next, the IVIgG F(ab')2 product was fractionated into F(ab')2 dimers, F(ab')2 monomers and Fab monovalent components by size exclusion high pressure liquid chromatography (HPLC) and retested in crossmatches which previously demonstrated inhibition. The percent of crossmatches that were inhibited by HPLC F(ab')2 IVIgG fractions in three separate experiments was statistically similar for pH 4.0 remonomerized dimers, 82%; pH 6.0 dimers, 50%; monomers, 64%; and monovalent Fab, 64% (p = 0.50). Soluble class I HLA antigen was undetectable in IVIgG F(ab')2 by an ELISA assay. In conclusion, IVIgG dimers and monomers appear to have similar immunomodulatory capacities, and separation of whole IVIgG products into dimer and monomer fractions does not appear to be warranted. Further, IVIgG products should be tested for optimal HLA antibody inhibition in vitro prior to in vivo therapy.

The introduction of new vaccines into developing countries.

The development and introduction of new vaccines is a costly and time consuming process. Unfortunately, those most in need--individuals in developing countries--are the last to receive these powerful disease preventing products. From the time a vaccine is first licensed in a developed country to the time most of the poor in developing countries have access to the vaccine can be 20-30 years. This delay is unacceptable. There is a great need to reduce this time span. This paper examines five ways of reducing the time span. Each of the five is essential and achieving success on all five will require a heightened level of international effort and coordination.

Immunomagnetic bead cell isolates reduce kidney donor cold ischemia time, STAT crossmatch time and histocompatibility test cost.

The use of immunomagnetic beads for STAT cadaveric crossmatching for renal transplantation reduces test cost by 50%, laboratory work-up time by 50% and cold ischemia time by 4 h as compared with the nylon wool method of T- and B-lymphocyte separation.

When perfectly HLA-matched kidneys are refused for transplant: implications for a national cooperative sharing system.

BACKGROUND: The transplant community attempts to maximize overall renal graft survival rates through nationwide sharing of perfectly-matched cadaveric kidneys. Although the number of such transplants is determined annually, the number available but not transplanted has never been assessed. There has also been no verification of the widespread claim that kidneys transplanted as paybacks for perfect matches are inferior. STUDY DESIGN: From records of the United Network for Organ Sharing, a complete accounting of six-antigen-matched kidney disposition was obtained, including a frequency distribution of reasons for refusal given when kidneys were refused for matched patients. Actuarial graft survival (GS) rates for matched, payback, and other cadaveric renal transplants were determined. RESULTS: Of the six-antigen-matched kidneys available, 97 percent were transplanted; 71 percent of those were accepted for matched patients. The two-year GS rate for matched patients was 84 percent, significantly higher than that for kidneys available for matched patients but transplanted into other patients (71.3 percent) and that for all other cadaveric kidneys (75.5 percent). Most reasons for refusal were related to donor quality. Kidneys refused for such reasons showed a 67.7 percent two-year GS rate in nonmatched patients and the highest rates of acute and chronic rejection and primary failure. The two-year GS rate for kidneys accepted as paybacks for matched kidneys (75.7 percent) was equivalent to that for all non-matched cadaveric kidneys (75.5 percent). CONCLUSIONS: If all normal-quality grafts refused for perfectly matched patients during 1990 through 1992 had been accepted for those patients, the number of transplants with typically superior survival rates could have increased by 25 percent, from 1,365 to 1,704. The payback requirement of the United Network for Organ Sharing does not seem to reduce the overall benefits of sharing perfectly matched kidneys nationwide.