Assessing the impact of aprepitant on response to dose-intensive cyclophosphamide, etoposide, and cisplatin (DICEP).

BACKGROUND: Despite evidence demonstrating the effectiveness of aprepitant for chemotherapy-induced nausea and vomiting (CINV), its use in stem cell transplant settings across Canada is not standard. While pharmacokinetic data exists, the clinical significance of cytochrome P450 3A4 (CYP 3A4) inhibition of cyclophosphamide by aprepitant is unclear. Reduced activation of cyclophosphamide may reduce the effectiveness of dose-intensive cyclophosphamide, etoposide, and cisplatin (DICEP). OBJECTIVES: To compare response rates to DICEP in patients with Hodgkin lymphoma (HL) and diffuse large B-cell lymphoma (DLBCL) in the presence and absence of aprepitant. METHODS: A retrospective review of patients who received full-dose DICEP for relapsed/refractory HL or DLBCL between June 1995 and September 2018 at the Foothills Medical Centre (FMC) in Calgary, Alberta, Canada was conducted. Descriptive statistics were used to assess response rate, as defined by the 2007 International Working Group response criteria. RESULTS: Of the 218 patients included in this study, 87.6% of patients in the control group and 88.5% of patients in the aprepitant group responded to DICEP (difference 0.025 [95% CI, -0.066 to 0.114], p = 0.827). Univariate analyses for age, sex, type of cancer, stage of cancer, number of prior relapses, and relapse status were not significant. No significant differences were observed for secondary outcomes. CONCLUSION: Response rates to DICEP in relapsed/refractory HL and DLBCL patients were similar regardless of aprepitant use. Considering these results and the effectiveness of aprepitant in CINV, its addition to standard antiemetic therapy in patients receiving DICEP should be given strong consideration in the transplant setting.

Prescribing practices of oncology pharmacists working in ambulatory cancer centers in Alberta.

OBJECTIVE: To describe and quantify independent prescribing of oncology pharmacists working in adult, ambulatory cancer centers in Alberta, Canada. METHODS: A retrospective chart review of oncology pharmacists prescribing in the electronic health record, ARIA® was conducted. Prescriptions from January 1, 2018 to June 30, 2018 were analyzed. Descriptive statistics were used to quantify prescription volume and class of medications prescribed. A cross-sectional analysis was then performed on a random sample to determine the type of prescription intervention and evaluate pharmacist documentation. RESULTS: Over 6 months, 3474 prescriptions were ordered by 33 clinically deployed pharmacists. The median number of medications prescribed was 7 per month (interquartile range: 1.50-27.00; Range: 0.17-79.5). When prescribing was standardized by pharmacist's time clinically deployed, the median was 21.67 (interquartile range: 5.00-79.67; range: 0.67-216.67) prescriptions per month per full-time equivalent. The most prescribed class of medication was antiemetic (24.1%). From a sample of 346 prescriptions, 172 (50%) were new medications initiated, 160 (46%) were the continuation of existing prescriptions and 14 (4%) were prescription dosage adjustments. Adherence to the specified documentation standards was 47%. CONCLUSIONS: Oncology pharmacists utilize their independent prescribing to initiate and continue supportive care medications for cancer patients. The prescribing volume varied greatly among pharmacists. Opportunities exist to further engage pharmacist prescribing.

Pharmacists' practices and views regarding management of sexual health in patients with cancer.

INTRODUCTION: Sexual health issues associated with cancer can significantly impact patients' psychosocial well-being and overall quality of life. These issues are frequently medication-related, placing pharmacists in an opportune position to manage sexual health concerns in patients with cancer. Currently, no literature exists exploring pharmacists' practices related to the management of sexual health in oncology patients. METHODS: An anonymous, descriptive, cross-sectional, web-based survey was conducted to elicit pharmacists' views and practices regarding managing sexual health in oncology patients. Pharmacists practicing in Canada who provide care to adult malignant hematology or oncology patients were eligible to participate. The survey was disseminated through the Canadian Association of Pharmacy in Oncology and through informal oncology pharmacy practitioner networks. RESULTS: Of the 102 pharmacists who participated, 96 completed the survey in its entirety. Most respondents were female, practiced in Alberta, and primarily saw oncology patients in outpatient cancer facilities. Although 85% of participants felt pharmacists should be involved in giving patients an opportunity to discuss sexual health, only 8% reported managing sexual health in at least 50% of their oncology patients. The most commonly agreed upon barriers to this were presence of family members and friends at appointments, lack of knowledge or training, limited time, and the belief that sexual health is not applicable to all oncology patients. CONCLUSIONS: This study explored pharmacists' views and practices regarding managing sexual health in patients with cancer. Several barriers were identified, which may aid in future development of resources to assist pharmacists in routinely addressing sexual health in oncology patients.

Multi-strain probiotics for extremely preterm infants: a randomized controlled trial.

BACKGROUND: Effects of probiotics on intestinal microbiota and feeding tolerance remain unclear in extremely low-birth-weight (ELBW) infants. METHODS: ELBW infants were randomly assigned to receive probiotics or no intervention. Stool samples were collected prior to, 2 and 4 weeks after initiation, and 2 weeks after probiotics cessation for infants in the probiotics group, and at matched postnatal age time points for infants in the control group. RESULTS: Of the 102 infants assessed for eligibility, sixty-two were included. Infants who received probiotics reached full enteral feeds sooner (Mean difference (MD) -1.8; 95% CI:-3.7 to -0.01 day), had a tendency toward lower incidence of hematochezia before hospital discharge (22.6% vs 3.2%; P = 0.053), and were less likely to require extensively hydrolyzed- or amino acids-based formulas to alleviate signs of cow's milk protein intolerance in the first 6 months of life (19.4% vs 51.6%; P = 0.008). Infants on probiotics were more likely to receive wide-spectrum antibiotics (64.5% vs 32.2%; P = 0.01). Multi-strain probiotics resulted in significant increase in fecal Bifidobacterium (P < 0.001) and Lactobacillus (P = 0.005), and marked reduction in fecal candida abundance (P = 0.04). CONCLUSION: Probiotics sustained intestinal Bifidobacterium and reduced time to achieve full enteral feeds in extremely preterm infants. Probiotics might improve tolerance for cow's milk protein supplements. CLINICAL TRIAL REGISTRATION: This trial has been registered at www. CLINICALTRIALS: gov (identifier NCT03422562). IMPACT: Probiotics may help extremely preterm infants achieve full enteral feeds sooner. Probiotics may improve tolerance for cow's milk protein supplements. Multi-strain probiotics can sustain intestinal Bifidobacterium and Lactobacillus until hospital discharge.

Toward optimization of cyclosporine concentration target to prevent acute graft-versus-host disease following myeloablative allogeneic stem cell transplant.

INTRODUCTION: Despite the common use of cyclosporine (CsA) for acute graft-versus-host disease (aGVHD) prophylaxis following allogeneic stem cell transplant, the optimal CsA trough target remains unknown. MATERIALS AND METHODS: Here, we report on outcomes of adult patients following myeloablative conditioning to identify an optimal CsA trough target and characterize the most relevant timeframe post-transplant for CsA trough targeting to minimize aGVHD. We retrospectively reviewed 399 consecutive patients who underwent first peripheral blood allogeneic stem cell transplant for hematological malignancies between January 2009 and December 2018. RESULTS: In the unadjusted and adjusted analyses, the incidence of grades 2-4 aGVHD was significantly higher among patients with an average CsA trough concentration <250 mcg/L compared to patients with an average CsA trough concentration ≥250 mcg/L during days 15-28 post-transplant (31.5% versus 18.8%, P = 0.037), with an odds ratio (OR) of 1.97 (95% confidence interval 1.04-3.71). In contrast, no correlations between CsA trough concentration and relapse, non-relapse mortality and overall survival was found. CONCLUSION: In conclusion, early post-transplant CsA trough concentrations are an important factor in the prophylaxis against aGVHD. Our findings suggest that CsA trough concentrations should be maximized between days 15-28 post-myeloablative transplant.

Impact of Weight-Band Dosing of Tinzaparin for Venous Thromboembolism Prophylaxis on Persistent Wound Drainage in Adult Patients Undergoing Hip and Knee Arthroplasty.

BACKGROUND: Persistent wound drainage and venous thromboembolism (VTE) are potential complications of total joint arthroplasty, and these risks can be challenging to balance in clinical practice. Anecdotal observation has suggested that following joint arthroplasty, persistent wound drainage occurs more frequently with higher body weight and higher doses of tinzaparin when compared with lower body weight and lower doses of tinzaparin. OBJECTIVE: The overall purpose of this study was to describe the impact of a tinzaparin weight-band dosing table for VTE prophylaxis on wound healing, thrombosis, and bleeding outcomes in patients undergoing total joint arthroplasty. METHODS: This retrospective chart review included patients who underwent total hip or knee arthroplasty and received tinzaparin for thromboprophylaxis per their weight-banding category. The primary outcome was the incidence of persistent wound drainage. Secondary outcomes include the occurrence of VTE and clinically important bleeding during hospital admission. RESULTS: A total of 231 patients were included in the analysis. There was no significant difference in persistent wound drainage between the 3 weight categories, and there were no differences in rates of VTE or clinically important bleeding. Concurrent use of low-dose acetylsalicylic acid was associated with a 3-fold increased risk of persistent wound drainage (risk ratio = 3.35; 95% CI = 2.14-5.24; P = 0.00003). CONCLUSION AND RELEVANCE: In joint arthroplasty patients, we observed no significant difference in rates of persistent wound drainage between various weight categories receiving different weight-banded doses of tinzaparin. Our results do not suggest that the current weight-band dosing table for tinzaparin needs to be adjusted to optimize patient outcomes.

AUCs and 123s: a critical appraisal of vancomycin therapeutic drug monitoring in paediatrics.

The revised vancomycin guidelines recommend implementing AUC24-based therapeutic drug monitoring (TDM) using Bayesian methods in both adults and paediatrics. The motivation for this change was accumulating evidence showing aggressive dosing to achieve high troughs, as recommended in the first guidelines for adults and extrapolated to paediatrics, is associated with increased nephrotoxicity without improving clinical outcomes. AUC24-based TDM requires substantial resources that may need to be diverted from other valuable interventions. It can therefore be justified only after certain assumptions are shown to be true: (i) there is a clear relationship between vancomycin efficacy and/or toxicity and the proposed therapeutic range; and (ii) maintaining exposure within the target range with AUC24-based TDM improves clinical outcomes and/or decreases toxicity. In this review, we critically appraise the scientific basis for these assumptions. We find studies evaluating the relationship between vancomycin AUC24/MIC and efficacy in adults and children do not offer strong support for the recommended lower limit of the proposed therapeutic range (i.e. AUC24/MIC ≥400). Nephrotoxicity in children increases in a stepwise manner along the vancomycin exposure continuum but it is unclear if one parameter (AUC24 versus trough) is a superior predictor. Overall, evidence in children suggests good-to-excellent correlation between AUC24 and trough. Most importantly, there is no convincing evidence that the method of vancomycin TDM has a causal role in improving efficacy or reducing toxicity. These findings question the need to transition to resource-intensive AUC24-based TDM over retaining trough-based TDM with lower targets to minimize nephrotoxicity in paediatrics.

Actual body weight dosing of temozolomide and overall survival in patients with glioblastoma.

BACKGROUND: Adult glioblastoma patients receiving standard radiation therapy and concurrent temozolomide chemotherapy have a median survival of 14.6 months. Based on the pivotal trial data by Stupp et al., temozolomide doses were calculated based on body surface area. However, no details regarding the weight used to calculate body surface area was included in the study. As a result, temozolomide doses have been variable across the province. METHODS: This retrospective chart review was conducted to determine the correlation between dose of first line temozolomide with overall survival. Patients between January 1st, 2009 and December 31st, 2014 who were newly diagnosed, pathology confirmed glioblastoma treated first line with temozolomide within Alberta Health Services were included in the study. Temozolomide doses above and below determined cut points were compared through the Kaplan-Meier method, then assessed using the log-rank test. RESULTS: A cut point of 97.8% of actual body weight calculated body surface area dosing was determined for concurrent phase temozolomide. At doses above this cut point, there was a statistically significant (p = 0.0158) increase of 0.3 years in median overall survival. As for toxicity concerns, there was a statistically significant increase in the proportion of temozolomide dose reductions due to toxicity in patients dosed above the cut point. CONCLUSION: Temozolomide doses at full actual body weight calculated body surface area dosing during the concurrent phase is required to achieve a similar median OS as seen in the pivotal trial by Stupp et al.

The impact of palliative care consults on deprescribing in palliative cancer patients.

PURPOSE: The transition from active cancer treatment to palliative care often results in a shift in drug risk-benefit assessment which requires the deprescribing of various medications. Deprescribing in palliative cancer patients can benefit patients by reducing their pill burden, decrease potential side effects, and potentially decrease healthcare costs. In addition, a change in patients' goals of care (GOC) necessitates the alteration of drug therapy which includes both deprescribing and the addition of medications intended to improve quality of life. Depending on a patient's GOC, a medication can be considered as inappropriate. OBJECTIVES: Primary: Comparison between potentially inappropriate medications (PIMs) prior to the palliative care consult (PCC) versus after the PCC. Secondary: Association between PIMs and GOC. METHODS: The study was a 1-year retrospective database review. The study included cancer patients seen by the PCC team at the University of Alberta Hospital. The OncPal guidelines were used to identify and determine the number of PIMs prior to the PCC and after the PCC. RESULTS: The reduction in PIMs prior to PCC versus after the PCC was statistically significant (p value < 0.001), demonstrating the PCC has a positive significant impact on deprescribing PIMs. For our secondary outcome, an overall decrease in PIMs was observed with the changes of GOC. The strength of the correlations was low (r < 0.1), and the p value was 0.056. CONCLUSION: This study shows the positive impact a PCC has on deprescribing and reveals the importance of using guidelines for deprescribing in palliative cancer patients.

Potassium disturbance associated with an inpatient childhood asthma pathway.

BACKGROUND: Paediatric asthma exacerbations in Alberta are treated via standardized order sets known as the Alberta Acute Childhood Asthma Pathway (ACAP). This pathway is utilized in paediatric tertiary hospitals and in remote and rural locations. Incidence, magnitude, and risk factors for hypokalemia in inpatients receiving salbutamol for asthma exacerbations via this pathway are presently unknown. OBJECTIVE: Establish incidence, magnitude, and risk factors for hypokalemia associated with salbutamol therapy as directed by a paediatric asthma pathway. METHODS: Retrospective cohort study using visit-level electronic medical data. Inpatients aged <18 years old receiving salbutamol via the ACAP with at least one potassium level were included. Hypokalemia was defined as mild (3.0 ≤ [K+] < 3.5 mEq/L), moderate (2.5 ≤ [K+] < 3.0 mEq/L), or severe ([K+] < 2.5 mEq/L), as measured in serum or blood gas. Binomial logistic regression was utilized to examine risk factors for hypokalemia, route of administration, location of lowest [K+], nil per os (NPO) status during admission, potassium supplementation, gender, and age. RESULTS: There were 821 patients screened for analysis and 433 patients were analyzed after exclusions. There was an incidence of hypokalemia of 38.8%. Of patients experiencing hypokalemia, 71.4% were mild, 25.6% moderate, and 3.0% severe. Risk factors included nebulized salbutamol, patient location (emergency department or paediatric intensive care unit), and age (>5 years) although these risk factors may actually represent patients receiving higher doses of salbutamol. CONCLUSIONS: The majority of the 38.8% of children experiencing hypokalemia associated with the ACAP were mild. Routine monitoring of potassium status in children receiving salbutamol per standardized pathway is recommended for children with described risk factors, and ideally within the first 12 hours of presentation.

Pediatric pharmacists' perspectives on essential skills and activities for community pharmacists caring for pediatric patients: A mixed-methods study.

BACKGROUND: Provision of care to pediatric patients represents a set of unique challenges for pharmacists. Pharmacists practising in pediatric-specialty areas (acute care or ambulatory) have unique perspectives on approaches to pediatric care that can be shared to support pharmacists less familiar with this group of patients in providing effective, patient-centred care. METHODS: This was a mixed-methods study using data from pharmacist interviews to quantify and qualitatively describe the approaches to care most commonly reported by pediatric-specialty pharmacists when asked to provide advice to pharmacists on providing pharmaceutical care to infants and children. Data were coded in duplicate using an inductive approach, and discrepancies were resolved by consensus. The number of times a theme (or subtheme) was mentioned and the number of pharmacists who mentioned it were used as markers of the relative importance of the content. RESULTS: The themes (and subthemes) that emerged as most important were clinical activities (dose checks, considering indication, using up-to-date height/weight), caregiver counselling (demonstrating measurement, discussing administration), medication safety (using consistent concentrations of liquids), compounded medications (risks of, use of caution), adherence (formulation considerations, palatability), avoiding use of over-the counter products (except analgesics/antipyretics) and use of external supports (colleagues, caregivers, resources). CONCLUSIONS: We present a collated and prioritized list of practical approaches for pharmacists to use when caring for pediatric patients across the spectrum of practice. Can Pharm J (Ott) 2020;153:xx-xx.

Dexmedetomidine Use in a Tertiary Care NICU: A Descriptive Study.

BACKGROUND: Continuous infusions of dexmedetomidine are increasingly used for sedation in critically ill pediatric patients. Emerging data suggest potential benefits when used for sedation in neonates, including reduced sedative requirements and earlier enteral feeds. OBJECTIVE: To describe the use, adverse effects, and signs of withdrawal in a cohort of neonates receiving dexmedetomidine, the majority of whom were receiving concomitant opioids. METHODS: This was a retrospective, descriptive review of 38 neonates receiving dexmedetomidine in a medical surgical neonatal intensive care unit, including data on duration of use, dose, adverse effects, weaning, and signs of withdrawal. RESULTS: Dexmedetomidine was used for a median of 183 hours, at a median maximum dose of 0.5 µg/kg/h. Premature infants were started on dexmedetomidine at a later chronological age than term infants (41 vs 9 days, P = 0.004). Of 18 patients receiving an opioid infusion at the time of dexmedetomidine initiation, 67% had a dose reduction in opioids by 24 hours. The majority (89%) of neonates had at least 1 potentially related adverse effect during the dexmedetomidine infusion, though no discontinuations were needed as a result. In all, 80% of patients had their dexmedetomidine gradually weaned off, and 71% had at least 1 sign of withdrawal. CONCLUSIONS AND RELEVANCE: In this cohort, dexmedetomidine was often used in a postsurgical setting, with concomitant opioids, over prolonged periods. These factors appear to affect and likely confound the rates of adverse effects and withdrawal signs from dexmedetomidine. Clinicians considering the use of dexmedetomidine in a similar population can draw guidance from our data.

Implementation of additional prescribing authorization among oncology pharmacists in Alberta.

PURPOSE: To describe the practice settings and prescribing practices of oncology pharmacists with additional prescribing authorization. METHODS: A descriptive, cross-sectional survey of all oncology pharmacists in Alberta was conducted using a web-based questionnaire over four weeks between March and April 2016. Pharmacists were identified from the Cancer Services Pharmacy Directory and leadership staff in Alberta Health Services. Descriptive statistics were used to describe the practice setting, prescribing practices, motivators to apply for additional prescribing authorization, and the facilitators and barriers of prescribing. Logistic regression was used to explore factors associated with having additional prescribing authorization. RESULTS: The overall response rate was 41% (71 of 175 pharmacists). Oncology pharmacists with additional prescribing authorization made up 38% of respondents. They primarily worked in urban, tertiary cancer centers, and practiced in ambulatory care. The top 3 clinical activities they participated in were medication reconciliation, medication counseling/education, and ambulatory patient assessment. Respondents thought additional prescribing authorization was most useful for ambulatory patient assessment and follow-up. Antiemetics were prescribed the most often. The median number of prescriptions written in an average week of clinical work was 5. Competence, self-confidence, and the potential impact on patient care/perceived impact on work environment were the strongest facilitators of prescribing. The strongest motivators to apply for additional prescribing authorization were relevancy to practice, the potential for increased efficiency, and advancing the profession. CONCLUSION: The current majority of oncology pharmacist prescribing in Alberta occurs in ambulatory care with a large focus on antiemetic prescribing. Pharmacists found additional prescribing authorization most useful for ambulatory patient assessment and follow-up.

Dexmedetomidine Use in a Pediatric Intensive Care Unit: A Retrospective Cohort Study.

BACKGROUND: Use of dexmedetomidine in critically ill pediatric patients is increasing despite limited data on effects on mechanical ventilation times, use of other sedatives, adverse effects, and withdrawal. OBJECTIVES: To describe the use and tolerability of dexmedetomidine in a large cohort of critically ill children. METHODS: This was a retrospective cohort study of patients receiving dexmedetomidine in a pediatric intensive care unit. Ethical approval was granted by the local review board. Data on dexmedetomidine administration, ventilatory support, other sedatives, adverse effects, and withdrawal were collected. RESULTS: There were 219 patients included. Dexmedetomidine was a first-line sedative in 47.9% of patients; the median infusion duration was 27 hours. Of patients on other sedatives at dexmedetomidine initiation, 39.5% had a dose reduction in those sedatives by 24 hours. Use of dexmedetomidine in noninvasively ventilated patients was common (19.6%), as was use in patients on no ventilatory support (35.6%). Patients receiving no ventilatory support used dexmedetomidine for shorter durations ( P = 0.001) and were less likely to have received prior sedatives ( P < 0.001). Adverse effects occurred in 42% of patients and were associated with younger age ( P = 0.001) and longer dexmedetomidine duration ( P < 0.001). The majority of patients (65%) were weaned off dexmedetomidine, and 80% of patients had at least one sign of withdrawal. CONCLUSIONS: Our data suggest substantial use in noninvasively ventilated patients. Adverse effects appeared more common in younger patients and those with prolonged infusions. A high rate of withdrawal effects was seen; no associations with age, dose, or duration were found.

Antibiotic Utilization Patterns in Patients with Ventilator-Associated Pneumonia: A Canadian Context.

This retrospective cohort study describes the patterns of antibiotic use for the treatment of ventilator-associated pneumonia (VAP) in the Calgary Zone of Alberta Health Services. Timing, appropriateness, and duration of antibiotics were evaluated in two hundred consecutive cases of VAP derived from 4 adult intensive care units (ICU). Antibiotic therapy was initiated in less than 24 hours from VAP diagnosis in 83% of cases. Although most patients (89%) received empiric therapy that demonstrated in vitro sensitivity to the identified pathogens, only 24% of cases were congruent with the 2008 Association of Medical Microbiology and Infectious Disease (AMMI) guidelines. Both ICU (p = 0.001) and hospital (p = 0.015) mortality were significantly lower and there was a trend for shorter ICU length of stay (p = 0.051) in patients who received appropriate versus inappropriate initial antibiotics. There were no outcome differences related to compliance with AMMI guidelines. This exploratory study provides insight into the use of antimicrobials for the treatment of VAP in a large Canadian health region. The discordance between the assessments of appropriateness of empiric therapy based on recovered pathogens versus AMMI guidelines is notable, emphasizing the importance of using as much as possible local microbiologic and antimicrobial resistance data.

Assessment of initial vancomycin dosing in neonates.

BACKGROUND: Vancomycin is recommended for optimal treatment of late-onset sepsis caused by coagulase-negative Staphylococcus in neonates. OBJECTIVES: To assess the performance of an empirical vancomycin dosing regimen in achieving target trough levels, and to revise this regimen if needed. METHODS: Data regarding doses and levels were collected and pharmacokinetic parameters were calculated, where possible, for neonates receiving vancomcyin in a neonatal intensive care unit. The primary measure was the percentage of neonates with initial prevancomycin levels of <10 mg/L, 10 mg/L to 20 mg/L and >20 mg/L. Secondary measures included the percentage of neonates with extrapolated trough levels in these ranges, total daily doses that achieved target levels (10 mg/L to 20 mg/L) and total daily doses/dosing intervals that were pharmacokinetically predicted to achieve trough levels of 15 mg/L. RESULTS: Of 153 infants started on the empirical regimen (15 mg/kg/day to 45 mg/kg/day, depending on postnatal age and weight), 34.2% initially achieved target trough levels (mean 8.7 mg/L). Analysis of actual doses and pharmacokinetically predicted doses required to reach target levels suggested increasing the empirical dosing for all neonatal age groups. The revised regimen used in the present study (20 mg/kg/day to 40 mg/kg/day, depending on postmenstrual age and postnatal age) was predicted to result in 72% of infants achieving initial target trough levels (mean 15.4 mg/L). CONCLUSIONS: A revised empirical vancomycin dosage regimen for neonates was required based on poor achievement of target trough levels (10 mg/L to 20 mg/L) using the previous regimen. The modified regimen is predicted to reach target trough levels more often and increase the mean initial trough levels achieved. This regimen requires clinical validation in an independent cohort in the future.

HISTORIQUE: La vancomycine est recommandée pour le traitement optimal du sepsis à apparition tardive causé par le staphylocoque à coagulase négative chez les nouveau-nés. OBJECTIFS: Évaluer le rendement d'une posologie empirique de vancomycine pour obtenir les concentrations minimales ciblées et réviser cette posologie, au besoin. MÉTHODOLOGIE: Les chercheurs ont colligé les données relatives aux doses et aux concentrations et calculé les paramètres pharmacocinétiques, dans la mesure du possible, chez les nouveau-nés d'une unité de soins intensifs néonatals qui recevaient de la vancomycine. La mesure primaire était le pourcentage de nouveau-nés dont les concentrations étaient inférieures à 10 mg/L, se situaient entre 10 mg/L et 20 mg/L et étaient supérieures à 20 mg/L avant l'administration de vancomycine. Les mesures secondaires incluaient le pourcentage de nouveau-nés dont les concentrations minimales extrapolées se situaient dans ces plages, dont les doses quotidiennes totales atteignaient les concentrations ciblées (10 mg/L à 20 mg/L) et dont le ratio entre les doses quotidiennes totales et l'intervalle entre les doses devait, sur le plan pharmacocinétique, atteindre des concentrations minimales de 15 mg/L. RÉSULTATS: Des 153 nourrissons à qui on avait d'abord administré la posologie empirique (15 mg/kg/jour à 45 mg/kg/jour, selon leur âge postnatal et leur poids), 34,2 % ont obtenu les concentrations minimales initiales ciblées (moyenne de 8,7 mg/L). D'après l'analyse des doses réelles et des doses prédites sur le plan pharmacocinétique pour atteindre les concentrations minimales ciblées, il semblait nécessaire d'accroître la posologie empirique dans tous les groupes d'âge néonatal. Cette analyse prédisait que la posologie révisée utilisée dans la présente étude (20 mg/kg/jour à 40 mg/kg/jour selon l'âge postmenstruel et l'âge postnatal) permettrait à 72 % des nourrissons d'obtenir les concentrations minimales initiales ciblées (moyenne de 15,4 mg/L). CONCLUSIONS: Il a fallu réviser la posologie empirique de vancomycine chez les nouveau-nés parce qu'ils n'atteignaient pas les concentrations minimales ciblées (10 mg/L à 20 mg/L) au moyen des posologies antérieures. Il est prévu que la posologie modifiée atteindra plus souvent les concentrations minimales ciblées et accroîtra la concentration minimale initiale ciblée moyenne obtenue. Cette posologie devra être validée sur le plan clinique auprès d'une cohorte indépendante.

Assessment of initial vancomycin dosing in neonates.

BACKGROUND: Vancomycin is recommended for optimal treatment of late-onset sepsis caused by coagulase-negative Staphylococcus in neonates. OBJECTIVES: To assess the performance of an empirical vancomycin dosing regimen in achieving target trough levels, and to revise this regimen if needed. METHODS: Data regarding doses and levels were collected and pharmacokinetic parameters were calculated, where possible, for neonates receiving vancomcyin in a neonatal intensive care unit. The primary measure was the percentage of neonates with initial prevancomycin levels of <10 mg/L, 10 mg/L to 20 mg/L and >20 mg/L. Secondary measures included the percentage of neonates with extrapolated trough levels in these ranges, total daily doses that achieved target levels (10 mg/L to 20 mg/L) and total daily doses/dosing intervals that were pharmacokinetically predicted to achieve trough levels of 15 mg/L. RESULTS: Of 153 infants started on the empirical regimen (15 mg/kg/day to 45 mg/kg/day, depending on postnatal age and weight), 34.2% initially achieved target trough levels (mean 8.7 mg/L). Analysis of actual doses and pharmacokinetically predicted doses required to reach target levels suggested increasing the empirical dosing for all neonatal age groups. The revised regimen used in the present study (20 mg/kg/day to 40 mg/kg/day, depending on postmenstrual age and postnatal age) was predicted to result in 72% of infants achieving initial target trough levels (mean 15.4 mg/L). CONCLUSIONS: A revised empirical vancomycin dosage regimen for neonates was required based on poor achievement of target trough levels (10 mg/L to 20 mg/L) using the previous regimen. The modified regimen is predicted to reach target trough levels more often and increase the mean initial trough levels achieved. This regimen requires clinical validation in an independent cohort in the future.

HISTORIQUE: La vancomycine est recommandée pour le traitement optimal du sepsis à apparition tardive causé par le staphylocoque à coagulase négative chez les nouveau-nés. OBJECTIFS: Évaluer le rendement d'une posologie empirique de vancomycine pour obtenir les concentrations minimales ciblées et réviser cette posologie, au besoin. MÉTHODOLOGIE: Les chercheurs ont colligé les données relatives aux doses et aux concentrations et calculé les paramètres pharmacocinétiques, dans la mesure du possible, chez les nouveau-nés d'une unité de soins intensifs néonatals qui recevaient de la vancomycine. La mesure primaire était le pourcentage de nouveau-nés dont les concentrations étaient inférieures à 10 mg/L, se situaient entre 10 mg/L et 20 mg/L et étaient supérieures à 20 mg/L avant l'administration de vancomycine. Les mesures secondaires incluaient le pourcentage de nouveau-nés dont les concentrations minimales extrapolées se situaient dans ces plages, dont les doses quotidiennes totales atteignaient les concentrations ciblées (10 mg/L à 20 mg/L) et dont le ratio entre les doses quotidiennes totales et l'intervalle entre les doses devait, sur le plan pharmacocinétique, atteindre des concentrations minimales de 15 mg/L. RÉSULTATS: Des 153 nourrissons à qui on avait d'abord administré la posologie empirique (15 mg/kg/jour à 45 mg/kg/jour, selon leur âge postnatal et leur poids), 34,2 % ont obtenu les concentrations minimales initiales ciblées (moyenne de 8,7 mg/L). D'après l'analyse des doses réelles et des doses prédites sur le plan pharmacocinétique pour atteindre les concentrations minimales ciblées, il semblait nécessaire d'accroître la posologie empirique dans tous les groupes d'âge néonatal. Cette analyse prédisait que la posologie révisée utilisée dans la présente étude (20 mg/kg/jour à 40 mg/kg/jour selon l'âge postmenstruel et l'âge postnatal) permettrait à 72 % des nourrissons d'obtenir les concentrations minimales initiales ciblées (moyenne de 15,4 mg/L). CONCLUSIONS: Il a fallu réviser la posologie empirique de vancomycine chez les nouveau-nés parce qu'ils n'atteignaient pas les concentrations minimales ciblées (10 mg/L à 20 mg/L) au moyen des posologies antérieures. Il est prévu que la posologie modifiée atteindra plus souvent les concentrations minimales ciblées et accroîtra la concentration minimale initiale ciblée moyenne obtenue. Cette posologie devra être validée sur le plan clinique auprès d'une cohorte indépendante.

Identification of a Conversion Factor for Dexmedetomidine to Clonidine Transitions.

OBJECTIVE: To determine a conversion factor for use when switching from dexmedetomidine infusion to enteral clonidine in critically ill neonates. METHODS: This was an observational, retrospective review of conversions from dexmedetomidine to -clonidine, performed in a neonatal intensive care unit (NICU) between January 2020 and December 2021. Both initial conversion factors and those resulting after a 48-hour titration period were examined. Sedation and withdrawal scores were measured, and doses were titrated based on a standardized practice within the unit. RESULTS: A total of 43 dexmedetomidine to clonidine conversions were included. The median (IQR) dexmedetomidine dose prior to conversion was 17.4 (11.3-24.0) mcg/kg/day (0.7 mcg/kg/hr) and the median (IQR) enteral clonidine dose post titration was 7.8 (4.7-9.3) mcg/kg/day (2 mcg/kg every 6 hours). This equated to a post-titration conversion factor of approximately 0.42. All neonates had also received opioid infusions while on dexmedetomidine and 60% were on concurrent opioids at the time of the clonidine conversion. CONCLUSIONS: Neonatal clinicians may find the conversion factor identified in this study a useful starting point when converting from dexmedetomidine infusion to enteral clonidine in practice and should be -reminded of the most important steps in conversions (monitoring and follow-up) owing to the variability in this patient group. More studies are needed to elucidate the impact of patient-specific factors on this -conversion process.

Changes in Acute Care Pharmacist Prescribing and Laboratory Ordering over Time: CAPLET Study.

Background: In Alberta, pharmacists may obtain additional prescribing authorization (APA) and a practice identification number (PRAC-ID) for ordering laboratory tests. Pharmacists working within Alberta Health Services were mandated by the employer to attain APA by 2018, whereas laboratory ordering has been in place since 2009. Five acute care sites within the Calgary Zone had a computerized provider order entry (CPOE) system that allowed tracking of these activities. Objectives: To describe changes in prescribing and laboratory ordering by acute care pharmacists over time and to compare these activities across hospitals, sites, and specialty teams. Methods: A retrospective, descriptive review of acute care pharmacist orders for medications and laboratory tests was completed using data from the CPOE system for the period 2018 to 2021. Results: Over the study period, the rates of prescribing and laboratory ordering by pharmacists increased by 67.5% (from 1423 to 2383 per full-time equivalent [FTE]) and by 5.5% (from 235 to 248 per FTE), respectively. Pharmacists at the 5 hospitals increased their prescribing rates during that time (by proportions ranging from 7% to 176%). Cardiology, intensive care, and mental health teams had the largest increases in prescribing rates, whereas mental health, hospitalist, and intensive care teams had the greatest increases in rates of laboratory ordering. In each year of the study, the most frequently ordered medication for adult patients was vancomycin, and the most frequently ordered laboratory test was measurement of vancomycin before dose administration. The proportion of medication orders conveyed verbally decreased from 60.0% to 47.4% over the study period. Conclusions: The application of expanded scope of practice increased among acute care pharmacists, to a greater extent for prescribing than for laboratory ordering; however, the proportion of verbal medication orders remains high, a situation that should be addressed to improve patient safety. This study showed that prescribing and laboratory ordering are complementary, given that the top medications and laboratory tests were frequently related. The results of this study can be used for practice development and as the basis for further research within an expanded CPOE system.

Contexte: En Alberta, les pharmaciens peuvent obtenir une autorisation de prescription élargie (APE) et un numéro d'identification de pratique (PRAC-ID) pour demander des analyses de laboratoire. Les pharmaciens travaillant dans les Services de santé de l'Alberta ont été sommés par leur employeur d'obtenir une APE avant 2018, alors que les demandes d'analyses de laboratoire sont en place depuis 2009. Cinq sites de soins aigus dans la zone de Calgary disposaient d'un système de saisie informatique des ordonnances médicales (CPOE) permettant de suivre ces activités. Objectifs: Décrire les changements en matière de prescription et de demande d'analyses de laboratoire par les pharmaciens de soins aigus au fil du temps et comparer ces activités entre les hôpitaux, les sites et les équipes spécialisées. Méthodologie: Un examen rétrospectif et descriptif des prescriptions de médicaments et des demandes d'analyses de laboratoire effectuées par les pharmaciens en soins aigus a été mené à l'aide des données du système de CPOE pour la période 2018 à 2021. Résultats: Au cours de la période de l'étude, les taux de prescription et de demande d'analyses de laboratoire par les pharmaciens ont augmenté respectivement de 67,5 % (de 1423 à 2383 par équivalent temps plein [ETP]) et de 5,5 % (de 235 à 248 par ETP). Le taux de prescription des pharmaciens de tous les hôpitaux a augmenté au cours de cette période (de 7 % à 176 %). Les équipes de cardiologie, de soins intensifs et de santé mentale ont enregistré les plus fortes augmentations des taux de prescription, tandis que celles de santé mentale, de soins hospitaliers et de soins intensifs ont enregistré les plus fortes augmentations des taux de demande d'analyses de laboratoire. Chaque année de l'étude, la vancomycine était le médicament le plus fréquemment prescrit pour les patients adultes et les analyses de laboratoire les plus fréquemment demandées portaient sur la mesure de la vancomycine avant l'administration de la dose. La part des prescriptions de médicament communiquées verbalement a diminué de 60,0 % à 47,4 % au cours de la période d'étude. Conclusions: L'application d'un champ de pratique élargi a augmenté chez les pharmaciens de soins aigus, dans une plus grande mesure pour la prescription que pour les demandes d'analyses de laboratoire. Cependant, la part des prescriptions de médicament communiquées verbalement demeure élevée ­ une situation qui devrait être corrigée pour améliorer la sécurité des patients. Cette étude a démontré que les prescriptions et les demandes d'analyses de laboratoire sont complémentaires, étant donné que les principaux médicaments et les principales analyses sont fréquemment liés. Les résultats de cette étude peuvent être utilisés pour le développement de la pratique et comme base pour des recherches ultérieures au sein d'un système de CPOE élargi.