Background and purpose
Juvenile myoclonic epilepsy (JME) is a common epilepsy syndrome for which treatment response is generally assumed to be good. We aimed to determine the prevalence and ...prognostic risk factors for refractoriness of JME.
Methods
We systematically searched PubMed and EMBASE and included 43 eligible studies, reporting seizure outcome after antiepileptic drug (AED) treatment in JME cohorts. We defined refractory JME as persistence of any seizure despite AED treatment and performed a random‐effects meta‐analysis to assess the prevalence of refractory JME and of seizure recurrence after AED withdrawal in individuals with well‐controlled seizures. Studies reporting potential prognostic risk factors in relation to seizure outcome were included for subsequent meta‐analysis of risk factors for refractoriness.
Results
Overall, 35% (95% confidence interval, 29–41%) of individuals (n = 3311) were refractory. There was marked heterogeneity between studies. Seizures recurred in 78% (95% confidence interval, 52–94%) of individuals who attempted to withdraw from treatment after a period of seizure freedom (n = 246). Seizure outcome by publication year suggested that prognosis did not improve over time. Meta‐analysis suggested six variables as prognostic factors for refractoriness, i.e. having three seizure types, absence seizures, psychiatric comorbidities, earlier age at seizure onset, history of childhood absence epilepsy and praxis‐induced seizures.
Conclusion
One‐third of people with JME were refractory, which is a higher prevalence than expected. Risk factors were identified and can be used to guide treatment and counselling of people with JME.
Prime editing is a versatile genome-editing technique that shows great promise for the generation and repair of patient mutations. However, some genomic sites are difficult to edit and optimal design ...of prime-editing tools remains elusive. Here we present a fluorescent prime editing and enrichment reporter (fluoPEER), which can be tailored to any genomic target site. This system rapidly and faithfully ranks the efficiency of prime edit guide RNAs (pegRNAs) combined with any prime editor variant. We apply fluoPEER to instruct correction of pathogenic variants in patient cells and find that plasmid editing enriches for genomic editing up to 3-fold compared to conventional enrichment strategies. DNA repair and cell cycle-related genes are enriched in the transcriptome of edited cells. Stalling cells in the G1/S boundary increases prime editing efficiency up to 30%. Together, our results show that fluoPEER can be employed for rapid and efficient correction of patient cells, selection of gene-edited cells, and elucidation of cellular mechanisms needed for successful prime editing.
Previous studies on the impact of the COVID-19 pandemic on the mental health of health-care workers have relied on self-reported screening measures to estimate the point prevalence of common mental ...disorders. Screening measures, which are designed to be sensitive, have low positive predictive value and often overestimate prevalence. We aimed to estimate prevalence of common mental disorders and post-traumatic stress disorder (PTSD) among health-care workers in England using diagnostic interviews.
We did a two-phase, cross-sectional study comprising diagnostic interviews within a larger multisite longitudinal cohort of health-care workers (National Health Service NHS CHECK; n=23 462) during the COVID-19 pandemic. In the first phase, health-care workers across 18 NHS England Trusts were recruited. Baseline assessments were done using online surveys between April 24, 2020, and Jan 15, 2021. In the second phase, we selected a proportion of participants who had responded to the surveys and conducted diagnostic interviews to establish the prevalence of mental disorders. The recruitment period for the diagnostic interviews was between March 1, 2021 and Aug 27, 2021. Participants were screened with the 12-item General Health Questionnaire (GHQ-12) and assessed with the Clinical Interview Schedule-Revised (CIS-R) for common mental disorders or were screened with the 6-item Post-Traumatic Stress Disorder Checklist (PCL-6) and assessed with the Clinician Administered PTSD Scale for DSM-5 (CAPS-5) for PTSD.
The screening sample contained 23 462 participants: 2079 participants were excluded due to missing values on the GHQ-12 and 11 147 participants due to missing values on the PCL-6. 243 individuals participated in diagnostic interviews for common mental disorders (CIS-R; mean age 42 years range 21–70; 185 76% women and 58 24% men) and 94 individuals participated in diagnostic interviews for PTSD (CAPS-5; mean age 44 years 23–62; 79 84% women and 15 16% men). 202 (83%) of 243 individuals in the common mental disorders sample and 83 (88%) of 94 individuals in the PTSD sample were White. GHQ-12 screening caseness for common mental disorders was 52·8% (95% CI 51·7–53·8). Using CIS-R diagnostic interviews, the estimated population prevalence of generalised anxiety disorder was 14·3% (10·4–19·2), population prevalence of depression was 13·7% (10·1–18·3), and combined population prevalence of generalised anxiety disorder and depression was 21·5% (16·9–26·8). PCL-6 screening caseness for PTSD was 25·4% (24·3–26·5). Using CAPS-5 diagnostic interviews, the estimated population prevalence of PTSD was 7·9% (4·0–15·1).
The prevalence estimates of common mental disorders and PTSD in health-care workers were considerably lower when assessed using diagnostic interviews compared with screening tools. 21·5% of health-care workers met the threshold for diagnosable mental disorders, and thus might benefit from clinical intervention.
UK Medical Research Council; UCL/Wellcome; Rosetrees Trust; NHS England and Improvement; Economic and Social Research Council; National Institute for Health and Care Research (NIHR) Biomedical Research Centre at the Maudsley and King's College London (KCL); NIHR Protection Research Unit in Emergency Preparedness and Response at KCL.
Background: Moral injury is defined as the strong emotional and cognitive reactions following events which clash with someone's moral code, values or expectations. During the COVID-19 pandemic, ...increased exposure to Potentially Morally Injurious Events (PMIEs) has placed healthcare workers (HCWs) at risk of moral injury. Yet little is known about the lived experience of cumulative PMIE exposure and how NHS staff respond to this.
Objective: We sought to rectify this knowledge gap by qualitatively exploring the lived experiences and perspectives of clinical frontline NHS staff who responded to COVID-19.
Methods: We recruited a diverse sample of 30 clinical frontline HCWs from the NHS CHECK study cohort, for single time point qualitative interviews. All participants endorsed at least one item on the 9-item Moral Injury Events Scale (MIES) Nash et al., 2013. Psychometric evaluation of the moral injury events scale. Military Medicine, 178(6), 646-652 at six month follow up. Interviews followed a semi-structured guide and were analysed using reflexive thematic analysis.
Results: HCWs described being routinely exposed to ethical conflicts, created by exacerbations of pre-existing systemic issues including inadequate staffing and resourcing. We found that HCWs experienced a range of mental health symptoms primarily related to perceptions of institutional betrayal as well as feeling unable to fulfil their duty of care towards patients.
Conclusion: These results suggest that a multi-facetted organisational strategy is warranted to prepare for PMIE exposure, promote opportunities for resolution of symptoms associated with moral injury and prevent organisational disengagement.
HIGHLIGHTS
Clinical frontline healthcare workers (HCWs) have been exposed to an accumulation of potentially morally injurious events (PMIEs) throughout the COVID-19 pandemic, including feeling betrayed by both government and NHS leaders as well as feeling unable to provide duty of care to patients.
HCWs described the significant adverse impact of this exposure on their mental health, including increased anxiety and depression symptoms and sleep disturbance.
Most HCWs interviewed believed that organisational change within the NHS was necessary to prevent excess PMIE exposure and promote resolution of moral distress.
Traumatic brain injury (TBI) is prevalent in veterans and may occur at any stages of their life (before, during, or after military service). This is of particular concern, as previous evidence in the ...general population has identified TBI as a strong risk factor for mild cognitive impairment (MCI), a known precursor of dementia.
This study aimed to investigate whether exposure to at least one TBI across the lifetime was a risk factor for MCI in ageing UK veterans compared to non-veterans.
This cross-sectional study comprised of data from PROTECT, a cohort study comprising UK veterans and non-veterans aged ≥ 50 years at baseline. Veteran and TBI status were self-reported using the Military Service History Questionnaire (MSHQ) and the Brain Injury Screening Questionnaire (BISQ), respectively. MCI was the outcome of interest, and was defined as subjective cognitive impairment and objective cognitive impairment.
The sample population comprised of veterans (
= 701) and non-veterans (
= 12,389). TBI was a significant risk factor for MCI in the overall sample (OR = 1.21, 95% CI 1.11-1.31) compared to individuals without TBI. The prevalence of TBI was significantly higher in veterans compared to non-veterans (69.9% vs 59.5%,
< .001). There was no significant difference in the risk of MCI between veterans with TBI and non-veterans with TBI (OR = 1.19, 95% CI 0.98-1.45).
TBI remains an important risk factor for MCI, irrespective of veteran status. The clinical implications indicate the need for early intervention for MCI prevention after TBI.
Staff in the National Health Service (NHS) are under considerable strain, exacerbated by the COVID-19 pandemic; whilst NHS Trusts provide a variety of health and wellbeing support services, there has ...been little research investigating staff perceptions of these services. We interviewed 48 healthcare workers from 18 NHS Trusts in England about their experiences of workplace health and wellbeing support during the pandemic. Reflexive thematic analysis identified that perceived stigma around help-seeking, and staffing shortages due to wider socio-political contexts such as austerity, were barriers to using support services. Visible, caring leadership at all levels (CEO to line managers), peer support, easily accessible services, and clear communication about support offers were enablers. Our evidence suggests Trusts should have active strategies to improve help-seeking, such as manager training and peer support facilitated by building in time for this during working hours, but this will require long-term strategic planning to address workforce shortages.
The link between poor cardiovascular health (CVH), lifestyle and mild cognitive impairment (MCI) has been well established in the general population. However, there is limited research exploring ...these associations in ageing UK veterans.
This study explored the risk of MCI and its association with nine CVH and lifestyle risk factors (including diabetes, heart disease, high cholesterol, high blood pressure, obesity, stroke, physical inactivity, the frequency of alcohol consumption and smoking) in UK veterans and non-veterans.
This prospective cohort study comprised data from the PROTECT study between 2014 and 2022. Participants comprised of UK military veterans and non-veterans aged ≥50 years at baseline. Veteran status was defined using the Military Service History Questionnaire. CVH and lifestyle risk factors were defined using a combination of self-report measures, medication history or physical measurements. MCI was defined as the presence of subjective and objective cognitive impairment.
Based on a sample of 9378 veterans (n = 488) and non-veterans (n = 8890), the findings showed the risk of MCI significantly reduced in veterans with obesity, those who frequently consumed alcohol and were physically inactive compared to non-veterans. The risk of MCI significantly increased in veterans with diabetes (hazards ratio HR = 2.22, 95% confidence interval CI 1.04-4.75, P ≤ 0.05) or high cholesterol (HR = 3.11, 95% CI 1.64-5.87, P ≤ 0.05) compared to veterans without.
This study identified CVH and lifestyle factors of MCI in UK veterans and non-veterans. Further work is needed to understand these associations and the underpinning mechanisms which could determine intervention strategies to reduce the risk of MCI.
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