Evaluation of the quality of patient involvement in a patient-led analysis of the lived experience of a rare disease.

BACKGROUND: Patients themselves are best placed to provide insights on the lived experience and to lead the analysis of such insights to bring the patient voice into peer-reviewed literature. In doing so, they can meet the authorship criteria for subsequent research publications. It is important to evaluate patient engagement to identify ways to improve future collaborations. Here, we describe the approach taken during a patient-led and patient co-authored analysis of the lived experience of generalized myasthenia gravis, which may be applicable to other indications. We also assessed the quality of patient engagement throughout the research project. METHODS: We used self-reported experience surveys based on the Patient Focused Medicines Development Patient Engagement Quality Guidance criteria for assessing patient engagement. The surveys were adapted to focus on individual projects and assessed eight domains using a five-point Likert scale. In September 2020, we invited eight patient council members to complete a self-reported experience survey following qualitative lived experience data generation. We calculated the average experience score as a percentage of the maximum possible score. Patient authors (n = 1) and non-patient authors (n = 3) were invited to complete a similar survey in November 2021, with questions customized for relevance, to evaluate the authorship experience following publication of the research. RESULTS: Overall, patient council members had a positive experience of taking part in this study, with an average experience score of 90% (71.6/80.0; n = 8). The patient author and non-patient authors rated their authorship experience highly, with average experience scores of 92% (78.0/85.0) and 97% (63.3/65.0), respectively. There were key aspects that contributed to the overall project success (e.g., ensuring that all participants were aligned on the project objectives at the outset and understood their roles and responsibilities). We also identified elements of the approach that could be improved in future collaborations. CONCLUSION: In this patient-led analysis, patient council members, patient authors and non-patient authors had a positive experience of being involved in the project. We gained useful insights into elements that contributed to the project's success and ways to improve future patient-led projects on the lived experience.

WHY DID WE DO THIS RESEARCH?: Involving patients in research is becoming more common. Listening to patients can help healthcare teams to better understand the impact of living with a condition. Some patients taking part in research can go on to be an author of an article that describes the findings. We describe how we assessed the quality of patient involvement in a research project to better understand views of patients living with a rare condition. HOW DID WE ASSESS PATIENT INVOLVEMENT?: We asked patients to complete surveys to find out about their experience of taking part in a patient-led analysis of a rare condition. This can highlight challenges that they may have faced during the project. WHAT WERE THE MAIN FINDINGS?: Patients who took part in this research and those who were authors of the research article had a positive experience. There were several key factors that helped the project to be a success. We also identified ways to improve future projects designed to gain patient insights on living with other conditions.

In vivo neurometabolic profiling to characterize the effects of social isolation and ketamine-induced NMDA antagonism: a rodent study at 7.0 T.

Continued efforts are undertaken to develop animal models of schizophrenia with translational value in the quest for much needed novel drugs. Existing models mimic specific neurobiological aspects of schizophrenia, but not its full complexity. Here, we used proton magnetic resonance spectroscopy ((1)H-MRS) to assess the metabolic profile in the prefrontal cortex (PFC) of two established models, rearing in social isolation and acute N-methyl-D-aspartate receptor (NMDA-R) antagonism and their combination. Rats reared in social isolation or group housed underwent (1)H-MRS at baseline and dynamically after ketamine challenge (25mg/kg, intraperitoneal) under isoflurane anesthesia. A 7 T animal scanner was used to perform spectra acquisition from the anterior cingulate/medial PFC. LCModel was used for metabolite quantification and effects of rearing and ketamine injection were analyzed. Social isolation did not lead to significant differences in the metabolic profile of the PFC at baseline. Ketamine induced a significant increase in glutamine in both groups with significance specifically reached by the group-housed animals alone. Only rats reared in social isolation showed a significant 11% γ-aminobutyric acid (GABA) decrease. This study provides preliminary evidence that social interactions in early life predict the glutamatergic and GABAergic response to acute NMDA-R blockade. The similarity between the prefrontal GABA reduction in patients with schizophrenia and in rats reared as social isolates after challenge with ketamine suggests good potential translational value of this combined animal model for drug development.

Pre-treatment with 3,4-methylenedioxymethamphetamine (MDMA) causes long-lasting changes in 5-HT2A receptor-mediated glucose utilization in the rat brain.

The current study examined the long-term effect of brief exposure to 3,4-methylenedioxymethamphetamine (MDMA) on local cerebral glucose utilization (LCGU) in specific brain regions immediately following administration of the 5-HT2A/2C receptor agonist, 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI). Wistar rats (post-natal day (PND) 28, n = 24) were administered MDMA (5 mg/kg, i.p.) or saline (1 ml/kg, i.p.) four times daily for 2 consecutive days and core body temperature was recorded. Fifty-five days later and 10 min following injection of DOI (1 mg/kg, i.p.) or saline, LCGU was measured using the [14C]2-deoxyglucose (2-DG) technique. In the 4 hours following the initial injection (PND 28), MDMA-treated rats exhibited significant hyperthermia compared with saline-treated controls (p < 0.05-0.01). Eight weeks later, immediately following DOI challenge, LCGU was significantly elevated (an increase of 47%, p < 0.05) in the nucleus accumbens of MDMA/DOI pretreated rats, compared with that in MDMA/saline pre-treated controls. A similar trend was observed in other areas such as the lateral habenula, somatosensory cortex and hippocampal regions (percentage changes of 27-41%), but these did not reach significance. Blood glucose levels were significantly elevated in both groups of DOI-treated rats (p < 0.05-0.01). Thus, brief exposure of young rats to an MDMA regimen previously shown to cause anxiety-like behaviour and modest serotonergic neurotoxicity (Bull et al., 2004) increased DOI-induced energy metabolism in the nucleus accumbens and tended to increase metabolism in other brain regions, including the hippocampus, consistent with the induction of long-term brain region specific changes in synaptic plasticity.