Romano A. Fois

Anticholinergic Activity of Commonly Prescribed Medications and Neuropsychiatric Adverse Events in Older People

This study sought to determine whether the presence of in vitro anticholinergic activity (AA) among different drugs is associated with reporting of neuropsychiatric adverse events (NPAEs) and whether age affects this relationship. Retrospective case/noncase analyses using Australias spontaneous Adverse Drug Reaction System (ADRS) database containing 150 475 reports determined crude and adjusted reporting odds ratios (RORs) for NPAEs for 23 drugs with various reported in vitro AA. Covariates were age (treated as a dichotomous variable [≥65 years]), gender, and concomitant use of antipsychotics, benzodiazepines, tricyclic antidepressants, and drugs with recognized inherent anticholinergic properties (anticholinergic drugs). The interaction effect between these covariates and each drug exposure category was examined. Age (≥65 years) has a significant association with greater odds relative to younger age for reporting NPAEs. Drugs with reported significant AA in vitro were not always associated with RORs greater than 1 for reporting NPAEs, highlighting a dissonance between the in vitro AA index and ADRS observations. Significant interactions were observed between age (≥65 years) and exposure to cimetidine, anticholinergic drugs, antipsychotics, and tricyclic antidepressants in modifying odds for reporting NPAEs, reinforcing the need for cautious use and monitoring of drugs with AA in older people.

Spontaneous adverse event reports associated with zolpidem in Australia 2001-2008.

A prominent media publicity cluster during 2007–2008 in Australia linked the common hypnotic zolpidem to adverse drug reaction reports of parasomnias, amnesia, hallucinations and suicidality. The collection of adverse drug reaction data through spontaneous reporting systems is a mainstay of drug safety monitoring, but a stimulated reporting event such as this often renders such data uninterpretable. As such, we aimed to investigate whether these associations were present before the media cluster and then to quantify the effect of stimulated reporting on those four specific outcomes. Using disproportionality analyses we compared zolpidem to all other drugs in the database, and then separately to each of all hypnotics, then all benzodiazepines, and then temazepam alone, and did so in every year from 2001 to 2008. Year‐by‐year analyses of Reporting odds ratios for zolpidem exposure and adverse events of interest, adjusted for a number of covariates, revealed an association between zolpidem exposure and parasomnias, amnesia and hallucination both before and after the cluster of media publicity beginning in early 2007. The odds ratios increased significantly after the media publicity for only parasomnias and amnesia. Suicidality was increased in some analyses, but limited data make this outcome difficult to interpret. We conclude that zolpidem adverse drug reaction reports have higher odds for parasomnia, amnesia, hallucination and perhaps suicidality compared to either all other drugs or hypnotics, even before the media publicity cluster. However, the extant literature and the limitations of these spontaneously reported adverse drug reaction data do not allow us to conclude that these events are related causally to zolpidem.

An exploration of Australian hospital pharmacists' attitudes to patient safety.

To explore the attitudes of Australian hospital pharmacists towards patient safety in their work settings.

Course experiences, satisfaction and career intent of final year pre-registration Australian pharmacy students.

Background In Australia, the profession of pharmacy has undergone many changes to adapt to the needs of the community. In recent years, concerns have been raised with evidence emerging of workforce saturation in traditional pharmacy practice sectors. It is not known how current final year pharmacy students’ perceive the different pharmacy career paths in this changing environment. Hence investigating students’ current experiences with their pharmacy course, interaction with the profession and developing an understanding of their career intentions would be an important step, as these students would make up a large proportion of future pharmacy workforce. Objective The objective of this study was thus to investigate final year students’ career perspectives and the reasons for choosing pharmacy, satisfaction with this choice of pharmacy as a tertiary course and a possible future career, factors affecting satisfaction and intention of future career paths. Methods A quantitative cross sectional survey of final year students from 3 Australian universities followed by a qualitative semi-structured interview of a convenience sample of final year students from the University of Sydney. Results ‘Interest in health and medicine’ was the most important reason for choosing pharmacy (n=238). The majority of students were ‘somewhat satisfied’ with the choice of pharmacy (35.7%) as a course and possible future career. Positive associations were found between satisfaction and reasons for joining pharmacy such as ‘felt pharmacy is a good profession’ (p=0.003) while negative associations included ‘joined pharmacy as a gateway to medicine or dentistry’ (p=0.001). Quantitate and qualitative results showed the most frequent perception of community pharmacy was ‘changing’ while hospital and pharmaceutical industry was described as ‘competitive’ and ‘research’ respectively. The highest career intention was community followed by hospital pharmacy. Conclusion Complex factors including university experiences are involved in shaping students’ satisfaction and perception of career. This may relate to challenges in the community pharmacy sector, job opportunities in hospital and limited understanding of the pharmaceutical industry. The results offer insight for the profession in terms of entry into various roles and also to pharmacy educators for their roles in shaping curricula and placement experiences that attract future graduates to defined career pathways in pharmacy.

Standardisation of the FAERS database: a systematic approach to manually recoding drug name variants†

The US Food and Drug Administration Adverse Event Reporting System (FAERS), one of the worlds largest spontaneous reporting systems, is difficult to use because of report duplication and a lack of standardisation in the recording of drug names. Unresolved data quality issues may distort statistical analyses, rendering the results difficult to interpret when detecting and monitoring adverse effects of pharmaceutical products. The aim of this study was to develop and implement a data cleaning protocol to identify and resolve drug nomenclature issues. The key ‘data treatment’ plan involved standardising drug names held in the FAERS database.

Evaluating the effectiveness of a peer- led education intervention to improve the patient safety attitudes of junior pharmacy students: a cross-sectional study using a latent growth curve modelling approach

Objective Despite the recognition that educating healthcare students in patient safety is essential, changing already full curricula can be challenging. Furthermore, institutions may lack the capacity and capability to deliver patient safety education, particularly from the start of professional practice studies. Using senior students as peer educators to deliver practice-based education can potentially overcome some of the contextual barriers in training junior students. Therefore, this study aimed to evaluate the effectiveness of a peer-led patient safety education programme for junior pharmacy students. Design A repeat cross-sectional design utilising a previously validated patient safety attitudinal survey was used to evaluate attitudes prior to, immediately after and 1 month after the delivery of a patient safety education programme. Latent growth curve (LGC) modelling was used to evaluate the change in attitudes of first-year students using second-year students as a comparator group. Setting Undergraduate university students in Sydney, Australia. Participants 175 first-year and 140 second-year students enrolled in the Bachelor of Pharmacy programme at the University of Sydney. Intervention An introductory patient safety programme was implemented into the first-year Bachelor of Pharmacy curriculum at the University of Sydney. The programme covered introductory patient safety topics including teamwork, communication skills, systems thinking and open disclosure. The programme consisted of 2 lectures, delivered by a senior academic, and a workshop delivered by trained final-year pharmacy students. Results A full LGC model was constructed including the intervention as a non-time-dependent predictor of change (χ2 (51)=164.070, root mean square error of approximation=0.084, comparative fit index=0.913, standardised root mean square=0.056). First-year students’ attitudes significantly improved as a result of the intervention, particularly in relation to internalising errors (p=0.010), questioning behaviours (p<0.001) and open disclosure (p=0.008). Conclusions Peer-led education is an effective method that can be adopted to improve junior pharmacy students’ attitudes towards patient safety.

Relationships Between Pharmacovigilance, Molecular, Structural, and Pathway Data: Revealing Mechanisms for Immune‐Mediated Drug‐Induced Liver Injury

Immune‐mediated drug‐induced liver injury (IMDILI) can be devastating, irreversible, and fatal in the absence of successful transplantation surgery. We present a novel approach that combines the methods of pharmacoepidemiology with in silico molecular modeling to identify specific features in toxic ligands that are associated with clinical features of IMDILI. Specifically, from pharmacovigilance data multivariate logistic regression identified 18 drugs associated with IMDILI (P < 0.00015). Eleven of these drugs, along with their known and proposed metabolites, constituted a training set used to develop a four‐point pharmacophore model (sensitivity 75%; specificity 85%). Subsequently, this information was combined with information from immune‐pathway reviews and genetic‐association studies and complemented with ligand‐protein docking simulations to support a hypothesis implicating two putative targets within separate, possibly interacting, immune‐system pathways: the major histocompatibility complex within the adaptive immune system and Toll‐like receptors (TLRs), in particular TLR‐7, which represent pattern recognition receptors of the innate immune system.

Validation of a survey tool to assess the patient safety attitudes of pharmacy students

Objective Patient safety education is a key strategy to minimise harm, and is increasingly being introduced into junior pharmacy curricula. However, currently there is no valid and reliable survey tool to measure the patient safety attitudes of pharmacy students. This study aimed to validate a modified survey tool, originally developed by Madigosky et al, to evaluate patient safety attitudes of junior pharmacy students. Design A 23-item cross-sectional patient safety survey tool was utilised to evaluate first and second year pharmacy students’ attitudes during May 2013 with both exploratory and confirmatory factor analyses performed to understand the psychometric properties of the survey tool and to establish construct validity. Setting Undergraduate university students in Sydney, Australia Participants 245 first year and 201 second year students enrolled in the Bachelor of Pharmacy Programme at The University of Sydney, Australia in May 2013. Results After exploratory factor analysis on first year student responses (55.76% variance explained) and confirmatory factor analysis on second year responses, a 5-factor model consisting of 14 items was obtained with satisfactory model fit (χ2 (66)=112.83, p<0.001, RMSEA=0.06, CFI=0.91) and nesting between year groups (Δχ2(7)=3.079, p=0.878). The five factors measured students’ attitudes towards: (1) being quality improvement focused, (2) internalising errors regardless of harm, (3) value of contextual learning, (4) acceptability of questioning more senior healthcare professionals’ behaviour and (5) attitude towards open disclosure. Conclusions This study has established the reliability and validity of a modified survey tool to evaluate patient safety attitudes of pharmacy students, with the potential for use in course development and evaluation.

Evaluation of a survey tool to measure safety climate in Australian hospital pharmacy staff

Background: Safety climate evaluation is increasingly used by hospitals as part of quality improvement initiatives. Consequently, it is necessary to have validated tools to measure changes. Objective: To evaluate the construct validity and internal consistency of a survey tool to measure Australian hospital pharmacy patient safety climate. Methods: A 42 item cross‐sectional survey was used to evaluate the patient safety climate of 607 Australian hospital pharmacy staff. Survey responses were initially mapped to the factor structure previously identified in European community pharmacy. However, as the data did not adequately fit the community pharmacy model, participants were randomly split into two groups with exploratory factor analysis performed on the first group (n = 302) and confirmatory factor analyses performed on the second group (n = 305). Results: Following exploratory factor analysis (59.3% variance explained) and confirmatory factor analysis, a 6‐factor model containing 28 items was obtained with satisfactory model fit (χ2 (335) = 664.61 p < 0.001, RMSEA = 0.06, CFI = 0.93, TLI = 0.92), internal reliability (&agr; > 0.643) and model nesting between the groups (&Dgr;χ2 (22) = 30.87, p = 0.10). Three factors (blame culture, organisational learning and working conditions) were similar to those identified in European community pharmacy and labelled identically. Three additional factors (preoccupation with improvement; comfort to question authority; and safety issues being swept under the carpet) highlight hierarchical issues present in hospital settings. Conclusions: This study has demonstrated the validity of a survey to evaluate patient safety climate of Australian hospital pharmacy staff. Importantly, this validated factor structure may be used to evaluate changes in safety climate over time. Highlights:Safety climate evaluation is increasingly used as part of improvement initiatives.No validated tool exists to measure Australian hospital pharmacy staff safety climate.This research has filled this gap by validating a survey modified for hospital.A 6 factor model containing 28 items was obtained.The factor structure may be used to evaluate changes in safety climate over time.

Consumer opinions on adverse events associated with medicines and vaccines

Introduction Despite the availability of an Australian consumer adverse event (AE) reporting system for over 50 years, reporting rates remain low. A comprehensive understanding of consumer perceptions and experiences regarding AEs is needed to further ascertain factors impacting their engagement in AE reporting. Aim The aim of this study was to explore consumer opinions about AEs potentially associated with medicines and vaccines, and their experiences and understanding of managing and reporting AEs. Methods Six focus groups were conducted across metropolitan Sydney with a total of 48 adult participants. A semi-structured focus group topic guide was developed to explore consumers’ understanding, experiences, and actions taken in relation to AEs; and perspectives on managing treatment benefits and harms. Discussions were audio-recorded with participant permission and transcribed verbatim. Transcripts were thematically analyzed. Results Consumers acknowledged the potential for side effects (SEs), however inaccurately estimated SE risk in response to verbal descriptors such as “common.” Consumer appraisal of treatment benefits and harms was influenced by factors such as medical condition(s), previous experiences, and beliefs. Although many had experienced SEs, consumers only reported them if considered severe or troublesome. Minimal awareness of consumer AE reporting systems was evident. Doctors were the primary avenue for reporting; consumers preferred doctors to act as the intermediary in reporting AEs to an independent body. Conclusion Consumers’ lack of awareness of AE reporting systems was evident. With the complexities inherent in benefit/harm risk appraisal, information seeking, and AE reporting preferences, better consumer understanding of AEs and the systems available for reporting is needed.