Characterization of the Benefits and Risks of Therapeutic Anticoagulation in Patients Admitted with Severe COVID-19 (CRITAC).

Background: Severe COVID-19 is associated with increased rates of thrombotic complications. Recent provincial recommendations in British Columbia have suggested providing thromboprophylaxis with therapeutic anticoagulation for hospital inpatients with severe COVID-19 who do not have a high risk of bleeding. Objectives: To characterize the rates of major bleeding, thrombotic events, complications from COVID-19, and adverse effects among patients with severe COVID-19 treated with therapeutic anticoagulation. Methods: This retrospective chart review involved patients with laboratory-confirmed COVID-19 who were admitted to 3 sites within a local health authority between April 1 and December 31, 2021, and received therapeutic anticoagulation for thromboprophylaxis. Results: After screening of 1036 patients, 72 patients were included in the study. The mean age of participants was 54 years, 63% (n = 45) were male, and 92% (n = 66) were receiving supplemental oxygen by nasal prongs on admission. The primary outcome, major bleeding, was experienced by 1 patient (1%). Increasing oxygen requirements resulting in progression to high-flow nasal cannula occurred in 11 patients (15%), and 5 patients (7%) required admission to the intensive care unit. One patient (1%) experienced a thrombotic event, and 1 patient (1%) had a minor bleed. The mean duration of hospitalization was 10 (standard deviation 10.8) days. One death occurred during the study period, and no cases of heparin-induced thrombocytopenia were observed. Conclusions: In this study of hospital inpatients with severe COVID-19 who were deemed to be at low risk of bleeding and who received therapeutic anticoagulation, there were low rates of both major bleeding and thrombotic events.

Contexte: Les cas graves de COVID-19 sont associés à des taux accrus de complications thrombotiques. De récentes recommandations provinciales en Colombie-Britannique proposent de fournir une thromboprophylaxie avec anticoagulation thérapeutique aux patients hospitalisés atteints d'une forme grave de COVID-19 qui ne présentent pas un risque élevé de saignement. Objectifs: Caractériser les taux d'hémorragies majeures, d'événements thrombotiques, de complications découlant de la COVID-19 et d'effets indésirables chez les patients atteints de COVID-19 sévère traités par anticoagulation thérapeutique. Méthodes: Cette revue rétrospective des dossiers portait sur des patients atteints de COVID-19 confirmée en laboratoire qui ont été admis dans 3 sites au sein d'une autorité sanitaire locale entre le 1er avril et le 31 décembre 2021 et qui ont reçu une anticoagulation thérapeutique pour la thromboprophylaxie. Résultats: Après la présélection de 1036 patients, 72 ont été inclus dans l'étude. L'âge moyen des participants était de 54 ans, 63 % (n = 45) étaient des hommes et 92 % (n = 66) recevaient un supplément d'oxygène par sonde nasale à l'admission. Le critère de jugement principal, une hémorragie majeure, a été observé chez 1 patient (1 %). Une augmentation des besoins en oxygène entraînant une progression vers une canule nasale à haut débit s'est produite chez 11 patients (15 %) et 5 patients (7 %) ont dû être admis à l'unité de soins intensifs. Un patient (1 %) a présenté un événement thrombotique et 1 patient (1 %) a eu un saignement mineur. La durée moyenne d'hospitalisation était de 10 jours (écart type 10,8). Un décès est survenu au cours de la période d'étude et aucun cas de thrombocytopénie induite par l'héparine n'a été observé. Conclusions: Dans cette étude portant sur des patients hospitalisés atteints d'une forme grave de COVID-19, considérés comme présentant un faible risque de saignement et ayant reçu une anticoagulation thérapeutique, les taux d'hémorragies majeures et d'événements thrombotiques étaient faibles.

Evaluating a Pharmacist-Initiated Care Bundle for Patients with Chronic Obstructive Pulmonary Disease.

Background: Chronic obstructive pulmonary disease (COPD) is a cause of significant morbidity and mortality, and management of patients with this complex disease remains a challenge. Pharmacists work within an interdisciplinary health care team to coordinate services and ensure that standards of care are met. A pharmacist-initiated care bundle provided in the outpatient setting has shown promising results in improving COPD management. Objective: To evaluate, in the acute care setting, the effectiveness of a pharmacist-initiated COPD care bundle in improving compliance with health care measures known to improve outcomes in patients with COPD. Methods: This retrospective chart review included patients with acute exacerbation of COPD admitted from May 14, 2019, to February 29, 2020. Completion rates for the 6 individual components of the COPD care bundle were compared between patients who did and did not receive the pharmacist-initiated intervention. A subgroup of 22 patients received the following additional interventions: documentation of the modified Medical Research Council score, assessment of COPD medications, and vaccination review and administration. Results: A total of 106 patients were included in the analysis, 53 patients in each of the control and intervention groups. The pharmacist-initiated intervention increased completion rates for the overall COPD care bundle from 2% to 17% (p = 0.003), for provision of the COPD flare-up action plan from 4% to 79% (p < 0.001), and for provision of smoking cessation education from 0% to 36% (p = 0.04); however, there was no significant difference in assessment by a respiratory therapist. For the subgroup that received additional interventions, vaccination reviews were conducted for 21 (96%) of the 22 patients, which led to 9 (41%) receiving a guideline-recommended vaccine. Conclusions: Pharmacist involvement in initiation of the care bundle significantly increased completion rates for the activities included in the care bundle.

Contexte: La maladie pulmonaire obstructive chronique (MPOC) est une cause d'une morbidité et d'une mortalité importantes, et la prise en charge des patients atteints de cette maladie complexe demeure un défi. Les pharmaciens travaillent au sein d'une équipe interdisciplinaire de soins de santé pour coordonner les services et s'assurer du respect des normes de soins. Un ensemble de soins initié par le pharmacien en milieu ambulatoire a donné des résultats prometteurs dans l'amélioration de la prise en charge de la MPOC. Objectif: Évaluer, dans le cadre des soins aigus, l'efficacité d'un ensemble de soins pour la MPOC initié par un pharmacien pour améliorer le respect des mesures de soins de santé connues pour améliorer les résultats chez les patients atteints de MPOC. Méthodes: Cet examen rétrospectif des dossiers comprenait des patients présentant une exacerbation aiguë de la MPOC admis du 14 mai 2019 au 29 février 2020. Les taux de réussite pour les 6 composantes individuelles de l'ensemble de soins pour la MPOC ont été comparés entre les patients ayant reçu et ceux n'ayant pas reçu l'intervention initiée par le pharmacien. Un sous-groupe de 22 patients a reçu des interventions supplémentaires : documentation du score modifié du Medical Research Council (mMRC), évaluation des médicaments pour la MPOC, et examen et administration de la vaccination. Résultats: Au total, 106 patients ont été inclus dans l'analyse : 53 patients dans le groupe de contrôle et 53 dans le groupe d'intervention. L'intervention initiée par le pharmacien a augmenté les taux d'adhésion à l'ensemble de soins pour la MPOC de 2 % à 17 % (p = 0,003), de 4 % à 79 % (p < 0,001) pour l'offre du plan d'action en cas de poussée de MPOC et de 0 % à 36 % (p = 0,04) pour l'éducation au sevrage tabagique; cependant, l'évaluation par un inhalothérapeute n'a permis de déceler aucune différence significative. Dans le sous-groupe ayant reçu des interventions supplémentaires, des examens de vaccination ont été menés chez 21 (96 %) des 22 patients; 9 patients (41 %) ont ainsi reçu un vaccin recommandé par les lignes directrices. Conclusions: La participation du pharmacien à l'initiation de l'ensemble de soins a augmenté de manière significative les taux de réussite des activités incluses dans l'ensemble de soins.

Assessing the clinical utilization of tranexamic acid by paramedics for patients with major trauma (ACUTE).

OBJECTIVES: This study aimed to characterize the clinical utilization of tranexamic acid (TXA) by paramedics in British Columbia (BC) for acute major trauma and to quantify the percentage of patients who received TXA among those who met the indications for administration. METHODS: A quality assurance review of eligible trauma patients across the province was performed using a convenience sample. Trauma patients between April 1, 2016 and March 31, 2017 with suspected or actual hemorrhage were selected if they met inclusion criteria (systolic blood pressure < 90 mm Hg ± heart rate > 120 beats per minute) and exclusion criteria (age < 16 years, injuries exclusively to the extremities). RESULTS: 35 of the 100 eligible patients assessed in this review received a dose of TXA from paramedics. All 35 of the patients received TXA within 180 min of injury regardless of their original location of injury in BC (mean: 50 min; range: 15-140 min). CONCLUSIONS: 35% of eligible patients identified in this study received TXA, which is an improvement over rates cited by previous Canadian literature. With further education opportunities for paramedics in BC and other EMS systems, there is potential to continue improving pre-hospital TXA administration rates.

RéSUMé: OBJECTIFS: Cette étude visait à caractériser l'utilisation clinique de l'acide tranexamique (TXA) par les ambulanciers paramédicaux de la Colombie-Britannique pour les traumatismes aigus majeurs et à quantifier le pourcentage de patients qui ont reçu du TXA parmi ceux qui répondaient aux indications d'administration. MéTHODES: Un examen de l'assurance qualité des patients traumatisés admissibles dans toute la province a été effectué à l'aide d'un échantillon de commodité. Les patients traumatisés entre le 1er avril 2016 et le 31 mars 2017 présentant une hémorragie suspectée ou réelle ont été sélectionnés s'ils répondaient aux critères d'inclusion (pression artérielle systolique < 90 mm Hg ± fréquence cardiaque > 120 battements par minute) et aux critères d'exclusion (âge < 16 ans, blessures exclusivement aux extrémités). RéSULTATS: 35 des 100 patients admissibles évalués dans le cadre de cet examen ont reçu une dose de TXA des ambulanciers paramédicaux. Les 35 patients ont tous reçu du TXA dans les 180 min suivant la blessure, quel que soit le lieu de leur blessure initiale en Colombie-Britannique (moyenne: 50 min; intervalle: 15 à 140 min). CONCLUSIONS: 35% des patients admissibles identifiés dans le cadre de cette étude ont reçu du TXA, ce qui représente une amélioration par rapport aux taux cités dans les publications canadiennes précédentes. Grâce aux possibilités de formation continue pour les ambulanciers en Colombie-Britannique et dans d'autres systèmes d'Aide médicale urgente (AMU), il est possible de continuer à améliorer les taux d'administration de la TXA en milieu préhospitalier.

Risk Evaluation for Antipsychotic Agents Used in Elderly Inpatients (REPAIR).

BACKGROUND: Antipsychotics have been approved for the treatment of certain psychiatric illnesses. However, these medications are also frequently used off label, and recent studies have suggested a concerning potential increase in the risk of death when used by elderly patients with dementia. Most of the available literature focusing on off-label use of antipsychotics comes from long-term care facilities; there is a lack of quantitative data for elderly patients in the acute care setting. This study was designed to examine this scenario and to identify potential quality improvement opportunities to minimize harm. OBJECTIVES: The primary objectives were to determine the prevalence of hospital-initiated off-label use of antipsychotics for elderly inpatients and to determine the plan for these drugs upon discharge. The secondary objectives included identifying the most common diagnosis and the most common agent used. METHODS: A retrospective cohort study was performed with a convenience sample. Patients included in the analysis were elderly adults (≥ 65 years) who had been admitted to either of 2 medical units at a community hospital between September 1 and November 8, 2014. Descriptive statistics were used to examine prevalence patterns for the off-label use of antipsychotics. RESULTS: A total of 250 patients were included in the analysis. Forty-five patients (18%, 95% confidence interval [CI] 13.7%-23.2%) received a hospital-initiated antipsychotic for off-label use during the admission. For 27 (60%, 95% CI 45.5%-73.0%) of these 45 patients, the off-label therapy was discontinued upon discharge or death, and for 13 (29%, 95% CI 17.7%-43.4%), the agent was continued upon discharge without a plan in place. The most frequent diagnosis was delirium, and the agent most frequently used was haloperidol. CONCLUSIONS: Off-label antipsychotic therapy was initiated for almost 1 in every 5 elderly patients receiving care in 2 medical units at a community hospital. These findings suggest a need to monitor and reassess the off-label use of these agents, especially at the time of discharge.

CONTEXTE: Les antipsychotiques ont été approuvés pour le traitement de certains troubles psychiatriques. Or, ces médicaments sont aussi fréquemment utilisés en dérogation des directives de l'étiquette et des études récentes ont supposé une potentielle augmentation préoccupante du risque de décès lorsqu'ils sont employés pour traiter des patients âgés atteints de démence. La majeure partie de la littérature portant sur l'emploi non conforme d'antipsychotiques provient de centres d'hébergement et de soins de longue durée. Or, on constate un manque de données quantitatives sur les patients âgés dans les milieux de soins de courte durée. La présente étude a été conçue pour examiner ce scénario et découvrir de potentielles occasions d'amélioration de la qualité en vue de réduire au minimum les risques de préjudice. OBJECTIFS: Les objectifs principaux étaient de déterminer la prévalence de l'emploi non conforme d'antipsychotiques amorcé à l'hôpital chez les patients aînés et de déterminer le plan relatif à la prescription de ces médicaments au moment du congé. Les objectifs secondaires incluaient de déterminer quels étaient le diagnostic le plus fréquent et le médicament le plus utilisé. MÉTHODES: Une étude de cohorte rétrospective a été menée à l'aide d'un échantillon de commodité. Les patients retenus pour l'analyse étaient des personnes âgées (de 65 ans et plus) ayant été admises à l'une des deux unités médicales dans un hôpital communautaire entre le 1er septembre et le 8 novembre 2014. Des statistiques descriptives ont été employées pour analyser les modèles de prévalence en ce qui concerne l'emploi non conforme d'antipsychotiques. RÉSULTATS: Au total, 250 patients ont été retenus pour l'analyse. Pendant l'hospitalisation, un antipsychotique a été amorcé hors conformité chez 45 patients (18 %, intervalle de confiance [IC] de 95 % de 13,7 % à 23,2 %). Pour 27 (60 %, IC de 95 % de 45,5 % à 73,0 %) de ces 45 patients, le traitement non conforme a été arrêté au moment du congé et, pour 13 autres (29 %, IC de 95 % de 17,7 %­43,4 %), le traitement a été poursuivi au congé sans mise en place d'un plan. Le diagnostic motivant le plus souvent l'emploi non conforme de ces médicaments était le délire et le médicament le plus employé était l'halopéridol. CONCLUSIONS: Le traitement non conforme par antipsychotique a été amorcé pendant le séjour à l'hôpital pour près d'un patient âgé sur cinq qui recevait des soins dans l'une des deux unités médicales d'un hôpital communautaire. Ces résultats laissent croire qu'une surveillance de l'emploi non conforme de ces médicaments et qu'une réévaluation d'un tel traitement sont nécessaires, particulièrement au moment du congé.

Systematic Review of Efficacy, Pharmacokinetics, and Administration of Intraventricular Aminoglycosides in Adults.

Due to increasing prevalence of intracranial device use and multidrug-resistant and nosocomial organisms, central nervous system (CNS) infections requiring treatment with intraventricular (IVT) aminoglycosides are becoming increasingly common. This article systematically reviews IVT aminoglycoside literature in adults and integrates available evidence to serve as a practical reference for clinicians. Medline (1946 to December 2015), Embase (1974 to December 2015), PubMed (1966 to December 2015), Google, and Google Scholar were searched using the term aminoglycoside combined individually with the terms IVT, meningitis, shunt infection, ventriculitis, and cerebral spinal fluid. Eighteen articles were included. IVT aminoglycosides were assessed in meningitis, ventriculitis, intracranial device infections and neurosurgery prophylaxis. No serious adverse effects following IVT aminoglycoside were reported. Dosages ranged from IVT gentamicin 4-10 mg daily, IVT tobramycin 5-10 mg daily, and IVT amikacin 5-50 mg daily. Duration of therapy should be individualized; however, continuing IVT antibiotics for 3 days and up to 21 days after cerebrospinal fluid (CSF) sterilization has been reported in literature. Most studies included concomitant intravenous antibiotic use. Therapeutic drug monitoring (TDM) was reported in five studies, with varying timing of CSF concentrations obtained. No clear relationship between CSF levels and efficacy or toxicity was evident. Based on current literature, IVT aminoglycosides for the treatment of sensitive gram-negative meningitis, ventriculitis, and CNS device-associated infections appear safe and effective. Optimal dosing regimens are unclear. It is reasonable to initiate IVT aminoglycoside at lowest dose in combination with IV therapy and continuing post CSF sterilization. Preservative-free formulations should be utilized to minimize adverse drug reactions. TDM should not be routinely utilized but reserved for more complicated patients. Further pharmacokinetic and clinical trials of IVT aminoglycosides are necessary to fill current therapeutic gaps. Due to the relatively limited cases of IVT aminoglycoside utilization, prospective, randomized, controlled trials are likely not feasible, and clinicians will have to rely on data from non-randomized and/or retrospective studies.

Evaluating outcomes of alternative dosing strategies for cefepime: a qualitative systematic review.

OBJECTIVE: To perform a qualitative systematic review of the evidence comparing traditional with prolonged intermittent or continuous infusions of cefepime based on clinical and pharmacodynamic outcomes. DATA SOURCES: PubMed (1946 to October 2014), EMBASE (1980 to October 2014), CENTRAL, Cochrane Database of Systematic Reviews, Web of Science, and International Pharmaceutical Abstracts (1970 to October 2014) were searched using the terms cefepime, pharmacokinetics, pharmacodynamics, drug administration, intravenous infusions, intravenous drug administration, continuous infusion, extended infusion, and intermittent therapy. Reference lists from relevant materials were reviewed. STUDY SELECTION AND DATA EXTRACTION: Articles evaluating administration regimens of cefepime, one of which included the traditional, manufacturer-recommended 0.5-hour infusion and the other a prolonged or continuous infusion were included. Prespecified clinical outcomes of interest included all-cause mortality, length of hospital stay, clinical cure, and adverse events. The primary pharmacodynamic outcome was percentage time of unbound drug concentration remaining above the minimum inhibitory concentration. DATA SYNTHESIS: In all, 18 studies were included; 6 studies assessed clinical outcomes, and 12 assessed pharmacodynamic outcomes. Prolonged or continuous infusions of cefepime achieved the pharmacodynamic targets more often than traditional infusions. The association of improved clinical outcomes with prolonged or continuous infusions is unclear. All-cause mortality was significantly decreased with the use of a prolonged cefepime infusion in a retrospective study. Two prospective, randomized studies demonstrated no statistically significant difference in mortality between prolonged and intermittent infusions. CONCLUSIONS: The available literature on prolonged and continuous infusions of cefepime demonstrated an improved achievement of pharmacodynamic targets; however, the effect on clinical outcomes is inconclusive. Well-designed prospective studies are required to determine optimal dosing and administration strategies.

Feasibility of ASsisTed WARfarin Dosing by Clinical Pharmacy Support Assistants (FAST-WARD Study).

BACKGROUND: Pharmacy-managed warfarin dosing has been established at Burnaby Hospital, in Burnaby, British Columbia, for over 10 years. With increases in the number and acuity of patients enrolled, it has become challenging to maintain a successful anticoagulation program. The clinical pharmacy support assistant (CPSA) program was initiated to support the provision of clinical pharmacy services. At the time of the study, Burnaby Hospital had 2 CPSAs. It was anticipated that the pharmacy-managed inpatient warfarin dosing service might benefit from support through the CPSA program to maintain a consistent level of delivery. OBJECTIVE: To examine the feasibility of CPSAs supporting the pharmacy-managed inpatient warfarin dosing service at Burnaby Hospital. Feasibility was based on 4 key parameters: knowledge base, accuracy of data collection, dosage recommendations, and time spent on the process. METHODS: An observational, prospective pilot study was conducted over 3 months. The CPSAs were given appropriate education and training, and their performance was assessed to determine the feasibility of CPSA-assisted warfarin dosing. The CPSAs had to achieve a priori target scores for each of the 4 parameters in order for CPSA-assisted warfarin dosing to be considered feasible. RESULTS: After the didactic sections, both CPSAs answered all review questions correctly. The accuracy of data collection (based on 60 patient encounters) was 98.3%. The warfarin regimens recommended by the CPSAs were similar to those recommended by the clinical pharmacists, with doses differing by a mean of 0.46 mg. For 39 (65%) of the 60 patient encounters, the dosing recommendations of CPSAs and clinical pharmacists were identical. The average time spent per patient encounter was 10.5 min. CONCLUSION: With appropriate training and education, it is feasible for CPSAs to support the pharmacy-managed inpatient warfarin dosing program at Burnaby Hospital.

CONTEXTE: Un programme d'ajustement posologique de la warfarine géré par le pharmacien est en place à l'hôpital Burnaby depuis plus de 10 ans. Comme le nombre de patients inscrits au programme s'accroît et que la gravité des cas augmente, il est maintenant difficile pour le programme d'anticoagulothérapie de conserver le même niveau de performance. Le programme d'assistant au soutien de la pharmacie clinique (ASPC) a été mis en place dans le but de soutenir la prestation de services de pharmacie clinique. Au moment de l'étude, l'hôpital Burnaby avait deux ASPC. Le service d'ajustement par le pharmacien de la posologie de la warfarine des patients hospitalisés pourrait bénéficier du soutien du programme d'ASPC afin de conserver un niveau de prestation uniforme. OBJECTIF: Étudier la possibilité pour les ASPC de soutenir le service d'ajustement par le pharmacien de la posologie de la warfarine des patients hospitalisés offert par l'hôpital Burnaby. La faisabilité était fondée sur quatre paramètres clés : la base de connaissances, l'exactitude de la collecte de données, les recommandations posologiques et le temps alloué au processus. MÉTHODES: Une étude pilote prospective observationnelle a été menée sur une période de trois mois. Les ASPC ont obtenu un enseignement et une formation adéquate et, suite à cela, leur travail a été évalué dans le but de déterminer si une aide à l'ajustement posologique de la warfarine est possible. Les ASPC devaient atteindre des scores prédéfinis a priori pour chacun des quatre paramètres pour que leur aide à l'ajustement posologique de la warfarine soit considérée comme faisable. RÉSULTATS: Après avoir participé aux volets didactiques, les deux ASPC ont répondu correctement à l'ensemble des questions d'évaluation. L'exactitude de la collecte de données (fondée sur 60 rencontres avec des patients) était de 98,3 %. Les schémas posologiques de warfarine recommandés par les assistants étaient semblables à ceux recommandés par les pharmaciens cliniciens et variaient en moyenne de 0,46 mg. Pour 39 (65 %) des 60 rencontres avec des patients, les recommandations posologiques des assistants étaient identiques à celles des pharmaciens cliniciens. Chaque rencontre durait en moyenne 10,5 minutes. CONCLUSION: À l'aide d'une formation et d'un enseignement adéquats, il est donc possible pour les ASPC de soutenir le programme d'ajustement par le pharmacien de la posologie de la warfarine des patients hospitalisés offert par l'hôpital Burnaby. [Traduction par l'éditeur].

Systematic review of efficacy, pharmacokinetics, and administration of intraventricular vancomycin in adults.

Central nervous system infections requiring treatment with intraventricular (IVT) vancomycin are becoming increasingly common with advent of intracranial devices and increasing prevalence of multi-drug resistant and nosocomial organisms. Administering vancomycin via IVT route bypasses the blood-brain barrier to allow localized and controlled delivery directly to the desired site of action, achieving high concentrations for more reliable bactericidal action. This article systematically reviews current literature on IVT vancomycin in adults, compiles current knowledge, and integrates available evidence to serve as a practical reference.Medline (1946-July 2012), Embase (1974-July 2012), and International Pharmaceutical Abstracts (1970-July 2012) were searched using terms vancomycin, intraventricular, shunt infection, cerebrospinal fluid, and intraventriculitis. Seventeen articles were included in this review. Indications for IVT vancomycin included meningitis unresponsive to intravenous antibiotics, ventriculitis, and intracranial device infections. No serious adverse effects following IVT vancomycin have been reported. Dosages reported in literature ranged from 0.075-50 mg/day, with the most evidence for dosages of 5 to 20 mg/day. Duration of therapy most commonly ranged from 7 to 21 days. Therapeutic drug monitoring was reported in 11 studies, with CSF vancomycin levels varying widely from 1.1 to 812.6 mg/L, without clear relationships between CSF levels and efficacy or toxicity. Using IVT vancomycin to treat meningitis, ventriculitis, and CNS device-associated infections appears safe and effective based on current evidence. Optimal regimens are still unclear, and dosing of IVT vancomycin requires intricate consideration of patient specific factors and their impact on CNS pathophysiology. Higher-quality clinical trials are necessary to characterize the disposition of vancomycin within CNS, and to determine models for various pathophysiological conditions to facilitate better understanding of effects on pharmacokinetic and pharmacodynamic parameters.

Assessment of clinical pharmacy interventions in the intensive care unit.

BACKGROUND: Clinical pharmacy services have been shown to reduce adverse drug events and health care costs. However, few studies have assessed their effect on patient outcomes in the intensive care unit (ICU). OBJECTIVE: To describe characteristics of ICU patients with documented pharmacist interventions and to evaluate the relationships between patients' complexity level and pharmacists' interventions and between pharmacists' interventions and mortality rate. METHODS: Inpatient records of admissions between January 1, 2004, and March 31, 2007, were analyzed to identify the presence of clinical pharmacy notes (CPNs). The characteristics of patients with and without CPNs were compared using descriptive statistics. For primary analysis of the association between patient complexity level and presence of CPNs, logistic regression modelling was performed to adjust for potential confounding. Logistic regression was also used to explore the possible association between CPNs and mortality. Finally, mortality analysis was carried out for patients with and without CPNs, with matching by complexity level. RESULTS: The main study cohort comprised 1561 patients: 333 (21.3%) with CPNs and 1228 (78.7%) with no CPNs. A greater proportion of those with a CPN had the highest complexity level: 295 (88.6%) of those with CPNs versus 660 (53.7%) of those with no CPNs. After adjustment for age and sex, the odds ratio for having a CPN among patients with complexity level 4 (relative to patients with lower complexity levels) was 8.20 (95% confidence interval 5.44-12.38). Mortality rates were not significantly different between the 2 groups: 26.7% (89/333) among patients with CPNs and 27.9% (343/1228) among those without CPNs (p = 0.66). After adjustment for age, sex, complexity level, and length of stay in the ICU, the presence of a CPN was not significantly associated with mortality. Mortality rates in the matched cohort (n = 1078) were also similar between patients with and without CPNs (89/333 [26.7%] and 226/745 [30.3%], respectively; p = 0.23), and the presence of a CPN was not significantly associated with mortality after adjustments for potential confounding factors. CONCLUSION: Documenting clinical pharmacy activities is essential for assessing pharmacists' impact on patient outcomes. These data suggest that ICU pharmacists prioritize clinical activities to care for the sickest patients.

CONTEXTE: Il a été montré que les services de pharmacie clinique réduisaient les événements indésirables liés aux médicaments et les coûts de soins de santé. En revanche, peu d'études ont évalué leurs effets sur les résultats thérapeutiques chez les patients des unités de soins intensifs (USI). OBJECTIF: Décrire les caractéristiques des patients des USI pour lesquels les pharmaciens avaient consignés des interventions et évaluer les liens entre le niveau de complexité de l'état des patients et les interventions des pharmaciens et entre les interventions des pharmaciens et le taux de mortalité. MÉTHODES: Les dossiers des patients hospitalisés entre le 1er janvier 2004 et le 31 mars 2007 ont été analysés à la recherche de notes de pharmaciens cliniciens (NPC). Les caractéristiques des patients dont le dossier comportait des NPC et de ceux dont le dossier n'en comportait pas ont été comparées au moyen de statistiques descriptives. L'analyse primaire de l'association entre le niveau de complexité de l'état des patients et la présence de NPC a été réalisée au moyen d'un modèle de régression logistique pour compenser les facteurs de confusion potentiels. Ce modèle a aussi été utilisé pour évaluer l'association possible entre les NPC et la mortalité. En dernier lieu, une analyse de mortalité a comparé les patients dont le dossier comportait des NPC à ceux dont le dossier n'en comportait pas, avec un appariement du niveau de complexité. RÉSULTATS: La principale cohorte de l'étude comptait 1561 patients : 333 (21,3 %) dont le dossier comportait des NPC et 1228 (78,7 %) dont le dossier n'en comportait pas. Une plus grande proportion des patients dont le dossier comportait des NPC présentaient le plus haut niveau de complexité : 295 (88,6 %) de ceux avec des NPC contre 660 (53,7 %) de ceux sans NPC. Après ajustement pour l'âge et le sexe, le risque relatif approché de NPC chez les patients présentant un niveau de complexité 4 (par rapport aux patients présentant un niveau de complexité moindre) était de 8,20 (intervalle de confiance à 95 % : 5,44 ­ 12,38). Les taux de mortalité n'étaient pas significativement différents entre les deux groupes : 26,7 % (89/333) chez les patients avec NPC et 27,9 % (343/1228) chez les patients sans NPC (p = 0,66). Après ajustement pour l'âge, le sexe, le niveau de complexité et la durée du séjour à l'USI, la présence d'une NPC au dossier n'était pas associée de façon significative à la mortalité. Les taux de mortalité au sein de la cohorte appariée (n = 1078) étaient également similaires entre les patients avec NPC et ceux sans NPC : respectivement 89/333 (26,7 %) et 226/745 (30,3 %) (p = 0,23); la présence d'une NPC n'a pas été associée de façon significative à la mortalité après ajustements pour les facteurs de confusion potentiels. CONCLUSION: La consignation des activités de pharmacie clinique est essentielle à l'évaluation de l'influence des pharmaciens sur les résultats cliniques pour les patients. Ces données suggèrent que les pharmaciens des USI accordent la priorité aux activités cliniques destinées aux soins des patients les plus malades. [Traduction par l'éditeur].

Validity Evidence for FASTHUG-MAIDENS, a Mnemonic for Identifying Drug-Related Problems in the Intensive Care Unit.

BACKGROUND: The mnemonic FASTHUG (Feeding, Analgesia, Sedation, Thromboembolic prophylaxis, Head of bed elevation, stress Ulcer prophylaxis, Glucose control) was developed by intensive care unit (ICU) physicians to ensure that key aspects of care are addressed during each patient encounter. Because this tool does not specifically target pharmacotherapy assessments, a modified version, FASTHUG-MAIDENS, was created, by changing the H to mean Hypoactive or Hyperactive delirium and adding M for Medication reconciliation; A for Antibiotics or Anti-infectives; I for Indications for medications; D for drug Dosing; E for Electrolytes, hematology, and other laboratory tests; N for No drug interactions, allergies, duplication, or side effects; and S for Stop dates. OBJECTIVE: To validate the use of FASTHUG-MAIDENS as a tool for identifying drug-related problems (DRPs) in the ICU. METHODS: This randomized, prospective validation study took place between January and May 2011 in the ICUs of 4 hospitals: 2 community-level ICUs and 2 tertiary referral ICUs. Each ICU had a dedicated ICU pharmacist and one or more pharmacy residents completing an ICU rotation as part of their pharmacy practice residency (total of 6 residents). The 6 pharmacy residents were randomly assigned to assess patients admitted to the ICU using FASTHUG-MAIDENS or standard monitoring practice. The mean proportion of DRPs per patient encounter identified by the residents (relative to DRPs identified by the ICU pharmacists) was the primary outcome, and the proportion of total DRPs identified in each group was assessed as a secondary end point. RESULTS: Pharmacy residents using the FASTHUG-MAIDENS mnemonic identified a significantly greater mean proportion of DRPs per patient encounter (73.2% versus 52.4%, p = 0.008) and a greater proportion of total DRPs (77.1% versus 52.5%, p < 0.001) than those assessing patients according to standard monitoring practice. CONCLUSION: In this sample, the mnemonic FASTHUG-MAIDENS was a useful tool to facilitate the capture of DRPs by pharmacy residents working in the ICU.

CONTEXTE: Le code mnémonique anglais FASTHUG (Feeding [alimentation], Analgesia [analgésie], Sedation [sédation], Thromboembolic prophylaxis [prophylaxie thromboembolique], Head of bed elevation [élévation de la tête du lit], stress Ulcer prophylaxis [prophylaxie des ulcères de stress], Glucose control [régulation de la glycémie]) a été imaginé par des médecins intensivistes pour s'assurer que certains aspects clés des soins sont pris en compte pour chaque consultation avec un patient. Comme cet outil ne vise pas spécifiquement les évaluations pharmacothérapeutiques, une version modifiée, FASTHUG-MAIDENS, a été créée, où l'on a remplacé le sens du H par Hypoactive or Hyperactive delirium (délire hypoactif ou hyperactif) et ajouté MAIDENS : Medication reconciliation (bilan comparatif des médicaments); Antibiotics or Anti-infectives (antibiotiques ou anti-infectieux); Indications for medications (indications des médicaments); drug Dosing (posologie des médicaments); Electrolytes, hematology and other laboratory tests (électrolytes, hématologie et autres épreuves de laboratoire); No drug interactions, allergies, duplication, or side effects (absence d'interactions médicamenteuses, d'allergies, de chevauchement ou d'effets secondaires); et Stop dates (dates de fin). OBJECTIF: Valider l'emploi du code mnémonique FASTHUG-MAIDENS comme outil pour dépister les problèmes pharmacothérapeutiques à l'unité des soins intensifs (USI). MÉTHODES: Cette étude de validation aléatoire et prospective a été menée entre janvier et mai 2011 dans les USI de quatre hôpitaux : deux USI de niveau communautaire et deux autres de référence de niveau tertiaire. Chaque USI possédait un pharmacien attitré et au moins un résident en pharmacie complétant un stage à l'USI dans le cadre de leur résidence en pratique pharmaceutique (pour un total de six résidents). Les six résidents en pharmacie ont été assignés au hasard pour évaluer les patients admis à l'USI au moyen du code FASTHUG-MAIDENS ou d'une méthode de suivi standard. Le pourcentage de problèmes pharmacothérapeutiques par consultation avec un patient cernés par les résidents (comparativement à ceux constatés par les pharmaciens intensivistes) était le principal paramètre d'évaluation et le pourcentage de problèmes pharmacothérapeutiques totaux relevés dans chaque groupe était le paramètre d'évaluation secondaire. RÉSULTATS: Les résidents en pharmacie qui ont utilisé le code mnémonique FASTHUG-MAIDENS ont cerné un pourcentage moyen significativement supérieur de problèmes pharmacothérapeutiques par consultation avec un patient (73,2 % contre 52,4 %, p = 0,008) et un pourcentage supérieur de problèmes pharmacothérapeutiques totaux (77,1 % contre 52,5 %, p < 0,001) que ceux qui ont évalué les patients au moyen d'une méthode de suivi standard. CONCLUSION: Dans cet échantillon, le code mnémonique FASTHUG-MAIDENS s'est révélé être un outil utile facilitant la détermination des problèmes pharmacothérapeutiques par les résidents en pharmacie travaillant dans une USI. [Traduction par l'éditeur].

The role of therapeutic drug monitoring of imatinib in patients with chronic myeloid leukemia and metastatic or unresectable gastrointestinal stromal tumors.

Imatinib mesylate is a tyrosine kinase inhibitor used as first-line treatment in Philadelphia chromosome-positive chronic myeloid leukemia (Ph+ CML) and metastatic or unresectable gastrointestinal stromal tumors (GIST). Therapeutic drug monitoring (TDM) for imatinib has been suggested to improve efficacy, assess compliance, and evaluate drug-drug interactions. Imatinib has proven efficacy in improving treatment response and survival in patients with Ph+ CML and GIST. Several analytical methods are available to quantify total plasma imatinib concentrations. A good relationship exists between total imatinib plasma concentrations and pharmacologic response. Clinical evaluation of pharmacologic response to imatinib alone may be insufficient given the long duration of therapy before clinical response in patients with Ph+ CML and GIST. Thus, the authors have used a previously published 9-step decision-making algorithm to evaluate the utility of TDM for imatinib. The suggested trough concentrations for improved complete cytogenetic or major molecular response in patients with Ph+ CML and improved time to progression for patients with GIST are >1000 and >1100 ng/mL, respectively. Imatinib exhibits interindividual pharmacokinetic variability. Increased apparent clearance of imatinib has been observed in chronic phase chronic myeloid leukemia and increased body weight. Decreased apparent clearance has been observed in renal impairment and patients on concomitant medications with potent inhibition of cytochrome P450 3A4. Duration of therapy in patients with Ph+ CML and GIST is lifelong. Based on the available evidence, TDM for imatinib may provide additional information on efficacy, compliance, and safety than clinical evaluation alone. Patients with suboptimal response to treatment, treatment failure, rare adverse events, drug interactions, or suspected nonadherence will attain the greatest benefit from TDM.

Evaluating outcomes associated with alternative dosing strategies for piperacillin/tazobactam: a qualitative systematic review.

OBJECTIVE: To perform a qualitative systematic review of the evidence comparing traditional strategies against prolonged intermittent or continuous infusion strategies for piperacillin/tazobactam, based on clinical and pharmacodynamic outcomes. DATA SOURCES: MEDLINE (1950-September 2011), EMBASE (1980-September 2011), and International Pharmaceutical Abstracts (1970-September 2011) were searched, using the terms piperacillin, tazobactam, pharmacokinetics, pharmacodynamics, dosing, and infusion. Reference lists from relevant publications were also reviewed. STUDY SELECTION AND DATA EXTRACTION: Articles evaluating the administration of piperacillin/tazobactam to adults and comparing at least 2 dosing regimens (1 of which included the traditional, manufacturer-recommended 30-minute infusion; the other, a prolonged or continuous infusion strategy) were included. Prespecified clinical outcomes of interest included mortality, clinical cures, and adverse events. The pharmacodynamic endpoint of interest was percent time of unbound drug concentration remaining above the minimum inhibitory concentration. DATA SYNTHESIS: Twelve studies were included in this review, 7 of which assessed clinical outcomes and 5 that assessed pharmacodynamic endpoints using Monte Carlo simulations. Prolonged or continuous infusions of piperacillin/tazobactam consistently achieved higher pharmacodynamic endpoints than did traditional infusions. The association of prolonged or continuous infusions with improved clinical outcomes, however, is unclear. Two retrospective studies found improved mortality rates with prolonged infusions (1 in a subgroup of patients with higher APACHE II [Acute Physiology and Chronic Health Evaluation II] scores), while another retrospective study found improved clinical cure rates with continuous infusions in patients with ventilator-associated pneumonia. These clinical benefits have not been substantiated in prospective randomized trials. No study has provided evidence of reduced adverse effects with prolonged or continuous infusions. CONCLUSIONS: The limited evidence available does not firmly support widespread adoption of administering piperacillin/tazobactam as prolonged intermittent or continuous infusions to improve clinical outcomes despite the achievement of higher pharmacodynamic targets in simulated studies. Retrospective studies indicate that critical care patients are the subgroup most likely to benefit from these dosing strategies. Well-designed prospective clinical trials are required to confirm potential benefits observed in retrospective studies.

Haloperidol dosing strategies in the treatment of delirium in the critically ill.

Delirium is the most common mental disturbance in critically-ill patients and results in significant morbidity and mortality. Haloperidol is a preferred agent for the treatment of delirium in this population because of its rapid onset of action and lack of hemodynamic effects. Despite its widespread use in the critical care setting, most of the relevant data are obtained from case series or extrapolated from non-critically-ill populations. This review provides an overview of haloperidol pharmacokinetics and a comprehensive summary of the evidence for various haloperidol dosing regimens in the treatment of delirium in critically-ill patients. A comprehensive literature search was conducted in Medline, Embase, and International Pharmaceutical Abstracts with "haloperidol", "delirium", "agitation", "critically-ill", and "intensive care" as keywords. Studies involving haloperidol for delirium prophylaxis, non-critical care settings, and terminally-ill subjects were excluded. Eleven studies were identified: four with intermittent IV haloperidol, four with continuous IV infusion haloperidol, two with oral/enteral haloperidol, and one with IM haloperidol. All of the case reports, case series, and descriptive studies have shown a benefit with haloperidol, but publication bias is likely present. Only three studies were controlled studies, but all had small sample sizes and methodological flaws. Randomized, double-blind, active-comparator trials of haloperidol with allocation concealment are needed. Subsequent research should focus on using validated delirium screening and assessment scales for more objective identification and measurement of delirium outcomes.

Analysis of Orders for QTc-Prolonging Medication for Intensive and Cardiac Care Unit Patients with Pre-existing QTc Prolongation (QTIPPP Study).

BACKGROUND: A prolonged QTc interval on electrocardiography is often used as a surrogate marker for ventricular arrhythmia. Medications that can prolong the QTc interval may increase the risk of cardiac complications, although the exact incidence is unknown. It is reasonable to assume that administration of QTc-prolonging medications to patients with pre-existing QTc prolongation will further increase the risk of cardiac consequences. This study was designed to examine the frequency of prescription of QTc-prolonging medications in such patients and to explore the potential for clinical pharmacists to minimize the associated risks. OBJECTIVES: The primary objective was to identify the number of patients with pre-existing prolonged QTc interval for whom QTc-prolonging medications were prescribed, from among all patients with orders for QTc-prolonging medications. The secondary objectives were to determine patterns of intervention by clinical pharmacists in these cases and to document any further QTc prolongation and occurrence of cardiac events. METHODS: A prospective, observational, quality assessment study was conducted over 4.5 months. Adult patients admitted to beds with cardiac monitoring by telemetry for whom one or more QTc-prolonging medications were ordered were eligible for inclusion. Patients were included if the QTc interval was longer than 450 ms on the most recent 12-lead electrocardiogram before the QTc-prolonging medication was ordered. These patients were followed to identify outcomes of interest after administration of QTc-prolonging medication. RESULTS: Overall, a QTc-prolonging medication was prescribed for 207 patients. Of these, 53 patients (26%) had pre-existing prolongation of the QTc interval. Clinical pharmacists made recommendations related to 28 medication orders; of these, 16 (57%) were accepted by the physician. Fifty-one (96%) of the 53 patients received at least one dose of QTc-prolonging medication and were monitored daily for complications. Nine (18%) of the 51 patients who underwent daily monitoring experienced at least one cardiac event. CONCLUSIONS: A substantial proportion (26%) of patients for whom QTc-prolonging medications were prescribed had pre-existing prolongation of the QTc interval. Clinical pharmacists may have a role in reducing the risk of subsequent complications.

Comparing outcomes of meropenem administration strategies based on pharmacokinetic and pharmacodynamic principles: a qualitative systematic review.

OBJECTIVE: To systematically review evidence comparing traditional and alternative dosing strategies for meropenem, based on clinical and pharmacoeconomic outcomes. DATA SOURCES: MEDLINE (1950-September 2009), EMBASE (1980-September 2009), and International Pharmaceutical Abstracts (1970-September 2009) were searched, using the terms meropenem, carbapenems, pharmacodynamics, and pharmacokinetics. Reference citations from publications identified were reviewed. STUDY SELECTION AND DATA EXTRACTION: Articles discussing administration of meropenem to adults with normal renal function and comparing at least 2 regimens, 1 of which included the manufacturer-recommended regimen of 0.5 g or 1 g every 8 hours infused over 30 minutes, with clinical, pharmacodynamic, or pharmacoeconomic endpoints, were included. The pharmacodynamic endpoint of interest was percent time that the unbound drug concentration exceeded the minimal inhibitory concentration for a bacterial pathogen. DATA SYNTHESIS: Sixteen studies were reviewed, which included 13 pharmacokinetic and dynamic assessments using Monte Carlo simulations, 5 clinical evaluations, and 3 pharmacoeconomic appraisals. Data on clinical and economic outcomes are largely nonrandomized retrospective analyses and case reports. Meropenem via intermittent prolonged infusion potentially increases the likelihood of achieving pharmacodynamic targets. However, a strong link with improved clinical outcomes is lacking. Smaller doses with shorter intervals appear to provide pharmacodynamic target attainment rates and clinical outcomes similar to those with traditional dosing, with potential pharmacoeconomic benefits. Meropenem via continuous infusion appears to increase the likelihood of achieving pharmacodynamic targets, compared with intermittent infusions. The sparsity of clinical evidence supporting this practice limits its broad application to practice. No studies have formally examined adverse effects with alternative dosing regimens. CONCLUSIONS: Meropenem alternative dosing strategies provide similar pharmacodynamic target attainment rates compared with traditional dosing strategies. Small doses with shorter interval dosing provide additional pharmacoeconomic benefits and similar clinical outcomes. Alternative dosing strategies for meropenem were largely studied in healthy subjects; individuals with pharmacokinetic parameters that differ significantly may be ideal subjects for empiric dose modification.

Therapeutic drug monitoring in the neurocritical care unit.

PURPOSE OF REVIEW: Various antiepileptics, sedative and anesthetic agents are used in the neurocritical care setting and therapeutic drug monitoring (TDM) has been proposed as a means to individualize dosing to ensure efficacy, avoid toxicity, and to account for drug-drug interactions. The purpose of this review is to highlight key articles relating to TDM published in the last 5 years with a focus on drug therapy for seizures, status epilepticus, and traumatic brain injury. RECENT FINDINGS: Current evidence supports TDM of first-generation antiepileptics, and free-level monitoring for phenytoin and valproic acid is recommended in the neurocritical care population. There are insufficient data to recommend routine TDM of second-generation antiepileptics at this time. In traumatic brain injury, routine TDM of barbiturate infusions appears to be of little value in guiding or evaluating patient response to therapy except to differentiate between drug-induced coma and brain death. Although TDM of sedative agents has been studied, the use of clinical sedation scales is preferred over TDM in evaluating a patient's level of sedation. SUMMARY: Therapeutic drug monitoring plays an important role in the care of patients in the neurocritical care setting but is applicable only to a limited number of drugs.