Analysis of the quality of patient therapeutic education and information in a high complexity reference hospital.

BACKGROUND AND OBJECTIVES: The application and monitoring of quality criteria in information and therapeutic patient education can identify areas to improve care. The objectives of this study were: (1) To analyze the characteristics of patient information materials, educational activities, and self-management programs, and (2) to determine health care provider (HCP) proposals on therapeutic patient education. MATERIALS AND METHODS: Using a cross-sectional study, an online questionnaire was sent to hospital departments in a high complexity reference hospital from September to December 2013 to record: (a) information materials, (b) patient educational activities, and self-management program characteristics, (c) HCP proposals. The materials were analyzed using Health Promoting Hospitals (HPH) recommendations. RESULTS: (1) An analysis was performed on 258 materials (leaflets [54%]) for chronic patients (86%), acute patients (7%), and the general population (7%). More than half (55%) lacked the authors, and 43% the year issued, and 69% followed HPH recommendations. (2) An evaluation was made of 70 educational activities and 37 self-management programs addressed to patients/relatives with diabetes/obesity, musculoskeletal disorders, COPD/asthma, pelvic-floor disorders, transplantation, bowel-inflammation/liver disease, hypertension, cancer, heart failure, acquired immune deficiency syndrome, chronic renal insufficiency, splenectomy, anticoagulation and older-patient dependence. The structure, process and outcome evaluation varied. (3) HCP proposals included: standardization of materials criteria, web accessibility, list of accredited websites, cross-sectional use, and HCP training in self-management education. CONCLUSIONS: The online questionnaire showed the weaknesses and strengths of patient information and education, and can be used to monitor their quantity and quality. These results help in the definition of a useful model to improve patient information and education policies.

Cwc21p promotes the second step conformation of the spliceosome and modulates 3' splice site selection.

Pre-mRNA splicing involves two transesterification steps catalyzed by the spliceosome. How RNA substrates are positioned in each step and the molecular rearrangements involved, remain obscure. Here, we show that mutations in PRP16, PRP8, SNU114 and the U5 snRNA that affect this process interact genetically with CWC21, that encodes the yeast orthologue of the human SR protein, SRm300/SRRM2. Our microarray analysis shows changes in 3' splice site selection at elevated temperature in a subset of introns in cwc21Δ cells. Considering all the available data, we propose a role for Cwc21p positioning the 3' splice site at the transition to the second step conformation of the spliceosome, mediated through its interactions with the U5 snRNP. This suggests a mechanism whereby SRm300/SRRM2, might influence splice site selection in human cells.

Ribosomal proteins as novel players in tumorigenesis.

Ribosome biogenesis is the most demanding energetic and metabolic expenditure of the cell. The nucleolus, a nuclear compartment, coordinates rRNA transcription, maturation, and assembly into ribosome subunits. The transcription process is highly coordinated with ribosome biogenesis. In this context, ribosomal proteins (RPs) play a crucial role. In the last decade, an increasing number of studies have associated RPs with extraribosomal functions related to proliferation. Importantly, the expression of RPs appears to be deregulated in several human disorders due, at least in part, to genetic mutations. Although the deregulation of RPs in human malignancies is commonly observed, a more complex mechanism is believed to be involved, favoring the tumorigenic process, its progression and metastasis. This review explores the roles of the most frequently mutated oncogenes and tumor suppressor genes in human cancer that modulate ribosome biogenesis, including their interaction with RPs. In this regard, we propose a new focus for novel therapies.

EULID project: European living donation and public health.

The choice of transplantation from a living donor offers advantages over a deceased donor. However, it also carries disadvantages related to donor risks in terms of health and safety. Furthermore, there are several controversial ethical aspects to be taken into account. Several national and international institutions and the scientific community have stated standards that have great influence on professional codes and legislations. Living organ donation and transplantation are to some extent regulated by parliamentary acts in most European countries. It is necessary to take a step forward to develop a legal framework to regulate all of these processes to guarantee the quality and to prevent illegal and nonethical practices. It is also necessary to develop and implement living donor protection practices not only in terms of physical health, but also to minimize potential impacts on the psychological, social, and economic spheres. Finally, an additional effort should be made to create a database model with recommendations for registration practices as part of the standardized follow-up care for the living donor. The European Living Donation (EULID) project's (http://www.eulivingdonor.eu/) main objective was to contribute to a European consensus to set standards and recommendations about legal, ethical, and living donor protection practices to guarantee the health and safety of living donors.

Attitude of health professionals toward cadaveric tissue donation.

INTRODUCTION: A positive attitude toward organ donation would be expected among health professionals from transplant centers with active donor activities. However, acceptance and knowledge about cadaveric tissue donation has been insufficiently studied. OBJECTIVE: The objective of this study was to analyze the knowledge and attitude of health professionals toward cadaveric tissue donation. METHODS: An anonymous survey composed of 23 questions was given to health professionals from 2 university hospitals with donation experience. Sociodemographic and professional characteristics were described to analyze knowledge and acceptance of cadaveric tissue donation. RESULTS: Among 600 distributed questionnaires we collected 514 completely answered surveys. Gender distribution was 399 females/115 males of ages ranging from 18-65 years, namely 18-28 years, 27%; 29-39 years, 31%; 40-50 years, 32%; and 51-65 years, 10%. Among the sample, 31% of health professionals had never been in contact with a transplant recipient. In this study 99.4% had knowledge about cadaveric organ donation compare with 89.7% about tissue donation. The knowledge about various types of tissue donation was as follows: eye, 96%; musculoskeletal, 87%; skin, 72%, and cardiovascular, 67%. In the sample, 93% and 92% accepted the opportunity to receive an organ or tissue transplantation, respectively. The acceptance of a tissue varied according to the type: cardiovascular, 93%; ocular, 94%; skin, 89%; and musculoskeletal, 87%. Participant acceptance of a relative's tissue donation was 74%, refusal was 22%, and with doubts was 4%. CONCLUSIONS: Insufficient knowledge about cadaveric tissue was demonstrated among health professionals more exposed to the donation process. These results highlighted the importance of health professional's education to facilitate public information about organ and tissue donation.

Telephone consent in tissue donation: effectiveness and efficiency in postmortem tissue generation.

UNLABELLED: One reason for the loss of donors is the impossibility to contact family members for an interview. We sought to determine the effectiveness [(donors/total deaths) x 100] and efficiency [(donors/potential donors) x 100] of the telephone interview to obtain tissue for transplant purposes. METHODS: A prospective, comparative cross-sectional study was performed on the personal and telephone interviews with family members during the tissue donation application process from January 1, 2004 to December 31, 2005. RESULTS: Of the 3625 deaths hospital registered, we obtained 770 potential donors (21%). On 65% of occasions (503/770), the interview was held personally; on 29% (222/770), it had to be held over the telephone; and on 6% (45/770), family members could not be located. The refusals by family members over the telephone represented 48% (106/222), and the refusals during personal interviews were 37% (188/503). A positive family answer was obtained over the telephone on 116/431 donations (27%), and in the physical presence of the coordinator for 315/431 donors (73%). The donations obtained over the telephone were only for corneas in 83% (96/116) of cases, and for multiple tissues in 17% (20/116). The donor-generation effectiveness reached 9% in personal interviews and 12% if the telephone interviews were included. The donor generation efficiency reached 43% for personal interviews and 59% when telephone interviews were included. The use of the telephone enabled a 16% increase in tissue generation with a year-on-year increase of 4%. CONCLUSIONS: The telephone has shown itself to be a useful tool for obtaining tissues postmortem.

Characterization of the organ donor with bacteremia.

INTRODUCTION: The presence of bloodstream infection in the donor is a common finding that could be transmitted to the recipient. To safely expand the donor pool, we examined its relevance. MATERIALS AND METHODS: We described the clinical characteristics of organ donors grafted in our center between 1997 and 2006 who had bacteremia detected in blood cultures obtained during organ procurement. RESULTS: Among 1353 organ donors, 75 were non-heart-beating donors type II and the others brain-dead donors. Only 186 donors (14%) showed bacteremia during retrieval. This mean age was 49.8 years (range 12 to 86 years, SD 18) including 63% men. Causes of death were cerebrovascular accident in 60%; craneoencephalic trauma, 25%; and other causes, 15%. The average length of the intensive care unit stay was 3 days (interquartile range: 2 to 7 days). Twenty-nine percent of donors presented previous infectious complications (90% from respiratory origin). The most prevalent pathogen isolated in blood cultures was coagulase negative Staphylococci (46,2%), followed by S aureus (15%), Streptococcus group viridans (9.1%), enterobacteria (9%), Enterococcus faecalis (7.5%) and gram-negative bacilli nonfermentative (6.2%). In 3.1%, the bloodstream infections were polymicrobial. The bronchial aspiration cultures were positive in 50% of cases and the urine culture in 8,6%. In 17% of donors the isolated microorganism was coincident between blood and bronchial cultures. Pseudomonas spp and S aureus were more common than the others (P = .004 and P = .058, respectively). CONCLUSIONS: The incidence of bacteremia in our cohort was 14%. The respiratory tract was the most common clinical focus. Pseudomonas spp or S aureus isolated in bronchial cultures are risk factors to develop bacteremia. According to these findings, it is important to start specific antibiotics against those microorganisms in the donor and the recipients.

Use of quality index in the evaluation of organ procurement and transplant programs in a University Hospital.

AIM: To evaluate organ procurement efficiency at Hospital Clinic of Barcelona (HCP), a University Hospital, in 2000 and 2003 compared with other Catalan, other Spanish, and American (US) results. METHODS: Efficacy rate of the donor procurement was calculated per million population per year (pmp/y). Efficacy rate in kidney, liver, and heart transplantation was calculated also in pmp/y. We evaluated 1-year graft survival. RESULTS: During this period, the average rate number of donors was 49.1 pmp/y in HCP, 38 in Catalonia, 33.4 in Spain, and 21.7 in the United States. The average rate of kidney transplantation was 74 pmp/y in HCP, 55 in Catalonia, 47 in Spain, and 24.6 in the United States. The average rate of liver transplantation was 44.5, 26.6, 23.2, and 18 pmp/y, respectively. The average rate of heart transplantation was 13.3, 8.5, 7.8, and 6.4 pmp/y, respectively. One-year graft survival in HCP was 90.6% for kidney, 89.5% for liver, and 88.2% for heart transplants. DISCUSSION: The results show that organ procurement and transplantation programs in HCP are efficient. The organizational model is based on a hospital transplant coordinator and efficient, well-trained transplant teams.

Functions, responsibilities, dedication, payment, organization, and profile of the hospital transplant coordination in Spain in 2002.

In Spain, the number of donors per million of population and the activity of transplantation is a direct consequence of the continued work of the hospital transplant coordinators. There are 146 procurement hospitals with approximately 534 transplant coordinators (13.6 coordinators per hospital and 12.7 per million of population). A voluntary survey of 74 Spanish transplant coordinators revealed 67.6% to be men and 32.4% women of average age 43 years with specialization of 75.7%, Intensive Care Medicine; 8.1%, Anesthesiology; 6.7%, Nephrologists; and the rest, General Surgery or without any specialization. Among the group who responded to the injury, 86.5% were doctors and 13.5%, nurses. The overall team is composed of 52% doctors, 27.7% nurses and others with 70.3% working part-time and 27%, full-time. Previous experience was noted to be less than 5 years among 51.4%, and more in the rest of the cases. The 85% work under medical direction by management. Their payment includes salary plus activity in 48.7% of the cases; 21.6%, only salary, and 18.9%, only activity. Each coordinator generates between 3 and 7 organ as well as 3 and 11 of tissue donors. In conclusion, comparing this data with the practice in the United States demonstrates the unique aspects of the Spanish system.

Optimizing cadaveric organ procurement: the catalan and Spanish experience.

The need to face the increasing gap between the supply and the demand of transplants has led to the development of a permanent network of trained medical staff responsible for the organ donation and removal process in all centers accredited for that process. In Spain, this activity received a specific budget, like any other medical activity in hospitals, and the responsible staff became accountable for performance. This system dramatically increased the number of potential donors referred, not only young donors with trauma, but also elderly donors dying from stroke. The effect was that the donation rate increased by more than 100% in 10 years (from 14 to 34 donors per million population). Consequently, so did all the transplant figures. In some areas, such as Catalonia, it has been demonstrated that sustained kidney transplant activity of over 60 procedures per million population can maintain or slightly decrease the waiting list, despite increasing incidence and prevalence of end-stage renal failure. Quality monitoring of the donation and retrieval process shows that there are still opportunities for improvement if all potential donors are referred and all technical problems are overcome. Living donation and nonheart beating organ retrieval should also be promoted.

Mycophenolic acid plasma concentrations: influence of comedication.

Mycophenolate mofetil (MMF) in combination with cyclosporine (CsA) or Tacrolimus (TAC) has been show to be a potent immunosuppressive agent. The authors assessed the mycophenolic acid (MPA) plasma levels achieved in clinical practice and evaluated the effect of concomitant administration of CsA and TAC . One hundred forty transplant patients (kidney: 120 and lung: 20) received a triple immunosuppression regimen of CsA or TAC, prednisone and MMF. Twenty-two renal transplant patients received double therapy with MMF and prednisone. There was no correlation between MMF dose and MPA trough concentrations (r = -0.0657). The medians (range) of the MPA dose-to-concentration ratio (D/C) in the CsA and TAC groups were 0.90 (0.11-8.33) and 0.56 (0.11-14.3), respectively (p < 0.0001). According to the post transplant period (1-3, 4-6 and >6 months), D/C values were significantly lower in patients receiving MMF and TAC than those receiving MMF and CsA in all three periods. MPA levels in patients treated with MMF and CsA were significantly lower than those obtained in double therapy. The D/C ratio in CsA-treated patients, increased significantly (p = 0.0005) when CsA level increased. There was no relationship between D/C ratio and TAC blood concentrations. These results suggest that CsA exerts an influence on MPA trough levels, although further work is required to characterize the mechanism of interaction.

Pharmacokinetics and pharmacodynamics of mycophenolic acid in stable renal transplant recipients treated with low doses of mycophenolate mofetil.

Suboptimal doses of mycophenolate mofetil (MMF) are frequently employed in renal transplant (Tx) patients, with drug-related side effects or low weight. The aim of this study was to compare the mycophenolic acid (MPA) pharmacokinetic profile and its pharmacodynamic effect on patients receiving either standard (2 g) or low (1.5 g or 1 g) MMF doses, in order to evaluate the therapeutic efficacy of such low doses in inhibiting IMPDH activity. Twenty-seven stable renal Tx recipients aged 18-65 years, with a post-Tx follow-up of 38.5 +/- 44.8 months (6-166 months), receiving 1 g (n = 10), 0.75 g (n = 7) and 0.5 g (n = 10) MMF twice a day in association with cyclosporine and prednisone, were included. The control group was made up of untreated healthy volunteers (n = 5). Plasma concentrations of MPA were analyzed by reverse-phase HPLC. IMPDH activity was determined in lymphocytes by the measurement of 3H release from [2,8-(3)H] hypoxantine. The mean value of areas under the concentration-time curves (AUC(0-12)) of MPA throughout the 12-h dosing interval in patients treated with 2 g was higher than the corresponding data in patients receiving 1.5 g or 1 g bid, but no statistical differences were observed between the three groups. There was no correlation between MPA-AUC(0-12) values and MMF dose (expressed in g/day or g/kg per day). Predose MPA concentrations correlated only weakly with the respective MPA-AUC(0-12) values (r2 from 0.385 to 0.655), whereas an acceptable correlation was observed between MPA Cmax and MPA-AUC(0-12) (r2 from 0.626 to 0.759) in 2 g, 1.5 g, and 1 g MMF groups. An inverse relationship between MPA concentrations and IMPDH activity was observed. In general, the maximum MPA concentration was achieved from 1 h to 2 h after dosing, and the maximum inhibition of IMPDH was also from 1 h to 2 h after dosing. The evaluation of IMPDH activity demonstrated that there was a significant statistical difference between samples from 0 to 1 h (P = 0.008) and 0 to 2 h (P = 0.04). In conclusion, concentration-time profiles of renal transplant recipients administered 0.75 g and 0.5 g twice a day are slightly lower than those from the 2 g group, but nor significantly. On the other hand, inhibition of IMPDH activity was comparable in the three groups, indicating considerable interindividual pharmacodynamic variability. Pharmacodynamic monitoring of the degree of immunosuppression and its correlation with MPA plasma concentrations will be assessed further in future studies.

Assessment of mycophenolic acid-induced immunosuppression: a new approach.

BACKGROUND: Mycophenolic acid (MPA), a metabolite of mycophenolate mofetil (MMF), is an immunosuppressive agent that inhibits inosine monophosphate dehydrogenase (IMPDH), a key enzyme in the ex novo synthesis of GTP. We measured IMPDH activity in peripheral blood mononuclear cells (PBMCs) from MMF-treated patients to evaluate the efficacy of MMF in individual patients. METHODS: IMPDH activity was measured by (3)H released from [2,8-(3)H]IMP that had been formed in the cells from added [2,8-(3)H]hypoxanthine in PBMCs of 35 renal transplant recipients treated with cyclosporin A and corticoids plus MMF: 2 g (n = 10), 1.5 g (n = 7), 1 g (n = 10), or 0 g (n = 8) per day. An alternative method, based on the capacity of the patients' sera to inhibit spontaneous proliferation of the CEM cell line, was also analyzed. RESULTS: The IMPDH activity of PBMCs in transplanted patients was highly variable. For the method based on CEM cell line proliferation: (a) cell proliferation was inhibited only in MMF-treated patients; (b) there was a clear postdose increase in inhibition; (c) inhibition was not affected by other immunosuppressants in vitro or in vivo; (d) inhibition from predose to predose sample was correlated; and (e) when the MMF dosage was <20 mg. kg(-1). day(-1), two groups of patients were identified, one that maintained a high inhibitory capacity in all dose intervals, and one with periods of low inhibitory capacity. CONCLUSIONS: Measurement of the inhibition of CEM cell line proliferation by sera from MMF-treated patients may be useful for evaluating the relative efficacy of MMF treatment in individual patients, especially those receiving low doses of MMF.

Multiple functions of an evolutionarily conserved RNA binding domain.

Ribosomal protein L30 of Saccharomyces cerevisiae binds to a distinct RNA structure to inhibit the splicing and the translation of its own transcript. Remarkably, the ortholog of L30 from the archaeon Sulfolobus acidocaldarius binds specifically to the same RNA fragment and inhibits splicing both in vitro and in vivo. Indeed, expression of Sulfolobus L30 in yeast severely reduces growth by limiting production of the endogenous L30. This conservation of binding specificity implies that the target of regulation in the RPL30 transcript mimics a site in the rRNA that has been conserved for more than a billion years. We identify this site, whose location suggests that L30, which has no apparent eubacterial ortholog, is responsible for establishing the orientation of a key bridge between the large and small ribosomal subunits.

The odyssey of a regulated transcript.

The transcript of the Saccharomyces cerevisiae gene, RPL30, is subject to regulated splicing and regulated translation, due to a structure that interacts with its own product, ribosomal protein L30. We have followed the fate of the regulated RPL30 transcripts in vivo. Initially, these transcripts abortively enter the splicing pathway, forming an unusually stable association with U1 snRNP. A large proportion of the unspliced molecules, however, are found in the cytoplasm. Most of these are still bound by L30, as only a small fraction are engaged in translation. Eventually, the unspliced RPL30 transcripts escape the grasp of L30, associate with ribosomes, and fall prey to nonsense mediated decay.