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Despite debilitating consequences, cancer-associated malnutrition often goes under-detected due to the lack of a standardised diagnostic tool (1). The Global Leadership Initiative on Malnutrition (GLIM) criteria was established in 2018 in order to standardise the diagnosis of malnutrition globally (2). The aim of this study was to determine the association between GLIM-diagnosed malnutrition and overall survival in a large cohort of patients with mixed-cancer types. This is the first study to stratify patients according to treatment intent and is one of the largest studies to identify reduced muscle mass using gold-standard CT analysis of body composition.
Patients receiving anti-cancer treatment for solid tumours were enrolled in a cross-sectional study to examine nutritional status between 2011-2016. The GLIM criteria was retrospectively applied. CT images at the third lumbar vertebrae (L3) were used to quantify skeletal muscle index and categorised according to previously published cut-points. Survival analysis was carried out using Kaplan-Meier curves and Cox-Regression.
Of 1405 patients enrolled, 52.5% were male. Mean age was 62 years (SD:12 years). The most common cancer diagnosis was gastrointestinal (44.5%) and 60.3% had metastatic disease. In total, 40.4% of participants were diagnosed with GLIM-malnutrition (14.8% had stage 1 moderate and 25.6% had stage 2 severe malnutrition). Median follow-up time was 102.4 months (95% CI 99.6–105.2 months). Median survival for those without malnutrition was 30.4 months (95% CI 23.5–37.2 months), versus 11.0 months (95% CI 6.6 – 15.4 months p<0.001) for those with stage 1 moderate and 10.0 months (95% CI 8.1–11.9 months p<0.001) for stage 2 severe malnutrition. Multivariate-analysis (controlling for gender, age, cancer site, GLIM-malnutrition and treatment intent) demonstrated a hazard ratio (HR) of death of 1.499 (95% CI 1.233–1.822, p<0.001) for stage 1 moderate and HR 1.548 (1.322–1.800, p<0.001) for stage 2 severe-malnutrition. The prevalence of stage 2 severe malnutrition was significantly higher in the palliative cohort (receiving supportive measures) (32.7%) when compared to patients being treated with curative intent (18.2%, p=0.004).
This study is one of the largest studies to date which uses CT analysis to accurately identify reduced muscle mass and confirms that the GLIM criteria can be used to predict overall survival in a large mixed-cancer cohort. These findings suggest that malnutrition, regardless of GLIM severity ranking has a significant impact on overall survival. Future research should focus on determining oncology specific cut-points for the GLIM criteria.
We present the serendipitous radio-continuum discovery of a likely Galactic supernova remnant (SNR) G305.4–2.2. This object displays a remarkable circular symmetry in shape, making it one of the most circular Galactic SNRs known. Nicknamed Teleios due to its symmetry, it was detected in the new Australian Square Kilometre Array Pathfinder (ASKAP) Evolutionary Map of the Universe (EMU) radio–continuum images with an angular size of 1 320$^{\prime\prime}$$\times$1 260$^{\prime\prime}$ and PA = 0$^\circ$. While there is a hint of possible H$\alpha$ and gamma-ray emission, Teleios is exclusively seen at radio–continuum frequencies. Interestingly, Teleios is not only almost perfectly symmetric, but it also has one of the lowest surface brightnesses discovered among Galactic SNRs and a steep spectral index of $\alpha$=–0.6$\pm$0.3. Our best estimates from Hi studies and the $\Sigma$–D relation place Teleios as a type Ia SNR at a distance of either $\sim$2.2 kpc (near-side) or $\sim$7.7 kpc (far-side). This indicates two possible scenarios, either a young (under 1 000 yr) or a somewhat older SNR (over 10 000 yr). With a corresponding diameter of 14/48 pc, our evolutionary studies place Teleios at the either early or late Sedov phase, depending on the distance/diameter estimate. However, our modelling also predicts X-ray emission, which we do not see in the present generation of eROSITA images. We also explored a type Iax explosion scenario that would point to a much closer distance of $\lt$1 kpc and Teleios size of only $\sim$3.3 pc, which would be similar to the only known type Iax remnant SN1181. Unfortunately, all examined scenarios have their challenges, and no definitive Supernova (SN) origin type can be established at this stage. Remarkably, Teleios has retained its symmetrical shape as it aged even to such a diameter, suggesting expansion into a rarefied and isotropic ambient medium. The low radio surface brightness and the lack of pronounced polarisation can be explained by a high level of ambient rotation measure (RM), with the largest RM being observed at Teleios’s centre.
About one-third of South African women have clinically significant symptoms of postpartum depression (PPD). Several socio-demographic risk factors for PPD exist, but data on medical and obstetric risk factors remain scarce for low- and middle-income countries and particularly in sub-Saharan Africa. We aimed to estimate the proportion of women with PPD and investigate socio-demographic, medical and obstetric risk factors for PPD among women receiving private medical care in South Africa (SA).
Methods
In this longitudinal cohort study, we analysed reimbursement claims from beneficiaries of an SA medical insurance scheme who delivered a child between 2011 and 2020. PPD was defined as a new International Classification of Diseases, 10th Revision diagnosis of depression within 365 days postpartum. We estimated the frequency of women with a diagnosis of PPD. We explored several medical and obstetric risk factors for PPD, including pre-existing conditions, such as HIV and polycystic ovary syndrome, and conditions diagnosed during pregnancy and labour, such as gestational diabetes, pre-term delivery and postpartum haemorrhage. Using a multivariable modified Poisson model, we estimated adjusted risk ratios (aRRs) and 95% confidence intervals (CIs) for factors associated with PPD.
Results
Of the 47,697 participants, 2,380 (5.0%) were diagnosed with PPD. The cumulative incidence of PPD increased from 0.8% (95% CI 0.7–0.9) at 6 weeks to 5.5% (5.3–5.7) at 12 months postpartum. PPD risk was higher in individuals with history of depression (aRR 3.47, 95% CI [3.14–3.85]), preterm delivery (1.47 [1.30–1.66]), PCOS (1.37 [1.09–1.72]), hyperemesis gravidarum (1.32 [1.11–1.57]), gestational hypertension (1.30 [1.03–1.66]) and postpartum haemorrhage (1.29 [0.91–1.85]). Endometriosis, HIV, gestational diabetes, foetal stress, perineal laceration, elective or emergency C-section and preeclampsia were not associated with a higher risk of PPD.
Conclusions
The PPD diagnosis rate was lower than anticipated, based on the PPD prevalence of previous studies, indicating a potential diagnostic gap in SA’s private sector. Identified risk factors could inform targeted PPD screening strategies.
Cardiometabolic diseases, including type 2 diabetes (T2DM) and cardiovascular disease (CVD), are common. Approximately one in three deaths annually are caused by CVD in Aotearoa New Zealand (AoNZ)(1). The Mediterranean dietary pattern is associated with a reduced risk of cardiometabolic disease in epidemiological and interventional studies(2,3). However, implementing the Mediterranean diet into non-Mediterranean populations can be challenging(4). Some of these challeanges include facilitating consumption of unfamiliar foods and the cultural and social context of food consumption. AoNZ produces a rich source of high-quality foods consistent with a Mediterranean dietary pattern. He Rourou Whai Painga is collaborative project combining contributions from food industry partners into a Mediterranean Diet pattern and providing foods, recipes and other support to whole household/whānau. The aim was to test if a New Zealand food-based Mediterranean diet (NZMedDiet) with behavioural intervention improves cardiometabolic health and wellbeing in individuals at risk. This presentation will review the background to the research, the process of forming a collaboration between researchers and the food industry, the design and implementation of a complex study design (see protocol paper)(5), with results from the initial randomised controlled trial. We conducted several pilot studies(6,7,8) to inform the final design of the research, which was a combination of two randomised controlled trials (RCT 1 and 2) and a longitudinal cohort study. RCT-1 compared 12-weeks of the NZMedDiet to usual diet in participants with increased cardiometabolic risk (metabolic syndrome severity score (MetSSS) >0.35). The intervention group were provided with food and recipes to meet 75% of their energy requirements, supported by a behavioural intervention to improve adherence. The primary outcome measure was MetSSS after 12 weeks. Two hundred individuals with mean (SD) age 49.9 (10.9)yrs with 62% women were enrolled with their household/whānau. After 12 weeks, the mean (SD) MetSSS was 1.0 (0.7) in the control (n = 98) and 0.8 (0.5) in the intervention (n = 102) group; estimated difference (95% CI) of -0.05 (-0.16 to 0.06), p=0.35. A Mediterranean diet score (PyrMDS) was greater in the intervention group 1.6 (1.1 to 2.1), p<0.001, consistent with a change to a more Mediterranean dietary pattern. Weight reduced in the NZMedDiet group compared with control (-1.9 kg (-2.0 to -0.34)), p=0.006 and wellbeing, assessed by the SF-36 quality of life questionnaire, improved across all domains p<0.001. In participants with increased cardiometabolic risk, food provision with a Mediterranean dietary pattern and a behavioural intervention did not improve a metabolic risk score but was associated with reduced weight and improved quality of life.
Patients with posttraumatic stress disorder (PTSD) exhibit smaller regional brain volumes in commonly reported regions including the amygdala and hippocampus, regions associated with fear and memory processing. In the current study, we have conducted a voxel-based morphometry (VBM) meta-analysis using whole-brain statistical maps with neuroimaging data from the ENIGMA-PGC PTSD working group.
Methods
T1-weighted structural neuroimaging scans from 36 cohorts (PTSD n = 1309; controls n = 2198) were processed using a standardized VBM pipeline (ENIGMA-VBM tool). We meta-analyzed the resulting statistical maps for voxel-wise differences in gray matter (GM) and white matter (WM) volumes between PTSD patients and controls, performed subgroup analyses considering the trauma exposure of the controls, and examined associations between regional brain volumes and clinical variables including PTSD (CAPS-4/5, PCL-5) and depression severity (BDI-II, PHQ-9).
Results
PTSD patients exhibited smaller GM volumes across the frontal and temporal lobes, and cerebellum, with the most significant effect in the left cerebellum (Hedges’ g = 0.22, pcorrected = .001), and smaller cerebellar WM volume (peak Hedges’ g = 0.14, pcorrected = .008). We observed similar regional differences when comparing patients to trauma-exposed controls, suggesting these structural abnormalities may be specific to PTSD. Regression analyses revealed PTSD severity was negatively associated with GM volumes within the cerebellum (pcorrected = .003), while depression severity was negatively associated with GM volumes within the cerebellum and superior frontal gyrus in patients (pcorrected = .001).
Conclusions
PTSD patients exhibited widespread, regional differences in brain volumes where greater regional deficits appeared to reflect more severe symptoms. Our findings add to the growing literature implicating the cerebellum in PTSD psychopathology.
Microbiomes are communities of microorganisms that form close associations with metazoan hosts and have important roles in host biological processes. With the advent of Next Generation Sequencing, the microbiomes of myriad animals and plants have been described. However, the microbiomes of parasites have received little attention, which is surprising considering their ecological and medical importance. This study characterizes, for the first time, the microbiome of Dujardinascaris helicina, a gastrointestinal nematode parasite of the American crocodile. Dujardinascaris helicina were isolated from crocodiles residing in two geographically separated habitats across Belize. Using 16S sequencing, we compare β-diversity between sampling locations using generalized linear mixed modeling. Our results show that D. helicina microbiomes differ in composition depending on location. We also show that D. helicina microbiomes show strong shifts toward consolidation of specific taxa when proximity to human modified environments increases.
Fasciolosis, a parasitic disease of ruminants, poses significant economic and animal-health challenges in Algeria. This study aimed to assess spatial, temporal, and species-specific patterns of fasciolosis prevalence across diverse agro-climatic zones and to estimate associated economic losses. Between 2013 and 2023, eight wilayas El-Tarf, Skikda, Jijel (Region I), Blida, Mila (Region II), and M’Sila, Medea, Laghouat (Region III) were surveyed. Systematic postmortem inspections of 1,569,392 animals (349,176 cattle; 982,669 sheep; 235,639 goats; 1,882 camels; 26 horses) were performed by qualified veterinarians, with liver and bile-duct examination for Fasciola. Data on region, species, year, and season were analyzed in R 4.4.0 using ANOVA, Kruskal–Wallis, Tukey’s post hoc tests, and principal component analysis (PCA). Economic losses were calculated from condemned liver weights in Blida, Laghouat, and Jijel, converted to USD. PCA distinguished three regional prevalence profiles, with PC1 (77.7% variance) separating overall prevalence levels. Region I exhibited the highest mean prevalence (2.47%), peaking at 3.54% in 2018 – significantly greater than Region II (1.39%) and Region III (1.96%) (p < 0.01). Cattle showed the greatest infection rate (mean 4.14%), significantly higher than sheep (1.32%; p < 0.001) and goats (0.25%; p < 0.001), while horses and camels remained uninfected. Seasonal analysis revealed highest prevalence in autumn and winter (≈2.1%) versus spring (≈1.5%). Economic losses totaled USD 10.6 million in Blida, USD 1.0 million in Laghouat, and USD 142.2 million in Jijel over the study period. Targeted control strategies, adapted to regional and seasonal risk patterns, are essential. Future work should investigate environmental and management factors driving regional differences and evaluate cost-effective interventions to mitigate fasciolosis impact in Algerian livestock.
Background: The WHO grade of meningioma was updated in 2021 to include homozygous deletions of CDKN2A/B and TERT promotor mutations. Previous work including the recent cIMPACT-NOW statement have discussed the potential value of including chromosomal copy number alterations to help refine the current grading system. Methods: Chromosomal copy number profiles were inferred from from 1964 meningiomas using DNA methylation. Regularized Cox regresssion was used to identify CNAs independenly associated with post-surgical and post-RT PFS. Outcomes were stratified by WHO grade and novel CNAs to assess their potential value in WHO critiera. Results: Patients with WHO grade 1 tumours and chromosome 1p loss had similar outcomes to those with WHO grade 2 tumours (median PFS 5.83 [95% CI 4.36-Inf] vs 4.48 [4.09-5.18] years). Those with chromosome 1p loss and 1q gain had similar outcomes to those with WHO grade 3 cases regardless of initial grade (median PFS 2.23 [1.28-Inf] years WHO grade 1, 1.90 [1.23-2.25] years WHO grade 2, compared to 2.27 [1.68-3.05] years in WHO grade 3 cases overall). Conclusions: We advocate for chromosome 1p loss being added as a criterion for a CNS WHO grade of 2 meningioma and addition of 1q gain as a criterion for a CNS WHO grade of 3.
Background: We previously developed a DNA methylation-based risk predictor for meningioma, which has been used locally in a prospective fashion. As a follow-up, we validate this model using a large prospective cohort and introduce a streamlined next-generation model compatible with newer methylation arrays. Methods: The performance of our next-generation predictor was compared with our original model and standard-of-care 2021 WHO grade using time-dependent receiver operating characteristic curves. A nomogram was generated by incorporating our methylation predictor with WHO grade and extent of resection. Results: A total of 1347 meningioma cases were utilized in the study, including 469 prospective cases from 3 institutions and a retrospective cohort of 100 WHO grade 2 cases for model validation. Both the original and next-generation models significantly outperformed 2021 WHO grade in predicting postoperative recurrence. Dichotomizing into grade-specific risk subgroups was predictive of outcome within both WHO grades 1 and 2 tumours (log-rank p<0.05). Multivariable Cox regression demonstrated benefit of adjuvant radiotherapy in high-risk cases specifically, reinforcing its informative role in clinical decision making. Conclusions: This next-generation DNA methylation-based meningioma outcome predictor significantly outperforms 2021 WHO grading in predicting time to recurrence. This will help improve prognostication and inform patient selection for RT.
Background: Meningiomas exhibit considerable heterogeneity. We previously identified four distinct molecular groups (immunogenic, NF2-wildtype, hypermetabolic, proliferative) which address much of this heterogeneity. Despite their utility, the stochasticity of clustering methods and the requirement of multi-omics data limits the potential for classifying cases in the clinical setting. Methods: Using an international cohort of 1698 meningiomas, we constructed and validated a machine learning-based molecular classifier using DNA methylation alone. Original and newly-predicted molecular groups were compared using DNA methylation, RNA sequencing, whole exome sequencing, and clinical outcomes. Results: Group-specific outcomes in the validation cohort were nearly identical to those originally described, with median PFS of 7.4 (4.9-Inf) years in hypermetabolic tumors and 2.5 (2.3-5.3) years in proliferative tumors (not reached in the other groups). Predicted NF2-wildtype cases had no NF2 mutations, and 51.4% had others mutations previously described in this group. RNA pathway analysis revealed upregulation of immune-related pathways in the immunogenic group, metabolic pathways in the hypermetabolic group and cell-cycle programs in the proliferative group. Bulk deconvolution similarly revealed enrichment of macrophages in immunogenic tumours and neoplastic cells in hypermetabolic/proliferative tumours. Conclusions: Our DNA methylation-based classifier faithfully recapitulates the biology and outcomes of the original molecular groups allowing for their widespread clinical implementation.
Background: Location-specific hematoma volume thresholds are associated with poor outcomes and can inform surgical trial inclusion criteria and clinical decision rules for hematoma evacuation. Methods: We performed a secondary analysis of the ATACH-2 and INTERACT2 clinical trials. We evaluated the associations between intraparenchymal location-specific hematoma volume cutoffs (basal ganglia, thalamus and lobar) and poor outcome (modified Rankin Scale 4-6). Using 24-hour CT scans, we calculated Youden’s index for each hematoma location to determine the optimal location-specific volume thresholds that predict outcomes. We calculated odds ratios (OR) of poor outcome through multivariable logistic regression models for each location. Results: Out of 1691 patients, 919, 551 and 221 were diagnosed with basal ganglia, thalamus and lobar intracerebral hemorrhage (ICH), respectively. Location-specific hematoma volume cutoffs most predictive of a poor outcome (mRS 4-6) were 22.24 mL for basal ganglia ICH (OR 4.82, 95% CI 3.19-7.27), 8.13 mL for thalamus ICH (OR 2.73, 95% CI 1.62-4.59) and 21.99 mL for lobar ICH (OR 6.31, 95% CI 2.53-15.74). Conclusions: Hematoma volumes associated with poor outcomes vary by location, supporting the idea that location-specific “hematoma volume tolerances” exist. Our results provide important data on location-specific hematoma volume tolerances to inform clinical trials in ICH management.
Background: Nipocalimab is a human IgG1 monoclonal antibody targeting FcRn that selectively reduces IgG levels without impacting antigen presentation, T- and B-cell functions. This study describes the effect of nipocalimab on vaccine response. Methods: Open-label, parallel, interventional study randomized participants 1:1 to receive intravenous 30mg/kg nipocalimab at Week0 and 15mg/kg at Week2 and Week4 (active) or no drug (control). On Day 3, participants received Tdap and PPSV®23 vaccinations and were followed through Wk16. Results: Twenty-nine participants completed the study and are included (active, n=15; control, n=14). Participants with a positive anti-tetanus IgG response was comparable between groups at Wk2 and Wk16, but lower at Wk4 (nipocalimab 3/15 [20%] vs control 7/14 [50%]; P=0.089). All maintained anti-tetanus IgG above the protective threshold (0.16IU/mL) through Wk16. While anti-pneumococcal-capsular-polysaccharide (PCP) IgG levels were lower during nipocalimab treatment, the percent increase from baseline at Wk2 and Wk16 was comparable between groups. Post-vaccination, anti-PCP IgG remained above 50mg/L and showed a 2-fold increase from baseline throughout the study in both groups. Nipocalimab co-administration with vaccines was safe and well-tolerated. Conclusions: These findings suggest that nipocalimab does not impact the development of an adequate IgG response to T-cell–dependent/independent vaccines and that nipocalimab-treated patients can follow recommended vaccination schedules.
Background: Trigeminal neuralgia (TN) is more common in multiple sclerosis (MS) patients than in the general population, likely due to demyelination impacting the trigeminal pathways. While brainstem lesions are associated with MS-TN, their precise role remains unclear. Methods: This study investigates the relationship between brainstem MS plaque location, TN symptoms, and treatment response. We retrospectively analyzed brain MRIs of MS-TN patients, segmenting and coregistering brainstem plaques in MNI space. A tractographic atlas of the trigeminal system was generated using high-resolution diffusion imaging from 30 patients. Lesion involvement was determined by intersection with the trigeminal tract, and its association with pain intensity and treatment outcomes was analyzed using linear regression. Results: Our research revealed 83% of MS-TN patients had brainstem lesions near the fourth ventricle. No single lesion hot spot was identified. Lesion volume did not predict symptom recurrence or treatment response. However, 97% of lesions intersected the trigeminal tract, supporting its association with TN symptoms. Conclusions: The strong overlap between lesions and the trigeminal tract suggests a potential pain generator in MS-TN. Further research is needed to determine whether similar lesions exist in asymptomatic MS patients and to confirm this hypothesis. Future studies will explore whether tract involvement better predicts clinical response to treatment.
Background: Neck vessel imaging is often performed in hyperacute stroke to allow neurointerventionalists to estimate access complexity. This study aimed to assess clinician agreement on catheterization strategies based on imaging in these scenarios. Methods: An electronic portfolio of 60 patients with acute ischemic stroke was sent to 53 clinicians. Respondents were asked: (1) the difficulty of catheterization through femoral access with a regular Vertebral catheter, (2) whether to use a Simmons or reverse-curve catheter initially, and (3) whether to consider an alternative access site. Agreement was assessed using Fleiss’ Kappa statistics. Results: Twenty-two respondents (7 neurologists, 15 neuroradiologists) completed the survey. Overall there was slight interrater agreement (κ=0.17, 95% CI: 0.10–0.25). Clinicians with >50 cases annually had better agreement (κ=0.22) for all questions than those with fewer cases (κ=0.07). Agreement did not significantly differ by imaging modality: CTA (κ=0.18) and MRA (κ=0.14). In 40/59 cases (67.80%), at least 25% of clinicians disagreed on whether to use a Simmons or reverse-curve catheter initially. Conclusions: Agreement on catheterization strategies remains fair at best. Our results suggest that visual assessment of pre-procedural vessels imaging is not reliable for the estimation of endovascular access complexity.
Background: Amyotrophic Lateral Sclerosis (ALS) leads to progressive functional decline and reduced survival. Identifying clinical predictors like ALSFRS-R and FVC is essential for prognosis and disease management. Understanding progression profiles based on diagnostic characteristics supports clinical trial design and assessment of treatment response. This study evaluates disease progression and survival predictors in ALS patients from the CNDR. Methods: 1565 ALS patients in the CNDR were analyzed to assess baseline ALSFRS-R, FVC, time from symptom onset to diagnosis, and their association with disease progression and survival. Results: At diagnosis, ALSFRS-R was 44.7 (SD = 5.46), with 72.3% scoring ≥44. Mean FVC was 84.2% (SD = 23.3), with 78.3% of patients having FVC ≥65%. ALSFRS-R declined at 1.06 points/month (SD = 1.33), with faster progression in patients diagnosed within 24 months (1.61 points/month). Patients with ALSFRS-R ≥44 had a median survival of 41.8 months, compared to 30.9 months for those <44 (p < 0.001). Similarly, FVC ≥65% was associated with longer survival (35.4 vs. 29.5 months, p = 0.002). Conclusions: ALSFRS-R and FVC at diagnosis predict survival and inform clinical decision-making. These findings highlight the importance of early diagnosis and targeted interventions to slow disease progression and improve patient outcomes.
Background: Brain-specific glial fibrillary acidic protein (GFAP) can discriminate stroke type [ischemic stroke (AIS), intracerebral hemorrhage (ICH), stroke mimics (SM)]. Novel point-of-care technology (GFAP levels <15 minutes) is a promising diagnostic tool. We aim to evaluate the feasibility of rapid GFAP analysis in acute stroke. Methods: Exploratory analysis of an ongoing prospective study of suspected undifferentiated stroke <24h from onset. Rapid plasma GFAP levels (pg/mL) are measured at hospital arrival using the i-STAT Alinity® instrument and commercially-available cartridges. Study endpoints include quantitative GFAP levels according to final diagnosis and time from stroke onset. Results: Among 200 patients (mean(±SD) 70.7±15.5 years, 44.5% female, median (IQR) NIHSS 9(4-19), diagnosis was AIS (n=132 (59 large-vessel occlusion), ICH (n=17), and SM (n=51). Median time from hospital arrival to GFAP result was 56.0 (47.0-69.5) minutes. Median rapid GFAP levels were highest in ICH (878.0 (70.5-3,906.5) pg/mL) compared to AIS (49.5 (29.0-95)pg/mL) and SM (29(29-64)pg/mL), p=0.001. Median GFAP was higher in AIS-known onset >4.5h (n=9) (110.0 (44.0-216.0) pg/mL) compared to AIS<4.5h (40.5 (29.0-68.8) pg/mL) (n=72), (p=0.047), while AIS-unknown onset (n=51) (68.0 (29.0-108.5) pg/mL) fell between these two groups, likely reflecting the subgroup’s heterogeneity. Conclusions: Preliminary findings suggest that rapid GFAP analysis is feasible in acute stroke and may inform treatment decisions.
Background: Tenecteplase is a genetically-modified variant of the tissue plasminogen activator alteplase, with increased fibrin-specificity, administered as a more convenient intravenous bolus. Recent data, from the AcT trial, have shown tenecteplase to be non-inferior to alteplase in patients with acute ischemic stroke (AIS) treated within 4.5 hours from symptom onset, the direction of effect favoring tenecteplase. As a result, the Heart and Stroke Foundation of Canada has added tenecteplase to the Stroke Best Practice Recommendations. However, its cost-effectiveness in the Canadian setting remains unknown. Methods: An analysis was performed to estimate the cost-effectiveness of tenecteplase compared to alteplase in the AIS population. The model structure combines a decision tree for the first 90 days post index stroke, where the 7 modified Rankin Scale (mRS) states are informed by the AcT trial, and a Markov model for the remainder of the lifetime horizon. Cost and utility values were derived from the literature and public sources. Canadian health care system and hospital perspectives were used. Results: This economic analysis demonstrates that tenecteplase is dominant compared to alteplase, providing more quality-adjusted life years at lower costs. Conclusions: Adding tenecteplase to hospital formularies for AIS would generate savings for the health care system while providing more benefits.
Background: Adverse effects and risks associated with glucocorticoid (GC) treatment are frequently encountered in immune-mediated neuromuscular disorders. However, significant variability exists in the management of these complications. Our aim was to establish international consensus guidance on the management of GC-related complications in neuromuscular disorders. Methods: An international task force of 15 experts was assembled to develop clinical recommendations for managing GC-related complications in neuromuscular patients. The RAND/UCLA Appropriateness Method (RAM) was employed to formulate consensus guidance statements. Initial statements were drafted following a comprehensive literature review and were refined based on anonymous expert feedback, with up to three rounds of email voting to achieve consensus. Results: Consensus was reached on statements addressing general patient care, monitoring during GC therapy, osteoporosis prevention, vaccinations, infection screening, and prophylaxis for Pneumocystis jiroveci pneumonia. A multidisciplinary approach to managing GC-related complications was highlighted as a key recommendation. Conclusions: This represents the first consensus guidance in the neurological literature on GC complications, and offer clinicians structured guidance on mitigating and managing common adverse effects associated with both short- and long-term GC use. They also provide a foundation for future debate, quality improvement, research work in this area.
There have been no culturally validated measures to screen for depression in Madagascar. In 2022–2023, we conducted qualitative studies in the Bay of Ranobe area in southwestern Madagascar to understand local mental health syndromes specific to this region. We found that the 8-item Patient Health Questionnaire (PHQ-8) shares symptoms with the general distress-like, depressive-like and grief-like syndromes elicited locally. We adapted the PHQ-8 to align with the unique symptoms found in the region that were missing from the measure. We administered the adapted PHQ-8 to 809 participants aged 16 and above. We found that the one-factor (Depression) model (root mean square error of approximation [RMSEA] = 0.046, standardized root mean square residual [SRMR] = 0.053, Comparative Fit Index [CFI] = 0.993 and Tucker–Lewis Index [TLI] = 0.991) had a better fit to our data than the two-factor (Cognitive–Affective and Somatic) model (RMSEA = 0.047, SRMR = 0.052, CFI = 0.994 and TLI = 0.990). The one-factor (Depression) model demonstrated good internal consistency (MacDonald’s omega coefficient $ {\omega}_0 $ = 0.81 and ordinal alpha $ {\alpha}_0 $ = 0.87). We conducted a multigroup confirmatory factor analysis to establish measurement invariance (MI) across four groups (sex, ethnicity, level of education and age group) and found that all levels of MI were achieved across groups. Our research provides a validated method to assess the probable prevalence of current depression in southwestern Madagascar.