Severe treatment-refractory antibody positive autoimmune autonomic ganglionopathy after mRNA COVID19 vaccination.

BACKGROUND: COVID-19 vaccine-associated peripheral and central neuroimmunological disorders have been well described. We present the case of a 56 year old male who developed α3-ganglionic AChR antibody positive Autoimmune Autonomic Ganglionopathy (AAG) after completion of a two-dose course of mRNA (Comirnaty) vaccination for COVID19. RESULTS: A previously hypertensive 56 year old male presented with the subacute onset of severe constipation, urinary retention, erectile dysfunction, sudomotor failure, sicca symptoms, non-reactive pupils and severe orthostatic hypotension shortly after receiving the second dose of an mRNA vaccine against COVID19. Autonomic testing revealed severe cardiovagal, adrenergic and sudomotor impairment, and tonic 'half-mast' pupils with evidence of sympathetic and parasympathetic denervation. Pathological α3-ganglionic ACHR antibodies were positive in serum as detected by a new flow cytometric immunomodulation assay. Malignancy was excluded. The patient was diagnosed with severe, treatment-refractory acute AAG. CONCLUSIONS: While autonomic dysfunction has been previously reported post-COVID19 vaccination, to our knowledge this is the first reported case of antibody-positive AAG in this setting. The severity of this case is in marked contrast to the existing literature on idiopathic antibody-positive autoimmune pandysautonomia.

Cost and effectiveness of prescribing emollient therapy for atopic eczema in UK primary care in children and adults: a large retrospective analysis of the Clinical Practice Research Datalink.

BACKGROUND: The Clinical Practice Research Datalink (CPRD) was used to evaluate the overall costs to the National Health Service, including healthcare utilisation, of prescribing emollients in UK primary care for dry skin and atopic eczema (DS&E). METHODS: Primary care patients in the UK were identified using the CPRD and their records were interrogated for the 2 years following first diagnosis of DS&E. Data from patients with (n = 45,218) and without emollient prescriptions (n = 9780) were evaluated. Multivariate regression models were used to compare healthcare utilisation and cost in the two matched groups (age, sex, diagnosis). Two sub-analyses of the Emollient group were performed between matched groups receiving (1) a colloidal oatmeal emollient (Aveeno-First) versus non-colloidal oatmeal emollients (Aveeno-Never) and (2) Aveeno prescribed first-line (Aveeno-First) versus prescribed Aveeno later (Aveeno-Subsequently). Logistic regression models calculated the odds of prescription with either potent / very potent topical corticosteroids (TCS) or skin-related antimicrobials. RESULTS: Costs per patient were £125.80 in Emollient (n = 7846) versus £128.13 in Non-Emollient (n = 7846) matched groups (p = 0.08). The Emollient group had fewer visits/patient (2.44 vs. 2.66; p < 0.0001) and lower mean per-visit costs (£104.15 vs. £113.25; p < 0.0001), compared with the Non-Emollient group. Non-Emollient patients had 18% greater odds of being prescribed TCS and 13% greater odds of being prescribed an antimicrobial than Emollient patients. In the Aveeno-First (n = 1943) versus Aveeno-Never (n = 1943) sub-analysis, costs per patient were lower in the Aveeno-First compared with the Aveeno-Never groups (£133.46 vs. £141.11; p = 0.0069). The Aveeno-Never group had ≥21% greater odds of being prescribed TCS or antimicrobial than the Aveeno-First group. In the Aveeno-First (n = 1357) versus Aveeno-Subsequently (n = 1357) sub-analysis, total costs were lower in the Aveeno-First group (£140.35 vs. £206.43; p < 0.001). Patients in the Aveeno-Subsequently group had 91% greater odds of being prescribed TCS and 75% greater odds of being prescribed an antimicrobial than the Aveeno-First group. CONCLUSIONS: Acknowledging limitations from unknown disease severity in the CRPD, the prescription of emollients to treat DS&E was associated with fewer primary care visits, reduced healthcare utilisation and reduced cost. Prescribing emollients, especially those containing colloidal oatmeal, was associated with fewer TCS and antimicrobial prescriptions. TRIAL REGISTRATION: The study is registered at http://isrctn.com/ISRCTN91126037 .

Training nurses in a competency framework to support adults with epilepsy and intellectual disability: the EpAID cluster RCT.

BACKGROUND: People with an intellectual (learning) disability (ID) and epilepsy have an increased seizure frequency, higher frequencies of multiple antiepileptic drug (AED) use and side effects, higher treatment costs, higher mortality rates and more behavioural problems than the rest of the population with epilepsy. The introduction of nurse-led care may lead to improvements in outcome for those with an ID and epilepsy; however, this has not been tested in a definitive clinical trial. OBJECTIVE: To determine whether or not ID nurses, using a competency framework developed to optimise nurse management of epilepsy in people with an ID, can cost-effectively improve clinical and quality-of-life outcomes in the management of epilepsy compared with treatment as usual. DESIGN: Cluster-randomised two-arm trial. SETTING: Community-based secondary care delivered by members of community ID teams. PARTICIPANTS: Participants were adults aged 18-65 years with an ID and epilepsy under the care of a community ID team and had had at least one seizure in the 6 months before the trial. INTERVENTIONS: The experimental intervention was the Learning Disability Epilepsy Specialist Nurse Competency Framework. This provides guidelines describing a structure and goals to support the delivery of epilepsy care and management by ID-trained nurses. MAIN OUTCOME MEASURES: The primary outcome was the seizure severity scale from the Epilepsy and Learning Disabilities Quality of Life questionnaire. Measures of mood, behaviour, AED side effects and carer strain were also collected. A cost-utility analysis was undertaken along with a qualitative examination of carers' views of participants' epilepsy management. RESULTS: In total, 312 individuals were recruited into the study from 17 research clusters. Using an intention-to-treat analysis controlling for baseline individual-level and cluster-level variables there was no significant difference in seizure severity score between the two arms. Altogether, 238 complete cases were included in the non-imputed primary analysis. Analyses of the secondary outcomes revealed no significant differences between arms. A planned subgroup analysis identified a significant interaction between treatment arm and level of ID. There was a suggestion in those with mild to moderate ID that the competency framework may be associated with a small reduction in concerns over seizure severity (standard error 2.005, 95% confidence interval -0.554 to 7.307; p = 0.092). However, neither subgroup showed a significant intervention effect individually. Family members' perceptions of nurses' management depended on the professional status of the nurses, regardless of trial arm. Economic analysis suggested that the competency framework intervention was likely to be cost-effective, primarily because of a reduction in the costs of supporting participants compared with treatment as usual. LIMITATIONS: The intervention could not be delivered blinded. Treatment as usual varied widely between the research sites. CONCLUSIONS: Overall, for adults with an ID and epilepsy, the framework conferred no clinical benefit compared with usual treatment. The economic analysis suggested that there may be a role for the framework in enhancing the cost-effectiveness of support for people with epilepsy and an ID. Future research could explore the specific value of the competency framework for those with a mild to moderate ID and the potential for greater long-term benefits arising from the continuing professional development element of the framework. TRIAL REGISTRATION: Current Controlled Trials ISRCTN96895428. FUNDING: This trial was funded by the NIHR Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 22, No. 10. See the NIHR Journals Library website for further project information.

Factors influencing donor and recipient decision making in adult-to-adult living donor liver transplantation: a survey of a non-transplant population.

BACKGROUND: This study aimed to (i) investigate the factors that influence donor and recipient decision making in adult-to-adult living donor liver transplantation (AALDLT); (ii) quantify the level of risk that would be acceptable to potential donors; and (iii) determine from whom an individual would be willing to receive a donation. METHODS: A self-administered questionnaire using hypothetical scenarios centred on AALDLT was created and administered to participants recruited from the waiting room of an orthopaedic outpatient clinic at a teaching hospital in Sydney (n = 105). The questionnaire asked participants to consider scenarios in which they either (i) were a potential donor for a family member or close friend or (ii) themselves required a liver transplant. RESULTS: Ninety-five (90%) participants expressed an in-principal willingness to consider living organ donation. The factors most important in deciding to be living liver donors were the probability of a good outcome for the recipient, the likelihood of the potential recipient's survival until a deceased donor liver became available and the risk of donor death. Donor death was also rated as the least acceptable donor outcome. Participants expressed a willingness to receive a donation from all proposed donor groups equally. CONCLUSIONS: The acceptability of hypothetical living organ donation was very high in the population group studied. Participants were also willing to accept significantly higher risks of complications from organ donation than they would actually be exposed to. Clinicians should feel encouraged to discuss the risks and benefits of living donation frankly with patients and their families.

Improving outcomes in adults with epilepsy and intellectual disability (EpAID) using a nurse-led intervention: study protocol for a cluster randomised controlled trial.

BACKGROUND: In adults with intellectual disability (ID) and epilepsy there are suggestions that improvements in management may follow introduction of epilepsy nurse-led care. However, this has not been tested in a definitive clinical trial and results cannot be generalised from general population studies as epilepsy tends to be more severe and to involve additional clinical comorbidities in adults with ID. This trial investigates whether nurses with expertise in epilepsy and ID, working proactively to a clinically defined role, can improve clinical and quality of life outcomes in the management of epilepsy within this population, compared to treatment as usual. The trial also aims to establish whether any perceived benefits represent good value for money. METHODS/DESIGN: The EpAID clinical trial is a two-arm cluster randomised controlled trial of nurse-led epilepsy management versus treatment as usual. This trial aims to obtain follow-up data from 320 participants with ID and drug-resistant epilepsy. Participants are randomly assigned either to a 'treatment as usual' control or a 'defined epilepsy nurse role' active arm, according to the cluster site at which they are treated. The active intervention utilises the recently developed Learning Disability Epilepsy Specialist Nurse Competency Framework for adults with ID. Participants undergo 4 weeks of baseline data collection, followed by a minimum of 20 weeks intervention (novel treatment or treatment as usual), followed by 4 weeks of follow-up data collection. The primary outcome is seizure severity, including associated injuries and the level of distress manifest by the patient in the preceding 4 weeks. Secondary outcomes include cost-utility analysis, carer strain, seizure frequency and side effects. Descriptive measures include demographic and clinical descriptors of participants and clinical services in which they receive their epilepsy management. Qualitative study of clinical interactions and semi-structured interviews with clinicians and participants' carers are also undertaken. DISCUSSION: The EpAID clinical trial is the first cluster randomised controlled trial to test possible benefits of a nurse-led intervention in adults with epilepsy and ID. This research will have important implications for ID and epilepsy services. The challenges of undertaking such a trial in this population, and the approaches to meeting these are discussed. TRIAL REGISTRATION: International Standard Randomised Controlled Trial Number: ISRCTN96895428 version 1.1. Registered on 26 March 2013.