General practice nurse perceptions of barriers and facilitators to implementation of best-practice dementia care recommendations-a qualitative interview study.

INTRODUCTION: With an aging population and a growing prevalence of people living with dementia, the demand for best-practice dementia care in general practice increases. There is an opportunity to better utilise the nurse role within the primary care team to meet this increasing demand in the provision of care for people living with dementia. However, general practice nurses have limited knowledge in the provision of best-practice care for people living with dementia and their carer(s). A number of best-practice dementia care recommendations contained in the Australian Clinical Practice Guidelines and Principles of Care for People with Dementia have been identified as highly relevant to the role of the general practice nurse. AIMS: To explore general practice nurses' perspectives on published best-practice dementia care recommendations relevant to their role and identify barriers and facilitators to their implementation into clinical practice. METHODS: Thirteen Australian general practice nurses took part in this qualitative interview study. The research questions for this study were addressed within a paradigmatic framework of social constructionism. Data were transcribed verbatim and thematically analysed. RESULTS: There was a high level of agreement between general practice nurses that the recommendations were important, reflected best-practice dementia care and were relevant to their role. However the recommendations were perceived as limited in their usefulness to nurses' clinical practice due to being too vague and lacking direction. Four main themes were identified describing barriers and facilitators to operationalising best-practice dementia care.: creating a comfortable environment; changing approach to care; optimising the general practice nurse role and working collaboratively. Nine sub-themes were described: physical environment; social environment; complexity of care; care planning for the family; professional role and identity, funding better dementia care, education, networking and resources; different roles, one team; and interagency communication. CONCLUSION: This study identified several factors that need addressing to support general practice nurses to integrate best-practice dementia care recommendations into daily clinical practice. The development of interventions needs to include strategies to mitigate potential barriers and enhance facilitators that they perceive impact on their delivery of best-practice care for people living with dementia and their carer(s). The knowledge gained in this study could be used to develop multi-faceted interventions informed by theoretical implementation change models to enable the general practice nurse to operationalise best-practice dementia care recommendations.

Ongoing shielding behavior one year post COVID-19: results from a longitudinal study of patients with inflammatory arthritis.

Many patients with inflammatory arthritis (IA) were instructed to shield during the COVID-19 pandemic. Despite the ending of lockdowns and vaccination, large proportions of IA patients were continuing to shield when it is no longer needed. Given the detrimental effects of shielding on mental and physical health, understanding the rates and reasons for shielding is needed to help clinicians advise patients accordingly. This study was a 12-month prospective study following participants with IA during the COVID-19 pandemic. The proportions of IA patients shielding at each time point were calculated. Additionally, regressions and odds ratios for shielding were determined to assess medication type, mental health, and risk perception. While the extent of shielding fluctuated over the year of lockdowns, nearly all IA patients (93.5%) were still engaging in some shielding in 2021, with nearly half (43%) still shielding most or all of the time. Medications that were previously considered higher risk were not significantly associated with higher rates of shielding (OR = 1.60, p = 0.29), but greater symptoms of depression in June 2020 (OR = 1.07, p = 0.03) was both associated with increased the odds of shielding in June 2021. The high rates of IA patients continuing to shield in 2021 put more strain on patients and professionals as social isolation is linked with worsening mental and physical health, as well as greater difficulty with self-management. It is important for clinicians to be aware of this trend to ease the stress on patients.

Mental health, quality of life and self-management behaviours: online evaluation of inflammatory arthritis patients over 1 year of COVID-19 lockdowns.

Objective: Patients with inflammatory arthritis were especially vulnerable to the psychosocial and health impacts of coronavirus disease 2019 (COVID-19) and the lockdowns. This study investigated the impact of these changes on mental health, physical health and quality of life for inflammatory arthritis patients over 1 year following the initial lockdown in the UK. Methods: Three hundred and thirty-eight participants with inflammatory arthritis completed an ambidirectional study consisting of online questionnaires at four time points for 1 year. The questionnaires assessed demographic information, inflammatory arthritis condition, mental health, physical symptoms, self-management behaviours, COVID-19 status and impacts. Means, linear regressions and structural equation modelling for mediations were conducted over 12 months. Results: Physical health concerns peaked during June 2020, then declined, but did not return to baseline. Depression was associated with worse quality of life at baseline, as shown by the beta coefficient, (ß= 0.94, P < 0.01), September (ß = 0.92, P < 0.01), November (ß= 0.77, P < 0.01) and 1 year (ß = 0.77, P < 0.01). Likewise, anxiety was associated with worse quality of life at baseline (ß = 1.92, P < 0.01), September (ß = 2.06, P < 0.01), November (ß = 1.66, P = 0.03) and 1 year (ß = 1.51, P = 0.02). The association between depression and quality of life was mediated by physical activity (ß= 0.13, P < 0.01) at baseline. The association between anxiety and quality of life was also mediated by physical activity (ß = 0.25, P = 0.04) at baseline. Conclusion: Physical health continued to be worse 1 year later compared with before the COVID-19 lockdowns in patients with inflammatory arthritis. Mental health showed long-term effects on quality of life, with an impact for ≥12 months. Lastly, physical activity mediated between mental health and quality of life in the short term.

Impact of COVID-19 on immunocompromised populations during the Omicron era: insights from the observational population-based INFORM study.

Background: Immunocompromised individuals are not optimally protected by COVID-19 vaccines and potentially require additional preventive interventions to mitigate the risk of severe COVID-19. We aimed to characterise and describe the risk of severe COVID-19 across immunocompromised groups as the pandemic began to transition to an endemic phase. Methods: COVID-19-related hospitalisations, intensive care unit (ICU) admissions, and deaths (01/01/2022-31/12/2022) were compared among different groups of immunocompromised individuals vs the general population, using a retrospective cohort design and electronic health data from a random 25% sample of the English population aged ≥12 years (Registration number: ISRCTN53375662). Findings: Overall, immunocompromised individuals accounted for 3.9% of the study population, but 22% (4585/20,910) of COVID-19 hospitalisations, 28% (125/440) of COVID-19 ICU admissions, and 24% (1145/4810) of COVID-19 deaths in 2022. Restricting to those vaccinated with ≥3 doses of COVID-19 vaccine (∼84% of immunocompromised and 51% of the general population), all immunocompromised groups remained at increased risk of severe COVID-19 outcomes, with adjusted incidence rate ratios (aIRR) for hospitalisation ranging from 1.3 to 13.1. At highest risk for COVID-19 hospitalisation were individuals with: solid organ transplant (aIRR 13.1, 95% confidence interval [95% CI] 11.2-15.3), moderate to severe primary immunodeficiency (aIRR 9.7, 95% CI 6.3-14.9), stem cell transplant (aIRR 11.0, 95% CI 6.8-17.6), and recent treatment for haematological malignancy (aIRR 10.6, 95% CI 9.5-11.9). Results were similar for COVID-19 ICU admissions and deaths. Interpretation: Immunocompromised individuals continue to be impacted disproportionately by COVID-19 and have an urgent need for additional preventive measures beyond current vaccination programmes. These data can help determine the immunocompromised groups for which targeted prevention strategies may have the highest impact. Funding: This study was funded by AstraZeneca UK.

Pretrial predictors of conflict response efficacy in the human prefrontal cortex.

The ability to perform motor actions depends, in part, on the brain's initial state. We hypothesized that initial state dependence is a more general principle and applies to cognitive control. To test this idea, we examined human single units recorded from the dorsolateral prefrontal (dlPFC) cortex and dorsal anterior cingulate cortex (dACC) during a task that interleaves motor and perceptual conflict trials, the multisource interference task (MSIT). In both brain regions, variability in pre-trial firing rates predicted subsequent reaction time (RT) on conflict trials. In dlPFC, ensemble firing rate patterns suggested the existence of domain-specific initial states, while in dACC, firing patterns were more consistent with a domain-general initial state. The deployment of shared and independent factors that we observe for conflict resolution may allow for flexible and fast responses mediated by cognitive initial states. These results also support hypotheses that place dACC hierarchically earlier than dlPFC in proactive control.

Lessons learnt from a community-driven digital social connection pilot program for people living with dementia: A qualitative interview study with key stakeholders.

INTRODUCTION: In response to COVID-19 and mandated physical distancing, a new digital social connection program was developed and implemented by the local community in a large regional town in western Victoria, Australia. This pilot program, the Digital Inclusion-Social Connections (DI-SC) program, aimed to support people living with dementia to use a digital device to access social connection activities. OBJECTIVE: The objective of this study is to inform the local community implementing the DI-SC program of key stakeholder experience of DI-SC process and outcomes to support future development and potential translation of digital social connections programs for people living with dementia. DESIGN: Three semi-structured focus groups and two interviews were conducted with a total of fifteen participants. Data was transcribed verbatim and thematically analysed. FINDINGS: Three main themes were identified describing factors as influencing the process and outcomes of the DI-SC program: understanding dementia; personal choice and control; and service planning and coordination. Six sub-themes were identified: matching capability; establishing a relationship; creating opportunities for different interactions; ownership of the device, program coordination and defining the volunteer digital mentor role. CONCLUSION: Key stakeholders perceived the DI-SC program as an acceptable way of supporting people living with dementia to engage in activities they found enjoyable promoting social connection with care partners and others. DI-SC program outcomes were impacted by inappropriate training and a lack of program coordination. The findings of this study may inform future development and implementation of digital social connection programs for vulnerable populations at risk of social isolation.

Best-practice recommendations to inform general practice nurses in the provision of dementia care: a Delphi study.

BACKGROUND: Worldwide, responsibility for dementia diagnosis and management is shifting to primary care, in particular to the general practitioner (GP). It has been acknowledged that primary care nurses, working collaboratively with GPs, have a role in dementia care by utilising their unique knowledge and skills. However, there are no best-practice guidelines or care pathways to inform nurses in general practice on what best-practice dementia care comprises and how to implement this into their practice. This study identified the recommendations in the Australian guidelines for dementia management most relevant to the role of the nurse working in general practice. METHODS: Seventeen experts active in clinical practice and/or research in primary care nursing in general practice participated in an online three-round Delphi study. RESULTS: All 17 participants were female with a nursing qualification and experienced in general practice clinical nursing and/or general practice nursing research. Five recommendations were identified as the most relevant to the role of the nurse in general practice. These recommendations all contained elements of person-centred care: the delivery of individualised information, ongoing support, including the carer in decision-making, and they also align with the areas where GPs want support in dementia care provision. CONCLUSION: This novel study identified best-practice dementia care recommendations specific to nurses in general practice. These recommendations will inform a model of care for nurses in the provision of dementia care that supports GPs and better meets the needs of people living with dementia and their carer(s).

The impact of a cognitive impairment support program on patients in an acute care setting: a pre-test post-test intervention study.

BACKGROUND: Patients with cognitive impairment are at greater risk of hospital acquired complications, longer hospital stays, and poor health outcomes compared to patients without cognitive impairment. The Cognitive Impairment Support Program is a multi-disciplinary approach to improve screening rates and awareness of patients with cognitive impairment and guide clinician response and communication during their hospitalisation to improve health outcomes. OBJECTIVE: This study evaluated the impact of implementing the Cognitive Impairment Support Program on patient hospital acquired complications, patient reported quality of life and staff satisfaction in an outer metropolitan hospital. DESIGN: A pre-test post-test design was used to collect data in two 6-month time periods between March 2020 and November 2021. PARTICIPANTS: Patients aged ≥ 65 years, admitted to a participating ward for > 24 h. INTERVENTION: The Cognitive Impairment Support Program consisted of four components: cognitive impairment screening, initiation of a Cognitive Impairment Care Plan, use of a Cognitive Impairment Identifier and associated staff education. MEASURES: The primary outcome was hospital acquired complications experienced by patients with cognitive impairment identified using clinical coding data. Secondary outcomes were patient quality of life and a staff confidence and perceived organisational support to care for patients with cognitive impairment. RESULTS: Hospital acquired complication rates did not vary significantly between the two data collection periods for patients experiencing cognitive impairment with a 0.2% (95% confidence interval: -5.7-6.1%) reduction in admissions with at least one hospital acquired complication. Patients in the post intervention period demonstrated statistically significant improvements in many items in two of the Dementia Quality of Life Measure domains: memory and everyday life. The staff survey indicated statistically significant improvement in clinical staff confidence to care for patients with cognitive impairment (p = 0.003), satisfaction with organisational support for patients (p = 0.004) and job satisfaction (p ≤ 0.001). CONCLUSION: This study provides evidence that a multicomponent Cognitive Impairment Support Program had a positive impact on staff confidence and satisfaction and patient quality of life. Broader implementation with further evaluation of the multicomponent cognitive impairment intervention across a range of settings using varied patient outcomes is recommended.

Online Patient-Reported Outcome Measure Engagement Is Dependent on Demographics and Locality: Findings From an Observational Cohort.

OBJECTIVE: Online patient-reported outcome measures (PROMs) enable remote collection of perceptions of health status, function, and well-being. We aimed to explore patterns of PROM completion in patients with early inflammatory arthritis (EIA) recruited to the National Early Inflammatory Arthritis Audit (NEIAA). METHODS: NEIAA is an observational cohort study design; we included adults from this cohort with a new diagnosis of EIA from May 2018 to March 2020. The primary outcome was PROM completion at baseline, 3 months, and 12 months. Mixed effects logistic regression and spatial regression models were used to identify associations between demographics (age, gender, ethnicity, deprivation, smoking, and comorbidity), clinical commissioning groups, and PROM completion. RESULTS: Eleven thousand nine hundred eighty-six patients with EIA were included, of whom 5331 (44.5%) completed at least 1 PROM. Patients from ethnic minority backgrounds were less likely to return a PROM (adjusted odds ratio [aOR] 0.57, 95% CI 0.48-0.66). Greater deprivation (aOR 0.73, 95% CI 0.64-0.83), male gender (aOR 0.86, 95% CI 0.78-0.94), higher comorbidity burden (aOR 0.95, 95% CI 0.91-0.99), and current smoker status (aOR 0.73, 95% CI 0.64-0.82) also reduced odds of PROM completion. Spatial analysis identified 2 regions with high (North of England) and low (Southeast of England) PROM completion. CONCLUSION: We define key patient characteristics (including ethnicity) that influence PROM engagement using a national clinical audit. We observed an association between locality and PROM completion, with varying response rates across regions of England. Completion rates could benefit from targeted education for these groups.

Characteristics associated with poor COVID-19 outcomes in people with psoriasis, psoriatic arthritis and axial spondyloarthritis: data from the COVID-19 PsoProtect and Global Rheumatology Alliance physician-reported registries.

OBJECTIVES: To investigate factors associated with severe COVID-19 in people with psoriasis (PsO), psoriatic arthritis (PsA) and axial spondyloarthritis (axSpA). METHODS: Demographic data, clinical characteristics and COVID-19 outcome severity of adults with PsO, PsA and axSpA were obtained from two international physician-reported registries. A three-point ordinal COVID-19 severity scale was defined: no hospitalisation, hospitalisation (and no death) and death. ORs were estimated using multivariable ordinal logistic regression. RESULTS: Of 5045 cases, 18.3% had PsO, 45.5% PsA and 36.3% axSpA. Most (83.6%) were not hospitalised, 14.6% were hospitalised and 1.8% died. Older age was non-linearly associated with COVID-19 severity. Male sex (OR 1.54, 95% CI 1.30 to 1.83), cardiovascular, respiratory, renal, metabolic and cancer comorbidities (ORs 1.25-2.89), moderate/high disease activity and/or glucocorticoid use (ORs 1.39-2.23, vs remission/low disease activity and no glucocorticoids) were associated with increased odds of severe COVID-19. Later pandemic time periods (ORs 0.42-0.52, vs until 15 June 2020), PsO (OR 0.49, 95% CI 0.37 to 0.65, vs PsA) and baseline exposure to TNFi, IL17i and IL-23i/IL-12+23i (OR 0.57, 95% CI 0.44 to 0.73; OR 0.62, 95% CI 0.45 to 0.87; OR 0.67, 95% CI 0.45 to 0.98; respectively; vs no disease-modifying antirheumatic drug) were associated with reduced odds of severe COVID-19. CONCLUSION: Older age, male sex, comorbidity burden, higher disease activity and glucocorticoid intake were associated with more severe COVID-19. Later pandemic time periods, PsO and exposure to TNFi, IL17i and IL-23i/IL-12+23i were associated with less severe COVID-19. These findings will enable risk stratification and inform management decisions for patients with PsO, PsA and axSpA during COVID-19 waves or similar future respiratory pandemics.

Nationally Informed Recommendations on Approaching the Detection, Assessment, and Management of Mild Cognitive Impairment.

Prior to the usual clinical symptoms of dementia, there can be subtle changes in cognitive function that differ from the normal age-related cognitive decline, which has been termed mild cognitive impairment (MCI). The increase in the numbers of individuals with possible MCI presenting to health care professionals, notably, General Practitioners (GPs), is going to rise dramatically in the coming years. With ever increasing demands on GPs, it is therefore timely to provide information that can be accessed by health care professionals to assist them in making appropriate diagnoses and to provide the most relevant, evidence-based treatment options. We have provided a comprehensive list of recommendations that aim to address key aspects of MCI in primary care. Specifically, these relate to detection and diagnosis; sharing the diagnosis, monitoring, and follow up; practical interventions to potentially delay progression; and personalizing care-planning, engagement, and patient motivation for the long term.

The Spatial Reach of Neuronal Coherence and Spike-Field Coupling across the Human Neocortex.

Neuronal coherence is thought to be a fundamental mechanism of communication in the brain, where synchronized field potentials coordinate synaptic and spiking events to support plasticity and learning. Although the spread of field potentials has garnered great interest, little is known about the spatial reach of phase synchronization, or neuronal coherence. Functional connectivity between different brain regions is known to occur across long distances, but the locality of synchronization across the neocortex is understudied. Here we used simultaneous recordings from electrocorticography (ECoG) grids and high-density microelectrode arrays to estimate the spatial reach of neuronal coherence and spike-field coherence (SFC) across frontal, temporal, and occipital cortices during cognitive tasks in humans. We observed the strongest coherence within a 2-3 cm distance from the microelectrode arrays, potentially defining an effective range for local communication. This range was relatively consistent across brain regions, spectral frequencies, and cognitive tasks. The magnitude of coherence showed power law decay with increasing distance from the microelectrode arrays, where the highest coherence occurred between ECoG contacts, followed by coherence between ECoG and deep cortical local field potential (LFP), and then SFC (i.e., ECoG > LFP > SFC). The spectral frequency of coherence also affected its magnitude. Alpha coherence (8-14 Hz) was generally higher than other frequencies for signals nearest the microelectrode arrays, whereas delta coherence (1-3 Hz) was higher for signals that were farther away. Action potentials in all brain regions were most coherent with the phase of alpha oscillations, which suggests that alpha waves could play a larger, more spatially local role in spike timing than other frequencies. These findings provide a deeper understanding of the spatial and spectral dynamics of neuronal synchronization, further advancing knowledge about how activity propagates across the human brain.SIGNIFICANCE STATEMENT Coherence is theorized to facilitate information transfer across cerebral space by providing a convenient electrophysiological mechanism to modulate membrane potentials in spatiotemporally complex patterns. Our work uses a multiscale approach to evaluate the spatial reach of phase coherence and spike-field coherence during cognitive tasks in humans. Locally, coherence can reach up to 3 cm around a given area of neocortex. The spectral properties of coherence revealed that alpha phase-field and spike-field coherence were higher within ranges <2 cm, whereas lower-frequency delta coherence was higher for contacts farther away. Spatiotemporally shared information (i.e., coherence) across neocortex seems to reach farther than field potentials alone.

Risk of severe COVID-19 outcomes associated with immune-mediated inflammatory diseases and immune-modifying therapies: a nationwide cohort study in the OpenSAFELY platform.

Background: The risk of severe COVID-19 outcomes in people with immune-mediated inflammatory diseases and on immune-modifying drugs might not be fully mediated by comorbidities and might vary by factors such as ethnicity. We aimed to assess the risk of severe COVID-19 in adults with immune-mediated inflammatory diseases and in those on immune-modifying therapies. Methods: We did a cohort study, using OpenSAFELY (an analytics platform for electronic health records) and TPP (a software provider for general practitioners), analysing routinely collected primary care data linked to hospital admission, death, and previously unavailable hospital prescription data. We included people aged 18 years or older on March 1, 2020, who were registered with TPP practices with at least 12 months of primary care records before March, 2020. We used Cox regression (adjusting for confounders and mediators) to estimate hazard ratios (HRs) comparing the risk of COVID-19-related death, critical care admission or death, and hospital admission (from March 1 to Sept 30, 2020) in people with immune-mediated inflammatory diseases compared with the general population, and in people with immune-mediated inflammatory diseases on targeted immune-modifying drugs (eg, biologics) compared with those on standard systemic treatment (eg, methotrexate). Findings: We identified 17 672 065 adults; 1 163 438 adults (640 164 [55·0%] women and 523 274 [45·0%] men, and 827 457 [71·1%] of White ethnicity) had immune-mediated inflammatory diseases, and 16 508 627 people (8 215 020 [49·8%] women and 8 293 607 [50·2%] men, and 10 614 096 [64·3%] of White ethnicity) were included as the general population. Of 1 163 438 adults with immune-mediated inflammatory diseases, 19 119 (1·6%) received targeted immune-modifying therapy and 181 694 (15·6%) received standard systemic therapy. Compared with the general population, adults with immune-mediated inflammatory diseases had an increased risk of COVID-19-related death after adjusting for confounders (age, sex, deprivation, and smoking status; HR 1·23, 95% CI 1·20-1·27) and further adjusting for mediators (body-mass index [BMI], cardiovascular disease, diabetes, and current glucocorticoid use; 1·15, 1·11-1·18). Adults with immune-mediated inflammatory diseases also had an increased risk of COVID-19-related critical care admission or death (confounder-adjusted HR 1·24, 95% CI 1·21-1·28; mediator-adjusted 1·16, 1·12-1·19) and hospital admission (confounder-adjusted 1·32, 1·29-1·35; mediator-adjusted 1·20, 1·17-1·23). In post-hoc analyses, the risk of severe COVID-19 outcomes in people with immune-mediated inflammatory diseases was higher in non-White ethnic groups than in White ethnic groups (as it was in the general population). We saw no evidence of increased COVID-19-related death in adults on targeted, compared with those on standard systemic, therapy after adjusting for confounders (age, sex, deprivation, BMI, immune-mediated inflammatory diseases [bowel, joint, and skin], cardiovascular disease, cancer [excluding non-melanoma skin cancer], stroke, and diabetes (HR 1·03, 95% CI 0·80-1·33), and after additionally adjusting for current glucocorticoid use (1·01, 0·78-1·30). There was no evidence of increased COVID-19-related death in adults prescribed tumour necrosis factor inhibitors, interleukin (IL)-12/IL­23 inhibitors, IL-17 inhibitors, IL-6 inhibitors, or Janus kinase inhibitors compared with those on standard systemic therapy. Rituximab was associated with increased COVID-19-related death (HR 1·68, 95% CI 1·11-2·56), with some attenuation after excluding people with haematological malignancies or organ transplants (1·54, 0·95-2·49). Interpretation: COVID-19 deaths and hospital admissions were higher in people with immune-mediated inflammatory diseases. We saw no increased risk of adverse COVID-19 outcomes in those on most targeted immune-modifying drugs for immune-mediated inflammatory diseases compared with those on standard systemic therapy. Funding: UK Medical Research Council, NIHR Biomedical Research Centre at King's College London and Guy's and St Thomas' NHS Foundation Trust, and Wellcome Trust.

Inpatient COVID-19 mortality has reduced over time: Results from an observational cohort.

BACKGROUND: The Covid-19 pandemic in the United Kingdom has seen two waves; the first starting in March 2020 and the second in late October 2020. It is not known whether outcomes for those admitted with severe Covid were different in the first and second waves. METHODS: The study population comprised all patients admitted to a 1,500-bed London Hospital Trust between March 2020 and March 2021, who tested positive for Covid-19 by PCR within 3-days of admissions. Primary outcome was death within 28-days of admission. Socio-demographics (age, sex, ethnicity), hypertension, diabetes, obesity, baseline physiological observations, CRP, neutrophil, chest x-ray abnormality, remdesivir and dexamethasone were incorporated as co-variates. Proportional subhazards models compared mortality risk between wave 1 and wave 2. Cox-proportional hazard model with propensity score adjustment were used to compare mortality in patients prescribed remdesivir and dexamethasone. RESULTS: There were 3,949 COVID-19 admissions, 3,195 hospital discharges and 733 deaths. There were notable differences in age, ethnicity, comorbidities, and admission disease severity between wave 1 and wave 2. Twenty-eight-day mortality was higher during wave 1 (26.1% versus 13.1%). Mortality risk adjusted for co-variates was significantly lower in wave 2 compared to wave 1 [adjSHR 0.49 (0.37, 0.65) p<0.001]. Analysis of treatment impact did not show statistically different effects of remdesivir [HR 0.84 (95%CI 0.65, 1.08), p = 0.17] or dexamethasone [HR 0.97 (95%CI 0.70, 1.35) p = 0.87]. CONCLUSION: There has been substantial improvements in COVID-19 mortality in the second wave, even accounting for demographics, comorbidity, and disease severity. Neither dexamethasone nor remdesivir appeared to be key explanatory factors, although there may be unmeasured confounding present.

The impact of COVID-19 on clinical care, self-management and mental health of patients with inflammatory arthritis.

OBJECTIVES: The coronavirus disease 2019 (COVID-19) lockdown and ongoing restrictions in the UK affected access to clinical care, self-management and mental health for many patients with inflammatory arthritis. The aim of this study was to determine the impact of lockdown on inflammatory arthritis clinical care, self-management, disease outcomes and mental health. METHODS: In total, 338 people with inflammatory arthritis participated in a prospective study, completing a series of online questionnaires. The questionnaires assessed demographics, inflammatory arthritis condition and management, clinical care, quality of life and mental health. Visual analogue scales (VASs) were completed at each assessment. Linear regression, controlling for confounders, was conducted to determine factors associated with physical and mental health outcomes. RESULTS: More than half of participants reported worsening VAS by >10 points for patient global assessment (PGA), pain, fatigue and emotional distress during the initial lockdown. Changes in clinical care were associated with worse PGA (b = 8.95, P = 0.01), pain (b = 7.13, P = 0.05), fatigue (b = 17.01, P < 0.01) and emotional distress (b = 12.78, P < 0.01). Emotional distress and depression were also associated with worse outcomes in PGA, pain and fatigue, whereas loneliness was not. In contrast, physical activity seemed to mitigate these effects. Loneliness did not show any associations with outcomes. Over time, these effects decreased or disappeared. CONCLUSION: Changes to clinical care owing to lockdown were associated with worse disease outcomes in patients with inflammatory arthritis. There has also been a clear impact on mental health, with possibly complex relationships between mental health and psychosocial factors. Physical activity emerged as a key influence on disease outcomes and mental health.

Alpha and broadband high-frequency activity track task dynamics and predict performance in controlled decision-making.

Intracranial recordings in human subjects provide a unique, fine-grained temporal and spatial resolution inaccessible to conventional non-invasive methods. A prominent signal in these recordings is broadband high-frequency activity (approx. 70-150 Hz), generally considered to reflect neuronal excitation. Here we explored the use of this broadband signal to track, on a single-trial basis, the temporal and spatial distribution of task-engaged areas involved in decision-making. We additionally focused on the alpha rhythm (8-14 Hz), thought to regulate the (dis)engagement of neuronal populations based on task demands. Using these signals, we characterized activity across cortex using intracranial recordings in patients with intractable epilepsy performing the Multi-Source Interference Task, a Stroop-like decision-making paradigm. We analyzed recordings both from grid electrodes placed over cortical areas including frontotemporal and parietal cortex, and depth electrodes in prefrontal regions, including cingulate cortex. We found a widespread negative relationship between alpha power and broadband activity, substantiating the gating role of alpha in regions beyond sensory/motor cortex. Combined, these signals reflect the spatio-temporal pattern of task-engagement, with alpha decrease signifying task-involved regions and broadband increase temporally locking to specific task aspects, distributed over cortical sites. We report sites that only respond to stimulus presentation or to the decision report and, interestingly, sites that reflect the time-on-task. The latter predict the subject's reaction times on a trial-by-trial basis. A smaller subset of sites showed modulation with task condition. Taken together, alpha and broadband signals allow tracking of neuronal population dynamics across cortex on a fine temporal and spatial scale.

Diagnostic delay is common for patients with axial spondyloarthritis: results from the National Early Inflammatory Arthritis Audit.

OBJECTIVES: Updated guidelines for patients with axial SpA (axSpA) have sought to reduce diagnostic delay by raising awareness among clinicians. We used the National Early Inflammatory Arthritis Audit (NEIAA) to describe baseline characteristics and time to diagnosis for newly referred patients with axSpA in England and Wales. METHODS: Analyses were performed on sociodemographic and clinical metrics, including time to referral and assessment, for axSpA patients (n = 784) recruited to the NEIAA between May 2018 and March 2020. Comparators were patients recruited to the NEIAA with RA (n = 9270) or mechanical back pain (MBP; n = 370) in the same period. RESULTS: Symptom duration prior to initial rheumatology assessment was longer in axSpA than RA patients (P < 0.001) and non-significantly longer in axSpA than MBP patients (P = 0.062): 79.7% of axSpA patients had symptom durations of >6 months, compared with 33.7% of RA patients and 76.0% of MBP patients. Following referral, the median time to initial rheumatology assessment was longer for axSpA than RA patients (36 vs 24 days; P < 0.001) and similar to MBP patients (39 days; P = 0.30). Of the subset of patients deemed eligible for early inflammatory arthritis pathway follow-up, fewer axSpA than RA patients had disease education provided (77.5% vs 97.8%) and RA patients reported a better understanding of their condition and treatment. CONCLUSION: Diagnostic delay in axSpA remains a major challenge despite improved disease understanding and updated referral guidelines. Disease education is provided to fewer axSpA than RA patients, highlighting the need for specialist clinics and support programmes for axSpA patients.

Association Between Tumor Necrosis Factor Inhibitors and the Risk of Hospitalization or Death Among Patients With Immune-Mediated Inflammatory Disease and COVID-19.

Importance: Although tumor necrosis factor (TNF) inhibitors are widely prescribed globally because of their ability to ameliorate shared immune pathways across immune-mediated inflammatory diseases (IMIDs), the impact of COVID-19 among individuals with IMIDs who are receiving TNF inhibitors remains insufficiently understood. Objective: To examine the association between the receipt of TNF inhibitor monotherapy and the risk of COVID-19-associated hospitalization or death compared with other commonly prescribed immunomodulatory treatment regimens among adult patients with IMIDs. Design, Setting, and Participants: This cohort study was a pooled analysis of data from 3 international COVID-19 registries comprising individuals with rheumatic diseases, inflammatory bowel disease, and psoriasis from March 12, 2020, to February 1, 2021. Clinicians directly reported COVID-19 outcomes as well as demographic and clinical characteristics of individuals with IMIDs and confirmed or suspected COVID-19 using online data entry portals. Adults (age ≥18 years) with a diagnosis of inflammatory arthritis, inflammatory bowel disease, or psoriasis were included. Exposures: Treatment exposure categories included TNF inhibitor monotherapy (reference treatment), TNF inhibitors in combination with methotrexate therapy, TNF inhibitors in combination with azathioprine/6-mercaptopurine therapy, methotrexate monotherapy, azathioprine/6-mercaptopurine monotherapy, and Janus kinase (Jak) inhibitor monotherapy. Main Outcomes and Measures: The main outcome was COVID-19-associated hospitalization or death. Registry-level analyses and a pooled analysis of data across the 3 registries were conducted using multilevel multivariable logistic regression models, adjusting for demographic and clinical characteristics and accounting for country, calendar month, and registry-level correlations. Results: A total of 6077 patients from 74 countries were included in the analyses; of those, 3215 individuals (52.9%) were from Europe, 3563 individuals (58.6%) were female, and the mean (SD) age was 48.8 (16.5) years. The most common IMID diagnoses were rheumatoid arthritis (2146 patients [35.3%]) and Crohn disease (1537 patients [25.3%]). A total of 1297 patients (21.3%) were hospitalized, and 189 patients (3.1%) died. In the pooled analysis, compared with patients who received TNF inhibitor monotherapy, higher odds of hospitalization or death were observed among those who received a TNF inhibitor in combination with azathioprine/6-mercaptopurine therapy (odds ratio [OR], 1.74; 95% CI, 1.17-2.58; P = .006), azathioprine/6-mercaptopurine monotherapy (OR, 1.84; 95% CI, 1.30-2.61; P = .001), methotrexate monotherapy (OR, 2.00; 95% CI, 1.57-2.56; P < .001), and Jak inhibitor monotherapy (OR, 1.82; 95% CI, 1.21-2.73; P = .004) but not among those who received a TNF inhibitor in combination with methotrexate therapy (OR, 1.18; 95% CI, 0.85-1.63; P = .33). Similar findings were obtained in analyses that accounted for potential reporting bias and sensitivity analyses that excluded patients with a COVID-19 diagnosis based on symptoms alone. Conclusions and Relevance: In this cohort study, TNF inhibitor monotherapy was associated with a lower risk of adverse COVID-19 outcomes compared with other commonly prescribed immunomodulatory treatment regimens among individuals with IMIDs.