Increasing Consent and Assent Rate for Organ and Tissue Donation: Communication About Donation-Telephone Advice by Psychologist.

A high percentage of family refusal is found for several outcomes in the Donor Register. Misconceptions and concerns regarding donation impede next of kin from making a well-considered decision. The donation request is the moment in which such concerns should be addressed by the requestor. The Communication about Donation-Telephone Advice by Psychologist (CaD-TAP) is a direct telephone intervention for requestors who are about to request the relatives for donation. The aim of this intervention is to improve requestors' communication skills regarding the donation request and thereby increase the consent rate for organ and/or tissue donation. The intervention started on the April 1, 2014, and lasted until December 31, 2014. To determine the effects, the consent and assent rates were compared between requestors who received the CaD-TAP intervention and those who did not. The requestors who received the CaD-TAP intervention (N = 141) had a significantly (P < .001) higher consent rate (58%) compared with the group who did not receive the intervention (N = 1563, consent rate: 34%). More tissue donor requestors received the intervention (74%) and most interventions took place outside office hours (82%). No significant difference was found in the effect of the intervention with regard to type of donation, time, or day. Furthermore, the intervention increased requestors' self-confidence in requesting for donation (P < .001), and a higher self-confidence indicated a significant association with increased consent rate. The intervention is unanimously experienced as positive and valuable by users. Based on these results the intervention is effective in increasing the consent rate for organ and tissue donation.

Shared Decision-Making in Kidney Patients: Involvement in Decisions Regarding the Quality of Deceased Donor Kidneys.

OBJECTIVES: This study examined whether kidney patients want to participate in decisions regarding the minimal acceptable quality of deceased donor kidneys. We also explored patients' opinions about the trade-off between a higher-quality organ with a longer waiting time vs a lower-quality organ with a shorter waiting time. METHODS: A questionnaire was distributed among kidney patients. Additionally, a sub-sample of these patients participated in in-depth interviews, which were analyzed using the grounded theory approach. RESULTS: Sixty-three percent of the patients wished to participate in decisions concerning the quality of a deceased donor kidney. The majority of the respondents indicated that they prefer a kidney of good quality and would therefore accept a longer waiting time. Responses to the qualitative interviews illustrated a more balanced choice regarding this trade-off. CONCLUSIONS: Many patients wish to be involved in deciding on the quality of the kidney, but it may evoke the experience of decisional conflicts when they have to make rational trade-offs between the desire for the best kidney at the expense of a longer waiting time.

Differential effects of donor-specific HLA antibodies in living versus deceased donor transplant.

The presence of donor-specific anti-HLA antibodies (DSAs) is associated with increased risk of graft failure after kidney transplant. We hypothesized that DSAs against HLA class I, class II, or both classes indicate a different risk for graft loss between deceased and living donor transplant. In this study, we investigated the impact of pretransplant DSAs, by using single antigen bead assays, on long-term graft survival in 3237 deceased and 1487 living donor kidney transplants with a negative complement-dependent crossmatch. In living donor transplants, we found a limited effect on graft survival of DSAs against class I or II antigens after transplant. Class I and II DSAs combined resulted in decreased 10-year graft survival (84% to 75%). In contrast, after deceased donor transplant, patients with class I or class II DSAs had a 10-year graft survival of 59% and 60%, respectively, both significantly lower than the survival for patients without DSAs (76%). The combination of class I and II DSAs resulted in a 10-year survival of 54% in deceased donor transplants. In conclusion, class I and II DSAs are a clear risk factor for graft loss in deceased donor transplants, while in living donor transplants, class I and II DSAs seem to be associated with an increased risk for graft failure, but this could not be assessed due to their low prevalence.

[Waiting list registration for kidney transplants must improve]. / Wachtlijstregistratie niertransplantatie moet beter.

OBJECTIVE: To investigate how the composition of the waiting list for postmortem kidney transplant has developed, and whether the waiting list reflects actual demand. DESIGN: Retrospective research and cohort study. METHOD: We used data from the period 2000-2014 from the Dutch Transplant Foundation, 'RENINE' and Eurotransplant. This concerned data on postmortem kidney donation, live donor transplants, the waiting list and kidney transplantation. RESULTS: The postmortem kidney transplant waiting list included transplantable (T) and non-transplantable (NT) patients. The number of T-patients declined from 1271 in 2000 to 650 in 2014, and the median waiting time between the start of dialysis and postmortem kidney transplant decreased from 4.1 years in 2006 to 3.1 years in 2014. The total number of patients on the waiting list, however, increased from 2263 in 2000 to 2560 in 2014 and in the same period the number of new patient registrations increased from 772 to 1212. In about 80% of the NT-patients the reason for their NT status was not registered. A cohort analysis showed that NT-patients have a 2-times lower chance of a postmortem kidney transplant and a 2-times higher chance of leaving the waiting list without transplantation or of live-donor transplantation. CONCLUSION: The demand for donor kidneys remains high. The increased number of transplants resulted in a declining waiting list for T-patients while the total waiting list is getting longer. Waiting list registration and maintenance need to be improved, to give better insight into the real demand.

Reactivation of Latent HPV Infections After Renal Transplantation.

Female renal transplant recipients (RTRs) have an increased risk for developing human papillomavirus (HPV)-related (pre)malignant lesions of the genital tract. This study aims to assess the genital prevalence of HPV before and after renal transplantation (RT). In female patients who were counseled for RT at the Radboud University Medical Center Nijmegen, the Netherlands, gynecological examination was performed at first visit, and 1 and 2 years later. HPV self-sampling and questionnaires on sexual behavior were performed every 3 months. In 65 patients who underwent RT, the high-risk human papillomavirus (hrHPV) prevalence as assessed with the highly sensitive SPF10 -LiPA25 test increased significantly from 19% before to 31% after RT (p = 0.045). Based upon the clinically validated Cobas 4800 HPV test, the hrHPV prevalence increased from 10% before to 14% after RT (p = 0.31). During follow-up, no changes in sexual behavior were reported. Thirty-three patients who did not undergo RT showed a hrHPV prevalence of 21% at study entry and of 27% after 12 months with the sensitive test, and a stable prevalence of 16% with the clinically validated test. The results of this study indicate that activation of latent HPV infections may contribute to the increased risk of HPV-related (pre)malignant lesions in female RTRs.

How can we reduce costs of solid-phase multiplex-bead assays used to determine anti-HLA antibodies?

Solid-phase multiplex-bead assays are widely used in transplantation to detect anti-human leukocyte antigen (HLA) antibodies. These assays enable high resolution detection of low levels of HLA antibodies. However, multiplex-bead assays are costly and yield variable measurements that limit the comparison of results between laboratories. In the context of a Dutch national Consortium study we aimed to determine the inter-assay and inter-machine variability of multiplex-bead assays, and we assessed how to reduce the assay reagents costs. Fifteen sera containing a variety of HLA antibodies were used yielding in total 7092 median fluorescence intensities (MFI) values. The inter-assay and inter-machine mean absolute relative differences (MARD) of the screening assay were 12% and 13%, respectively. The single antigen bead (SAB) inter-assay MARD was comparable, but showed a higher lot-to-lot variability. Reduction of screening assay reagents to 50% or 40% of manufacturers' recommendations resulted in MFI values comparable to 100% of the reagents, with an MARD of 12% or 14%, respectively. The MARD of the 50% and 40% SAB assay reagent reductions were 11% and 22%, respectively. From this study, we conclude that the reagents can be reliably reduced at least to 50% of manufacturers' recommendations with virtually no differences in HLA antibody assignments.

Controlled donation after circulatory death in the Netherlands: more organs, more efforts.

BACKGROUND: The Netherlands was one of the first countries in Europe to stimulate controlled donation after circulatory death (cDCD) at a national level in addition to donation after brain death (DBD). With this program the number of organ transplants increased, but it also proved to have challenges as will be shown in this 15-year review. METHODS: Data about deceased organ donation in the Netherlands, from 2000 until 2014, were analysed taking into account the whole donation process from donor referral to the number of organs transplanted. RESULTS: Donor referral increased by 58%, from 213 to 336 donors per year, and the number of organs transplanted rose by 42%. Meanwhile the contribution of cDCD donors increased from 14% in 2000 to 54% in 2014 among all referrals. The organs were transplanted from 92-99% of referred DBD donors, but this percentage was significantly lower for cDCD donors and also decreased from 86% in 2000-2002 to 67% in 2012-2014. In 16% of all referred cDCD donors, organs were not recovered because donors did not die within the expected two-hour time limit after withdrawal of life- upporting treatment. Furthermore, cDCD is more often performed at a higher donor age, which is associated with a lower percentage of transplanted organs. CONCLUSION: Although cDCD resulted in more transplants, the effort in donor recruitment is considerably higher. Important challenges in cDCD that need further attention are the time limit after withdrawal of life-supporting treatment and donor age, as well as the possibilities to stimulate non-renal transplants including the heart by machine preservation.

The Course and Predictors of Health-Related Quality of Life in Living Kidney Donors: A Systematic Review and Meta-Analysis.

A better understanding of the course and risk factors for impaired long-term health-related quality of life (HRQoL; ie, physical, psychological, and social-relational functioning) after kidney donation might help clinicians improve the care of live kidney donors. This systematic review and meta-analysis summarizes prospective studies about the course and predictors of HRQoL in living kidney donors. Studies indicate that shortly after donation, donors have lower HRQoL, with minor to moderate changes in psychological and social-relational functioning and major changes in physical functioning. At 3-12 months after donation, HRQoL returned to baseline or was slightly reduced, particularly for fatigue, but scores were still comparable to general population norms. Results were mainly robust across surgery techniques. A limited number of studies examined risk factors for impaired HRQoL, with low psychological functioning before donation as the most consistent predictor. Based on these results, clinicians can inform potential donors that, on average, kidney donors have high long-term HRQoL; however, donors with low psychological functioning at baseline are those most at risk of impaired long-term HRQoL. Future studies should focus on other potentially relevant predictors of postdonation HRQoL, including donor eligibility criteria and donor-recipient relationships, to optimize screening and interventions for donors at risk.

Cervicovaginal HPV infection in female renal transplant recipients: an observational, self-sampling based, cohort study.

Immunosuppressive treatment of organ transplant recipients is associated with an increase in the occurrence of human papillomavirus (HPV) related anogenital (pre)malignancies. This cohort study investigated the genotype-specific prevalence of HPV infections in a large cohort of female renal transplant recipients (RTRs). Participants self-collected a cervicovaginal sample for detection and genotyping of HPV. Besides, they completed a questionnaire regarding sociodemographic variables, medical data and sexual behavior. Anogenital screening was offered to all HPV-positive participants. A total number of 218 female RTRs was included. The prevalence of mucosal HPV infections was 27.1% and 17.4% for high risk HPV in particular. The studied cohort showed a broad range of HPV genotypes and multiple HPV genotypes were found in 27.1% of HPV-positive patients. Seven participants were identified with occult premalignant anogenital lesions. In conclusion, this study shows a high point-prevalence of HPV in female RTRs (age-matched West-European general population: 9-10%) with a shift in the distribution of genotypes as compared with the general population. Moreover, a substantial number of patients with occult premalignancies was identified. The introduction of self-sampling for HPV positivity can help in early detection of (pre)malignant anogenital lesions in this vulnerable population.

The PROCARE consortium: toward an improved allocation strategy for kidney allografts.

Kidney transplantation is the best treatment option for patients with end-stage renal failure. At present, approximately 800 Dutch patients are registered on the active waiting list of Eurotransplant. The waiting time in the Netherlands for a kidney from a deceased donor is on average between 3 and 4 years. During this period, patients are fully dependent on dialysis, which replaces only partly the renal function, whereas the quality of life is limited. Mortality among patients on the waiting list is high. In order to increase the number of kidney donors, several initiatives have been undertaken by the Dutch Kidney Foundation including national calls for donor registration and providing information on organ donation and kidney transplantation. The aim of the national PROCARE consortium is to develop improved matching algorithms that will lead to a prolonged survival of transplanted donor kidneys and a reduced HLA immunization. The latter will positively affect the waiting time for a retransplantation. The present algorithm for allocation is among others based on matching for HLA antigens, which were originally defined by antibodies using serological typing techniques. However, several studies suggest that this algorithm needs adaptation and that other immune parameters which are currently not included may assist in improving graft survival rates. We will employ a multicenter-based evaluation on 5429 patients transplanted between 1995 and 2005 in the Netherlands. The association between key clinical endpoints and selected laboratory defined parameters will be examined, including Luminex-defined HLA antibody specificities, T and B cell epitopes recognized on the mismatched HLA antigens, non-HLA antibodies, and also polymorphisms in complement and Fc receptors functionally associated with effector functions of anti-graft antibodies. From these data, key parameters determining the success of kidney transplantation will be identified which will lead to the identification of additional parameters to be included in future matching algorithms aiming to extend survival of transplanted kidneys and to diminish HLA immunization. Computer simulation studies will reveal the number of patients having a direct benefit from improved matching, the effect on shortening of the waiting list, and the decrease in waiting time.

Treatment efficacy of hypertension in kidney transplant recipients in the Netherlands.

BACKGROUND: Hypertension in kidney transplant recipients jeopardises graft and patient survival. Guidelines suggest blood pressure targets of ≤130/80 mmHg and sodium intake <90 mmol/day. METHODS: Since the efficacy of antihypertensive treatment among kidney transplant recipients is unknown, we analysed data on office-based blood pressure and use of antihypertensive drugs from the Netherlands Organ Transplant Registry on 5415 kidney transplant recipients. Additionally, we studied dosages, prevalence of treatment-resistant hypertension and 24-hour sodium excretion in 534 kidney transplant recipients from our centre to explore possibilities for therapy optimisation. RESULTS: In patients registered in the Netherlands Organ Transplant Registry, median blood pressure was 134/80 mmHg (interquartile range 122-145/70-85). In 77.2%, the blood pressure was ≥130/80 mmHg; of these patients 10.4% had no registered use, 30.0% used one and 25.9% used ≥3 classes of antihypertensive agents. Parameters from our centre were comparable: 78.7% had a median blood pressure of ≥130/80 mmHg of whom 14.5% had no registered use of antihypertensives and 26.4% used ≥3 classes. Sub-maximal dosages were prescribed in 74.0% of the kidney transplant recipients with a blood pressure of ≥130/80 mmHg while using at least one antihypertensive agent. Treatment-resistant hypertension was present in 7.7%. Median 24-hour sodium excretion was 147 mmol/day (interquartile range 109-195). CONCLUSIONS: This study suggests that therapeutic optimisation of antihypertensive treatment in kidney transplant recipients is, in theory, frequently possible by intensifying pharmacological treatment and by providing more advice on dietary sodium restrictions.

Low-pressure pneumoperitoneum during laparoscopic donor nephrectomy to optimize live donors' comfort.

Nowadays, laparoscopic donor nephrectomy (LDN) has become the gold standard to procure live donor kidneys. As the relationship between donor and recipient loosens, it becomes of even greater importance to optimize safety and comfort of the surgical procedure. Low-pressure pneumoperitoneum has been shown to reduce pain scores after laparoscopic cholecystectomy. Live kidney donors may also benefit from the use of low pressure during LDN. To evaluate feasibility and efficacy to reduce post-operative pain, we performed a randomized blinded study. Twenty donors were randomly assigned to standard (14 mmHg) or low (7 mmHg) pressure during LDN. One conversion from low to standard pressure was indicated by protocol due to lack of progression. Intention-to-treat analysis showed that low pressure resulted in a significantly longer skin-to-skin time (149 ± 86 vs. 111 ± 19 min), higher urine output during pneumoperitoneum (23 ± 35 vs. 11 ± 20 mL/h), lower cumulative overall pain score after 72 h (9.4 ± 3.2 vs. 13.5 ± 4.5), lower deep intra-abdominal pain score (11 ± 3.3 vs. 7.5 ± 3.1), and a lower cumulative overall referred pain score (1.8 ± 1.9 vs. 4.2 ± 3). Donor serum creatinine levels, complications, and quality of life dimensions were not significantly different. Our data show that low-pressure pneumoperitoneum during LDN is feasible and may contribute to increase live donors' comfort during the early post-operative phase.

Poor early graft function impairs long-term outcome in living donor kidney transplantation.

BACKGROUND: Poor early graft function (EGF) after living donor kidney transplantation (LDKT) has been found to decrease rejection-free graft survival rates. However, its influence on long-term graft survival remains inconclusive. METHODS: Data were collected on 472 adult LDKTs performed between July 1996 and February 2010. Poor EGF was defined as the occurrence of delayed or slow graft function. Slow function was defined as serum creatinine above 3.0 mg/dL at postoperative day 5 without dialysis. RESULTS: The incidence of slow and delayed graft function was 9.3 and 4.4%, respectively. Recipient overweight, pretransplant dialysis and warm ischemia were identified as risk factors for the occurrence of poor EGF. The rejection-free survival was worse for poor EGF as compared to immediate graft function with an adjusted hazard ratio (HR) of 6.189 (95% CI 4.075-9.399; p < 0.001). Long-term graft survival was impaired in the poor EGF group with an adjusted HR of 4.206 (95% CI 1.839-9.621; p = 0.001). CONCLUSIONS: Poor EGF occurs in 13.7% of living donor kidney allograft recipients. Both, rejection-free and long-term graft survivals are significantly lower in patients with poor EGF as compared to patients with immediate graft function. These results underline the clinical relevance of poor EGF as phenomenon after LDKT.

Mortality due to pulmonary embolism, myocardial infarction, and stroke among incident dialysis patients.

BACKGROUND: It is has been suggested that dialysis patients have lower mortality rates for pulmonary embolism than the general population, because of platelet dysfunction and bleeding tendency. However, there is limited information whether dialysis is indeed associated with a decreased mortality risk from pulmonary embolism. OBJECTIVE: The aim of our study was to evaluate whether mortality rate ratios for pulmonary embolism were lower than for myocardial infarction and stroke in dialysis patients compared with the general population. METHODS: Cardiovascular causes of death for 130,439 incident dialysis patients registered in the ERA-EDTA Registry were compared with the cardiovascular causes of death for the European general population. RESULTS: The age- and sex-standardized mortality rate (SMR) from pulmonary embolism was 12.2 (95% CI 10.2-14.6) times higher in dialysis patients than in the general population. The SMRs in dialysis patients compared with the general population were 11.0 (95% CI 10.6-11.4) for myocardial infarction, 8.4 (95% CI 8.0-8.8) for stroke, and 8.3 (95% CI 8.0-8.5) for other cardiovascular diseases. In dialysis patients, primary kidney disease due to diabetes was associated with an increased mortality risk due to pulmonary embolism (HR 1.9; 95% CI 1.0-3.8), myocardial infarction (HR 4.1; 95% CI 3.4-4.9), stroke (HR 3.5; 95% CI 2.8-4.4), and other cardiovascular causes of death (HR 3.4; 95% CI 2.9-3.9) compared with patients with polycystic kidney disease. CONCLUSIONS: Dialysis patients were found to have an unexpected highly increased mortality rate for pulmonary embolism and increased mortality rates for myocardial infarction and stroke.

The natural history of clinical operational tolerance after kidney transplantation through twenty-seven cases.

We report here on a European cohort of 27 kidney transplant recipients displaying operational tolerance, compared to two cohorts of matched kidney transplant recipients under immunosuppression and patients who stopped immunosuppressive drugs and presented with rejection. We report that a lower proportion of operationally tolerant patients received induction therapy (52% without induction therapy vs. 78.3%[p = 0.0455] and 96.7%[p = 0.0001], respectively), a difference likely due to the higher proportion (18.5%) of HLA matched recipients in the tolerant cohort. These patients were also significantly older at the time of transplantation (p = 0.0211) and immunosuppression withdrawal (p = 0.0002) than recipients who rejected their graft after weaning. Finally, these patients were at lower risk of infectious disease. Among the 27 patients defined as operationally tolerant at the time of inclusion, 19 still display stable graft function (mean 9 ± 4 years after transplantation) whereas 30% presented slow deterioration of graft function. Six of these patients tested positive for pre-graft anti-HLA antibodies. Biopsy histology studies revealed an active immunologically driven mechanism for half of them, associated with DSA in the absence of C4d. This study suggests that operational tolerance can persist as a robust phenomenon, although eventual graft loss does occur in some patients, particularly in the setting of donor-specific alloantibody.

Deleterious influence of prolonged warm ischemia in living donor kidney transplantation.

BACKGROUND: Recent studies investigating early graft function (EGF) after living donor kidney transplantation (LDKT) identified prolonged warm ischemia time (WIT) as a risk factor for the occurrence of poor EGF. The latter is associated with long-term graft loss; therefore the question arises whether prolonged WIT affects long-term outcomes in LDKT. METHODS: Data were collected on 472 consecutive adult LDKTs. Patients were divided according to the total WIT into 3 groups with short (<30 minutes), intermediate (30-45 minutes), or prolonged (>45 minutes) WIT. RESULTS: Of all patients, 193 (40.9%) experienced short, 249 (52.8%) intermediate, and 30 (6.4%) prolonged WIT. Prolonged WIT was a significant risk factor for the occurrence of poor EGF with an adjusted odds ratio of 4.252 (95% confidence interval [CI), 1.914 -9.447). Long-term graft survival was impaired in patients with prolonged WIT, with an adjusted hazard ratio of 3.163 (95% CI, 1.202-8.321). Multivariate analysis revealed determinants of prolonged WIT, including laparoscopic procurement, recipient overweight, right donor kidney, and multiple renal arteries. CONCLUSION: Prolonged WIT impairs long-term graft survival in LDKT. This finding underlines the need to develop strategies to avoid the occurrence of prolonged WIT in LDKT.

Preservation of kidneys from controlled donors after cardiac death.

BACKGROUND: Donation after cardiac death (DCD) expands the pool of donor kidneys, but is associated with warm ischaemic injury. Two methods are used to preserve kidneys from controlled DCD donors and reduce warm ischaemic injury: in situ preservation using a double-balloon triple-lumen catheter (DBTL) inserted via the femoral artery and direct cannulation of the aorta after rapid laparotomy. The aim of this study was to compare these two techniques. METHODS: This was a retrospective cohort study of 165 controlled DCD procedures in two regions in the Netherlands between 2000 and 2006. RESULTS: There were 102 donors in the DBTL group and 63 in the aortic group. In the aortic group the kidney discard rate was lower (4·8 versus 28·2 per cent; P < 0·001), and the warm (22 versus 27 min; P < 0·001) and the cold (19 versus 24 h; P < 0·001) ischaemia times were shorter than in the DBTL group. Risk factors for discard included preservation with the DBTL catheter (odds ratio (OR) 5·19, 95 per cent confidence interval 1·88 to 14·36; P = 0·001) and increasing donor age (1·05, 1·02 to 1·07; P < 0·001). Warm ischaemia time had a significant effect on graft failure (hazard ratio 1·04, 1·01 to 1·07; P = 0·009), and consequently graft survival was higher in the aortic cannulation group (86·2 per cent versus 76·8 per cent in the DBTL group at 1 year; P = 0·027). CONCLUSION: In this retrospective study, direct aortic cannulation appeared to be a better method to preserve controlled DCD kidneys.

Continuation of cinacalcet immediately after renal transplantation: a prospective cohort study.

BACKGROUND: Cinacalcet is used for treating secondary hyperparathyroidism in dialysis patients, but it is currently unknown whether it can safely be continued immediately after renal transplantation. METHODS: We prospectively studied renal transplant recipients with secondary hyperparathyroidism who were receiving cinacalcet before transplantation and continued treatment afterwards (n = 29) at a dose of 30 mg/day. Cinacalcet dose was titrated to serum calcium. Patients were followed for 6 months. Incidence of hypercalcemia, serum calcium and intact PTH (iPTH) were analyzed. Tacrolimus levels, acute rejection rate and renal function were compared with an age and sex matched control group. RESULTS: In 16 patients hypercalcemia was observed after transplantation. Severe hypercalcemia (>= 2.87 mmol/l) (n = 4) and hypocalcemia (n = 2) were infrequent. No difference in acute rejection rate or renal function between the cinacalcet and the control group was found. There also was no clinically relevant influence of cinacalcet on tacrolimus levels. CONCLUSIONS: Our study shows that cinacalcet can safely be continued immediately after renal transplantation. Studies are needed to determine if continuation of cinacalcet is better than early withdrawal. Also, the optimum dose of cinacalcet and the long-term effects of cinacalcet after renal transplantation must be defined.

Pharmacokinetics of two generic co-formulations of lopinavir/ritonavir for HIV-infected children: a pilot study of paediatric Lopimune versus the branded product in healthy adult volunteers.

OBJECTIVES: To determine the pharmacokinetic profiles of lopinavir and ritonavir in two newly developed generic co-formulations for HIV-infected children (Lopimune paediatric tablets and granules, 100/25 mg of lopinavir/ritonavir, Cipla Pharmaceuticals), and to compare these with the branded product (Kaletra). METHODS: This Phase I, comparative, open-label, three-period, single-dose, crossover study was designed as a pilot study to exclude large (>40%) differences in the exposure to lopinavir. Single doses of medication, normalized to 400 mg of lopinavir, were administered on an empty stomach, 1 week apart. A 32 h pharmacokinetic curve was recorded. In an additional part of the study, in five of the same volunteers, a pharmacokinetic curve was recorded after administration of the Lopimune granules and Kaletra oral solution, both with food. RESULTS: Twelve healthy subjects were enrolled (four females). The median (range) age, height and body weight were 24 (21-55) years, 1.79 (1.63-1.95) m and 72 (51-87) kg, respectively. The median [interquartile range (IQR)] AUC(0-t) of lopinavir was 71.8 (48.8-93.5), 38.7 (28.7-52.2) and 58.7 (42.5-79.4) mg.h/L with Kaletra tablets, Lopimune granules and Lopimune paediatric tablets, all taken on an empty stomach, respectively. The respective C(max) values were 7.2 (5.8-8.3), 4.6 (4.1-5.2) and 6.5 (5.0-7.1) mg/L after intake of the different formulations. When comparing the Lopimune formulations with the reference product Kaletra, for all parameters the differences were statistically significant (P

[More potential organ donors than actual donations in 52 intensive-care units in the Netherlands, 2001-2004]. / Orgaandonorpotentieel in 52 intensivecareafdelingen in Nederland groter dan het aantal gerealiseerde donatieprocedures, 2001-2004.

OBJECTIVE: To assess the number of potential organ donors and the main reasons why organ donation is not performed. DESIGN: Retrospective. METHOD: The number of potential heart-beating (HB) and non-heart-beating (NHB) donors was assessed by reviewing the medical records of 588o patients who died between 2001 and 2004 in 52 intensive-care units (ICUs) in 30 hospitals. The number of actual donations was also assessed. RESULTS: The potential of HB donors was 2.5 to possibly 6.6% of all ICU deaths and HB donation was performed in 1.9% of all ICU deaths. The potential of NHB donors of category III was at least 4.2% of all ICU deaths and NHB donation was performed in 1.0% of all ICU deaths. The main difficulty in the donation process was objection from family members, which was reported in 45% of all potential HB and NHB donors and in 59% of all donation requests to relatives. Of the potential HB and NHB donors 7.3% were not identified as potential donors. CONCLUSION: These results confirm that organ-donor potential is greater than the number of actual donations. Objection from family members is the main limiting factor.