Noradrenaline-induced changes in cerebral blood flow in health, traumatic brain injury and critical illness: a systematic review with meta-analysis.

BACKGROUND: Noradrenaline is a standard treatment for hypotension in acute care. The precise effects of noradrenaline on cerebral blood flow in health and disease remain unclear. METHODS: We systematically reviewed and synthesised data from studies examining changes in cerebral blood flow in healthy participants and patients with traumatic brain injury and critical illness. RESULTS: Twenty-eight eligible studies were included. In healthy subjects and patients without critical illness or traumatic brain injury, noradrenaline did not significantly change cerebral blood flow velocity (-1.7%, 95%CI -4.7-1.3%) despite a 24.1% (95%CI 19.4-28.7%) increase in mean arterial pressure. In patients with traumatic brain injury, noradrenaline significantly increased cerebral blood flow velocity (21.5%, 95%CI 11.0-32.0%), along with a 33.8% (95%CI 14.7-52.9%) increase in mean arterial pressure. In patients who were critically ill, noradrenaline significantly increased cerebral blood flow velocity (20.0%, 95%CI 9.7-30.3%), along with a 32.4% (95%CI 25.0-39.9%) increase in mean arterial pressure. Our analyses suggest intact cerebral autoregulation in healthy subjects and patients without critical illness or traumatic brain injury., and impaired cerebral autoregulation in patients with traumatic brain injury and who were critically ill. The extent of mean arterial pressure changes and the pre-treatment blood pressure levels may affect the magnitude of cerebral blood flow changes. Studies assessing cerebral blood flow using non-transcranial Doppler methods were inadequate and heterogeneous in enabling meaningful meta-analysis. CONCLUSIONS: Noradrenaline significantly increases cerebral blood flow in humans with impaired, not intact, cerebral autoregulation, with the extent of changes related to the severity of functional impairment, the extent of mean arterial pressure changes and pre-treatment blood pressure levels.

Association of Premorbid Anxiety and Depression Symptoms in Concussion Recovery in Collegiate Student-Athletes.

BACKGROUND: Mental health disorders are linked to prolonged concussion symptoms. However, the association of premorbid anxiety/depression symptoms with postconcussion return-to-play timelines and total symptom burden is unclear. OBJECTIVE: To examine the association of self-reported premorbid anxiety/depression symptoms in collegiate student-athletes with (1) recovery times until asymptomatic, (2) return-to-play, and (3) postconcussion symptom burden. STUDY DESIGN: Athletes in the Concussion Assessment, Research and Education Consortium completed baseline concussion assessments (Sport Concussion Assessment Tool [SCAT3] and Brief Symptom Inventory-18 [BSI-18]). Athletes were tested postinjury at <6 hours, 24 to 48 hours, time of asymptomatic and start of return-to-play protocol, unrestricted return-to-play, and 6 months after injury. Injured athletes were categorized into 4 groups based on BSI-18 scores: (1) B-ANX, elevated anxiety symptoms only; (2) B-DEP, elevated depression symptoms only; (3) B-ANX&DEP, elevated anxiety and depression symptoms; and (4) B-NEITHER, no elevated anxiety or depression symptoms. Relationship between age, sex, BSI-18 group, SCAT3 total symptom and severity scores, and time to asymptomatic status and return-to-play was assessed with Pearson's chi-squared test and robust analysis of variance. LEVEL OF EVIDENCE: Level 3. RESULTS: Among 1329 athletes with 1352 concussions, no respondents had a self-reported premorbid diagnosis of anxiety/depression. There was no difference in time until asymptomatic or time until return-to-play between BSI-18 groups (P = 0.15 and P = 0.11, respectively). B-ANX, B-DEP, and B-ANX&DEP groups did not have higher total symptom or severity scores postinjury compared with the B-NEITHER group. CONCLUSION: Baseline anxiety/depression symptoms in collegiate student-athletes without a mental health diagnosis are not associated with longer recovery times until asymptomatic, longer time to return-to-play, or higher postconcussion total symptom and severity scores compared with athletes without baseline symptoms. CLINICAL RELEVANCE: Anxiety and depression symptoms without a clear mental health diagnosis should be considered differently from other comorbidities when discussing prolonged recovery in collegiate student-athletes.

Temporal trends in disparities in COVID-19 seropositivity among Canadian blood donors.

BACKGROUND: In Canada's largest COVID-19 serological study, SARS-CoV-2 antibodies in blood donors have been monitored since 2020. No study has analysed changes in the association between anti-N seropositivity (a marker of recent infection) and geographic and sociodemographic characteristics over the pandemic. METHODS: Using Bayesian multi-level models with spatial effects at the census division level, we analysed changes in correlates of SARS-CoV-2 anti-N seropositivity across three periods in which different variants predominated (pre-Delta, Delta and Omicron). We analysed disparities by geographic area, individual traits (age, sex, race) and neighbourhood factors (urbanicity, material deprivation and social deprivation). Data were from 420 319 blood donations across four regions (Ontario, British Columbia [BC], the Prairies and the Atlantic region) from December 2020 to November 2022. RESULTS: Seropositivity was higher for racialized minorities, males and individuals in more materially deprived neighbourhoods in the pre-Delta and Delta waves. These subgroup differences dissipated in the Omicron wave as large swaths of the population became infected. Across all waves, seropositivity was higher in younger individuals and those with lower neighbourhood social deprivation. Rural residents had high seropositivity in the Prairies, but not other regions. Compared to generalized linear models, multi-level models with spatial effects had better fit and lower error when predicting SARS-CoV-2 anti-N seropositivity by geographic region. CONCLUSIONS: Correlates of recent COVID-19 infection have evolved over the pandemic. Many disparities lessened during the Omicron wave, but public health intervention may be warranted to address persistently higher burden among young people and those with less social deprivation.

Bioinspired Genetic and Chemical Engineering of Protein Hydrogels for programable Multi-responsive Actuation.

Protein hydrogels with tailored stimuli-responsive features and tunable stiffness have garnered considerable attention due to the growing demand for biomedical soft robotics. However, integrating multiple responsive features toward intelligent yet biocompatible actuators remains challenging. Here, we report a facile approach that synergistically combines genetic and chemical engineering for the design of protein hydrogel actuators with programable complex spatial deformation. Genetically engineered silk-elastin-like proteins (SELPs) were encoded with stimuli-responsive motifs and enzymatic crosslinking sites via simulation-guided genetic engineering strategies. Chemical modifications of the recombinant proteins were also used as secondary control points to tailor material properties, responsive features, and anisotropy in SELP hydrogels. As a proof-of-concept example, diazonium coupling chemistry was exploited to incorporate sulfanilic acid groups onto the tyrosine residues in the elastin domains of SELPs to achieve patterned SELP hydrogels. These hydrogels can be programmed to perform various actuations, including controllable bending, buckling, and complex deformation under external stimuli, such as temperature, ionic strength, or pH. With the inspiration of genetic and chemical engineering in natural organisms, this work offers a predictable, tunable, and environmentally sustainable approach for the fabrication of programmed intelligent soft actuators, with implications for a variety of biomedical materials and bio-robotics needs. This article is protected by copyright. All rights reserved.

Productivity loss by cancer stage in patients newly diagnosed with hepatocellular carcinoma: A claims database analysis.

BACKGROUND: New cancer diagnoses are associated with employment decrease, workplace absenteeism, and attributable costs to employers. OBJECTIVE: To estimate the workplace productivity loss in the year following a new diagnosis of early-, intermediate-, or advanced-stage hepatocellular carcinoma (HCC) in commercially insured US adults. METHODS: We conducted a retrospective cohort study using Merative MarketScan commercial claims to identify incident HCC diagnoses from 2010 to 2020. Patients were stratified into early-, intermediate-, or advanced-stage cohorts based on presence of secondary malignancy codes or first treatment received. Mean workdays lost and attributable cost in the year following a new diagnosis were calculated using the Kaplan-Meier sample averages to account for censoring. An exploratory analysis was conducted on subgroups in the early and advanced cohorts to assess productivity loss in patients with and without treatment. RESULTS: Mean workdays lost in the year following a new HCC diagnosis among the early, intermediate, and advanced cohorts was 22.6 days (95% CI = 16.0-29.8), 17.4 days (95% CI = 11.9-23.2), and 19.5 days (95% CI = 15.6-23.6), respectively. Corresponding indirect costs were $6,031(95% CI = $4,270-$7,953), $4,644 (95% CI = $3,176-$6,192), and $5,204 (95% CI = $4,163-$6,298). Early-stage patients without a liver transplant and advanced-stage patients who received systemic therapy had 19.7 (95% CI = 12.7-27.4) and 22.0 (95% CI = 16.6-27.7) mean workdays lost, respectively. CONCLUSIONS: Productivity loss varies by stage and appears to be higher in early-stage patients who receive more intensive treatments in the first year following a new HCC diagnosis.

Association between ATP luminometry of feeding equipment and environmental and health parameters of preweaned calves on dairy farms.

The objective of this study was to examine the influence of different environmental factors on ATP luminometry measurements of feeding equipment and to investigate associations with health of preweaned calves and the levels of ATP identified through luminometry. On 50 commercial dairy farms in Quebec, Canada, ATP luminometry measurements (in relative light units (RLU)) were obtained using the direct swabbing technique with Hygiena UltraSnap swabs and a liquid rinsing technique with the same swab for automatic milk feeders (AMF), bottles, buckets, esophageal tube feeders (ET), milk replacer, nipples and water. During this visit, environmental factors (including temperature, air draft, humidity, ammonia, and bacterial count) were collected and a clinical examination (including respiratory score and fecal score) was performed for all preweaned calves present at the farm. This process was repeated 4 times in a year, leading to collection of luminometer results, environmental parameters, and overall health of calves for each season per farm. Overall, a difference in luminometer results was seen between the different periods sampled for all feeding equipment (except the ET), milk replacer and water, showing higher RLU values in spring and summer and lower values in autumn and winter. When comparing RLU measurements with environmental factors, only a low to negligible correlation could be found. When feeding equipment was classified as not contaminated or contaminated based on previously described cut-off values, a good agreement within a farm for the different seasons was noticed only for nipples (Gwet's agreement AC1 = 0.64), with a poor to moderate agreement for other feeding equipment. Regarding the different models of nipples, 'Peach Teat' nipples showed higher RLU values compared with 'Merricks' nipples models. An association was seen between the proportion of preweaned calves suffering from diarrhea on the farm and the contamination of AMF based on ATP luminometry (logistic regression estimate = 0.52, P = 0.04). For other feeding equipment, milk replacer and water, no significant associations were found. This study showed that ATP luminometry measurements of feeding equipment from preweaned calves are susceptible to seasonality and type of nipple. Thus, these factors should be taken into consideration when interpreting results. Additionally, an association could be made between diarrhea in preweaned calves and the contamination of AMF based on ATP luminometry, showing the potential clinical importance of this on-farm hygiene assessment tool.

Advances and challenges in modeling inherited peripheral neuropathies using iPSCs.

Inherited peripheral neuropathies (IPNs) are a group of diseases associated with mutations in various genes with fundamental roles in the development and function of peripheral nerves. Over the past 10 years, significant advances in identifying molecular disease mechanisms underlying axonal and myelin degeneration, acquired from cellular biology studies and transgenic fly and rodent models, have facilitated the development of promising treatment strategies. However, no clinical treatment has emerged to date. This lack of treatment highlights the urgent need for more biologically and clinically relevant models recapitulating IPNs. For both neurodevelopmental and neurodegenerative diseases, patient-specific induced pluripotent stem cells (iPSCs) are a particularly powerful platform for disease modeling and preclinical studies. In this review, we provide an update on different in vitro human cellular IPN models, including traditional two-dimensional monoculture iPSC derivatives, and recent advances in more complex human iPSC-based systems using microfluidic chips, organoids, and assembloids.

Tofacitinib in Pediatric Ulcerative Colitis: A Retrospective Multicenter Experience.

BACKGROUND: Tofacitinib has recently been approved for treatment of moderate-to-severe ulcerative colitis (UC) in adults, yet pediatric data are limited. This international multicenter study describes the effectiveness and safety of tofacitinib in pediatric UC. METHODS: This is a retrospective review of children diagnosed with UC treated with tofacitinib from 16 pediatric centers internationally. The primary outcome was week 8 corticosteroid-free clinical remission (Pediatric Ulcerative Colitis Activity Index <10). Secondary outcomes were clinical response (≥20-point decrease in Pediatric Ulcerative Colitis Activity Index) at week 8, corticosteroid-free clinical remission at week 24, and colectomy rate and adverse safety events through to last follow-up. The primary outcome was calculated by the intention-to-treat principle. RESULTS: We included 101 children with a mean age at diagnosis of 12.8 ±â€…2.8 years and a median disease duration of 20 months (interquartile range [IQR], 10-39 months). All had treatment failure with at least 1 biologic agent, and 36 (36%) had treatment failure with 3 agents. Median follow-up was 24 weeks (IQR, 16-54 weeks). Sixteen (16%) children achieved corticosteroid-free clinical remission at week 8, and an additional 30 (30%) demonstrated clinical response. Twenty (23%) of 88 children achieved corticosteroid-free clinical remission at week 24. A total of 25 (25%) children underwent colectomy by median 86 days (IQR, 36-130 days). No serious drug-related adverse events were reported; there was 1 case of herpes zoster and 2 cases of minor blood test perturbations. CONCLUSIONS: In this largest real-life pediatric cohort to date, tofacitinib was effective in at least 16% of patients with highly refractory UC by week 8. Adverse events were minor and largely consistent with adult data.

Tofacitinib, widely reported in adult ulcerative colitis, has very limited pediatric data. This international collaboration is the largest pediatric study on the efficacy and safety of tofacitinib to date, providing important supportive data to clinicians and regulators.

DEVELOPING THERAPIES FOR C3G: REPORT OF THE KIDNEY HEALTH INITIATIVE C3G TRIAL ENDPOINTS WORK GROUP.

Randomized clinical trials are underway to evaluate the efficacy of novel agents targeting the alternative complement pathway in patients with C3G, a rare glomerular disease. The Kidney Health Initiative (KHI) convened a panel of experts in C3G to: (1) assess the data supporting the use of the prespecified trial endpoints as measures of clinical benefit; and (2) opine on efficacy findings they would consider compelling as treatment(s) for C3G in native kidneys. Two subpanels of the C3G Trial Endpoints Work group reviewed the available evidence and uncertainties for the association between the three prespecified endpoints -- (1) proteinuria; (2) estimated glomerular filtration rate (eGFR); and (3) histopathology -- and anticipated outcomes. The full work group provided feedback on the summaries provided by the subpanels and on what potential treatment effects on the proposed endpoints they would consider compelling to support evidence of an investigational product's effectiveness for treating C3G. Members of the full work group agreed with the characterization of the data, the evidence, and uncertainties, supporting the endpoints. Given the limitations of the available data, the workgroup was unable to define a minimum threshold for change in any of the endpoints that might be considered clinically meaningful. The workgroup concluded that a favorable treatment effect on all three endpoints would provide convincing evidence of efficacy in the setting of a therapy that targeted the complement pathway. A therapy might be considered effective in the absence of complete alignment in all three endpoints if there was meaningful lowering of proteinuria and stabilization or improvement in eGFR. The panel unanimously supported efforts to foster data sharing between academic and industry partners to address the gaps in the current knowledge identified by the review of the endpoints in the aforementioned trials.

Spatially informed gene signatures for response to immunotherapy in melanoma.

PURPOSE: We aim to improve the prediction of response or resistance to immunotherapies in melanoma patients. This goal is based on the hypothesis that current gene signatures predicting immunotherapy outcomes show only modest accuracy due to the lack of spatial information about cellular functions and molecular processes within tumors and their microenvironment. EXPERIMENTAL DESIGN: We collected gene expression data spatially from three cellular compartments defined by CD68+macrophages, CD45+leukocytes and S100B+tumor cells in 55-immunotherapy-treated melanoma specimens using Digital Spatial Profiling-Whole Transcriptome Atlas (DSP-WTA). We developed a computational pipeline to discover compartment-specific gene signatures and determine if adding spatial information can improve patient stratification. RESULTS: We achieved robust performance of compartment-specific signatures in predicting the outcome to ICI in the discovery cohort. Of the three signatures, S100B signature showed the best performance in the validation cohort (N=45). We also compared our compartment-specific signatures with published bulk signatures and found the S100B tumor spatial signature outperformed previous signatures. Within the 8-gene S100B signature, 5 genes (PSMB8, TAX1BP3, NOTCH3, LCP2, NQO1) with positive coefficients predict the response and 3 genes (KMT2C, OVCA2, MGRN1) with negative coefficients predict the resistance to treatment. CONCLUSION: We conclude that the spatially defined compartment signatures utilize tumor and TME-specific information, leading to more accurate prediction of treatment outcome, and thus merit prospective clinical assessment.

Investigation of oxygen packaging to maintain beef color stability and microbiology safety after periods of long-term superchilled storage.

This study aimed to develop an appropriate modified atmosphere packaging (MAP) system for displayed beef steaks following long-term superchilled (-1 °C) storage. After superchilled storage for 0, 2, 8, or 16 weeks, beef loins were fabricated into steaks and displayed with 20%, 50%, or 80% O2-MAP under chilled conditions. At each storage point, after display for 0, 3, 7, or 10 days, instrumental color, myoglobin redox forms percentage, lipid oxidation, total viable count (TVC), and total volatile basic nitrogen (TVB-N) were evaluated. Meat color stability decreased, with prolonged storage period and display time. When the storage period was within 8 weeks, under all the above MAP conditions, the display time for the beef steaks was up to 10 days. Considering 80% O2-MAP promoted lipid oxidation, 50% and 80% O2-MAP were not recommended for displaying steaks for more than 10 and 7 days respectively after 16 weeks of storage. However, 20%, 50%, or 80% O2-MAP could maintain 3 days of microbial shelf-life according to TVC and TVB-N results. Additionally, after long-term superchilled storage for 16 weeks, the various O2 concentrations had minimal impact on microbiota succession during the MAP display period. Furthermore, beef steaks packaged under various MAP systems exhibited similar microbial compositions, with the dominant bacteria alternating between Lactobacillus and Carnobacterium. This study provided practical guidance for improving beef color stability after long-term superchilled storage.

Prevalence and disease burden of peripheral neuropathy in the general population in Mexico city: a cross-sectional epidemiological study.

OBJECTIVE: Peripheral neuropathy (PN) is one of the most common diseases of the peripheral nervous system. Symptoms range from mild sensory signs to severe neuropathic pain. Untreated PN is progressive and can lead to complications and impair quality of life (QoL). However, PN prevalence is underestimated in the general population and affected individuals often remain undiagnosed. This study aimed to contribute to the global generation of prevalence data and determine sociodemographic and disease-related characteristics of PN sufferers. METHODS: This cross-sectional study collected information on PN prevalence and associated factors in the adult population (40-65 years) of the Mexico City area. Participants were recruited in public places and screened for PN using the Michigan Neuropathy Screening Instrument (MNSI). Subjects with PN answered the Neuropathy Total Symptom Score-6 (NTSS-6), the Short Form-36 Health Survey (SF-36), and the QoL Pharmacoeconomic Questionnaire. Statistical analysis included descriptive methods and calculation of PN prevalence with 95% confidence intervals. RESULTS: Of 3066 participants, 448 had PN based on the MNSI physical examination. The overall PN prevalence was 14.6%, with the highest (18.9%) seen in subjects aged 61-65 years. PN was undiagnosed in 82.6%, and 62.9% had never heard of PN. Although half of all subjects had only mild PN symptoms, QoL was impacted in 91.8%. CONCLUSIONS: The results confirm that PN prevalence in the general population is high. Despite the disease burden, most affected persons are undiagnosed and unaware of the disease. Almost all felt their QoL was impacted. The data highlight the need to raise awareness and identify undiagnosed individuals to prevent complications.

Re-Imagining Child Welfare to Support Children and Families.

Children and adolescents in foster care include many of the most severely traumatized victims of child abuse and neglect. They deserve the best possible care and treatment, yet their outcomes remain poor. The persistence of poor outcomes for youth in foster care reflects challenges of psychiatric diagnostic formulation and of service system design/access, both areas in which child and adolescent psychiatrists have a key role to improve care and outcomes.

COVID19 and the Follies of History: Forebodings that Forewarned is Not Forearmed.

COVID-19 was the first pandemic of the internet age. Beginning at a time of great societal division in the United States (and globally), pandemic responses were further beleaguered by the viral proliferation of information, disinformation, and propaganda-collectively, an "infodemic." Polarized, blinkered views of the crisis precluded a balanced consideration of objectives, opportunities, and ineluctable trade-offs between the risks of actions and corresponding inactions. The results were lapses in both directions, greatly amplifying the pandemic toll. Persistence of this costly fractiousness is now spawning monocular critiques of the pandemic response, with neglect of essential nuance. There is a better pandemic that might have been, and the chance for far better responses to the next- but only if the follies of this history are lessons learned and applied. Failing that, the risk looms that having been amply forewarned of our liabilities, we will fail to be forearmed.

Joint-specific regulation of homeobox D10 expression in rheumatoid arthritis fibroblast-like synoviocytes.

Rheumatoid arthritis (RA) is a systemic immune-mediated disease characterized by joint inflammation and destruction. The disease typically affects small joints in the hands and feet, later progressing to involve larger joints such as the knees, shoulders, and hips. While the reasons for these joint-specific differences are unclear, distinct epigenetic patterns associated with joint location have been reported. In this study, we evaluated the unique epigenetic landscapes of fibroblast-like synoviocytes (FLS) from hip and knee synovium in RA patients, focusing on the expression and regulation of Homeobox (HOX) transcription factors. These highly conserved genes play a critical role in embryonic development and are known to maintain distinct expression patterns in various adult tissues. We found that several HOX genes, especially HOXD10, were differentially expressed in knee FLS compared with hip FLS. Epigenetic differences in chromatin accessibility and histone marks were observed in HOXD10 promoter between knee and hip FLS. Histone modification, particularly histone acetylation, was identified as an important regulator of HOXD10 expression. To understand the mechanism of differential HOXD10 expression, we inhibited histone deacetylases (HDACs) with small molecules and siRNA. We found that HDAC1 blockade or deficiency normalized the joint-specific HOXD10 expression patterns. These observations suggest that epigenetic differences, specifically histone acetylation related to increased HDAC1 expression, play a crucial role in joint-specific HOXD10 expression. Understanding these mechanisms could provide insights into the regional aspects of RA and potentially lead to therapeutic strategies targeting specific patterns of joint involvement during the course of disease.

Assessing avian influenza surveillance intensity in wild birds using a One Health lens.

Wildlife disease surveillance, particularly for pathogens with zoonotic potential such as Highly Pathogenic Avian Influenza Virus (HPAIV), is critical to facilitate situational awareness, inform risk, and guide communication and response efforts within a One Health framework. This study evaluates the intensity of avian influenza virus (AIV) surveillance in Ontario's wild bird population following the 2021 H5N1 incursion into Canada. Analyzing 2562 samples collected between November 1, 2021, and October 31, 2022, in Ontario, Canada, we identify spatial variations in surveillance intensity relative to human population density, poultry facility density, and wild mallard abundance. Using the spatial scan statistic, we pinpoint areas where public engagement, collaborations with Indigenous and non-Indigenous hunter/harvesters, and working with poultry producers, could augment Ontario's AIV wild bird surveillance program. Enhanced surveillance at these human-domestic animal-wildlife interfaces is a crucial element of a One Health approach to AIV surveillance. Ongoing assessment of our wild bird surveillance programs is essential for strategic planning and will allow us to refine approaches and generate results that continue to support the program's overarching objective of safeguarding the health of people, animals, and ecosystems.

Process evaluation of a data-driven quality improvement program within a cluster randomised controlled trial to improve coronary heart disease management in Australian primary care.

BACKGROUND: This study evaluates primary care practices' engagement with various features of a quality improvement (QI) intervention for patients with coronary heart disease (CHD) in four Australian states. METHODS: Twenty-seven practices participated in the QI intervention from November 2019 -November 2020. A combination of surveys, semi-structured interviews and other materials within the QUality improvement in primary care to prevent hospitalisations and improve Effectiveness and efficiency of care for people Living with heart disease (QUEL) study were used in the process evaluation. Data were summarised using descriptive statistical and thematic analyses for 26 practices. RESULTS: Sixty-four practice team members and Primary Health Networks staff provided feedback, and nine of the 63 participants participated in the interviews. Seventy-eight percent (40/54) were either general practitioners or practice managers. Although 69% of the practices self-reported improvement in their management of heart disease, engagement with the intervention varied. Forty-two percent (11/26) of the practices attended five or more learning workshops, 69% (18/26) used Plan-Do-Study-Act cycles, and the median (Interquartile intervals) visits per practice to the online SharePoint site were 170 (146-252) visits. Qualitative data identified learning workshops and monthly feedback reports as the key features of the intervention. CONCLUSION: Practice engagement in a multi-featured data-driven QI intervention was common, with learning workshops and monthly feedback reports identified as the most useful features. A better understanding of these features will help influence future implementation of similar interventions. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry (ANZCTR) number ACTRN12619001790134.

Perspectives on the diagnosis and management of functional cognitive disorder: An international Delphi study.

BACKGROUND: Current proposed criteria for functional cognitive disorder (FCD) have not been externally validated. We sought to analyse the current perspectives of cognitive specialists in the diagnosis and management of FCD in comparison with neurodegenerative conditions. METHODS: International experts in cognitive disorders were invited to assess seven illustrative clinical vignettes containing history and bedside characteristics alone. Participants assigned a probable diagnosis and selected the appropriate investigation and treatment. Qualitative, quantitative and inter-rater agreement analyses were undertaken. RESULTS: Eighteen diagnostic terminologies were assigned by 45 cognitive experts from 12 countries with a median of 13 years of experience, across the seven scenarios. Accurate discrimination between FCD and neurodegeneration was observed, independently of background and years of experience: 100% of the neurodegenerative vignettes were correctly classified and 75%-88% of the FCD diagnoses were attributed to non-neurodegenerative causes. There was <50% agreement in the terminology used for FCD, in comparison with 87%-92% agreement for neurodegenerative syndromes. Blood tests and neuropsychological evaluation were the leading diagnostic modalities for FCD. Diagnostic communication, psychotherapy and psychiatry referral were the main suggested management strategies in FCD. CONCLUSIONS: Our study demonstrates the feasibility of distinguishing between FCD and neurodegeneration based on relevant patient characteristics and history details. These characteristics need further validation and operationalisation. Heterogeneous labelling and framing pose clinical and research challenges reflecting a lack of agreement in the field. Careful consideration of FCD diagnosis is advised, particularly in the presence of comorbidities. This study informs future research on diagnostic tools and evidence-based interventions.