Erythrocytosis and thrombotic events in kidney transplant recipients prescribed a sodium glucose cotransport-2 inhibitor.

INTRODUCTION: The safety and efficacy of sodium glucose cotransport-2 inhibitors (SGLT2i) in kidney transplant recipients remains uncertain. Transplant recipients may be at risk of thrombosis because of post-transplant erythrocytosis and SGLT2i are associated with an increase in hematocrit. METHODS: We determined SGLT2i use, the change in hematocrit and incidence of thrombotic events in kidney transplant recipients in 1700 prevalent patients in our center. RESULTS: Among the 42 patients treated with SGLT2i, the mean pre-transplant hematocrit was 31%, and none of the patients had a hematocrit ≥50%. The mean percent change in hematocrit measured at an average of 53 days after initiation of an SGLT2i was 11% and four patients (10%) had a hematocrit ≥ 50%. The mean hematocrit measured 3 months after treatment was 42% and two patients (5%) had a hematocrit ≥50%. One patient had a cerebellar stroke 14 months post-SGLT2i initiation when the hemoglobin was 173 grams/liter, and the hematocrit was 52%. CONCLUSIONS: All patients had a sustained increase in hematocrit 3 months after SGLT2i treatment. Hematocrit ≥50% occurred in 10%, and one patient had a thrombotic event that may or may not have been related to an increase in hematocrit. Clinicians may consider monitoring for erythrocytosis after starting and SGLT2i in kidney transplant recipients.

Use of sodium-glucose co-transporter 2 inhibitors in solid organ transplant recipients with pre-existing type 2 or post-transplantation diabetes mellitus: A systematic review.

INTRODUCTION: Sodium-Glucose Co-Transporter 2 (SGLT2) inhibitors have demonstrated kidney, cardiovascular and mortality benefits in the general population; however, the evidence is limited in solid organ transplant recipients. The aim of this systematic review was to evaluate the current efficacy and safety data of SGLT2 inhibitors in adult kidney, heart, lung, and liver transplant recipients with pre-existing type 2 or post-transplantation diabetes mellitus. METHOD: We searched MEDLINE, MEDLINE Epub, CENTRAL, CDSR, EMBASE, CINAHL, and sources of unpublished literature. All primary interventional and observational studies on SGLT2 inhibitors in transplant recipients were included. Clinical outcomes included mortality, cardiovascular and kidney events, and adverse events such as graft rejection. Surrogate markers including hemoglobin A1c (HbA1c) and weight reduction were also evaluated. RESULTS: Of the 17 studies that were included in this systematic review, there were 15 studies on kidney transplant recipients (n = 2417 patients) and two studies on heart transplant recipients (n = 122 patients). There was only one randomized controlled trial which evaluated 49 kidney transplant patients over 24 weeks. Overall, studies were heterogeneous in study design, sample size, duration of diabetes, time to SGLT2 inhibitor initiation post-transplantation (ranging from 0.88 to 11 years post kidney transplant; five to 5.7 years post heart transplant) and follow-up (ranging from 0.4 to 5.25 years in kidney transplant patients; 0.75 to one year in heart transplant patients). Only one retrospective study evaluated mortality as a part of a composite outcome in kidney transplant patients; however, study limitations restrict generalizability of results. Overall, studies could not confirm clinical cardiovascular and kidney benefits in the transplant population. Findings suggested that SGLT2 inhibitors may improve glycemic control; however, they are associated with urinary tract infection. Diabetic ketoacidosis and acute kidney injury also occurred in these studies, with precipitating factors such as infection and acute heart failure exacerbation. CONCLUSIONS: While SGLT2 inhibitors are promising agents with expanding indications in the non-transplant population, these agents may not be suitable for all solid organ transplant recipients, and close monitoring (e.g. for urinary tract infections) and patient education (e.g. sick day management) are essential if these agents are initiated. Evidence is based on short-term findings and suggests an association with hemoglobin A1c reduction and increased adverse events. Further long-term randomized controlled trials are needed to evaluate the effect of SGLT2 inhibitors on clinically important outcomes, including mortality reduction, in solid organ transplant recipients.

Characterization of Cytomegalovirus Viremia in Renal Transplant Recipients.

BACKGROUND: Kidney transplantation, while improving outcomes for patients with end-stage renal disease, comes with a risk of potentially life-threatening infections such as infection with cytomegalovirus (CMV), a virus associated with allograft rejection, organ dysfunction, and increased mortality. OBJECTIVES: To characterize whether the choice and dose of immunosuppressant therapy and the duration of antiviral prophylaxis after transplant are associated with the incidence of CMV viremia. METHODS: This study was a retrospective review of all kidney-only transplant recipients at the authors' centre from 2012 to 2016, with a minimum 1 year of follow-up. Patients with CMV viremia (defined as serum CMV viral load greater than 1000 IU/mL) were compared with patients who did not have viremia to investigate potential demographic and treatment-related risk factors. RESULTS: A total of 653 patients were included in the study, of whom 161 (25%) met the criteria for CMV viremia. In univariate analysis, patients with CMV viremia had older age (55 versus 53 years, p = 0.038) and lower mean body weight (75 versus 79 kg, p = 0.015); in addition, the CMV viremia group included larger proportions of patients with Asian descent (40% [64/161] versus 21% [104/492]) and donor-positive/recipient-negative CMV serostatus (29% [47/161] versus 14% [70/492]). With respect to immunosuppressant therapy, patients with CMV viremia more frequently received antithymocyte globulin (ATG) induction (50% [80/161] versus 28% [138/492], p < 0.001) and received a higher weight-based cumulative ATG dose (mean 4.5 versus 4.1 mg/kg, p = 0.038). The multivariate analysis retained use of ATG, cumulative dose of ATG, Asian descent, and CMV serostatus as risk factors for CMV viremia. No statistically significant differences were found for the maintenance immunosuppressant dosing or duration of antiviral prophylaxis. CONCLUSIONS: Use of ATG for induction and higher weight-based dose of ATG were associated with an increased risk of CMV viremia. In addition, a component of race may also be involved, with patients of Asian descent being at higher risk. No differences were found in the maintenance dose of immunosuppression or the duration of antiviral prophylaxis.

CONTEXTE: La transplantation rénale, bien qu'elle améliore les résultats des patients atteints d'insuffisance rénale en phase terminale, s'accompagne d'un risque d'infections potentiellement mortelles telles que l'infection par le cytomégalovirus (CMV) : un virus associé au rejet d'allogreffe, à un dysfonctionnement d'organe et à une plus grande mortalité. OBJECTIFS: Caractériser si le choix et la dose du traitement immunosuppresseur et la durée de la prophylaxie antivirale après la transplantation sont associés à l'incidence de virémie à CMV. MÉTHODES: Cette étude était un examen rétrospectif de tous les receveurs d'une transplantation rénale uniquement mené au centre des auteurs de 2012 à 2016, avec un suivi d'au moins 1 an. Les patients atteints de virémie à CMV (définie comme une charge virale sérique CMV supérieure à 1000 UI/mL) ont été comparés à des patients sans virémie; cette comparaison avait pour but d'étudier les facteurs de risque démographiques ou liés aux traitements. RÉSULTATS: L'étude comprenait 653 patients, dont 161 (25 %) répondaient aux critères de virémie à CMV. En analyse univariée, l'âge des patients atteints de virémie à CMV était plus élevé (55 contre 53 ans, p = 0,038) et leur poids corporel moyen était moins élevé (75 contre 79 kg, p = 0,015); en outre, le groupe des patients atteints de virémie à CMV comprenait une plus grande proportion de patients d'origine asiatique (40 % [64/161] contre 21 % [104/492]) et de statut sérologique CMV donneur positif/receveur négatif (29 % [47/161] contre 14 % [70/492]). En ce qui concerne le traitement immunosuppresseur, les patients atteints de virémie à CMV ont reçu plus fréquemment une induction de sérum anti-lymphocytaire (SAL) (50 % [80/161] contre 28 % [138/492], p < 0,001) ainsi qu'une dose cumulative de SAL plus élevée en fonction du poids (moyenne de 4,5 contre 4,1 mg/kg, p = 0,038). L'analyse multivariée a retenu l'utilisation du SAL, la dose cumulative de SAL, l'origine asiatique et le statut sérologique du CMV comme facteurs de risque de virémie à CMV. Aucune différence statistiquement significative n'a été trouvée pour la posologie d'entretien des immunosuppresseurs ou la durée de la prophylaxie antivirale. CONCLUSIONS: L'utilisation du SAL pour l'induction et une dose plus élevée de SAL en fonction du poids étaient associées à un risque accru de virémie à CMV. De plus, une composante raciale pourrait également être impliquée ­ les patients d'origine asiatique étant plus à risque. Aucune différence n'a été trouvée dans la posologie d'entretien des immunosuppresseurs ou la durée de la prophylaxie antivirale.

Canadian Society of Transplantation White Paper: Ethical and Legal Considerations for Alcohol and Cannabis Use in Solid Organ Listing and Allocation.

Alcohol and cannabis use as a contraindication to organ transplantation is a controversial issue. Until recently, patients in Canada with alcohol-associated liver disease were required to demonstrate abstinence for 6 mo to receive a liver transplant. There is no equivalent rule that is applied consistently for cannabis use. There is some evidence that alcohol and cannabis use disorder pretransplant could be associated with worse outcomes posttransplantation. However, early liver transplantation for patients with alcohol-associated liver disease in France and in the United States has led to challenges of the 6-mo abstinence rule in Canada in the media. It has also resulted in several legal challenges arguing that the rule violates human rights laws regarding discrimination in the provision of medical services and that the rule is also unconstitutional (this challenge is still before the court). Recent legalization of cannabis use for adults in Canada has led to questions about the appropriateness of limiting transplant access based on cannabis use. The ethics committee of the Canadian Society of Transplantation was asked to provide an ethical analysis of cannabis and alcohol abstinence policies. Our conclusions were as follows: neither cannabis use nor the 6-mo abstinence rule for alcohol use should be an absolute contraindication to transplantation, and transplant could be offered to selected patients, further research should be conducted to ensure evidence-based policies; and the transplant community has a duty not to perpetuate stigma associated with alcohol and cannabis use disorders.

Evaluation of Physical Assessment Education for Practising Pharmacists: A Cross-Sectional Survey.

BACKGROUND: Pharmacists are now seeking to incorporate physical assessment (PA) into their practices. This trend prompted the creation, by the British Columbia Branch of the Canadian Society of Hospital Pharmacists, of a 30-h course specifically designed for practising pharmacists. OBJECTIVE: To evaluate pharmacists' knowledge, skills, and confidence in performing PA after completing the course. METHODS: All course participants were invited to complete 2 anonymous online surveys, immediately and 6 months after course completion. RESULTS: Of the 218 participants, 82 (38%) responded to the survey administered immediately after the course, and 77 (35%) completed this survey in full. About half of the respondents (39/79 [49%]) reported use of PA on a real patient before taking the course. Lack of formal training and lack of comfort were the most frequently selected barriers to performing PA. All respondents (79/79) agreed that the course had improved their knowledge of PA, 96% (76/79) agreed that it had improved their skills, and 90% (71/79) agreed that it had improved their ability to care for patients. In addition, 61% (48/79) and 67% (53/79), respectively, agreed that they felt confident performing PA and intervening with regard to a patient's drug therapy on the basis of physical findings. Thirty-eight (17%) of the course participants completed the 6-month follow-up survey. In that survey, the most frequently selected barrier to performing PA was lack of time. Paired data, available for 23 respondents, showed a significant increase in use of PA on real patients over time (p = 0.013 by χ2 test). However, there was no significant improvement in confidence in performing PA or intervening on a patient's drug therapy on the basis of physical findings (p > 0.05 by 2-sided t test). The primary limitation of this study was potential responder bias. CONCLUSIONS: A PA course designed for pharmacists improved participants' self-reported knowledge and skills, as well as self-perceived ability to care for patients. Six months after the course, two-thirds of respondents had used PA in practice. However, there was no improvement in confidence in performing such assessments or using the findings to intervene on a patient's drug therapy.

CONTEXTE: Les pharmaciens cherchent désormais à ajouter l'examen physique à leurs pratiques. Cette tendance a motivé la section britannocolombienne de la Société canadienne des pharmaciens d'hôpitaux à créer un cours de 30 heures conçu spécialement pour les pharmaciens en exercice. OBJECTIF: Évaluer les connaissances, les compétences et le degré d'aisance des pharmaciens ayant suivi le cours portant sur la réalisation d'examens physiques. MÉTHODES: Tous les participants au cours ont été invités à remplir deux sondages anonymes en ligne: l'un à la fin du cours et l'autre six mois après la fin du cours. RÉSULTATS: Des 218 participants, 82 (38 %) ont répondu partiellement au sondage mené immédiatement à la fin du cours et 77 (35 %) y ont répondu en entier. Environ la moitié des répondants (39/79 [49 %]) ont indiqué avoir réalisé un examen physique en situation réelle avant d'avoir suivi le cours. Les facteurs les plus fréquents propres à dissuader le pharmacien de réaliser un examen physique étaient l'absence de formation officielle et le manque d'aisance. Tous les répondants ont indiqué que le cours avait accru leurs connaissances de l'examen physique, 96 % (76/79) ont affirmé qu'il avait amélioré leurs compétences et 90 % (71/79) ont déclaré qu'il avait amélioré leur capacité à soigner les patients. De plus, 61 % (48/79) et 67 % d'entre eux (53/79) ont indiqué respectivement qu'ils se sentaient à l'aise de réaliser des examens physiques et d'agir sur la pharmacothérapie du patient en fonction des résultats de l'examen. Trente-huit (17 %) participants ont répondu au sondage mené six mois après le cours. Ce sondage a révélé que le manque de temps était le facteur le plus souvent évoqué pour faire obstacle à la réalisation d'examens physiques. Des données appariées de 23 répondants ont montré une augmentation significative du recours à l'examen physique en situation réelle au fil du temps (p = 0,013 par test χ2). Cependant, on n'a noté aucune amélioration significative de l'aisance à réaliser des examens physiques ou à agir sur la pharmacothérapie d'un patient en fonction des résultats d'un examen physique (p > 0,05 par un test t bilatéral). La principale limite de la présente étude était un biais potentiel dans les réponses. CONCLUSIONS: Un cours sur l'examen physique conçu pour les pharmaciens a amélioré les connaissances et les compétences autodéclarées des participants ainsi que ce qu'ils croient être leurs capacités à soigner les patients. Six mois après le cours, deux tiers des répondants avaient réalisé un examen physique dans leur pratique. Cependant, on n'a noté aucune amélioration de l'aisance à réaliser de tels examens ou à en utiliser les résultats pour agir sur la pharmacothérapie du patient.

Common Questions and Misconceptions in the Management of Renal Transplant Patients: A Guide for Health Care Providers in the Posttransplant Setting.

Once renal transplant recipients are stabilized and require less frequent follow-up with their transplant team, health care providers outside of the transplant setting play an integral role in patients' ongoing medical care. Given renal transplant recipients' inherent complexity, these health care providers often seek consult regarding decisions that may affect transplant-related medications or outcomes. In this review, we discuss answers to 10 of the questions commonly posed to our renal transplant team by other health care providers.

A vexing case of bone pain in a renal transplant recipient: Voriconazole-induced periostitis.

Immunosuppression increases the risk of opportunistic infections including fungal infections in solid organ transplant recipients. Voriconazole is used to treat invasive aspergillus infections but prolonged usage may rarely lead to periostitis. Increased plasma fluoride concentration leading to osteoblastic upregulation is thought to be the catalyst, and symptom reversal occurs with discontinuation of the offending agent. A renal transplant recipient who was on voriconazole for invasive aspergillosis developed diffuse debilitating symmetrical bone pain. Having ruled out other neurological, metabolic, and drug etiologies, voriconazole-induced periostitis was diagnosed. Increased plasma fluoride level was documented, but bone scan was non-specific. A therapeutic discontinuation of voriconazole and switch to posaconazole provided rapid symptom resolution. The patient accidently restarted voriconazole as an outpatient resulting in the same symptomology, and thus provided further evidence that this was drug related. Voriconazole-induced periostitis is a described entity in immunosuppressed solid organ transplant patients who are treated with a prolonged course of voriconazole. This case study is novel in that it demonstrates drug induced periostitis in a renal transplant recipient who developed debilitating periostitis within a short time after starting voriconazole and equally rapid resolution once it was discontinued. We conclude that patients treated with voriconazole should be routinely monitored for periostitis.

Creation of a Natural Health Products Database for Assessing Safety for Patients with Chronic Kidney Disease or Renal Transplant.

INTRODUCTION: There is a lack of published safety information on the use of natural health products (NHPs) for patients with chronic kidney disease (CKD) or renal transplant. OBJECTIVE: To create an online database to provide evidence-based safety recommendations for commonly used NHPs, specific to patients with CKD or renal transplant. METHODS: NHPs used by CKD and transplant patients in British Columbia were identified from the records of the BC Provincial Renal Agency. For each NHP, several databases (MEDLINE, Embase, Lexi-Natural Products, PubMed Dietary Supplement Subset, and Natural Medicines) were searched for any information pertaining to dosage, adverse drug reactions, drug interactions, immunomodulatory effects, and pharmacokinetics in patients with renal disease. Each NHP was given 1 of 4 safety ratings: likely safe, possibly safe, possibly unsafe, and likely unsafe. An NHP was classified as "possibly unsafe" for patients with renal transplant if it had demonstrated in vitro immunomodulatory effects and/or significant interactions with transplant medications due to effects on the cytochrome P450 3A4 isozyme. RESULTS: Of the 19 627 BC-registered patients with renal disease (as of August 2014), 4122 (21%) were using one or more NHPs. The Herbal-CKD website (www.herbalckd.com) was created in 2015 to provide information about 47 commonly used NHPs and 2 known nephrotoxins (aristolochic acid and silver). This website provides a systematic evaluation of safety information for selected NHPs for patients with CKD (both nondialysis and dialysis-dependent) and kidney transplant. The most common NHP safety classification was "possibly safe", reflecting the paucity of studies in renal populations and the availability of safety data for the general population. Limitations of the website include difficulty in interpreting and generalizing the safety literature because most NHP formulations are not standardized, and others are combination products. CONCLUSION: The website www.herbalckd.com provides an easy-to-use, evidence-based tool for health care professionals to assess the safety of NHPs for CKD and transplant patients.

CONTEXTE: On observe qu'il n'existe que très peu d'information publiée sur l'innocuité des produits de santé naturels (PSN) pour les patients souffrant d'insuffisance rénale chronique ou ayant subi une greffe rénale. OBJECTIF: Créer une base de données en ligne qui sert à fournir des recommandations de sécurité fondées sur des données probantes au sujet des PSN les plus employés spécifiquement à l'intention des patients atteints d'insuffisance rénale chronique ou ayant subi une greffe rénale. MÉTHODES: Les PSN utilisés par les patients souffrant d'insuffisance rénale chronique ou ayant subi une greffe rénale ont été répertoriés d'après les dossiers de la BC Provincial Renal Agency. Pour chaque PSN, plusieurs bases de données (MEDLINE, Embase, Lexi-Natural Products, PubMed Dietary Supplement Subset et Natural Medicines) ont été interrogées afin d'y chercher des informations sur la posologie, les réactions indésirables aux médicaments, les interactions médicamenteuses, les effets immunomodulateurs et la pharmacocinétique chez les patients atteints d'insuffisance rénale. Chaque PSN s'est vu attribuer l'un de quatre degrés de sécurité : probablement sécuritaire, possiblement sécuritaire, possiblement nocif et probablement nocif. Un PSN était classé « possiblement nocif ¼ pour les patients ayant subi une greffe rénale s'il a manifesté in vitro des effets immunomodulateurs ou des interactions importantes avec les médicaments antirejet à cause de l'isozyme 3A4 du cytochrome P450. RÉSULTATS: Parmi les 19 627 patients insuffisants rénaux inscrits en Colombie-Britannique, 4 122 (21 %) utilisaient au moins un PSN (en date d'août 2014). Le site Web HerbalCKD (www.herbalckd.com) a été créé en 2015 afin de fournir de l'information sur 47 des PSN les plus utilisés et sur deux néphrotoxines connues (l'acide aristolochique et l'argent). Ce site Web offre une évaluation systématique des informations sur l'innocuité de PSN choisis qui pourraient être utilisés par les patients souffrant d'insuffisance rénale chronique (dialysés ou non) ou ayant subi une greffe rénale. Les PSN étaient le plus souvent classés sous « possiblement sécuritaire ¼, ce qui souligne le peu d'études auprès des populations souffrant de troubles rénaux et la disponibilité de données sur l'innocuité dans la population générale. Parmi les limites du site Web, on compte la difficulté à interpréter et à généraliser la littérature sur l'innocuité parce que la plupart des formules de PSN ne sont pas normalisées et que certains PSN sont un mélange de substances. CONCLUSION: Le site Web www.herbalckd.com représente pour les professionnels de la santé un outil simple et fondé sur des données probantes leur permettant d'évaluer l'innocuité de PSN pour les patients atteints d'insuffisance rénale chronique ou ayant subi une greffe rénale.

Clinical Pharmacokinetic Monitoring of Leflunomide in Renal Transplant Recipients with BK Virus Reactivation: A Review of the Literature.

Leflunomide is an immunosuppressive drug with in vitro and initial observational evidence of antiviral activity against BK virus (BKV), a pathogen that causes opportunistic infection upon reactivation in renal transplant recipients. Leflunomide is considered an ancillary option to immunosuppression reduction in the management of BKV reactivation. Plasma or blood concentrations of teriflunomide, the active metabolite of leflunomide, are commonly monitored because of high leflunomide doses being used, known inter-individual variability in pharmacokinetics, and hepatotoxicity risk. However, the utility of clinical pharmacokinetic monitoring for leflunomide is as yet unclear. A literature search of MEDLINE (1946-December 2016), EMBASE (1974-December 2016), the CENTRAL database, and Google Scholar was performed to identify relevant English-language articles. Further articles were identified from references in relevant literature. A previously published 9-step decision-making algorithm was used to assess the available literature and determine the utility of clinical pharmacokinetic monitoring for leflunomide. Teriflunomide is readily measurable in the plasma or blood, but a clear relationship between concentration and efficacy or toxicity is lacking, and its therapeutic range is not well-established. Efficacy and toxicity endpoints such as renal function and BKV clearance can be readily assessed without measuring teriflunomide concentrations. Pharmacokinetic parameters are affected by genetic polymorphisms in cytochrome P450 CYP2C19 and ABCG2 genes. Therefore, routine clinical pharmacokinetic monitoring of leflunomide cannot be recommended based on current available evidence. However, it may provide clinical benefit in difficult situations when patients demonstrate a lack of therapeutic response or exhibit signs of drug toxicity.

Evaluation of Heparin Anticoagulation Protocols in Post-Renal Transplant Recipients (EHAP-PoRT Study).

BACKGROUND: Disturbances in hemostasis are common among renal transplant recipients. Because of the risk of thromboembolism and graft loss after transplant, a prophylactic heparin protocol was implemented at St Paul's Hospital in Vancouver, British Columbia, in 2011. Therapeutic heparin is sometimes prescribed perioperatively for patients with preexisting prothrombotic conditions. There is currently limited literature on the safety and efficacy of heparin use in the early postoperative period. OBJECTIVES: The primary objectives were to document, for patients who underwent renal transplant, the incidence of major bleeding and of thrombosis in those receiving therapeutic heparin, prophylactic heparin, and no heparin anticoagulation in the early postoperative period and to compare these rates for the latter 2 groups. The secondary objectives included a comparison of the risk factors associated with major bleeding and thrombosis. METHODS: Adult patients who received a renal transplant at St Paul's Hospital between January 2008 and July 2013 were included in this retrospective cohort study. Electronic health records and databases were used to divide patients into the 3 heparin-use cohorts, to identify cases of major bleeding and thrombosis, and to characterize patients and events. The Fisher exact test was used for the primary outcome analysis, and descriptive statistics were used for all other outcomes. RESULTS: A total of 547 patients were included in the analysis. Major bleeding was observed in 6 (46%) of the 13 patients who received therapeutic heparin; no cases of thrombosis occurred in these patients. Major bleeding occurred in 8 (3.0%) of the 266 patients who received prophylactic heparin and 9 (3.4%) of the 268 who received no heparin (p > 0.99). Thrombosis occurred in 1 (0.4%) and 3 (1.1%) of these patients, respectively (p = 0.62). Major bleeding occurred more frequently among patients with a low-target heparin protocol, but 61% of values for partial thromboplastin time were above target. A larger proportion of deceased-donor transplant recipients who had major bleeding were taking antiplatelet agents, relative to living-donor transplant recipients. CONCLUSION: Therapeutic use of heparin increased the risk of bleeding among renal transplant recipients, but there were no cases of thrombosis. Prophylactic use of heparin did not increase the risk of bleeding and prevented proportionately more cases of thrombosis relative to no anticoagulation; this result supports the continued use of prophylaxis.

CONTEXTE: Les troubles de l'hémostase sont courants chez les patients ayant subi une transplantation rénale. Comme il existe des risques de thromboembolie et de perte du greffon après une greffe, un protocole d'administration d'héparine prophylactique a été mis en place en 2011 à l'hôpital Saint-Paul de Vancouver, en Colombie-Britannique. On prescrit parfois l'héparine thérapeutique en période périopératoire à certains patients affligés d'un état prothrombotique préexistant. Il n'y a actuellement que peu de documentation sur la sécurité et l'efficacité de l'utilisation d'héparine au début de la période postopératoire. OBJECTIFS: Les objectifs principaux étaient de documenter les incidences de cas d'hémorragie importante et de thrombose chez les patients ayant subi une transplantation rénale et ayant reçu des doses thérapeutiques d'héparine, des doses prophylactiques d'héparine ou aucun anticoagulant au début de la période postopératoire ainsi que de comparer les incidences des cas entre les deux derniers groupes. Les objectifs secondaires incluaient la comparaison des facteurs de risque associés à une hémorragie importante et à une thrombose. MÉTHODES: Les patients adultes retenus dans la présente étude de cohorte rétrospective avaient subi une greffe rénale à l'hôpital Saint-Paul entre janvier 2008 et juillet 2013. Des dossiers de santé informatisés et des bases de données ont servi à séparer les patients en trois cohortes selon l'utilisation ou non et la dose d'héparine afin de déceler les cas d'hémorragie importante et de thrombose et afin d'offrir un portrait des patients et des événements. Le test exact de Fisher a été employé pour l'analyse des principaux paramètres alors que l'on a utilisé des statistiques descriptives pour tous les autres paramètres. RÉSULTATS: Au total, 547 patients ont été retenus pour l'analyse. Des hémorragies importantes ont été observées chez 6 (46 %) des 13 patients ayant reçu de l'héparine thérapeutique. Aucune thrombose n'a été relevée chez ces patients. Des hémorragies importantes ont été observées chez 8 (3,0 %) des 266 patients ayant reçu de l'héparine prophylactique et chez 9 (3,4 %) des 268 patients n'ayant pas reçu d'héparine (p > 0,99). Des thromboses ont été observées respectivement chez 1 (0,4 %) et 3 (1,1 %) de ces patients (p = 0,62). Un plus grand nombre de patients ont souffert d'hémorragies importantes avec un protocole à valeurs cibles inférieures pour l'administration d'héparine, mais 61 % des valeurs pour le temps de thromboplastine partielle étaient au-dessus de la cible. Parmi les patients qui ont souffert d'hémorragies importantes et dont le donneur était décédé, une plus grande proportion prenaient des antiplaquettaires. CONCLUSION: L'administration thérapeutique d'héparine a accru les risques d'hémorragie chez les greffés rénaux, mais il n'y a pas eu de cas de thrombose. L'administration prophylactique d'héparine n'a pas augmenté les risques d'hémorragie et elle a permis d'éviter proportionnellement plus de cas de thrombose que l'absence d'anticoagulant; ce résultat vient appuyer l'utilisation d'héparine prophylactique.

A budget impact analysis of the introduction of erythropoiesis stimulating agent subsequent entry biologics for the treatment of anemia of chronic kidney disease in Canada.

BACKGROUND: In Europe, epoetin subsequent entry biologics (SEBs) have been in use since 2007. Canadian patents of erythropoietin stimulating agents are expiring in 2014, therefore it is predicted that epoetin SEBs will penetrate the Canadian market in the near future. OBJECTIVE: To estimate the economic impact and costs offsets associated with the uptake and use of one or more epoetin SEBs in Canada for the treatment of anemia in chronic kidney disease. DESIGN: A Canada-wide epidemiological-based budget impact analysis was conducted to estimate cost outcomes under two scenarios: with and without the availability of epoetin SEB. SETTING: The analysis was conducted from the perspective of the Canadian healthcare payer, over a 5-year time horizon from 2015 to 2019. PATIENTS: Patients included in the model were those with chronic kidney disease stages 3 to 5, who have renal anemia and require treatment with erythropoietin stimulating agents. METHODS: Only direct medical costs pertaining to drug acquisition of currently available erythropoietin stimulating agents in Canada were incorporated in the model. Cost of epoetin SEBs, market shares, uptake rates, and other model inputs were estimated from published sources or databases. No discounting of future costs was applied. RESULTS: Based on our analysis, under market phenomena similar to those seen in the Europe and without considering potential switching from originator epoetin to epoetin SEB, we could expect that Canadian adoption of epoetin SEBs could result in $35 million (2013 CAD, year 1) to $50 million (year 5) cost savings annually, with cumulative savings of $221 million after 5 years. In one-way sensitivity analyses, model variables with substantial impact on cost savings were the prevalence of chronic kidney disease and epoetin SEB uptake rates. LIMITATIONS: We did not take into account costs associated with overhead, administration, or adverse events. CONCLUSION: The advent of SEBs represents an opportunity to relieve financial pressure in our healthcare system. Under the assumption that the efficacy and safety of epoetin SEBs are non-inferior to originator products, we have shown that the adoption of epoetin SEBs can lead to cost savings for the Canadian payer.

CONTEXTE: L'époétine biosimilaire est utilisée en sol européen depuis 2007. Puisque les brevets d'utilisation des agents stimulant l'érythropoïèse (ASE) viennent à échéance en 2014, il est à prévoir que l'époétine biosimilaire, qui est un produit biologique ultérieur, fera son entrée sur le marché canadien dans un avenir rapproché. OBJECTIFS: Estimer l'impact économique et les coûts de compensation qui découlent de l'utilisation d'une ou de plusieurs formes d'époétines biosimilaires, dans le traitement de l'anémie associée à la maladie rénale chronique, au Canada. TYPE D'ÉTUDE: Une analyse d'impact budgétaire pancanadienne basée sur des données épidémiologiques a été réalisée afin d'estimer les coûts reliés à deux scénarios éventuels: le premier avec époétine biosimilaire sur le marché, et le deuxième sans cette disponibilité. CONTEXTE: L'analyse a été menée à partir de la perspective du contribuable au système de soins de santé canadien, sur un horizon de cinq ans, soit de 2015 à 2019. PARTICIPANTS: Le modèle ne tient compte que des patients atteints d'une maladie rénale chronique de stades 3 à 5, souffrant d'anémie reliée à la maladie rénale, et nécessitant un traitement avec des agents stimulant l'érythropoïèse. MÉTHODES: Les seuls coûts pris en compte par le modèle sont les coûts médicaux directs découlant de l'achat des agents stimulant l'érythropoïèse disponibles au Canada. Les coûts reliés à l'époétine biosimilaire, les parts de marché, les coûts de compensation, et les autres entrées du modèle ont été estimés à partir de sources publiées ou de bases de données. Aucune actualisation des coûts futurs n'a été estimée. RÉSULTATS: Selon notre analyse, qui ne tient pas compte de la possibilité d'utiliser l'époétine biologique de référence avant de passer à l'époétine biosimilaire, et sous des conditions de marché similaires à celles observées en Europe, l'adoption à l'échelle canadienne de l'époétine biosimilaire pourrait résulter en une économie de 35 millions $ (2013 $ CAN, année 1) à 50 millions $ (année 5) par année, pour une économie cumulative potentielle de 221 millions $ après cinq ans. L'analyse de sensibilités unidirectionnelles montre que la prévalence de la maladie rénale chronique et les coûts de compensation reliés à l'époétine biosimilaire sont les variables du modèle ayant le plus d'impact économique. LIMITES DE L'ÉTUDE: Nous n'avons pas tenu compte des frais généraux, d'administration, ou découlant d'imprévus. CONCLUSION: Les produits biologiques ultérieurs peuvent aider à alléger les difficultés financières de notre système de santé actuel. En supposant que l'époétine biosimilaire présente une efficacité et une innocuité qui ne sont pas inférieures à celles des époétines biologiques de référence, nous montrons que l'utilisation de l'époétine biosimilaire peut mener à des économies pour le contribuable canadien.

Potential impact of subsequent entry biologics in nephrology practice in Canada.

PURPOSE OF REVIEW: Subsequent entry biologics may soon be a reality in Canadian nephrology practice. Along with opportunities to reduce health care costs, these agents pose unique challenges that must be met for successful implementation. Understanding the experiences around the globe in both regulatory affairs and implementation will be a valuable guide for Canadian clinicians. This report provides an executive summary of the information required to guide decisions to use or implement subsequent entry biologics by comparing Canadian regulations to other developed nations, discussing their clinical issues and predicting their impact on the Canadian market and nephrology practice. We hope that this review will assist clinicians and policy makers to navigate this complex subject and to make informed decisions in the best interest of their patients. SOURCES OF INFORMATION: Sources of information include published literature and reports available in the public domain including guidelines obtained from regulatory agencies and information shared by Pharmaceutical companies. Lastly, we generated information from our own focus group consisting of nephrologists, a regulatory body representative, a hospital formulary representative, a patient representative, a hospital administrator, and a health economist. FINDINGS: There exists a common and robust approach in the G20 countries for approval and regulation of subsequent entry biologics. Although by definition these agents do not have advantages (other than costs) or disadvantages compared to the original biologic, there are potential concerns and economic uncertainties regarding their implementation. Where SEBs are on the market, their market share is variable and modest. LIMITATIONS: We did not purchase third party reports for up to the minute marketing data. Since there are no subsequent entry biologics currently on the Canadian market, the information is only predictive. IMPLICATIONS: The nephrology community will have to work with patients, payers, and regulatory bodies to ensure safe and effective use of subsequent entry biologics. Cost savings can be achieved but these agents should only be used after fully understanding their unique challenges. At this time, they should not be automatically substitutable and only used for Health Canada-approved indications. Only through good pharmacovigilence will health care providers and patients become better informed.

OBJECTIF DE LA REVUE: L'utilisation des produits biologiques ultérieurs pourrait bientôt devenir réalité en néphrologie au Canada. Ces agents, qui permettent possiblement des réductions de coûts en soins de santé, présentent des défis particuliers qui doivent être évalués pour une introduction réussie sur le marché. À cet effet, arriver à comprendre les différentes expériences qui se sont déroulées partout dans le monde en matière de réglementation et de mise en œuvre de ces agents est un exercice précieux qui pourrait guider les praticiens canadiens. Ce rapport fournit un résumé des informations requises pour guider la prise de décision pour l'utilisation et l'introduction des produits biologiques ultérieurs : comparaison des réglementations canadiennes à celles d'autres pays; discussion des enjeux cliniques entourant les produits biologiques ultérieurs et prévision de l'impact de leur utilisation sur le marché canadien et sur la pratique de la néphrologie. Nous espérons que cette revue aidera les cliniciens et les décideurs dans l'exploration de ce sujet complexe et dans une prise de décision optimale pour leurs patients. SOURCES D'INFORMATION: Plusieurs sources d'information ont été utilisées, dont des publications et des rapports du domaine public, sous la forme de lignes directrices d'organismes de réglementation et de documents provenant de compagnies pharmaceutiques. De plus, nous avons utilisé l'information générée par notre propre groupe de discussion. Ce dernier est composé de néphrologues, d'un représentant d'organisme de réglementation, d'un représentant de la Liste des médicaments des hôpitaux, un représentant des patients, d'un directeur d'hôpital et d'un économiste de la santé. RÉSULTATS: Dans les pays membres du G20, il existe une approche robuste communément adoptée pour l'approbation et la réglementation des produits biologiques ultérieurs. Par définition, ces agents ne présentent aucun avantage (sauf économique),ou désavantage particulier lorsqu'on les compare aux produits biologiques originaux, mais certaines préoccupations persistent quant à leur introduction sur le marché. Par ailleurs, lorsque les produits biologiques ultérieurs sont disponibles sur le marché, leur part de marché reste modeste et variable. LIMITES DE L'ÉTUDE: Nous n'avons pas fait l'acquisition de rapports en provenance de tiers contenant des données de commercialisation récentes. De plus, puisqu'il n'existe pas de produits biologiques ultérieurs sur le marché canadien à l'heure actuelle, l'information de cette revue n'est que de nature prédictive. IMPLICATIONS: L'ensemble des néphrologues auront à collaborer avec les organismes de régulation, les patients, et les contribuables afin d'assurer une utilisation efficace des produits biologiques ultérieurs. Des économies peuvent être réalisées, mais ces agents ne devront être utilisés qu'après avoir tout à fait compris les défis particuliers qu'ils présentent. En ce moment, ils ne peuvent pas remplacer automatiquement d'autres produits et ne devraient être utilisés que selon les recommandations officielles de Santé Canada. Ce n'est qu'en exerçant une bonne pharmacovigilance que les patients et prestataires de soins de santé deviendront mieux informés.

Efficacy and safety data of subsequent entry biologics pertinent to nephrology practice: a systematic review.

BACKGROUND: Subsequent entry biologics (SEBs) may soon be a reality in Canadian nephrology practice. Understanding the worldwide experience with these agents will be valuable to Canadian clinicians. OBJECTIVES: To compare the efficacy and safety data between SEBs used in nephrology practice and their reference biologic. DESIGN: Systematic review. SOURCES OF INFORMATION: Ovid MEDLINE, EMBASE, Cochrane Database of Systematic Reviews, Database of Abstracts of Review of Effects, Cochrane Central Register of Controlled Trials. PATIENTS: Adult patients with chronic kidney disease (CKD). METHODS: Our systematic review follows the process outlined by Cochrane Reviews. For efficacy data, all randomized controlled trials (RCTs), quasi-RCTs and observational trials in nephrology practice were included. For safety data, case series, case reports, review articles in nephrology practice and pharmacovigilance programs were included as well. RESULTS: Only epoetin SEBs trials were published in the literature. Ten studies involving three different epoetin SEBs (epoetin zeta, HX575 and epoetin theta) were included. The mean epoetin dose used did not differ significantly between the SEBs and the reference product. For epoetin zeta and epoetin theta, the mean hemoglobin levels achieved in the studies were similar between the SEBs and the reference epoetin. The HX 575 studies reported a mean absolute change in hemoglobin within the predefined equivalence margin, when compared with the reference biologic. In terms of safety data, 2 cases of pure-red-cell aplasia were linked to the subcutaneous administration of HX 575. Otherwise, the rate of adverse drug reactions was similar when epoetin SEBs were compared with the reference biologic. LIMITATIONS: Our analysis is limited by the paucity of information available on SEB use in nephrology with the exception of epoetin SEBs. Methodological flaw was found in one of the epoetin zeta studies which accounted for 45% of pooled results. CONCLUSIONS: Little clinical difference was found between epoetin SEBs and the reference product. Although not deemed clinically important, the financial implication of a possible dose difference between epoetin zeta and reference product should be considered in pharmacoeconomic studies. Ongoing trials are expected to address the risk of pure-red-cell aplasia with HX 575.

CONTEXTE: Il est possible que les produits biologiques ultérieurs (PBU) soient bientôt utilisés en néphrologie. Afin de guider la pratique en néphrologie au Canada, il est important de comprendre l'ensemble des expériences produites, à l'échelle mondiale, en matière d'efficacité et d'innocuité de ces agents. OBJECTIFS: Comparer les données relatives à l'efficacité et l'innocuité entre les PBU utilisés en néphrologie et leurs médicaments biologiques de référence. TYPE D'ÉTUDE: Revue systématique. SOURCES DE DONNÉES: La recherche en vue de la revue de littérature a été effectuée en interrogeant les bases de données suivantes : Ovid Medline, Embase, la base de données de revues systématiques Cochrane Reviews, la Database of Abstracts of Reviews of Effects, et la Cochrane Central Register Controlled Trials. PATIENTS: Les patients d'âge adulte atteints de néphropathie chronique. MÉTHODES: Notre revue systématique suit la méthode suggérée par la Collaboration Cochrane (Cochrane Reviews). Pour les données se rapportant à l'efficacité, l'ensemble des essais randomisés contrôlés (ERC) et des modèles quasi expérimentaux et des études observationnelles du domaine de la néphrologie ont été comptabilisés. Pour les données se rapportant à l'innocuité, tous les ERC, les modèles quasi expérimentaux, les études observationnelles, les études ou séries de cas, ainsi que les revues d'articles en néphrologie clinique et de programmes en pharmacovigilance ont été comptabilisés. RÉSULTATS: Nous nous sommes attardés à l'époétine biologique ultérieure, puisqu'aucune documentation sur d'autres produits biologiques ultérieurs (PBU) n'était disponible. Nous avons utilisé dix études présentant trois époétines biologiques ultérieures différentes (époétine zeta, époétine HX575 et époétine thêta). Il n'existait pas de différence significative entre les doses moyennes des PBU et d'époétine biologique de référence. La dose moyenne d'époétine utilisée ne variait pas de façon significative entre les PBU et le produit de référence. Pour les époétines zeta et thêta, les taux moyens d'hémoglobine obtenus dans les diverses études entre les PBU et les époétines de référence étaient similaires. Les études se rapportant à l'époétine HX575 montraient un changement absolu du taux moyen d'hémoglobine à l'intérieur de l'intervalle d'équivalence prédéfini, lorsque comparé au médicament biologique de référence. En ce qui concerne les données d'innocuité, deux cas d'érythroblastopénie chronique acquise ont été liés à l'administration sous-cutanée de l'époétine HX575. Sinon, les taux d'effets indésirables recensés pour l'époétine biologique ultérieure et son médicament biologique de référence étaient similaires. LIMITES DE L'ÉTUDE: Notre analyse est limitée par la rareté de l'information accessible sur l'utilisation des PBU en néphrologie, à l'exception de l'époétine biologique ultérieure. Une faille sur le plan méthodologique a été retrouvée dans une des études sur l'époéine zeta. Celle-ci se rapportait à 45 % des résultats regroupés. CONCLUSIONS: Peu de différences sur le plan clinique ont été trouvées entre l'époétine biologique ultérieure et l'époétine de référence. Même si elles ne sont pas cliniquement significatives, les répercussions financières qui sont entraînées par la possible différence de dose entre l'époétine zeta et le produit de référence devraient être considérées dans les études pharmacoéconomiques. Il existe certaines préoccupations entourant les risques d'érythroblastopénie chronique acquise et l'époétine HX575, mais des essais présentement en cours tentent de faire le tour de la question. WHAT WAS KNOWN BEFORE: SEBs pertinent to nephrology practice are available commercially in other countries. Epoetin SEBs have been compared with reference epoetins in clinical studies involving CKD patients. WHAT THIS ADDS: This systematic review summarizes the efficacy data comparing epoetin SEBs to the reference epoetins in patients with CKD and provides an overview of the European experience in terms of safety data for epoetin SEBs. No other SEBs pertinent to nephrology practice have published data as yet.

Multi-intervention management of calciphylaxis: a report of 7 cases.

Calcific uremic arteriolopathy (calciphylaxis) is a devastating but rare complication seen predominantly in dialysis patients that often is fatal. Because of the rarity of the disease and the multifactorial nature of its cause, no clinical trials have been conducted to date to determine the best therapy for the condition. We report a case series of 7 patients at a single institution in whom a systematic multi-interventional treatment strategy was implemented, consisting of trigger-agent cessation (calcium-based phosphate binders, alphacalcidol, and warfarin), wound management, and antibiotic therapy, supplemented by intensified hemodialysis (4 hours daily for 7 days followed by 5-6 times weekly), intravenous sodium thiosulfate (12.5-25 g intravenously 3 times a week), and attempted oxygen therapy (given through a face mask or hyperbaric chamber as tolerated by patient circumstance). Treatments selected were based on literature review, consensus discussion, and attempts to address the physiologic disturbances that underlie the condition. All 7 patients identified with biopsy-proven calcific uremic arteriolopathy were treated with this regimen in 2007-2010, with 6 of 7 showing complete recovery. We suggest that consistent implementation of a multi-interventional approach may alter the course of this devastating disease. Further studies are needed to confirm and extend these findings.

Evaluation of anemia management by algorithms in patients with chronic kidney disease who are not receiving dialysis.

BACKGROUND: Anemia commonly develops in patients with chronic kidney disease and is strongly associated with adverse clinical outcomes. There are currently no published studies evaluating the efficacy of a nurse-driven anemia-management protocol for patients with chronic kidney disease who are not receiving dialysis. OBJECTIVES: To evaluate the efficacy of an anemia-management protocol in terms of achieving hemoglobin and transferrin saturation levels within the target range, as well as associated utilization of medications, relative to individualized dosing of medications by nephrologists. METHODS: An algorithm for nurse-driven management of anemia was introduced in April 2009 at a kidney function clinic in a large urban centre. The charts of patients with chronic kidney disease who were not undergoing dialysis were reviewed before (July to December 2007) and after (July to December 2009) implementation of the protocol. Patients' data for hemoglobin, transferrin saturation, and doses of iron and erythropoiesis-stimulating agents were collected for each of the 6-month study periods. RESULTS: In total, 390 patients were treated for anemia before and 434 patients after introduction of the protocol. The anemia-management protocol was non-inferior to individualized dosing for maintenance of hemoglobin levels within the target range of 110-120 g/L: percentage of measured levels within target range 33.3% (485/1456) before versus 34.2% (504/1472) after (absolute difference 0.9 percentage points, 95% confidence interval [CI] -2.5 to 4.4). The criteria for non-inferiority were not met for maintenance of transferrin saturation within the target range of 22%-50%: percentage of levels within target range 58.8% (374/636) before versus 56.9% (403/708) after (absolute difference 1.9 percentage points, 95% CI -3.4 to 7.2). There were no statistically significant differences in mean doses of epoetin alfa, darbepoetin, or iron before and after introduction of the protocol. Similarly, there were no statistically significant differences in number of dose changes for epoetin alfa, darbepoetin, or iron. CONCLUSION: The nurse-driven anemia-management protocol was non-inferior to dosing by nephrologists in terms of managing hemoglobin levels. It would be reasonable to use an anemia-management protocol for patients with chronic kidney disease who are not receiving dialysis.

Best possible medication history for hemodialysis patients obtained by a pharmacy technician.

BACKGROUND: Outpatients undergoing hemodialysis are at high risk for adverse drug events. Limited resources make it challenging for pharmacists to routinely obtain a best possible medication history (BPMH). OBJECTIVES: The primary objective was to determine whether, for patients undergoing hemodialysis, a pharmacy technician has the skills to obtain a BPMH that would allow a pharmacist to identify drug-related problems. The secondary objectives were to determine the number and types of medication discrepancies and drug-related problems identified and the time required by the technician to complete the BPMH. METHODS: All patients treated in the hemodialysis unit during the study period were included, except for those who required an interpreter or were unable to participate in an in-person interview. A single technician was taught how to interview patients according to a structured format. For each patient, the technician's BMPH was verified by a pharmacist. The agreement rate between technician and pharmacists was determined, along with the number and types of discrepancies and drug-related problems identified. RESULTS: The technician interviewed 99 patients. Of the 1334 medication orders reviewed, the technician and pharmacists agreed on all but 15 (agreement rate 98.9%). A total of 358 medication discrepancies were noted for 93 patients (3.8 discrepancies per patient). Of these, 210 (59%) were undocumented intentional discrepancies, and 148 (41%) were unintentional discrepancies (most commonly errors of commission). Of the 135 drug-related problems identified, the majority involved dosing problems or nonadherence. The technician required an average of 17 min for each interview. CONCLUSION: An adequately trained technician was capable of interviewing patients to create a BPMH. A variety of medication discrepancies and drug-related problems were identified. Generation of a BPMH by a technician is a useful approach allowing pharmacists to identify drug-related problems.

Utility of anti-xa monitoring in children receiving enoxaparin for therapeutic anticoagulation.

Although enoxaparin is used to treat thromboembolism in children, current treatment guidelines are largely extrapolated from adults. The objectives of this study were to determine: i) correlation between enoxaparin dose and anti-factor Xa (anti-Xa) level, ii) intra-patient variability, and iii) whether dose or anti-Xa level is a predictor of outcomes. A retrospective chart review was conducted on all hospitalized patients receiving enoxaparin in a tertiary care pediatric institution. Simple linear regression, coefficient of variation (CV), and Student's t-test were used to analyze the objectives. Eighty treatment courses with interpretable anti-Xa levels were analyzed. Mean patient age was 6.5 years. Mean enoxaparin dose was 1.10 mg/kg q12h. Correlation between initial dosing and anti-Xa level was poor; R(2) = 0.0307 and 0.0237 for patients > 2 months with and without cardiac or renal diseases, respectively. Four out of seven patients ≤ 2 months of age compared to 4/32 patients > 2 months had a CV > 40%. Similarly, 4/12 cardiac patients compared to 4/27 non-cardiac patients had a CV > 40%. Neither dose nor anti-Xa level predicted treatment success or adverse reactions (P > .05). These results suggest a need to reexamine the use of anti-Xa levels for guiding enoxaparin therapy. Further prospective studies are warranted to clarify whether routine or selective anti-Xa monitoring should be recommended in pediatric patients.

Patient characteristics associated with nonprescription drug use in intentional overdose.

OBJECTIVE: Over-the-counter (OTC) medications remain freely available to suicidal patients, despite their potential lethality and common use in suicide. The study's main objective was to identify patient characteristics, particularly psychiatric diagnosis associated with the use of OTC medications in intentional overdose. METHODS: We retrospectively reviewed 95 charts from patients who presented to St Paul's Hospital from August 1, 1997, to July 31, 1998, with a discharge diagnosis of intentional drug overdose. Univariate analysis was carried out to identify potential risk markers for OTC medication use, and logistic regression was performed using these variables. RESULTS: When the variables age, sex, and concurrent psychiatric diagnoses were controlled, use of OTC medications in overdose was significantly lower in patients with a DSM-IV diagnosis of substance abuse (OR 0.11, P = 0.005) and in those who possessed prescription medications at the time of overdose (OR 0.18, P = 0.007). Most patients in this cohort (82%) had at least 1 of these 2 traits. Although not statistically significant, younger patients appeared more likely to choose OTC medications for overdose. CONCLUSION: Suicide-prone patients with a diagnosis of substance abuse and who possess prescription medications are unlikely to use OTC medications in overdose. For this cohort, this represents a relatively small proportion of patients whom clinicians should consider to be at greater risk for attempting suicide when using OTC medication, especially acetaminophen.

Pretreatment with ibuprofen to prevent electroconvulsive therapy-induced headache.

BACKGROUND: Although electroconvulsive therapy (ECT) has been widely recognized as an effective treatment for severe depression and various other psychiatric illnesses, adverse effects have been frequently reported, especially a high incidence of headache. Analgesics, such as acetaminophen, narcotics, or nonsteroidal anti-inflammatory drugs (NSAIDs), are commonly used to treat ECT-induced headache. The objective of this study was to determine whether pretreatment with ibuprofen would prevent the onset or decrease the severity of headache that occurs after ECT. METHOD: All inpatients on the psychiatric units who required ECT treatment were asked to participate in the study. Thirty-four patients were randomly assigned to receive either ibuprofen, 600 mg, or placebo orally 90 minutes prior to the initial ECT session, with the alternate treatment given for the second ECT treatment. Patients were asked to complete a questionnaire prior to and after the first 2 ECT treatments regarding the pattern, severity, and onset of headache. Severity of the headache was measured on a visual analogue scale (VAS). RESULTS: Ten patients experienced headache in neither treatment arm, while 7 patients experienced headache in both treatment arms. Eleven patients experienced headache with placebo but not with ibuprofen, while 2 patients experienced headache with ibuprofen but not with placebo. Ibuprofen was significantly more effective than placebo in preventing the onset of headache post-ECT (p =.022). The mean +/- SD VAS headache scores were 1.49 +/- 1.54 and 0.54 +/- 0.91 in the placebo and ibuprofen arms, respectively. Ibuprofen was significantly more effective than placebo in reducing the severity of ECT-induced headache (p =.007). CONCLUSION: Ibuprofen premedication reduced the frequency and severity of headache post-ECT and should be considered for appropriate patients who suffer from ECT-induced headache.