Patient and Public Involvement (PPI) in evidence synthesis: how the PatMed study approached embedding audience responses into the expression of a meta-ethnography.

BACKGROUND: Patient and public involvement (PPI) has become enshrined as an important pillar of health services empirical research, including PPI roles during stages of research development and analysis and co-design approaches. Whilst user participation has been central to qualitative evidence synthesis (QES) for decades, as seen in the Cochrane consumer network and guidelines, meta-ethnography has been slow to incorporate user participation and published examples of this occurring within meta-ethnography are sparse. In this paper, drawing upon our own experience of conducting a meta-ethnography, we focus on what it means in practice to 'express a synthesis' (stage 7). We suggest the methodological importance of 'expression' in Noblit and Hare's seven stage process (Noblit, GW and Hare, RD. Meta-ethnography: synthesizing qualitative studies, 1988) has been overlooked, and in particular, opportunities for PPI user participation within it. METHODS: Meta-ethnography comprises a seven-stage process of evidence synthesis. Noblit and Hare describe the final 7th stage of the meta-ethnography process as 'expression of synthesis', emphasizing co-construction of findings with the audience. In a previous study we conducted a meta-ethnography exploring patient and student experience of medical education within primary care contexts. We subsequently presented and discussed initial meta-ethnography findings with PPI (students and patients) in focus groups and interviews. We transcribed patient and student PPI interpretations of synthesis findings. As a research team, we then translated these into our existing meta-ethnography findings. RESULTS: We describe, with examples, the process of involving PPI in stage 7 of meta-ethnography and discuss three methodological implications of incorporating PPI within an interpretative approach to QES: (1) we reflect on the construct hierarchy of user participants' interpretations and consider whether incorporating these additional 1st order, 2nd level constructs implies an additional logic of 3rd order 2nd level constructs of the QES team; (2) we discuss the link between PPI user participation and what Noblit and Hare may have meant by ideas of 'expression' and 'audience' as integral to stage 7; and (3) we link PPI user participation to Noblit and Hare's underlying theory of social explanation, i.e. how expression of the synthesis is underpinned by ideas of translation and that the synthesis must be 'translated in the audience's (user participants) particular language'. CONCLUSIONS: The paper aims to complement recent attempts in the literature to refine and improve guidance on conducting a meta-ethnography, highlighting opportunities for PPI user participation in the processes of interpretation, translation and expression. We discuss the implications of user participation in meta-ethnography on ideas of 'generalisability'.

Acute toxicity of 3,4-methylenedioxymethamphetamine (MDMA) in Sprague-Dawley and Dark Agouti rats.

Ingestion of MDMA ("ecstasy") by humans can cause acute toxicity manifested by hyperthermia and death. Demethylenation of MDMA is catalyzed by cytochrome P-450 2D6 (CYP2D6) and cytochrome P-450 2D1 (CYP2D1) in humans and rats, respectively, and is polymorphically expressed. It has been proposed that CYP2D6 deficiency may account for the unexplained toxicity of MDMA. The female Dark Agouti rat is deficient in CYP2D1, and serves as a model for the human poor metabolizer. We investigated thermogenic and locomotor actions of MDMA in adult female Sprague-Dawley (CYP2D1 replete) and Dark Agouti rats. MDMA (2, 5, and 10 mg/kg) and saline were injected subcutaneously at ambient temperatures of 22 and 31 degrees C. There was no difference in core temperature responses between the two rat strains. Hypothermia occurred in the first 30 min and temperature elevation thereafter. MDMA increased locomotor activity in Sprague-Dawley but not in Dark Agouti rats. However, MDMA had pronounced lethal effects at 31 degrees C ambient in the Dark Agouti rats only. We conclude that the poor metaboliser phenotype may predispose to lethality, but the mechanism is as yet unknown.

A classification for adverse drug events.

There is considerable evidence that a large number of patients suffer adverse events arising from their health-care management. A significant proportion of these iatrogenic injuries occur as a result of medication errors. Before prevention strategies can be developed, it is necessary to understand the types of errors that are occurring. In order to set priorities, it is necessary to identify the frequency and impact of the various types of medication errors. To fully investigate medication incidents, it is necessary to classify the information in a way that allows the frequencies, causes and contributing factors to be analysed. The development of a sub-branch of the 'Generic Occurrence Classification', specific to medication incidents, allows this analysis to occur.

An analysis of Australian adverse drug events.

Previous research has shown that there is a high error rate associated with medication use, resulting in significant patient morbidity and mortality, as well as increasing health care costs. Analysis of available Australian data on adverse drug events shows that incident monitoring and retrospective medical record review provide different, but complementary 'windows' into the errors that occur. While retrospective medical record review provides information on the frequency of specific adverse drug events, incident monitoring gives an insight into the contributing factors. From this information, priorities can be set and preventative strategies can be developed.

Towards safer drug use in general practice.

A voluntary, anonymous incident-monitoring study was set up to identify and characterize events or circumstances which could have or did harm a patient in general practice. The study included 673 practitioners who made 2582 reports, of which half (n = 1294) involved medication problems. Amongst these reports, 1556 adverse drug events (ADE) were identified. More common in general practice than in hospitals were problems with therapeutic use (26% vs. 8%), and prescribing of contraindicated medications (15% vs. 5%). In the latter group, 64 reports (4%) involved the prescription of a medication to which the patient was known to be allergic, 66 (4%) involved medication for which there was a recognized potential for a drug interaction, and 68 (4%) involved contraindicated medications due to pathophysiological factors. It was estimated that computer-based prescribing with decision support could eliminate at least a third of these problems in general practice. Further studies are needed to develop this and other preventive strategies.

A classification for incidents and accidents in the health-care system.

Problems that arise from health-care management, rather than from a disease process, are now recognized as making a substantial contribution to patient morbidity and mortality and to the cost of health care. However, most classifications of these problems do not provide sufficient detail to allow comparisons or to develop better strategies for the prevention, detection and management of these problems. A 'Generic Occurrence Classification' was developed to record their salient features, place them in context and elicit any system or human error-based contributing factors. This was done by an iterative process in which 'natural categories', identified from over 2000 incidents and 800 adverse events, were placed in a hierarchical structure created using software written in Microsoft Visual Basic; data were stored in a Microsoft Access database. This was shown to be a valid and reliable way to compare incidents and accidents from different sources and to allow sufficient detail to be retrieved to develop preventive strategies.