An external facilitation intervention to increase uptake of an adverse drug event reporting intervention.

Background: Adverse drug events (ADEs) are a leading cause of emergency department visits and hospital admissions in Canada. ActionADE prevents repeat ADEs by enabling clinicians to document and communicate standardized ADE information across care settings. We used an external facilitation intervention to promote the uptake of ActionADE in four hospitals in British Columbia, Canada. This study examined whether, how and in what context external facilitation influenced the uptake of ActionADE. Methods: In this convergent-parallel mixed-methods study, an external facilitator used a four-step iterative process to support site champions using context-specific implementation strategies to increase the ADE reporting rate at their sites. We extracted archival data to assess implementation determinants before and after the implementation of the external facilitation and implementation strategies. We also retrieved data on the mean monthly counts of reported ADEs for each user from the ActionADE server. Zero-inflated Poisson models were used to examine changes in mean monthly counts of reported ADEs per user between pre-intervention (June 2021 to October 2021) and intervention (November 2021 to March 2022) periods. Results: The external facilitator and site champions co-created three functions: (1) educate pharmacists about what and how to report in ActionADE, (2) educate pharmacists about the impact of ActionADE on patient outcomes, and (3) provide social support for pharmacists to integrate ADE reporting into clinical workflows. Site champions used eight forms to address the three functions. Peer support and reporting competition were the two common strategies used by all sites. Sites' responses to external facilitation varied. The rate of mean monthly counts of reported ADEs per user significantly increased during the intervention period compared to the pre-intervention period at LGH (RR: 3.74, 95% CI 2.78 to 5.01) and RH (RR: 1.43, 95% CI 1.23 to 1.94), but did not change at SPH (RR: 0.68, 95% CI: 0.43 to 1.09) and VGH (RR: 1.17, 95% CI 0.92 to 1.49). Leave of absence of the clinical pharmacist champion and failure to address all identified functions were implementation determinants that influenced the effectiveness of external facilitation. Conclusion: External facilitation effectively supported researchers and stakeholders to co-create context-specific implementation strategies. It increased ADE reporting at sites where clinical pharmacist champions were available, and where all functions were addressed.

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

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

Urinary Tract Infections in Long-term Care: Evaluation of Uropathogens, Antibiotic Susceptibility, and Empiric Treatment.

Objective To devise a residential empiric treatment algorithm, describe common uropathogens associated with urinary tract infections (UTIs) in residential care, assess all-pathogen and non-ESBL (extended-spectrum beta-lactamase) Escherichia coli antibiotic susceptibilities, and report the percentage of antibiotic use. Design A retrospective chart review of 198 residents with positive urine cultures from September 2019 to September 2020. Setting Institutional long-term care facility. Participants The exclusion criteria were negative urine culture, mixed organisms on urine culture, no antibiotic treatment, signs and symptoms of systemic infection, hospitalization because of systemic infection, and intravenous antibiotic treatment. The entire population was screened. Results The most prevalent pathogens were non-ESBL E. coli (29%), Proteus mirabilis (12%), Klebsiella pneumoniae (8%), and ESBL E. coli (8%). All-pathogen susceptibilities were 79.6% (amoxicillin/clavulanate), 64.1% (nitrofurantoin), 50.5% (sulfamethoxazole/trimethoprim), 43.7% (cephalexin), 42.7% (amoxicillin), and 41.8% (ciprofloxacin). Amoxicillin/clavulanate (96.7%), nitrofurantoin (90.0%) and sulfamethoxazole/trimethoprim (83.3%) demonstrated the highest non-ESBL E. coli susceptibilities. Nitrofurantoin was the most prescribed antibiotic (21%), followed by amoxicillin/clavulanate (19%) and ciprofloxacin (17%). Conclusion Based on the data, amoxicillin/clavulanate and nitrofurantoin are appropriate first-line options for empiric treatment of symptomatic cystitis in this long-term care facility, with sulfamethoxazole/trimethoprim as an alternative. Ciprofloxacin was overprescribed despite its low susceptibilities to commonly encountered pathogens, which emphasizes the need for a UTI empiric treatment algorithm tailored towards residential care.

Therapeutic drug monitoring in the neurocritical care unit.

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

A systematic review of limited sampling strategies for platinum agents used in cancer chemotherapy.

Despite evidence in the literature suggesting that a strong correlation exists between the pharmacokinetic parameters and pharmacodynamic effect of anticancer agents, many of these agents are still dosed by body surface area. Therapeutic drug monitoring with the aim of pharmacokinetic-guided dosing would not only maintain target concentrations associated with efficacy but may potentially minimise the likelihood of dose-related systemic toxicities. The pharmacokinetic parameter that displays the best correlation with the pharmacodynamics of anticancer drugs is the area under the plasma concentration-time curve (AUC). However, accurate determination of the AUC requires numerous blood samples over an extended interval, which is not feasible in clinical practice. Therefore, limited sampling strategies (LSSs) have been proposed as a means to accurately and precisely estimate pharmacokinetic parameters with a minimal number of blood samples. LSSs have been developed for many drugs, particularly ciclosporin and other immunosuppressants, as well as for certain anticancer drugs. This systematic review evaluates LSSs developed for the platinum compounds and categorises 18 pertinent citations according to criteria adapted from the US Preventive Services Task Force. Thirteen citations (four level I, six level II-1, three level II-2) pertained to LSSs for carboplatin, four citations (one level II-1, one level II-2, two level III) to cisplatin LSSs, and one citation (level II-2) to nedaplatin. Based on the current evidence, it appears that LSSs may be useful for pharmacokinetic-guided dosage adjustments of carboplatin in both adults and children with cancer. Although some validation studies suggest that LSSs can be extended to different cancer populations or different chemotherapy regimens, other studies dispute this finding. Although the use of LSSs to predict the pharmacokinetic parameters of cisplatin and nedaplatin appear promising, the quality of evidence from published studies does not support routine implementation at this time.LSSs represent one approach in which clinicians can make specific dosage adjustments for individual patients to optimise outcomes. However, the limitations of these strategies must also be taken into consideration. There is also a need for prospective studies to demonstrate that application of LSSs for platinum agents ultimately improves patient response and decreases systemic toxicities.