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

An RxLR effector from phytophthora infestans prevents re-localisation of two plant NAC transcription factors from the endoplasmic reticulum to the nucleus

The plant immune system is activated following the perception of exposed, essential and invariant microbial molecules that are recognised as non-self. A major component of plant immunity is the transcriptional induction of genes involved in a wide array of defence responses. In turn, adapted pathogens deliver effector proteins that act either inside or outside plant cells to manipulate host processes, often through their direct action on plant protein targets. To date, few effectors have been shown to directly manipulate transcriptional regulators of plant defence. Moreover, little is known generally about the modes of action of effectors from filamentous (fungal and oomycete) plant pathogens. We describe an effector, called Pi03192, from the late blight pathogen Phytophthora infestans, which interacts with a pair of host transcription factors at the endoplasmic reticulum (ER) inside plant cells. We show that these transcription factors are released from the ER to enter the nucleus, following pathogen perception, and are important in restricting disease. Pi03192 prevents the plant transcription factors from accumulating in the host nucleus, revealing a novel means of enhancing host susceptibility

Functionally Redundant RXLR Effectors from <em>Phytophthora infestans</em> Act at Different Steps to Suppress Early flg22-Triggered Immunity

Genome sequences of several economically important phytopathogenic oomycetes have revealed the presence of large families of so-called RXLR effectors. Functional screens have identified RXLR effector repertoires that either compromise or induce plant defense responses. However, limited information is available about the molecular mechanisms underlying the modes of action of these effectors in planta. The perception of highly conserved pathogen- or microbe-associated molecular patterns (PAMPs/MAMPs), such as flg22, triggers converging signaling pathways recruiting MAP kinase cascades and inducing transcriptional re-programming, yielding a generic anti-microbial response. We used a highly synchronizable, pathogen-free protoplast-based assay to identify a set of RXLR effectors from Phytophthora infestans (PiRXLRs), the causal agent of potato and tomato light blight that manipulate early stages of flg22-triggered signaling. Of thirty-three tested PiRXLR effector candidates, eight, called Suppressor of early Flg22-induced Immune response (SFI), significantly suppressed flg22-dependent activation of a reporter gene under control of a typical MAMP-inducible promoter (pFRK1-Luc) in tomato protoplasts. We extended our analysis to Arabidopsis thaliana, a non-host plant species of P. infestans. From the aforementioned eight SFI effectors, three appeared to share similar functions in both Arabidopsis and tomato by suppressing transcriptional activation of flg22-induced marker genes downstream of post-translational MAP kinase activation. A further three effectors interfere with MAMP signaling at, or upstream of, the MAP kinase cascade in tomato, but not in Arabidopsis. Transient expression of the SFI effectors in Nicotiana benthamiana enhances susceptibility to P. infestans and, for the most potent effector, SFI1, nuclear localization is required for both suppression of MAMP signaling and virulence function. The present study provides a framework to decipher the molecular mechanisms underlying the manipulation of host MAMP-triggered immunity (MTI) by P. infestans and to understand the basis of host versus non-host resistance in plants towards P. infestans

An exploratory study of the patient experience of pharmacist supplementary prescribing in a secondary care mental health setting

Background: Management of chronic disease has become an increasing challenge to the National Health Service in the United Kingdom. The introduction of supplementary prescribing was seen as a possible mechanism to address the needs of this patient group. Individuals with mental illness were considered particularly suitable for management in this way.Objective: To explore the views and experiences of patients with mental illness on being managed by a pharmacist supplementary prescriber in a secondary care outpatient setting.Methods: A study of patient experiences utilising semi-structured interviews and self-completion diaries was adopted. Eleven patients participated in the study. Data were analysed utilising code and retrieve, and content analysis respectively.Results: Patients valued the increased accessibility to, and continuity of, their prescriber compared with their experience of other healthcare professionals. Patients reported they were able to trust the pharmacist’s knowledge of medication, were provided with sufficient information regarding reasons for treatment and side effects, and felt that they had an active role in decisions concerning their healthcare.Conclusions: This exploratory study showed that patients had positive views of being managed by a supplementary prescriber. However, it should be noted that the number of participants was small. It is therefore important that further, more wide ranging research is conducted to evaluate pharmacist prescribing within mental health settings

Nem doente, nem vítima: o atendimento às "lesões autoprovocadas" nas emergências Neither ill, nor victim: the self-injury in the emergency care

Este artigo aborda as concepções e práticas de profissionais de saúde relativas aos casos de "lesões autoprovocadas". Problematiza-se o hiato existente entre sua formação profissional baseada no modelo biomédico e suas práticas de trabalho, nas quais estão presentes dimensões não contempladas pela biomedicina. A referência empírica da pesquisa é um hospital público de emergências na cidade de São Paulo. O estudo de natureza qualitativa foi desenvolvido por meio de observação dos atendimentos, consulta a prontuários médicos e entrevistas com profissionais de saúde. A questão que emerge diz respeito ao modelo de inteligibilidade da doença, baseado no corpo como lócus privilegiado do cuidado, e a doença como um evento de caráter fortuito ou acidental. Contrariamente, as situações de lesões autoprovocadas (tentativas de suicídio, abuso de drogas e álcool) são abordadas como eventos carregados de intencionalidade, resultantes de uma escolha, de uma opção, o que acarreta a não identificação de seus autores como doentes ou vítimas a demandar cuidados.<br>This paper shows concepts and practices of health professionals regarding cases of self-injury. It is problematized the existent gap between professionals training based in the biomedical model and practices, in which are presented dimension not considered for biomedicine. The empiric reference is a public emergency hospital in the city of São Paulo. The qualitative nature study was developed by observing attendances, consults to medical records and interviews with health professionals. The underlying question is related to intelligibility model of the illness, based in the body as a privileged locus of care, and illness as accidental event. Contradictively, self-injury situations (suicide attempts, drug and alcohol abuse) are analyzed as intentionally events, consequence of a choice, implicating no identification of their authors as patients or victims of care