Predictive factors of long-term follow-up attendance in very long-term childhood cancer survivors.

BACKGROUND: Long-term follow-up (LTFU) clinics have been developed but only some childhood cancer survivors (CCS) attend long-term follow-up (LTFU). OBJECTIVE: To identify factors that influence LTFU attendance. METHODS: Five-year CCS treated for a solid tumor or lymphoma in Gustave Roussy before 2000, included in the FCCSS cohort (French Childhood Cancer Survivor Study), aged >18 years and alive at the date of the LTFU Clinic opening (January 2012) were invited to a LTFU visit. Factors associated with attendance at the LTFU clinic between 2012 and 2020 were estimated using logistic regression analyses. Analyses included different types of factors: clinical (tumor characteristics, cancer treatments, late effects), medical (medical expenses were used as a proxy of survivor's health status), social (deprivation index based on census-tract data relating to income, educational level, proportion of blue-collar workers, and unemployed people living in the area of residence), and spatial (distance to the LTFU clinic). RESULTS: Among 2341 CCS contacted (55% males, mean age at study, 45 years; SD ± 10 years; mean age at diagnosis, 6 years; SD ± 5 years), 779 (33%) attended at least one LTFU visit. Initial cancer-related factors associated with LTFU visit attendance were: treatment with both radiotherapy and chemotherapy (odds ratio [OR], 4.02; 95% CI, 2.11-7.70), bone sarcoma (OR, 2.43; 95% CI, 1.56-3.78), central nervous system primitive tumor (OR, 1.65; 95% CI, 1.02-2.67), and autologous hematopoietic cell transplant (OR, 2.07; 95% CI, 1.34-3.20). Late effects (OR, 1.70; 95% CI, 1.31-2.20), highest medical expenses (OR, 1.65; 95% CI, 1.22-2.22), living in the most advantaged area (OR vs. the most deprived area = 1.60; 95% CI, 1.15-2.22), and shorter distance from LTFU care center (<12 miles) also increased attendance. CONCLUSIONS: Patients who are apparently healthy as well as socially disadvantaged and living far away from the center are less likely to attend LTFU care. PLAIN LANGUAGE SUMMARY: Among 2341 adult childhood cancer survivors contacted between 2012 and 2020, 33% attended at least one long-term follow-up visit. Clinical factors related to attendance were multimodal treatment of first cancer (combining chemotherapy and radiotherapy), stem cell transplant, type of diagnosis (bone tumor and central nervous system primitive tumor), late effects (at least one disease among second malignancy, heart disease, or stroke), and highest medical expenses. In addition, the study identified social and spatial inequalities related to attendance, with independent negative effects of distance and social deprivation on attendance, even though the medical costs related to the long-term follow-up examinations are covered by the French social security system.

Surveillance after childhood cancer: are survivors with an increased risk for cardiomyopathy regularly followed-up?

BACKGROUND: We aimed to study adherence to cardiac screening in long-term childhood cancer survivors (CCS) at high risk of cardiomyopathy. METHODS: This study involved 976 5-year CCS at high risk for cardiomyopathy from the French Childhood Cancer Survivor Study. Determinants of adherence to recommended surveillance were studied using multivariable logistic regression models. Association of attendance to a long-term follow-up (LTFU) visit with completion of an echocardiogram was estimated using a Cox regression model. RESULTS: Among participants, 32% had an echocardiogram within the 5 previous years. Males (adjusted RR [aRR] 0.71, 95% CI 0.58-0.86), survivors aged 36-49 (aRR 0.79, 95% CI 0.64-0.98), Neuroblastoma (aRR 0.53, 95% CI 0.30-0.91) and CNS tumour survivors (aRR 0.43, 95% CI 0.21-0.89) were less likely to adhere to recommended surveillance. Attendance to an LTFU visit was associated with completion of an echocardiogram in patients who were not previously adherent to recommendations (HR 8.20, 95% CI 5.64-11.93). CONCLUSIONS: The majority of long-term survivors at high risk of cardiomyopathy did not adhere to the recommended surveillance. Attendance to an LTFU visit greatly enhanced the completion of echocardiograms, but further interventions need to be developed to reach more survivors.

Québec health care professionals' perspectives on organ donation after medical assistance in dying.

BACKGROUND: Medical assistance in dying (MAID) has been legal in Québec since December 2015 and in the rest of Canada since July 2016. Since then, more than 60 people have donated their organs after MAID. Such donations raise ethical issues about respect of patients' autonomy, potential pressure to choose MAID, the information given to potential donors, the acceptability of directed donations in such a context and the possibility of death by donation. The objective of this study was to explore Québec professionals' perspectives on the ethical issues related to organ donation after MAID. METHODS: We conducted semi-directed interviews with 21 health care professionals involved in organ donation such as intensivists and intensive care nurses, operating room nurses, organ donation nurses and coordinators. RESULTS: The participants were all favourable to organ donation after MAID in order to respect patients' autonomy. They also favoured informing all potential donors of the possibility of donating organs. They highlighted the importance of assessing donors' reasons for requesting MAID during the assessment. They were divided on directed donation, living donation before MAID and death by donation. CONCLUSION: Organ donation after MAID was widely accepted among the participants, based on the principle of respect for the donor's autonomy. The findings of this study only provide the perspectives of Québec health care professionals involved in organ donation. Future studies are needed to gather other stakeholders' perspectives on this issue as well as patients' and families' experiences of organ donation after MAID.

Organ donation after medical assistance in dying or cessation of life-sustaining treatment requested by conscious patients: the Canadian context.

In June 2016, following the decision of the Supreme Court of Canada to decriminalise assistance in dying, the Canadian government enacted Bill C-14, legalising medical assistance in dying (MAID). In 2014, the province of Quebec had passed end-of-life care legislation making MAID available as of December 2015. The availability of MAID has many implications, including the possibility of combining this practice with organ donation through the controlled donation after cardiac death (cDCD) protocol. cDCD most often occurs in cases where the patient has a severe neurological injury but does not meet all the criteria for brain death. The donation is subsequent to the decision to withdraw life-sustaining treatment (LST). Cases where patients are conscious prior to the withdrawal of LST are unusual, and have raised doubts as to the acceptability of removing organs from individuals who are not neurologically impaired and who have voluntarily chosen to die. These cases can be compared with likely scenarios in which patients will request both MAID and organ donation. In both instances, patients will be conscious and competent. Organ donation in such contexts raises ethical issues regarding respect for autonomy, societal pressure, conscientious objections and the dead-donor rule. In this article, we look at relevant policies in other countries and examine the ethical issues associated with cDCD in conscious patients who choose to die.

Optimisation of choline testing using Florence Iodine reagent, including comparative sensitivity and specificity with PSA and AP tests.

The detection of semen in forensic science is essential in cases of sexual assault but can be problematic in the absence of spermatozoa. Choline is known to occur in high concentrations in seminal fluid and the Florence Iodine test for its detection has been used in forensic science for many years, however very little is documented regarding its sensitivity and specificity in forensic casework. This paper describes the optimisation of the choline Florence Iodine test (FI) and investigates the sensitivity and specificity of the test against different body fluids, food and drink substances, cleaning products and laboratory chemicals. Comparative testing against Acid Phosphatase (AP) and Prostate Specific Antigen (PSA Seratec®) tests is described and shows that the FI test has greater specificity than the PSA test which cross reacts with a number of body fluids.

Compatible Donor and Recipient Pairs' Perspectives on Participation in Kidney Paired Donation Programs: A Mixed-Methods Study.

BACKGROUND: Compatible pair participation in kidney paired donation (KPD) may increase the likelihood of finding suitable matches for all registered pairs. Retrospective studies have shown variable enthusiasm for participating in KPD in compatible pairs. OBJECTIVE: The study objective was to gather potential living donor (PLD) and transplant candidate (TC) perspectives on compatible pair participation in KPD. DESIGN: Surveys and qualitative interviews. SETTING: Three transplant programs in Canada: Centre hospitalier de l'Université de Montréal in Montreal (Québec), Vancouver General Hospital, and St. Paul's Hospital in Vancouver (British Columbia). PATIENTS: Both PLDs and TCs undergoing evaluation for donation/transplantation between 2016 and 2018 at 3 transplant programs in Canada. METHODS: Descriptive statistical analysis was performed for the results of the survey and thematic and content analysis method was used for the content of the qualitative interviews. RESULTS: A total of 116 PLDs and 111 TCs completed surveys and an additional 18 PLDs and 17 TCs underwent semi-directed interviews. Of those surveyed, 61.2% of PLDs and 76.6% of TCs reported a willingness to participate in KPD as a compatible pair. The possibility of a more optimally matched kidney for the TC and policies ensuring prioritization of the TC for repeat transplantation in the event of early graft failure increased willingness to participate in KPD. Major concerns expressed during the interviews included the desire to retain the emotional bond of directed donation, the fear of chain breaks or donor reneging, delays in transplantation, and additional travel associated with participation in KPD. LIMITATION: The limitations of this study are that it was conducted in only 3 Canadian transplant programs and that the interviews and surveys were in French and in English. As a consequence, the results may not be reflective of the views of individuals not living in these 2 provinces and from ethnic minority populations. CONCLUSION: Most of the compatible PLDs and TCs surveyed were willing to participate in KPD. Ensuring timely transplantation and a more optimal match for TCs and offering a policy of reciprocity to ensure timely repeat transplantation for compatible recipients if their allograft fails post KPD transplant may further increase compatible pair participation in KPD.

CONTEXTE: La participation de paires d'individus compatibles au don croisé d'un rein (DCR) peut augmenter la probabilité de trouver des donneurs et receveurs compatibles pour tous les individus enregistrés. Des études rétrospectives ont montré un enthousiasme variable des paires d'individus compatibles à participer au DCR. OBJECTIFS: Cette étude visait à recueillir les points de vue de donneurs vivants potentiels et de candidats à la greffe sur la participation de paires d'individus compatibles au DCR. TYPE D'ÉTUDE: Sondages et interviews qualitatives. CADRE: Trois programmes de transplantation canadiens : le centre hospitalier de l'Université de Montréal à Montréal (Québec), de même que le Vancouver General Hospital et le St Paul's Hospital de Vancouver (Colombie-Britannique). SUJETS: Les donneurs vivants potentiels (DVP) et les candidats à la greffe (CG) ayant fait l'objet d'une évaluation pour un don ou une transplantation dans trois programmes de transplantation canadiens entre 2016 et 2018. MÉTHODOLOGIE: Une méthode d'analyse statistique descriptive a servi à analyser les résultats du sondage, tandis que le contenu des interviews qualitatives a été analysé à l'aide de méthodes d'analyse thématique et de contenu. RÉSULTATS: En tout, 116 DVP et 111 CG ont répondu au sondage, alors que 18 DVP et 17 CG supplémentaires ont été rencontrés pour des entrevues semi-dirigées. Parmi les répondants au sondage, 61,2 % des DVP et 76,6 % des CG ont indiqué qu'ils seraient prêts à participer au DCR en tant que membre d'une paire d'individus compatibles. La possibilité pour le CG d'obtenir un rein avec un meilleur match et les politiques assurant la priorisation du CG pour une transplantation répétée en cas d'échec précoce de la greffe ont augmenté la volonté de participer au DCR. Parmi les principales préoccupations exprimées au cours des entrevues figuraient notamment le désir de préserver le lien émotionnel du don dirigé, la peur d'une rupture dans la chaîne, la peur du renoncement du donneur, les possibles retards pour la transplantation et les déplacements supplémentaires associés à une participation au DCR. LIMITES: L'étude est limitée par le fait qu'elle n'a été réalisée que dans trois programmes canadiens de transplantation et que les entrevues et les sondages n'étaient menés qu'en français et en anglais. Les résultats pourraient par conséquent ne pas refléter les opinions des personnes issues des minorités ethniques ou ne résidant pas dans ces deux provinces. CONCLUSION: La majorité des DVP et des CG compatibles qui ont été interrogés étaient ouverts à participer au don croisé d'un rein. Il est possible d'augmenter la participation de paires d'individus compatibles au don croisé d'un rein. Pour ce faire, on doit assurer une par un meilleur match optimale et une greffe en temps opportun pour les candidats à la transplantation; il faut également offrir une politique de réciprocité assurant une greffe répétée en temps opportun aux receveurs compatibles dont l'allogreffe échoue après un DCR.

Organ Transplantation for Foreign Nationals in Canada: A Survey of Transplant Professionals.

BACKGROUND: Transplantation for foreign nationals (non-citizens and non-residents) (FNs) in Canada is a complex issue. Currently, there are no Canadian guidelines for the provision of organ transplantation for FNs, and no empirical data on this issue or on transplant professionals' practices are available. OBJECTIVE: This project aimed to gather empirical data on transplant professionals' perspectives and practices regarding transplantation for FNs. DESIGN: Survey research design. SETTING: A Web-based survey of members of the Canadian Society of Transplantation (CST). PARTICIPANTS: All members of the CST were invited to participate between April and June 2016. MEASUREMENTS: Multiple-choice questions were developed to capture participants' attitudes toward different fictitious clinical scenarios in which an FN needed a transplant, their experiences with FNs, their attitude toward FNs in need of transplantation, their knowledge about relevant institutional and organ donation organization (ODO) policies, and their perspectives on a quota. There were two questions with a five-point Likert scale to measure respondents' agreement with statements related to possible policy options and arguments for and against transplantation for FNs. There was one open-ended question about the content of transplant programs' policies on transplantation for FNs. METHODS: Descriptive statistical analysis were performed. RESULTS: A total of 87 transplant professionals completed the survey. Over the 4-year period from 2012 to 2016, 47.1% of respondents dealt with at least one situation of listing or performing a transplant for an FN. Only 19.5% of respondents reported that their transplant program had a policy about transplantation for FNs and 59.7% did not know if their ODO had such a policy. When asked about policy options, 47.5% disagreed with a policy of no transplantation for FNs and 41.4% agreed with offering transplantation for FNs in some circumstances (including life-saving and non-life-saving organs). Study participants agreed that transplantation should not be offered to FNs traveling to Canada specifically for transplantation, that FNs should not be transplanted with organs not suitable for Canadian citizens and that there should not be a transplantation quota for FNs. Participants also seem to be more inclined to offer transplantation of life-saving organs, particularly for children. LIMITATIONS: The major limitation of this study is the low response rate of transplant professionals to this survey. CONCLUSION: This is the first study to describe Canadian transplant professionals' perspectives on transplantation for FNs. The findings of this study will be of interest for future policy development on access to transplantation for FNs. Further studies are needed to gather various key stakeholders' perspectives on this issue, as well as to analyze the legal and ethical issues and the economics, to develop future policies.

CONTEXTE: Au Canada, les greffes d'organes chez des ressortissants étrangers (RÉ), soit des non-résidents ou des non-citoyens, sont un enjeu complexe. Actuellement, au pays, aucune ligne directrice n'existe quant aux greffes d'organes à des RÉ et aucune donnée empirique sur cette question ni sur les pratiques professionnelles en transplantation n'est disponible. OBJECTIF: Ce projet visait à colliger les données empiriques faisant état des pratiques et de l'avis des professionnels en transplantation au sujet des greffes d'organes à des RÉ. TYPE D'ÉTUDE: Étude par sondage. CADRE: Un sondage en ligne mené auprès des membres de la Société Canadienne de transplantation. PARTICIPANTS: Tous les membres de la Société canadienne de transplantation ont été invités à participer à l'étude entre avril et juin 2016. MESURES: Des questions à choix multiples ont été développées pour connaître l'avis des participants sur différents scénarios fictifs dans lesquels un RÉ nécessitait une transplantation d'organe. Les questions visaient également à connaître l'expérience des répondants auprès des RÉ, leur connaissance des politiques pertinentes de leur organisation institutionnelle et de leur organisme de dons d'organe, de même que leur avis sur un quota. Deux questions sous forme d'échelle de Likert mesuraient le degré d'accord des répondants sur des énoncés liés à de possibles politiques et leur position (pour ou contre) sur des arguments à l'égard de la transplantation d'organes à des RÉ. Enfin, une question à développement portait sur les politiques du programme de transplantation au sujet des greffes d'organes à des RÉ. MÉTHODOLOGIE: On a procédé par analyze statistique descriptive. RÉSULTATS: Au total, 87 professionnels de la transplantation ont complété le sondage. Sur une période de quatre ans (2012-2016), 47,1 % des répondants avaient soit inscrit un RÉ sur la liste, soit pratiqué une transplantation chez un RÉ. Seuls 19,5 % des répondants ont déclaré que leur programme de transplantation comportait une politique sur la transplantation d'organes à des RÉ, alors que 59,7 % ignoraient si leur organisme de dons d'organes prévoyait une telle politique. Lorsque questionnés sur les possibles politiques, 47,5 % des répondants étaient en désaccord avec une politique qui refuserait la greffe aux RÉ, et 41,4 % étaient d'accord pour offrir la transplantation aux RÉ dans certaines circonstances, que l'organe soit essentiel ou non à la survie. Les participants s'entendaient sur plusieurs points: 1) la greffe ne devrait pas être offerte aux RÉ qui voyagent au Canada spécifiquement dans cet objectif; 2) les RÉ ne devraient pas être greffés avec des organes jugés inappropriés pour les citoyens Canadiens et; 3) aucun quota de transplantation ne devrait être établi pour les greffes aux RÉ. Les participants semblaient aussi plus enclins à proposer une greffe pour un organe vital, particulièrement aux enfants. LIMITES: La principale limite de cette étude est le faible taux de réponse des professionnels de la transplantation. CONCLUSION: Il s'agit de la première étude exposant l'avis des professionnels de la transplantation Canadiens à l'égard des greffes d'organes aux RÉ. Les résultats de cette étude serviront à l'élaboration de politiques sur l'accès aux greffes d'organes par des RÉ. D'autres études sont toutefois nécessaires pour connaître la position de divers intervenants clés sur le sujet, de même que pour analyzer les enjeux légaux, éthiques et économiques, en vue d'élaborer les futures politiques.

What does patient engagement mean for Canadian National Transplant Research Program Researchers?

PLAIN ENGLISH SUMMARY: In recent years, the importance of involving patients in research has been increasingly recognized because it increases the relevance and quality of research, facilitates recruitment, enhances public trust and allows for more effective dissemination of results. The Canadian National Transplant Research Program (CNTRP) is an interdisciplinary research team looking at a variety of issues related to organ and tissue donation and transplantation. The aim of this study was to gather the perspectives of CNTRP researchers on engaging patients in research.We conducted interviews with 10 researchers who attended a national workshop on priority-setting in organ donation and transplant research. The researchers viewed patient engagement in research as necessary and important. They also considered that patients could be engaged at every step of the research process. Participants in this study identified scientific language, time, money, power imbalance, patient selection and risk of tokenism as potential barriers to patient engagement in research. Training, adequate resources and support from the institution were identified as facilitators of patient engagement.This study showed a positive attitude among researchers in the field of organ donation and transplantation. Further studies are needed to study the implementation and impact of patient engagement in research within the CNTRP. ABSTRACT: Background Involving patients in research has been acknowledged as a way to enhance the quality, relevance and transparency of medical research. No previous studies have looked at researchers' perspectives on patient engagement (PE) in organ donation and transplant research in Canada. Objective The aim of this study was to gather the perspectives of Canadian National Transplant Research Program (CNTRP) researchers on PE in research. Methods We conducted semi-structured interviews with ten researchers who attended a national workshop on priority-setting in organ donation and transplant research. The interviews were digitally recorded and transcribed verbatim, and the transcripts were subjected to qualitative thematic and content analyses. Results The researchers viewed PE in research as necessary and important. PE was a method to incorporate the voice of the patient. They also considered that patients could be engaged at every step of the research process. The following were identified as the main barriers to PE in research: (i) scientific jargon; (ii) resources (time and money); (iii) tokenism; (iv) power imbalance; and (v) patient selection. Facilitating factors included (i) training for patients and researchers, (ii) adequate resources and (iii) institutional support. Conclusion This study revealed a favourable attitude and willingness among CNTRP researchers to engage and partner with patients in research. Further studies are needed to assess the implementation of PE strategy within the CNTRP and its impact.

Limitations of current in vitro models for testing the clinical potential of epigenetic inhibitors for treatment of pediatric ependymoma.

BACKGROUND: Epigenetic modifications have been shown to play an important role in the classification and pathogenesis of the pediatric brain tumor ependymoma, suggesting they are a potential therapeutic target. RESULTS: Agents targeting epigenetic modifications inhibited the growth and induced the death of ependymoma cells with variable efficiency. However, this was often not at clinically achievable doses. Additionally, DNA methylation profiling revealed a lack of similarity to primary ependymomas suggesting alterations were induced during culture. Toxicity to fetal neural stem cells was also seen at similar drug concentrations. CONCLUSIONS: Agents targeting epigenetic modifications were able to inhibit the growth and induced the death of ependymoma cells grown in vitro. However, many agents were only active at high doses, outside clinical ranges, and also resulted in toxicity to normal brain cells. The lack of similarity in DNA methylation profiles between cultured cells and primary ependymomas questions the validity of using in vitro cultured cells for pre-clinical analysis of agents targeting epigenetic mechanisms and suggests further investigation using models that are more appropriate should be undertaken before agents are taken forward for clinical testing. MATERIALS AND METHODS: The effects of agents targeting epigenetic modifications on the growth and death of a panel of ependymoma cell lines was investigated, as well as toxicity to normal fetal neural stem cells. The ependymoma cell lines were characterized using DNA methylation profiling.

Kidney Transplant Recipients' Perspectives on Cardiovascular Disease and Related Risk Factors After Transplantation: A Qualitative Study.

BACKGROUND: Cardiovascular disease (CVD) is a major cause of mortality among kidney transplant recipients (KTRs). These patients have a high prevalence of risk factors, such as hypertension, diabetes, and dyslipidemia. Despite regular medical care, few of them reach the recommended therapeutic targets. The objective of this study is to describe KTRs' perspectives on CVD and related risk factors, as well as their priorities for posttransplant care. METHODS: Twenty-six KTRs participated in a semistructured interview about their personal experience and offered their perspectives on CVD risk factors posttransplant. The interview was digitally recorded and the transcripts were analyzed using a thematic and content methodology. RESULTS: CVD and related risk factors appear to be underestimated and trivialized. Only 2 of 26 patients identified CVD prevention and treatment as a priority. The most important posttransplant priorities identified by patients were related to immunosuppressive drugs (13 of 26), posttransplant follow-up (10) and graft survival (9). However, 21 of 26 patients stated they wanted to be better informed about posttransplant CVD risk factors. CONCLUSIONS: CVD and related risk factors are not a priority for KTRs, and the importance of CVD is underestimated and trivialized. KTRs did recommend that tailored information be provided by various professionals and at several points in the transplantation process. This knowledge will help us develop a new approach to increase awareness of posttransplant CVD and related risk factors.

Perspectives of Patients, Caregivers and Researchers on Research Priorities in Donation and Transplantation in Canada: A Pilot Workshop.

BACKGROUND: It is vitally important to seek input from key stakeholders to increase the quality and relevance of health-related research and accelerate its adoption into practice. Patients and caregivers have rarely been involved in setting research priorities in the transplantation and donation field. The objectives of this explorative study are: (i) to discuss research priorities within the Canadian National Transplant Research Program during a priority-setting exercise with patients, caregivers, organ donors and researchers and (ii) to compare the identified priorities with research published in 2 prestigious transplantation journals. METHODS: A pilot workshop attended by 10 patients and caregivers and 5 researchers was held in Montréal (Quebec, Canada) in August 2014 to identify research priorities. Priorities were identified using a thematic analysis of the workshop transcription conducted by multiple coders. These priorities were compared with the topics of research articles published in 2 major transplantation journals between 2012 and 2014. RESULTS: The themes of the 10 research priorities identified by study participants were related to different research domains: social, cultural, and environmental health factors (4); biomedical or clinical (4); and research about health systems and services (2). 26.7% of the research articles published were related to the identified priorities. Thirteen percent looked at ways to improve graft survival and 8.5% looked at the development of tolerance, 2 priorities identified by participants. Fewer than 5% examined the other 8 research priorities identified as important by workshop participants. CONCLUSIONS: This is the first study reporting patients' and researchers' priorities in the field of transplantation and donation in Canada. There is a discrepancy between topics that key stakeholders find important and research published in 2 major transplantation journals. The research priorities identified during our initial workshop will be validated through a national survey and workshop.

Is it ethical to prescribe generic immunosuppressive drugs to renal transplant patients?

PURPOSE OF THE REVIEW: This review was conducted to determine the ethical acceptability of prescribing generic immunosuppressive drugs to renal transplant patients. SOURCES OF INFORMATION: The literature search was conducted using Pubmed and Google Scholar. FINDINGS: The use of generic immunosuppressive drugs (ISDs) in transplantation is a controversial topic. There is a consensus among transplant societies that clinical data is lacking and that caution should be exercised. The reluctance to use generic ISDs in organ transplantation is partly related to the fact that most are "critical dose drugs", and that either low dosing or overdosing could have serious adverse consequences for both patients and society (i.e., the loss of scarce organs). In this paper, we examine the various ethical issues involved such as distributive justice, physician duties, risks versus benefits, conflict of interest, informed consent, and logistical and economic issues. LIMITATIONS: Our analysis was limited by the paucity of clinical data on generic ISDs and the absence of health economics studies to quantify the benefits of prescribing generic ISDs. IMPLICATIONS: Our study led us to conclude that it would be ethical to prescribe generic ISDs provided certain conditions were met. These include regulatory safeguards to minimize the risks of substitution; education of patients; and further clinical and health economics studies to better inform clinicians, patients and society of the risks and costs related to drug substitution.

BUT DE L'ARTICLE: Le but de cet article est de questionner s'il est éthique de prescrire des immunosuppresseurs génériques aux patients transplantés d'un rein. SOURCES D'INFORMATIONS: Nous avons effectué une recension des écrits en utilisant Pubmed et Google Scholar. RÉSULTATS: La prescription d'immunosuppresseurs génériques en transplantation rénale est un sujet controversé. Les sociétés savantes sont en accord sur le fait qu'il y a un manque de données cliniques et que la prudence est de mise. Une des explications à cette attitude réfractaire est le fait que les immunosuppresseurs sont considérés comme des « médicaments à dose critique ¼. Par conséquent, leur surdosage ou leur sous-dosage peut avoir des conséquences désastreuses pour le patient et la société (i.e., la perte d'un greffon). Dans cet article, nous examinerons les enjeux éthiques impliqués dans ce débat tels que la justice distributive, les devoirs des médecins, l'analyse des risques et des bénéfices, le conflit d'intérêt, le consentement éclairé ainsi que des enjeux logistiques et économiques. LIMITES: Les données cliniques existantes sont insuffisantes et limitent notre analyse. De plus, l'absence d'analyse économique sur l'utilisation d'immunosuppresseurs génériques constitue une autre limite à notre étude. IMPLICATIONS: Suite à cette analyse, nous pouvons conclure qu'il serait éthique de prescrire des immunosuppresseurs génériques dans certaines circonstances. Celles-ci incluent la mise en place de mesures qui minimisent les risques de substitution, l'éducation des patients et la réalisation d'études cliniques et économiques afin de mieux informer les cliniciens, les patients et la société sur les risques reliés à la prescription de ces médicaments ainsi qu'aux coûts associés.

Effectiveness of a parent training program "Incredible Years" in a child protection service.

OBJECTIVE: This study aims to evaluate the effectiveness of a parent training program in improving parenting practices, parents' feeling of self-efficacy and parents' perception of their child's behavior, implemented in a child protection service, with trained professionals from the agency acting as facilitators. METHOD: Thirty-five parents monitored in a child protection service for child neglecting behaviors participated either in the intervention group (n=26) or were on the waiting list (n=9). The program implemented (Incredible Years) lasted 16 weeks, was in a group format, and aimed: (1) to develop a harmonious parent-child relationship; (2) to support parents in learning and consistently applying effective practices; (3) to improve problem solving and communication skills within families and with teachers. A repeated measures design was used to test the program's effects on parenting practices, parents' feeling of self-efficacy, parents' perception of their child's behavior, and parents' satisfaction. Parents were tested twice, during a 19-week interval, before and after the parent training program. RESULTS: Analyses of variance comparing Intervention and Control groups with repeated measures (pre- and post-test measures) revealed that the program has a positive impact on parenting practices (harsh discipline, physical punishment, praise/incentive, appropriate discipline and positive verbal discipline) and parents' perception of their child's behavior (frequency of behavioral problems and number of problematic behaviors). No change on clear expectations from parents, or on parents' self-efficacy was observed. CONCLUSION: Though the implementation of an evidence-based parent training program by professionals in a child protection service presents specific challenges, results suggest that it can contribute to improvements in parenting practices and in parents' perception of their child's behavior.

Crystallization and preliminary X-ray crystallographic analysis of p24, a component of the potato nuclear factor PBF-2.

The Solanum tuberosum (potato) nuclear factor PBF-2 is implicated in pathogen-induced expression of the pathogenesis-related gene PR-10a. Crystals of the DNA-binding component of PBF-2, p24, have been obtained at 277 K in 20 mM Tris-HCl pH 8.0. Recombinant protein with a His tag at its C-terminus was overexpressed in Escherichia coli in the presence and absence of selenomethionine and was purified using a combination of HiTrap affinity columns and gel-filtration chromatography. Crystals suitable for structural analysis were obtained for both native and selenomethionine-labelled proteins and yielded diffraction data at 100 K that were processed to 2.3 and 2.8 A resolution, respectively. The p24 protein crystals belong to space group P2(1)2(1)2(1), with unit-cell parameters a = 69.4 (69.1), b = 89.4 (90.5), c = 144.1 (144.3) A. The asymmetric unit contains four protomers, giving a crystal volume per protein mass (V(M)) of 2.23 A(3) Da(-1) and a solvent content of 45% by volume.

A new family of plant transcription factors displays a novel ssDNA-binding surface.

The crystal structure of p24, the single-stranded DNA (ssDNA) binding subunit of the plant defense transcription factor PBF-2, has been determined to 2.3 A resolution. p24 is representative of a novel family of ubiquitous plant-specific proteins that we refer to as the Whirly family because of their quaternary structure. PBF-2 is composed of four p24 molecules that interact through a helix-loop-helix motif. This interaction produces a central pore, with beta-strands radiating outwards, resulting in a whirligig appearance to the quaternary structure. The noncrystallographic C(4) symmetry arrangement of p24 subunits is novel for ssDNA binding proteins and may explain the binding specificity of PBF-2. This structural arrangement also supports the role of PBF-2 in binding melted promoter regions to modulate gene expression.