Preliminary evidence for a role of apolipoprotein E alleles in identifying haemodialysis patients at high vascular risk

Conventional risk factors have very low predictive power in identifying haemodialysis patients at high risk of vascular accidents. A role for apolipoprotein E isotypes was looked for in a small, but rigorously defined, cohort of longterm haemodialysis patients. In individuals with high vascular risk, as identified by higher common carotid intima/media thickness, we found an excess of apolipoprotein E4 alleles. This preliminary result requires confirmation in large patient cohorts.      

Chronic and intradialytic effects of high-flux hemodialysis on tumor necrosis factor-alpha production: relationship to endotoxins.

Tumor necrosis factor-alpha (TNF alpha) likely plays a role in hemodialysis-associated complications. As TNF alpha is mainly produced by monocytes in response to endotoxins, we studied its production and the presence of circulating endotoxins in patients dialyzed on polyacrylonitrile (PAN) membrane. Spontaneous production of TNF alpha was observed in patients before the dialysis session and increased during the session. Endotoxins were present in serum from patients chronically dialyzed with PAN and increased during hemodialysis session. In addition, intradialytic decrease in CD14 antigen expression on circulating monocytes, which could be caused by endotoxins, was found. The continuous presence of low amounts of circulating endotoxins between sessions may explain the chronic increase in TNF alpha secretion, while high amounts of circulating endotoxins may account for intradialytic oversecretion of TNF alpha and downmodulation of CD14. We suggest that endotoxin-free dialysates should be a prerequisite for the use of high-flux membranes.     

Leishmaniasis: a rare cause of unexplained fever in a renal graft recipient.

We report a case of visceral leishmaniasis in a 38-year-old renal transplant recipient living in an endemic country. Antimonial derivatives induced a rapid remission. A review of the literature disclosed 8 cases of this association with a fatal fulminant outcome in 5 cases. We suggest that the specific immunosuppression used in renal transplant patients might facilitate the development of a dormant infection and in these patients the misleading presentation may delay the diagnosis. Moreover special caution with treatment of leishmaniasis must be taken in renal transplant because of possible interactions between antimony compounds and ciclosporin metabolites. In renal transplant patients living in endemic countries, visceral leishmaniasis should be kept in mind as a potential cause of unexplained long-standing fever and considered as an opportunistic infection.     

Prenatal diagnosis of the fragile X syndrome: loss of mutation owing to a double recombinant or gene conversion event at the FMR1 locus.

The fragile X syndrome, an X linked mental retardation syndrome, is caused by an expanded CGG repeat in the first exon of the FMR1 gene. In patients with an expanded repeat the FMR1 promoter is methylated and, consequently, the gene is silenced and no FMR1 protein (FMRP) is produced, thus leading to the clinical phenotype. Here we describe a prenatal diagnosis performed in a female from a fragile X family carrying a large premutation. In chorionic villus DNA of the male fetus the normal maternal CGG allele and a normal pattern on Southern blot analysis were found in combination with the FRAXAC2 and DXS297 allele of the maternal at risk haplotype. A second chorionic villus sampling was performed giving identical results on DNA analysis and, in addition, expression of FMRP was shown by immunohistochemistry. We concluded that the male fetus was not affected with the fragile X syndrome. Subsequent detailed haplotype analysis showed a complex recombination pattern resembling either gene conversion or a double crossover within a 20 kb genomic region.     

Cost-Effectiveness Assessment of Monitoring Abiraterone Levels in Metastatic Castration-Resistant Prostate Cancer Patients

ObjectivesAbiraterone acetate is registered for the treatment of metastatic castration-sensitive and resistant prostate cancer (mCRPC). Treatment outcome is associated with plasma trough concentrations (C_min) of abiraterone. Patients with a plasma C_min below the target of 8.4 ng/mL may benefit from treatment optimization by dose increase or concomitant intake with food. This study aims to investigate the cost-effectiveness of monitoring abiraterone C_min in patients with mCRPC.MethodsA Markov model was built with health states progression-free survival, progressed disease, and death. The benefits of monitoring abiraterone C_min followed by a dose increase or food intervention were modeled via a difference in the percentage of patients achieving adequate C_min taking a healthcare payer perspective. Deterministic and probabilistic sensitivity analyses were performed to assess uncertainties and their impac to the incremental cost-effectiveness ratio (ICER).ResultsMonitoring abiraterone followed by a dose increase resulted in 0.149 incremental quality-adjusted life-years (QALYs) with €22 145 incremental costs and an ICER of €177 821/QALY. The food intervention assumed equal effects and estimated incremental costs of €7599, resulting in an ICER of €61 019/QALY. The likelihoods of therapeutic drug monitoring (TDM) with a dose increase or food intervention being cost-effective were 8.04%and 81.9%, respectively.ConclusionsMonitoring abiraterone followed by a dose increase is not cost-effective in patients with mCRPC from a healthcare payer perspective. Monitoring in combination with a food intervention is likely to be cost-effective. This cost-effectiveness assessment may assist decision making in future integration of abiraterone TDM followed by a food intervention into standard abiraterone acetate treatment practices of mCRPC patients.     

Toward a Fully Fledged Integration of Spiritual Care and Medical Care

In this article, we aimed to set out current problems that hinder a fully fledged integration of spiritual and medical care, which address these obstacles. We discuss the following five statements: 1) spiritual care requires a clear and inclusive definition of spirituality; 2) empirical evidence for spiritual care interventions should be improved; 3) understanding patients' experiences of contingency is paramount to deliver effective spiritual care; 4) attention to spiritual needs of patients is a task for every health care practitioner; 5) courses on spirituality and spiritual care should be mandatory in the medical curriculum. Current problems might be overcome by speaking each other's language, which is crucial in interdisciplinary research and in good interdisciplinary collaboration. Using a clear and inclusive definition of spirituality and substantiating spiritual care using medical standards of evidence-based practice is a way to speak each other's language and to increase mutual understanding. Furthermore, including spirituality in the medical curriculum would raise awareness of medical practitioners for their task of attending to patients' spiritual needs and, subsequently, to better and more appropriate referral for spiritual care.