Sharing Adverse Drug Event Reports Between Hospitals and Community Pharmacists to Inform Re-dispensing: An Analysis of Reports and Process Outcomes.

INTRODUCTION: Adverse drug events (ADEs) are a leading cause of unplanned hospital visits. We designed ActionADE, an online ADE reporting platform, and integrated it with PharmaNet, British Columbia's (BC's) provincial medication dispensing system, to overcome identified barriers in ADE reporting and communicate ADEs to community pharmacies. Our objectives were to characterise ADEs reported in ActionADE, explore associations between patients' age, sex and ADE characteristics, and estimate the re-dispensation rate of culprit medications in community pharmacies. METHODS: We conducted a prospective observational study of ADE reporting in four BC hospitals between April 1, 2020 and October 31, 2022. We described the characteristics of ADEs reported into ActionADE, used logistic regression modelling to examine associations between age and sex and ADE characteristics, and calculated rates of avoided culprit drug re-dispensations using community pharmacists' responses to ActionADE alerts. RESULTS: In total, 3591 ADE reports were initiated by hospital clinicians, 3174 of which were included in this analysis. Serious or life-threatening ADEs resulting in permanent disability, hospitalisation, extended hospitalisation, and/or death accounted for 28.5% (906/3174; 95% CI 27.0-30.1%) of reports. Males were more likely to have non-adherence reported compared to females and experienced life threatening ADEs at a younger age than females. Of 592 patients who had ≥ 1 adverse drug reaction or allergy report (a subset of ADEs) transmitted to community pharmacies, 200 subsequently attempted to re-fill the culprit or a same class drug. Community pharmacists responded to preventative alerts by avoiding re-dispensation in 33.0% (66/200; 95% CI 26.5-39.5%). INTERPRETATION: ActionADE is the first interoperable system that communicates ADEs via a central medication database to community pharmacies. Every 10th ADE reported in ActionADE and shared to PharmaNet resulted in community pharmacists' avoiding one culprit or same class drug re-exposure. Further research is needed to understand ActionADE's impact on patient and health system outcomes.

Out-of-hospital management of unresponsive, apneic, witnessed opioid overdoses: a case series from a supervised consumption site.

OBJECTIVES: There are conflicting recommendations for lay rescuer management of patients who are unresponsive and apneic due to opioid overdose. We evaluated the management of such patients at an urban supervised consumption site. METHODS: At a single urban supervised consumption site in Vancouver, BC, we conducted a retrospective chart review and administrative database linkage of consecutive patients who were unresponsive and apneic following witnessed opioid overdose between January 1, 2012 and December 31, 2017. We linked these visits with regional hospital records to define the entire care episode, which concluded when the patient was discharged from the supervised consumption site, ED, or hospital, or died. The primary outcome was successful resuscitation, defined as alive and neurologically intact (ambulatory and speaking coherently, or alert and oriented, or Glasgow Coma Scale 15) at the conclusion of the care episode. Secondary outcomes included mortality and predefined complications of resuscitation. RESULTS: We collected 767 patients, with a median age of 43 and 81.6% male, with complete follow-up on 763 patients (99.5%). All patients were managed with oxygen and ventilation (100%, 95% CI 0.995-1.0); 715 (93.2%, 95% CI 0.911-0.949) received naloxone; no patients underwent chest compressions (0%, 95% CI 0-0.005). All patients with complete follow-up were alive and neurologically intact at the end of their care episode (100%, 95% CI 0.994-1.0). Overall, 191 (24.9%) patients were transported to hospital, and 15 (2.0%) patients required additional naloxone after leaving the supervised consumption site; 16 (2.1%) developed complications, and 1 patient was admitted to hospital. CONCLUSIONS: At an urban supervised consumption site, all unresponsive, apneic patients with witnessed opioid overdose were successfully resuscitated with oxygen and/or naloxone. No patients required chest compressions.

RéSUMé: OBJECTIFS: Il existe des recommandations contradictoires concernant la prise en charge par des secouristes non professionnels des patients qui ne réagissent pas et sont apnéiques en raison d'une surdose d'opioïdes. Nous avons évalué la prise en charge de ces patients dans un site urbain de consommation supervisée. MéTHODES: Dans un seul site de consommation supervisée urbain à Vancouver, en Colombie-Britannique, nous avons effectué un examen rétrospectif des dossiers et un couplage de bases de données administratives de patients consécutifs qui étaient insensibles et apnéiques après avoir été témoins d'une surdose d'opioïdes entre le 1er janvier 2012 et le 31 décembre 2017. Le résultat primaire était la réussite de la réanimation, définie comme étant vivante et neurologiquement intacte (ambulatoire et parlant de manière cohérente, ou alerte et orientée, ou échelle de coma de Glasgow 15) à la fin de l'épisode de soins. Les résultats secondaires comprenaient la mortalité et les complications prédéfinies de la réanimation. RéSULTATS: Nous avons recueilli 767 patients, avec un âge médian de 43 ans et 81,6 % d'hommes, avec un suivi complet de 763 patients (99,5 %). Tous les patients ont été pris en charge avec de l'oxygène et la ventilation (100 %, IC à 95 % : 0,995-1,0) ; 715 (93,2 %, IC à 95 % : 0,911-0,949) ont reçu de la naloxone ; aucun patient n'a subi de compressions thoraciques (0 %, IC à 95 % : 0-0,005). Tous les patients ayant fait l'objet d'un suivi complet étaient vivants et intacts sur le plan neurologique à la fin de leur épisode de soins (100 %, IC à 95 % : 0,994-1,0). Dans l'ensemble, 191 (24,9 %) patients ont été transportés à l'hôpital, et 15 (2,0 %) patients ont eu besoin de naloxone supplémentaire après avoir quitté le site de consommation supervisée ; 16 (2,1 %) ont développé des complications, et 1 patient a été admis à l'hôpital. CONCLUSIONS: Dans un centre de consommation supervisée urbain, tous les patients apnéiques non réceptifs ayant été témoins d'une surdose d'opioïdes ont été réanimés avec succès avec de l'oxygène et/ou de la naloxone. Aucun patient n'a eu besoin de compressions thoraciques.

Comparison of rates of opioid withdrawal symptoms and reversal of opioid toxicity in patients treated with two naloxone dosing regimens: a retrospective cohort study.

INTRODUCTION: When managing opioid overdose (OD) patients, the optimal naloxone regimen should rapidly reverse respiratory depression while avoiding opioid withdrawal. Published naloxone administration guidelines have not been empirically validated and most were developed before fentanyl OD was common. In this study, rates of opioid withdrawal symptoms (OW) and reversal of opioid toxicity in patients treated with two naloxone dosing regimens were evaluated. METHODS: In this retrospective matched cohort study, health records of patients who experienced an opioid OD treated in two urban emergency departments (ED) during an ongoing fentanyl OD epidemic were reviewed. Definitions for OW and opioid reversal were developed a priori. Low dose naloxone (LDN; ≤0.15 mg) and high dose naloxone (HDN; >0.15 mg) patients were matched in a 1:4 ratio based upon initial respiratory rate (RR). The proportion of patients who developed OW and who met reversal criteria were compared between those treated initially with LDN or HDN. Odds ratios (OR) for OW and opioid reversal were obtained via logistic regression stratified by matched sets and adjusted for age, sex, pre-naloxone GCS, and presence of non-opioid drugs or alcohol. RESULTS: Eighty LDN patients were matched with 299 HDN patients. After adjustment, HDN patients were more likely than LDN patients to have OW after initial dose (OR = 8.43; 95%CI: 1.96, 36.3; p = 0.004) and after any dose (OR = 2.56; 95%CI: 1.17, 5.60; p = 0.019). HDN patients were more likely to meet reversal criteria after initial dose (OR = 2.73; 95%CI: 1.19, 6.26; p = 0.018) and after any dose (OR = 6.07; 95%CI: 1.81, 20.3; p = 0.003). CONCLUSIONS: HDN patients were more likely to have OW but also more likely to meet reversal criteria versus LDN patients.

Identification of fat mass and obesity associated (FTO) protein expression in cardiomyocytes: regulation by leptin and its contribution to leptin-induced hypertrophy.

The recently-identified fat mass and obesity-associated (FTO) protein is associated with various physiological functions including energy and body weight regulation. Ubiquitously expressed, FTO was identified in heart homogenates although its function is unknown. We studied whether FTO is specifically expressed within the cardiac myocyte and its potential role pertaining to the hypertrophic effect of the adipokine leptin. Most experiments were performed using cultured neonatal rat cardiomyocytes which showed nuclei-specific FTO expression. Leptin significantly increased FTO expression which was associated with myocyte hypertrophy although both events were abrogated by FTO knockdown with siRNA. Administration of a leptin receptor antibody to either normal or obese rats significant reduced myocardial FTO protein expression. Responses in cardiomyocytes were accompanied by JAK2/STAT3 activation whereas JAK2/STAT3 inhibition abolished these effects. Expression of the cut-like homeobox 1(CUX1) transcriptional factor was significantly increased by leptin although this was restricted to the cathepsin L-dependent, proteolytically-derived shorter p110CUX1 isoform whereas the longer p200CUX1 protein was not significantly affected. Cathepsin L expression and activity were both significantly increased by leptin whereas a cathepsin L peptide inhibitor or siRNA specific for CUX1 completely prevented the leptin-induced increase in FTO expression. The cathepsin L peptide inhibitor or siRNA-induced knockdown of either CUX1 or FTO abrogated the hypertrophic response to leptin. Two other pro-hypertrophic factors, endothelin-1 or angiotensin II had no effect on FTO expression and FTO knockdown did not alter the hypertrophic response to either agent. This study demonstrates leptin-induced FTO upregulation in cardiomyocytes via JAK2/STAT3- dependent CUX1 upregulation and suggests an FTO regulatory function of leptin. It also demonstrates for the first time a functional role of FTO in the cardiomyocyte.