Aude Motulsky

In situ-forming pharmaceutical organogels based on the self-assembly of L-alanine derivatives.

AbstractPurpose. To characterize novel pharmaceutical organogels based on the self-assembly of L-alanine derivatives in hydrophobic vehicles. Methods. The gelation properties of N-lauroyl-L-alanine (LA) and N-lauroyl-L-alanine methyl ester (LAM) were investigated in the presence of various solvents. Gel-sol and sol-gel transitions were evaluated by the inverse flow method, and gelation kinetics were determined by turbidimetry. The in vitro release kinetics of labeled dextran physically dispersed in the oil-based organogel was assessed in phosphate-buffered saline. In situ formation of the implants was evaluated in rats by subcutaneously injecting a solution containing LAM, an oil, and a water-diffusible inhibitor of self-assembly (ethanol). Results. The LAM-containing formulations showed a hysteretic gelling behavior with transition temperatures between 10 and 55°C. Gelation kinetics exhibited a lag time of 10 and 30 min at 25 and 37°C, respectively. In vitro, fluorescein isothiocyanate-dextran was released from the gel in a sustained manner with less than 6% released after 20 days. The addition of ethanol to the LAM/oil mixture inhibited gelation and allowed subcutaneous injection of the solution at room temperature. After injection, ethanol diffusion led to the formation of a solid implant. Conclusions. Low-molecular weight self-assembling organogelators may allow the preparation of novel in situ-forming hydrophobic implants.

Tyrosine-based rivastigmine-loaded organogels in the treatment of Alzheimer’s disease

Organogels can be prepared by immobilizing an organic phase into a three-dimensional network coming from the self-assembly of a low molecular weight gelator molecule. In this work, an injectable subcutaneous organogel system based on safflower oil and a modified-tyrosine organogelator was evaluated in vivo for the delivery of rivastigmine, an acetylcholinesterase (AChE) inhibitor used in the treatment of Alzheimers disease. Different implant formulations were injected and the plasmatic drug concentration was assayed for up to 35 days. In parallel, the inhibition of AChE in different brain sections and the biocompatibility of the implants were monitored. The pharmacokinetic profiles were found to be influenced by the gel composition, injected dose and volume of the implant. The sustained delivery of rivastigmine was accompanied by a significant prolonged inhibition of AChE in the hippocampus, a brain structure involved in memory. The implant induced only a minimal to mild chronic inflammation and fibrosis, which was comparable to poly(D,L-lactide-co-glycolide) in situ-forming implants. These findings suggest that tyrosine-based organogels could represent an alternative approach to current formulations for the sustained delivery of cholinesterase inhibitors.

Treatment Indications for Antidepressants Prescribed in Primary Care in Quebec, Canada, 2006-2015

This pharmacoepidemiology study uses national Canadian electronic medical record data to describe treatment indications for antidepressants and temporal trends in antidepressant prescribing for depression in Quebec, Canada, from 2006 through 2015.

Off-label indications for antidepressants in primary care: descriptive study of prescriptions from an indication based electronic prescribing system

Objective To examine off-label indications for antidepressants in primary care and determine the level of scientific support for off-label prescribing. Design Descriptive study of antidepressant prescriptions written by primary care physicians using an indication based electronic prescribing system. Setting Primary care practices in and around two major urban centres in Quebec, Canada. Participants Patients aged 18 years or older who visited a study physician between 1 January 2003 and 30 September 2015 and were prescribed an antidepressant through the electronic prescribing system. Main outcome measures Prevalence of off-label indications for antidepressant prescriptions by class and by individual drug. Among off-label antidepressant prescriptions, the proportion of prescriptions in each of the following categories was measured: strong evidence supporting use of the prescribed drug for the respective indication; no strong evidence for the prescribed drug but strong evidence supporting use of another drug in the same class for the indication; or no strong evidence supporting use of the prescribed drug and all other drugs in the same class for the indication. Results 106 850 antidepressant prescriptions were written by 174 physicians for 20 920 adults. By class, tricyclic antidepressants had the highest prevalence of off-label indications (81.4%, 95% confidence interval, 77.3% to 85.5%), largely due to a high off-label prescribing rate for amitriptyline (93%, 89.6% to 95.7%). Trazodone use for insomnia was the most common off-label use for antidepressants, accounting for 26.2% (21.9% to 30.4%) of all off-label prescriptions. For only 15.9% (13.0% to 19.3%) of all off-label prescriptions, the prescribed drug had strong scientific evidence for the respective indication. For 39.6% (35.7% to 43.2%) of off-label prescriptions, the prescribed drug did not have strong evidence but another antidepressant in the same class had strong evidence for the respective indication. For the remaining 44.6% (40.2% to 49.0%) of off-label prescriptions, neither the prescribed drug nor any other drugs in the class had strong evidence for the indication. Conclusions When primary care physicians prescribed antidepressants for off-label indications, these indications were usually not supported by strong scientific evidence, yet often another antidepressant in the same class existed that had strong evidence for the respective indication. There is an important need to generate and provide physicians with evidence on off-label antidepressant use to optimise prescribing decisions.

Using mobile devices for inpatient rounding and handoffs: an innovative application developed and rapidly adopted by clinicians in a pediatric hospital

Objective: To describe the usage of a novel application (The FLOW) that allows mobile devices to be used for rounding and handoffs. Materials and Methods: The FLOW provides a view of patient data and the capacity to enter short notes via personal mobile devices. It was deployed using a “bring-your-own-device” model in 4 pilot units. Social network analysis (SNA) was applied to audit trails in order to visualize usage patterns. A questionnaire was used to describe user experience. Results: Overall, 253 health professionals used The FLOW with their personal mobile devices from October 2013 to March 2015. In pediatric and neonatal intensive care units (ICUs), a median of 26–26.5 notes were entered per user per day. Visual network representation of app entries showed that usage patterns were different between the ICUs. In 127 questionnaires (50%), respondents reported using The FLOW most often to enter notes and for handoffs. The FLOW was perceived as having improved patient care by 57% of respondents, compared to usual care. Most respondents (86%) wished to continue using The FLOW. Discussion: This study shows how a handoff and rounding tool was quickly adopted in pediatric and neonatal ICUs in a hospital setting where patient charts were still paper-based. Originally developed as a tool to support informal documentation using smartphones, it was adapted to local practices and expanded to print sign-out documents and import notes within the medicolegal record with desktop computers. Interestingly, even if not supported by the nursing administrative authorities, the level of use for data entry among nurses and doctors was similar in all units, indicating close collaboration in documentation practices in these ICUs.

Connecting primary care clinics and community pharmacies through a nationwide electronic prescribing network: A qualitative study

Background The use of medication is at the heart of primary care, but is also the cause for major health concerns. It is therefore important to examine the prescription of medication process. Objective This study identifies the barriers and facilitators perceived by community pharmacists and primary care physicians concerning the adoption of a nationwide electronic prescribing (e-prescribing) network in the province of Quebec, Canada. Methods We used purposive sampling to identify the most intensive users of the e-prescribing network. We conducted phone and in-person interviews. Interviews were transcribed, and we analysed their content with NVivo, using the clinical adoption framework (CAF) for the codification of the data. Results We interviewed 33 pharmacists, 2 pharmacy technicians, 11 physicians and 3 clinic managers. Adoption of the e-prescribing network was fairly low. The respondents underlined adaptation of their work environment, openness to change and perception of benefits as facilitators to the adoption of the network. However, important barriers were perceived, including system quality issues and paper prescriptions being the only legal document in the prescribing process. Even if respondents recognised that the e-prescribing network can offer substantial benefits to the prescribing process, issues still persisted and raised barriers to the full use of such a network, especially in a context where different local information systems are connected within a nationwide e-prescribing network. Conclusion This study, based on the CAF, provides a better understanding of the factors related to the adoption of a nationwide e-prescribing network connecting primary care clinics and community pharmacies. Where this study fits in? Electronic prescribing could improve the processes related to the use and dispensation of drugs in health care, but their adoption is still poor in the North American context. Research on the topic of adoption of electronic prescribing is still limited, particularly among health professionals other than physicians. This study, based on the clinical adoption framework (CAF), provides a better understanding of the factors related to the adoption of a nationwide electronic prescribing network connecting primary care clinics and community pharmacies in the province of Quebec, Canada.

Improving patient safety and efficiency of medication reconciliation through the development and adoption of a computer-assisted tool with automated electronic integration of population-based community drug data: the RightRx project

Abstract Background and Objective Many countries require hospitals to implement medication reconciliation for accreditation, but the process is resource-intensive, thus adherence is poor. We report on the impact of prepopulating and aligning community and hospital drug lists with data from population-based and hospital-based drug information systems to reduce workload and enhance adoption and use of an e-medication reconciliation application, RightRx. Methods The prototype e-medical reconciliation web-based software was developed for a cluster-randomized trial at the McGill University Health Centre. User-centered design and agile development processes were used to develop features intended to enhance adoption, safety, and efficiency. RightRx was implemented in medical and surgical wards, with support and training provided by unit champions and field staff. The time spent per professional using RightRx was measured, as well as the medication reconciliation completion rates in the intervention and control units during the first 20 months of the trial. Results Users identified required modifications to the application, including the need for dose-based prescribing, the role of the discharge physician in prescribing community-based medication, and access to the rationale for medication decisions made during hospitalization. In the intervention units, both physicians and pharmacists were involved in discharge reconciliation, for 96.1% and 71.9% of patients, respectively. Medication reconciliation was completed for 80.7% (surgery) to 96.0% (medicine) of patients in the intervention units, and 0.7% (surgery) to 82.7% of patients in the control units. The odds of completing medication reconciliation were 9 times greater in the intervention compared to control units (odds ratio: 9.0, 95% confidence interval, 7.4-10.9, P < .0001) after adjusting for differences in patient characteristics. Conclusion High rates of medication reconciliation completion were achieved with automated prepopulation and alignment of community and hospital medication lists.

Usage and accuracy of medication data from nationwide health information exchange in Quebec, Canada

Objective (1) To describe the usage of medication data from the Health Information Exchange (HIE) at the health care system level in the province of Quebec; (2) To assess the accuracy of the medication list obtained from the HIE. Methods A descriptive study was conducted utilizing usage data obtained from the Ministry of Health at the individual provider level from January 1 to December 31, 2015. Usage patterns by role, type of site, and tool used to access the HIE were investigated. The list of medications of 111 high risk patients arriving at the emergency department of an academic healthcare center was obtained from the HIE and compared with the list obtained through the medication reconciliation process. Results There were 31 022 distinct users accessing the HIE 11 085 653 times in 2015. The vast majority of pharmacists and general practitioners accessed it, compared to a minority of specialists and nurses. The top 1% of users was responsible of 19% of access. Also, 63% of the access was made using the Viewer application, while using a certified electronic medical record application seemed to facilitate usage. Among 111 patients, 71 (64%) had at least one discrepancy between the medication list obtained from the HIE and the reference list. Conclusions Early adopters were mostly in primary care settings, and were accessing it more frequently when using a certified electronic medical record. Further work is needed to investigate how to resolve accuracy issues with the medication list and how certain tools provide different features.