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.

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.

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.

Antibiotic Prescribing Practices for Urinary Tract Infection in a Pediatric Emergency Department: Is This a Problem Worth Cefix-ing?

Background: Pediatric urinary tract infection (UTI) is associated with diagnostic and therapeutic challenges. Objective: To determine the least-broad-spectrum oral antibiotic that would cover 80% of pathogens from lower (afebrile) and upper (febrile) UTIs in a Canadian pediatric emergency department (ED). Methods: This retrospective case series involved children discharged from the ED between September 2020 and February 2021 with a diagnosis of UTI and collection of a sample for urinalysis that had growth on culture. Results: Of 188 patients who met the inclusion criteria, 184 (97.9%) were discharged on antibiotics. Culture results indicated a UTI in 170 cases (92.4% of those discharged on antibiotics). The 95 urinary isolates from lower UTIs were susceptible to cephalexin (n = 81, 85.3%), cefixime (n = 78, 82.1%), nitrofurantoin (n = 76, 80.0%), trimethoprim-sulfamethoxazole (TMP-SMX) (n = 64, 67.4%), and amoxicillin (n = 55, 57.9%). The 75 urinary isolates from upper UTIs were susceptible to cefixime (n = 71, 94.7%), TMP-SMX (n = 57, 76.0%), and amoxicillin (n = 48, 64.0%). The mean prescribed duration of antibiotic therapy was 8.3 days for patients with a lower UTI and 9.1 days for those with an upper UTI (mean difference 0.80 days, 95% confidence interval 0.05-1.54). Conclusions: Empiric treatment with cephalexin or nitrofurantoin would have been successful for almost all lower UTIs. More complete reporting of cephalexin minimal inhibitory concentrations might have allowed use of this drug for most upper UTIs. Although there was a trend toward shorter duration of therapy for lower versus upper UTI, lower UTIs were always treated for longer than recommended by current guidelines.

Contexte: L'infection des voies urinaires (IVU) pédiatrique présente des défis diagnostiques et thérapeutiques. Objectif: Déterminer l'antibiotique oral à large spectre le moins élevé qui couvrirait 80 % des pathogènes des IVU inférieures (sans fièvre) et des IVU supérieures (avec fièvre) dans un service d'urgences pédiatriques canadien. Méthodes: Cette série de cas rétrospective impliquait des enfants sortis du service des urgences entre septembre 2020 et février 2021 avec un diagnostic d'IVU et la collecte d'un échantillon pour une analyse d'urine avec croissance dans la culture d'urine. Résultats: Parmi les 188 patients répondant aux critères d'inclusion, 184 (97,9 %) ont reçu des antibiotiques au moment du congé. Les résultats de la culture ont indiqué une IVU dans 170 cas (92,4 % des patients ayant reçu des antibiotiques au moment du congé). Les 95 isolats urinaires des IVU inférieures étaient sensibles à la céphalexine (n = 81, 85,3 %), au céfixime (n = 78, 82,1 %), à la nitrofurantoïne (n = 76, 80,0 %), au triméthoprime-sulfaméthoxazole (TMP-SMX) (n = 64, 67,4 %) et à l'amoxicilline (n = 55, 57,9 %). Les 75 isolats urinaires des IVU supérieures étaient sensibles au céfixime (n = 71, 94,7 %), au TMP-SMX (n = 57, 76,0 %) et à l'amoxicilline (n = 48, 64,0 %). La durée moyenne de prescription d'antibiotiques était de 8,3 jours pour les patients atteints d'une IVU inférieure et de 9,1 jours pour ceux atteints d'une IVU supérieure (différence moyenne 0,80 jours, IC à 95 % 0,05­1,54). Conclusions: Un traitement empirique avec la céphalexine ou la nitrofurantoïne aurait été efficace pour la grande majorité des infections urinaires inférieures. Un rapport plus complet des concentrations minimales inhibitrices de la céphalexine aurait peut-être permis d'utiliser ce médicament pour la plupart des infections urinaires supérieures. Bien qu'il y ait eu une tendance vers une durée de traitement plus courte pour les infections urinaires inférieures par rapport aux infections urinaires supérieures, les infections urinaires inférieures étaient toujours traitées plus longtemps que ce qui est recommandé par les lignes directrices actuelles.

The Alberta Telestewardship Network: Building a platform to enable capacity building in antimicrobial stewardship-results of an initial pilot study.

Background: Resources to improve antimicrobial stewardship (AS) are limited, but a telestewardship platform can enable capacity building and scalability. The Alberta Telestewardship Network (ATeleNet) was designed to focus on outreach across the province of Alberta, Canada, and facilitate AS activities. Methods: Outreach occurred virtually between pharmacists and physicians in hospital and long-term care settings throughout Alberta via secure, enterprise video conferencing software on both desktop and mobile devices. We used a quantitative questionnaire adapted from the telehealth usability questionnaire to capture the health provider's experience during each session. The questionnaire consisted of 39 questions, and a 5-point Likert scale was used to assess the degree of agreement and collate responses into a descriptive analysis. Results: A total of 33 pilot consultations were completed between July 6, 2020 and December 15, 2021. The majority (22, 85%) of respondents agreed that video conference-based virtual sessions are an acceptable means to provide health care and that they were able to express themselves effectively to other health care professionals (23, 88%). Respondents agreed the system was simple to use (23, 96%), and that they could become productive quickly using the system (23, 88%). Overall, 24 (92%) respondents were satisfied or very satisfied with the virtual care platform. Conclusions: We implemented and evaluated a telehealth consultation and collaborative care service between AS providers at multiple centres. AHS has since prioritized similar workflows, including access to specialists in acute care, as part of their virtual health strategy. Evaluation results will be shared with provincial stakeholders for further strategic planning and deployment.

Historique: Les ressources pour améliorer la gérance antimicrobienne (GA) sont limitées, mais une plateforme de télégérance peut favoriser le renforcement des capacités et l'échelonnabilité. L'Alberta Telestewardship Network (réseau de télégérance de l'Alberta, ou ATeleNet) a été conçu pour mettre l'accent sur le rayonnement dans la province de l'Alberta, au Canada et pour faciliter les activités de GA. Méthodologie: Le rayonnement s'est produit virtuellement entre des pharmaciens et des médecins d'établissements hospitaliers et d'établissements de soins de longue durée de l'Alberta par logiciel de visioconférence sécurisé sur des ordinateurs de bureau et des appareils mobiles. Les chercheurs ont utilisé un questionnaire quantitatif adapté du questionnaire sur la convivialité de la télésanté pour saisir l'expérience du dispensateur de soins lors de chaque séance. Le questionnaire était composé de 39 questions, et une échelle de Likert de cinq points a permis d'évaluer le degré d'entente et de recueillir les réponses dans une analyse descriptive. Résultats: Au total, les chercheurs ont effectué 33 consultations pilotes entre le 6 juillet 2020 et le 15 décembre 2021. La majorité des répondants (n = 22, 85 %) ont convenu que les séances en visioconférence représentaient un moyen acceptable de fournir des soins de santé et leur permettaient de s'exprimer avec efficacité auprès des autres professionnels de la santé (n = 23, 88 %). Les répondants ont indiqué que le système était facile à utiliser (n = 23, 96 %), et qu'ils pouvaient vite devenir productifs (n = 23, 88 %). Dans l'ensemble, 24 répondants (92 %) étaient satisfaits ou très satisfaits de la plateforme de soins virtuels. Conclusions: Les chercheurs ont lancé et évalué une consultation en télésanté et un service de soins coopératifs entre fournisseurs de GA de multiples centres. Depuis, les Services de santé de l'Alberta ont priorisé des processus de travail semblables dans leur stratégie de santé virtuelle, y compris pour l'accès à des spécialistes en soins aigus. Les résultats de l'évaluation seront transmis à des intervenants provinciaux en vue d'une planification et d'un déploiement stratégiques.

Impact of dexmedetomidine in conjunction with a weaning protocol on post-surgical opioid use in a neonatal intensive care unit.

STUDY OBJECTIVE: To describe the impact of protocol-driven dexmedetomidine (and clonidine) use on opioid exposure in post-surgical neonates. DESIGN: Retrospective chart review. SETTING: A Level III, surgical NICU. PATIENTS: Surgical neonates who received clonidine or dexmedetomidine concomitantly with an opioid for sedation and/or analgesia post-operatively. INTERVENTION: Implementation of a standardized sedation/analgesia weaning protocol. MEASUREMENTS AND MAIN RESULTS: There were clinically, although not statistically, significant reductions in opioid wean duration (240 vs. 227 h, p = 0.82), total opioid duration (604 vs. 435 h, p = 0.23), and total opioid exposure (91 vs. 51 mg ME/kg, p = 0.13), and limited impact on NICU outcomes or pain/withdrawal scores with use of the protocol. Increases in use of medications in alignment with the protocol (e.g., scheduled acetaminophen and opioids weaned first) were noted. CONCLUSIONS: We have been unable to demonstrate a reduction in opioid exposure with use of alpha-2 agonists alone; addition of a weaning protocol showed a reduction in opioid duration and exposure (although not statistically significant). At this point, dexmedetomidine and clonidine should not be introduced outside standardized protocols with scheduled acetaminophen post-operatively.

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.

Characteristics and Outcomes of Alberta Lymphoma Patients with a History of Immunosuppressive therapy for Autoimmune Conditions.

BACKGROUND: Other iatrogenic immunosuppression associated lymphoproliferative disorders (Oii-LPD) is rare subset of lymphoma. There are limited published data on the clinical characteristics and outcomes of this patient population. The primary objective of this study was to describe the clinical characteristics and outcomes of Alberta patients diagnosed with lymphoma following immunosuppressive therapy for autoimmune conditions. Secondary objectives included describing the incidence of Oii-LPD, proportions of subtypes of lymphoma diagnosed and the nature of immunosuppressants used. The outcomes of patients with iatrogenic immunodeficiency-associated diffuse large B cell lymphoma (DLBCL) were compared against a matched control group of patients with de novo DLBCL. PATIENTS AND METHODS: The study is a descriptive retrospective cohort study with a matched historical control comparison for patients with DLBCL. Alberta lymphoma patients, diagnosed from January 2011 to December 2019, with a history of iatrogenic immunosuppression were identified and described. RESULTS: The incidence of Oii-LPD was 1% of total Alberta lymphoma cases. Majority of this cohort were diagnosed with DLBCL (54.9%) and the most common immunosuppressive agents were methotrexate (62%), hydroxychloroquine (42%), and TNF inhibitors (31%). Survival was not different between Oii-LPD DLBCL and de novo DLBCL with 5-year survival rates of 64.1% and 67%, respectively (HR 1.11 [95% CI, 0.64-1.94]). CONCLUSION: Oii-LPD are rare with the most frequent subtype being DLBCL occurring in the setting of methotrexate use. In this population-based analysis, the outcomes of iatrogenic immunodeficiency-associated DLBCL were not significantly different from those of de novo DLBCL patients.

Supplementation with a probiotic mixture accelerates gut microbiome maturation and reduces intestinal inflammation in extremely preterm infants.

Probiotics are increasingly administered to premature infants to prevent necrotizing enterocolitis and neonatal sepsis. However, their effects on gut microbiome assembly and immunity are poorly understood. Using a randomized intervention trial in extremely premature infants, we tested the effects of a probiotic product containing four strains of Bifidobacterium species autochthonous to the infant gut and one Lacticaseibacillus strain on the compositional and functional trajectory of microbiome. Daily administration of the mixture accelerated the transition into a mature, term-like microbiome with higher stability and species interconnectivity. Besides infant age, Bifidobacterium strains and stool metabolites were the best predictors of microbiome maturation, and structural equation modeling confirmed probiotics as a major determinant for the trajectory of microbiome assembly. Bifidobacterium-driven microbiome maturation was also linked to an anti-inflammatory intestinal immune milieu. This demonstrates that Bifidobacterium strains are ecosystem engineers that lead to an acceleration of microbiome maturation and immunological consequences in extremely premature infants.

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.

Clinical Utility of Switching to Insulin Degludec From Other Basal Insulins in Adult Patients With Type 1 or Type 2 Diabetes.

OBJECTIVES: The effects of switching Canadians from other basal insulins to degludec (IDeg) in an outpatient setting are unknown. Our aim in this study was to evaluate the clinical effectiveness and safety of switching insulin-treated adults with either type 1 (T1DM) or type 2 (T2DM) diabetes mellitus to IDeg. METHODS: This was a retrospective observational cohort study of Albertans who were switched to IDeg between December 1, 2018, and December 1, 2019, and followed until March 1, 2020. We used administrative databases (provincial cohort) and electronic medical records (clinic cohort) to gather data and interrupted time series for the primary outcome analysis. RESULTS: We analyzed a provincial cohort of 5,294 patients, 287 of whom were also included in the clinic cohort (T1DM, n=80; T2DM, n=207). After switching to IDeg, glycated hemoglobin (A1C) decreased by -0.3 (95% confidence interval [CI], -0.4% to -0.2%) and the reduction in A1C was maintained throughout the follow-up period. Rates of all-cause hospitalizations/emergency department visits per patient were not affected (hospitalizations pre-switch 0.07 [95% CI, 0.07 to 0.08], post-switch 0.08 [95% CI, 0.06 to 0.09], p=0.45; ED visits pre-switch 0.25 [95% CI, 0.23 to 0.27], post-switch 0.26 [95% CI, 0.23 to 0.29], p=0.27). In the clinic cohort, at switch, there was an average basal insulin dose reduction of 11.2% (T1DM), 12.3% (T2DM) and 16.3% (patients with insulin resistance). CONCLUSIONS: Patients with inadequate glycemic control or who find their basal insulin dosing inconvenient may benefit from switching to Ideg, with the potential for small improvementa in A1C at lower basal insulin doses.

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.

Antimicrobial Stewardship at Birth in Preterm Infants: Not Just About a Decrease!

BACKGROUND: Early-onset sepsis results in increased morbidity and mortality in preterm infants. Antimicrobial Stewardship Programs (ASPs) address the need to balance adverse effects of antibiotic exposure with the need for empiric treatment for infants at the highest risk for early-onset sepsis. METHODS: All preterm infants <34 weeks gestational age born during a 6-month period before (January 2017-June 2017) and a 6-month period after (January 2019-June 2019) implementation of ASP in May 2018 were reviewed. The presence of perinatal sepsis risk factors, eligibility for, versus treatment with initial empiric antibiotics was compared. RESULTS: Our cohort comprised 479 infants with a mean of 30 weeks gestation and birth weight of 1400 g. Demographics were comparable, with more Cesarean section deliveries in the post-ASP cohort. Any sepsis risk factor was present in 73.6% versus 68.4% in the pre- versus post-ASP cohorts (P = 0.23). Fewer infants were treated with antibiotics in the later cohort (60.4%) compared with the earlier cohort (69.7%; P = 0.04). Despite the presence of risk factors (preterm labor in 93% and rupture of membranes in 60%), 42% of infants did not receive initial antibiotics. Twenty percent with no perinatal sepsis risk factors were deemed low-risk and not treated. CONCLUSIONS: Implementation of a neonatal ASP decreased antibiotic initiation at birth. Antibiotic use decreased (appropriately) in the subgroup with no perinatal sepsis risk factors. Of concern, some infants were not treated despite risk factors, such as preterm labor/rupture of membrane. Neonatal ASP teams need to be aware of potentially unintended consequences of their initiatives.

Risk Factors for Preoperative Hyperglycemia in Surgical Patients with Diabetes: A Case-Control Study.

BACKGROUND: Patients with diabetes are more likely to undergo a surgical procedure than the rest of the population, and it is well established that preoperative hyperglycemia is associated with adverse surgical outcomes. However, it is currently unknown what factors increase the odds of preoperative hyperglycemia in people with diabetes. OBJECTIVE: To identify patient characteristics that increase the risk of preoperative hyperglycemia. METHODS: This retrospective case-control study compared 100 patients with preoperative hyperglycemia on admission for elective surgery at South Health Campus in Calgary, Alberta (blood glucose > 10.9 mmol/L) with 200 controls who did not have preoperative hyperglycemia on admission for elective surgery (blood glucose ≤ 10.9 mmol/L). Multivariate logistic regression was used to identify risk factors for preoperative hyperglycemia. RESULTS: In the univariate analysis, age, number of comorbidities, increasing glycated hemoglobin (HbA1c), type of diabetes, type of procedure, and diabetes medications (non-insulin, insulin, both, or none) were associated with increased odds of preoperative hyperglycemia (p < 0.05). However, in the adjusted analysis, only increasing HbA1c (odds ratio [OR] 1.69, 95% confidence interval [CI] 1.36-2.12) and type 1 diabetes (OR 4.24, 95% CI 1.11-16.21, relative to type 2 diabetes) were associated with preoperative hyperglycemia. CONCLUSIONS: These results can help clinicians to identify patients who may be at increased risk of hyperglycemia before an elective procedure. They also allow for treatment of those who would benefit most from additional guidance with regard to preoperative glucose management.

CONTEXTE: Les patients diabétiques sont plus susceptibles que le reste de la population de subir une intervention chirurgicale, et il est bien connu que l'hyperglycémie préopératoire est associée à des résultats chirurgicaux indésirables. Cependant, on ignore actuellement quels facteurs augmentent ce risque chez les personnes atteintes de diabète. OBJECTIF: Déterminer les caractéristiques des patients qui augmentent le risque d'hyperglycémie préopératoire. MÉTHODES: Cette étude cas-témoins rétrospective a comparé 100 patients présentant une hyperglycémie préopératoire à l'admission pour une intervention chirurgicale non urgente au South Health Campus de Calgary, en Alberta (glycémie > 10,9 mmol/L) avec 200 témoins qui n'en présentaient pas (glycémie ≤ 10,9 mmol/L). La détermination des facteurs de risque d'hyperglycémie préopératoire s'est faite par régression logistique multivariée. RÉSULTATS: Dans l'analyse univariée, l'âge, le nombre de comorbidités, l'augmentation du taux d'hémoglobine glyquée (HbA1c), le type de diabète, le type d'intervention et les médicaments contre le diabète (non-insuline, insuline, les deux ou aucun) étaient associés à un risque accru d'hyperglycémie préopératoire (p < 0,05). Cependant, dans l'analyse ajustée, seuls l'augmentation de l'HbA1c (rapport de cotes [RC] 1,69; intervalle de confiance [IC] à 95 % 1,36­2,12) et le diabète de type 1 (RC 4,24; IC à 95 % 1,11­16,21, par rapport au diabète de type 2) étaient associés à une hyperglycémie préopératoire. CONCLUSIONS: Ces résultats peuvent aider les cliniciens à repérer les patients qui pourraient présenter un plus grand risque d'hyperglycémie avant une intervention non urgente. Ils permettent également de traiter ceux qui bénéficieraient le plus de conseils supplémentaires en matière de gestion préopératoire de la glycémie.

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.

An assessment of the impact of dexmedetomidine on opioid use in a neonatal intensive care unit.

OBJECTIVE: To evaluate the impact of dexmedetomidine on opioid use in neonates. METHODS: A retrospective chart review of neonates that received dexmedetomidine compared to matched historical controls in a surgical tertiary NICU. The primary endpoint was overall opioid exposure. Secondary endpoints included the duration of regular opioid use, duration of opioid wean, duration of mechanical ventilation, and time to achieve full enteral feeds. RESULTS: There were no statistically significant differences in opioid exposure (60.3 vs 42.6 mcg ME/kg, p = .25), duration (583 vs 340 h, p = .07), or wean duration (261 vs 147 h, p = .12) between the two cohorts. In fact, these parameters showed clinically, if not statistically, significant increases in the dexmedetomidine cohort. Opioid exposure per day, length of NICU stay, duration of mechanical ventilation, and days to full enteral feeds did not differ between cohorts. CONCLUSION: This retrospective cohort study did not show reduced opioid exposure in surgical neonates receiving dexmedetomidine, which is in contrast to other literature. It highlights the limitations of using a medication without appropriate guidance and assessment tools to support its use.

Clinical outcome of chronic myeloid leukemia patients who switch from first-line therapy with a second generation tyrosine kinase inhibitor to an alternative TKI.

While second generation tyrosine kinase inhibitors (2GTKIs) are highly effective therapies for chronic myeloid leukemia (CML), a significant minority of patients who initiate a 2GTKI will require a switch to an alternative TKI. The long-term outcomes of those who require a change in therapy after front-line 2GTKI therapy are largely undescribed. Here we describe the clinical outcomes associated with switch to an alternative TKI after first-line therapy with a 2GTKI. Of 232 patients who initiated a 2GTKI during the study period, 76 (33 %) switched to an alternative TKI. Reasons for switching included intolerance (79 %) and resistance (21 %). Among the 60 patients who switched due to intolerance, 53 (88 %) were able to achieve or maintain a major molecular response (MMR) with 5-year progression-free survival (PFS) 90.5 % (95 % CI 90.4-90.6 %). Amongst the 16 patients who switched due to resistance, 8 patients (50 %) were able to achieve MMR with 5-year PFS 80.4 % (95 % CI 80.2-80.6 %). Most patients who switched due to intolerance remained on their second-line TKI. Approximately 25 % of patients who initiate first-line 2GTKI in a real world setting will ultimately switch to an alternate TKI due to intolerance. Patients who switch for intolerance continue to enjoy excellent clinical 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.