Improving the spontaneous reporting of suspected adverse drug reactions: An overview of systematic reviews

Aim: To conduct an overview of systematic reviews examining interventions to stimulate spontaneous reporting of suspected adverse drug reactions (ADRs) by healthcare professionals (HCPs) and/or patients/carers. Methods: Systematic reviews published since 1 January 2000 were identified and the included publications categorized in relation to the 4Es (education, engineering, economics and enforcement). Results: Almost all studies were aimed at HCPs. Educational initiatives were most often used and, in most studies, were associated with improvements in quantity and/or quality of reports, at least in the short term. Lectures/presentations and regular reminders (eg, verbal or by e‐mail) were the educational methods most often identified by systematic reviews. Engineering initiatives were also generally effective, including improving the availability of reporting forms, electronic ADR reporting, modification of reporting procedures/policies or the reporting form and assistance to complete the form. Evidence for the benefit of economic incentives (eg, monetary rewards, lottery tickets, days off work, “giveaways” and educational credits) was often clouded by the potential effects of other concomitant initiatives, and any possible associated improvements often disappeared rapidly after incentives were discontinued. Conclusion: Educational and engineering strategies appear to be the interventions most often associated with improvements in reporting rates by HCPs, at least in the short to medium term. However, the evidence for sustained impact is weak. The available data were insufficient to clearly identify the separate impact of economic strategies. Further work is also needed to examine the effects of these strategies on reporting by patients, carers and the public

The All Wales Medicines Strategy Group: 18 years' experience of a national medicines optimisation committee

Aims To review the medicines optimisation activities of the All Wales Medicines Strategy Group (AWMSG), a committee established in 2002 to advise the Welsh Government on “all matters related to prescribing”. Although AWMSG conducts other activities (e.g., health technology appraisal for medicines), we focus here on its role in advising on medicines optimisation. Methods Prescribing indicators have been used in Wales to measure change, together with data on volumes and costs of medicines dispensed. A range of improvement strategies have been categorised under the “four Es”, namely educational initiatives, economic incentives, “engineering” and “enforcement”. Results AWMSG has helped health professionals in NHS Wales to reduce harm and waste, and to reduce inappropriate local or regional duplication and variation. Specific initiatives include the achievement of major cost savings by supporting increased generic prescribing and an “invest to save” approach related to prescribing of hypnotics and tranquillisers, non-steroidal anti-inflammatory drugs (NSAIDs) and proton pump inhibitors. AWMSG also successfully commissioned the introduction of a single national in-patient medication chart for Wales in 2004. Ongoing priorities include a focus on reducing prescribing of certain medicines deemed “low value for prescribing” and on optimising the use of biosimilar medicines. Conclusions Since 2002, AWMSG has acted as a national medicines optimisation committee in Wales. From the outset, pharmacists and clinical pharmacologists have collaborated closely and shared their complementary expertise to make a much greater contribution to the safe, effective and cost-effective use of medicines than either group could have achieved by working separately

Changes in suspected adverse drug reaction reporting via the Yellow Card scheme in Wales following the introduction of a National Reporting Indicator

AIMS: This study aimed to assess the impact of a National Reporting Indicator (NRI) on rates of reporting of suspected adverse drug reactions using the Yellow Card scheme following the introduction of the NRI in Wales (UK) in April 2014. METHODS: Yellow Card reporting data for general practitioners and other reporting groups in Wales and England for the financial years 2014–15 (study period 1) and 2015–16 (study period 2) were obtained from the Medicines and Healthcare Products Regulatory Agency and compared with those for 2013–14 (pre‐NRI control period). RESULTS: The numbers of Yellow Cards submitted by general practitioners in Wales were 271, 665 and 870 in the control period, study period 1 and study period 2, respectively. This is equivalent to an increase of 145% in study period 1 and 221% in study period 2 compared with the 12‐month control period (2013–14). Corresponding increases in England were 17% and 37%, respectively (P < .001 chi–squared test). The numbers of Yellow Cards submitted by other groups in Wales were 906, 795 and 947 in each of the study periods. CONCLUSIONS: Introduction of the NRI corresponded with a significant increase in the number of Yellow Cards submitted by general practitioners in Wales. General practitioner reporting rates continued to increase year on year through to 2018–19 with the NRI still in place. No concomitant change was found in reporting rates by other groups in the health boards in Wales

Antidepressant prescribing patterns and adverse events following introduction of a National Prescribing Indicator to monitor dosulepin usage in Wales

Aims: Limiting use of the antidepressant dosulepin has been encouraged due to associated risks of toxicity. In April 2011, the All Wales Medicines Strategy Group introduced a National Prescribing Indicator (NPI) to monitor dosulepin usage. The aim of this study was to investigate antidepressant prescribing patterns, and selected adverse events in patients prescribed dosulepin following introduction of the NPI. Methods: An e‐cohort study was conducted. Adult patients receiving regular dosulepin prescriptions between October 2010 and March 2011 were included. Characteristics of patients who were continued on dosulepin, were switched to an alternative antidepressant or whose dosulepin was discontinued following introduction of the NPI were compared. Results: In total, 4121 patients were included. Of these, 1947 (47%) continued dosulepin, 1487 (36%) were switched and 692 (17%) discontinued. Of the 692 who discontinued, 92% did not receive a prescription for another antidepressant during the follow‐up period. Patients whose dosulepin was discontinued were older and were less commonly coprescribed benzodiazepines. During follow‐up, recorded incidence of selected adverse events was low across all groups and no significant difference was observed. Conclusion: Over half of patients had discontinued dosulepin at the end of the period when the NPI was in place. Further interventions may have been required to have a greater impact on prescribing. This study provides some reassurance that dosulepin discontinuation can be a successful strategy, and that the risk of the adverse events investigated was unlikely to have been greater in those who had dosulepin discontinued than in those in whom dosulepin had been continued

Prescribing costs of hypoglycaemic agents and associations with metabolic control in Wales; a national analysis of primary care data

Aims: There has been a dramatic increase in hypoglycaemic agent expenditure. We assessed the variability in prescribing costs at the practice level and the relationship between expenditure and the proportion of patients achieving target glycaemic control. Methods: We utilized national prescribing data from 406 general practices in Wales. This was compared against glycaemic control (percentage of patients achieving a HbA1c level < 59 mmol/mol in the preceding 12 months). Analyses were adjusted for the number of patients with diabetes in each general practice and the Welsh Index of Multiple Deprivation. Results: There was considerable heterogeneity in hypoglycaemic agent spend per patient with diabetes, Median = £289 (IQR 247–343) range £31.1–£1713. Higher total expenditure was not associated with improved glycaemic control B(std) = −0.01 (95%CI –0.01, 0.002) p = 0.13. High‐spend practices spent more on SGLT2 inhibitors (16 vs. 9% p < 0.001) and GLP‐1 agonists (13 vs. 11% p < 0.001) and less on insulin (34 vs. 42% p < 0.001), biguanides (9 vs. 11% p = 0.001) and sulphonylureas (2 vs. 3% p < 0.001) than low spend practices. There were no differences in the pattern of drug prescribing between high spend practices with better glycaemic control (mean 68% of patients HbA1c <59 mmol/mol) and those with less good metabolic control (mean 58% of patients HbA1c <59 mmol/mol). Conclusions: Spend on hypoglycaemic agents is highly variable between practices and increased expenditure per patient is not associated with better glycaemic control. Whilst newer, more expensive agents have additional benefits, in individuals where these advantages are more marginal widespread use of these agents has important cost implications

Mutation of hilD in a Salmonella Derby lineage linked to swine adaptation and reduced risk to human health

Salmonella enterica variants exhibit diverse host adaptation, outcome of infection, and associated risk to food safety. Analysis of the distribution of Salmonella enterica serovar Derby (S. Derby) subtypes in human and swine identified isolates with a distinct PFGE profile that were significantly under-represented in human infections, consistent with further host adaptation to swine. Here we show that isolates with this PFGE profile form a distinct phylogenetic sub-clade within S. Derby and exhibit a profound reduction in invasion of human epithelial cells, and a relatively small reduction in swine epithelial cells. A single missense mutation in hilD, that encodes the master-regulator of the Salmonella Pathogenicity Island 1 (SPI-1), was present in the adapted lineage. The missense mutation resulted in a loss of function of HilD that accounted for reduced invasion in human epithelial cells. The relatively small impact of the mutation on interaction with swine cells was consistent with an alternative mechanism of invasion in this pathogen-host combination

Spatial development of a turbulent boundary layer subjected to freestream turbulence

The spatial development of a turbulent boundary layer (TBL) subjected to freestream turbulence (FST) is investigated experimentally in a water channel for friction Reynolds numbers up to Reτ=5060. Four different FST intensities are generated with an active grid, ranging from a low-turbulence reference case to u′∞/U∞=12.5%. Wall-normal velocity scans are performed with laser doppler velocimetry at three positions downstream of the grid. There are two combating influences as the flow develops: the TBL grows while the FST decays. Whilst previous studies have shown the wake region of the TBL is suppressed by FST, the present measurements demonstrate that the wake recovers sufficiently far downstream. For low levels of FST, the near-wall variance peak grows as one moves downstream, whereas high FST results in an initially high variance peak that decays with streamwise position. These results are mirrored in the evolution of the spectrograms, where low FST results in the emergence of an outer spectral peak as the flow evolves, while high FST sees an initially high outer spectral peak decay in space. This finding is significant as it suggests the FST does not permanently mature the TBL ahead of its natural evolution. Finally, it is explicitly demonstrated that it is not sufficient to characterize the TBL solely by conventional parameters such as Reτ, but that the level of FST and the evolution of the two flows must also be considered