Background: The efficacy and safety of lecanemab have previously been evaluated in the Phase 3 randomized clinical trial, Clarity AD (NCT03887455). Methods: A Markov cohort model was developed to estimate the cost-effectiveness of lecanemab versus standard of care (SoC) in patients with mild cognitive impairment (MCI) or mild dementia due to Alzheimer’s disease (AD), with confirmed beta-amyloid (Aβ) pathology, from a Canadian societal perspective. Health states were determined by Clinical Dementia Rating-Sum of Boxes (CDR-SB) scores. Transitions between health states during month 0-18 were estimated from Clarity AD. Beyond month 18, relative efficacy for lecanemab in the form of the hazard ratio for time-to-worsening of CDR-SB was applied to literature-based transition probabilities. The model included the effects of lost productivity and impact on carer health-related quality of life. Results: The incremental cost-effectiveness ratio (ICER) for lecanemab vs SoC was estimated to be CAD 62,751 per QALY gained. The probability that lecanemab was cost-effective at a threshold of CAD 100,000 was estimated to be 88.5%. Conclusions: Lecanemab represents a cost-effective option for the treatment for early AD from the Canadian societal perspective. The results of this analysis can be used to inform clinical and economic decision making.

Background: Drug-resistant epilepsy (DRE), defined by persistent seizures despite appropriate anti-seizure medication trials, affects about one-third of individuals with epilepsy. Deep brain stimulation (DBS) has emerged as a promising avenue for improved seizure control. This project reviews existing publications to better understand the neuromodulation parameters used in DBS, aiming to inform clinical decisions on optimizing treatment parameters in patients living with DRE. Methods: A comprehensive literature search of PubMed and Google Scholar was conducted using the keywords “DBS,” “epilepsy,” and “parameters.” Only original studies reporting specific stimulation parameters were included, with meta-analyses and review papers excluded. A weighted Pearson correlation, using study sample size as the weight, examined frequency, pulse width, seizure reduction, and responder rate. Results: So far, 28 studies (1997-2024) have been reviewed, encompassing a total of 1,054 patients, with study size ranging from 1-250 patients. Electrode targets included the hippocampus, ANT, amygdala, centromedian nucleus, and STN. DBS frequencies ranged from 60–333 Hz, and pulse widths from 40–450 µs. Pearson correlation results suggest moderate frequencies (130–145 Hz) and wider pulse widths (300–450 µs) correlate with better seizure reduction and higher responder rates. Conclusions: These results support a formal meta-analysis to further investigate neuromodulation parameters to improve outcomes for DRE patients.

Background: Self-injurious behaviours (SIB) are repetitive, non-accidental movements that result in physical damage inflicted upon oneself, without suicidal intent. SIB are prevalent among children with autism spectrum disorder and can lead to permanent disability or death. Neuromodulation at a locus of neural circuitry implicated in SIB, the nucleus accumbens (NAc), may directly influence these behaviours. Methods: We completed a phase I, open-label clinical trial of deep brain stimulation (DBS) of the NAc in children with severe, treatment-refractory SIB (ClinicalTrials.gov NCT03982888). Participants were monitored for 12 months following NAc-DBS to assess the primary outcomes of safety and feasibility. Secondary outcomes included serial assessments of SIB, ambulatory actigraphy, and changes in brain glucose metabolism induced by DBS. Results: Six children underwent NAc-DBS without any serious adverse events. NAc-DBS resulted in significant reductions in SIB and SIB-associated behaviours across multiple standardized scales, concurrent with clinically meaningful improvements in quality-of-life. Ambulatory actigraphy showed reductions in high-amplitude limb movements and positron emission tomography revealed treatment-induced reductions in metabolic activity within the thalamus, striatum, and temporoinsular cortex. Conclusions: This first-in-children phase 1 clinical trial demonstrates the safety and feasibility of NAc-DBS in children with severe, refractory SIB at high risk of physical injury and death and supports further investigations.

The First Large Absorption Survey in H i (FLASH) is a large-area radio survey for neutral hydrogen in and around galaxies in the intermediate redshift range $0.4\lt z\lt1.0$, using the 21-cm H i absorption line as a probe of cold neutral gas. The survey uses the ASKAP radio telescope and will cover 24,000 deg$^2$ of sky over the next five years. FLASH breaks new ground in two ways – it is the first large H i absorption survey to be carried out without any optical preselection of targets, and we use an automated Bayesian line-finding tool to search through large datasets and assign a statistical significance to potential line detections. Two Pilot Surveys, covering around 3000 deg$^2$ of sky, were carried out in 2019-22 to test and verify the strategy for the full FLASH survey. The processed data products from these Pilot Surveys (spectral-line cubes, continuum images, and catalogues) are public and available online. In this paper, we describe the FLASH spectral-line and continuum data products and discuss the quality of the H i spectra and the completeness of our automated line search. Finally, we present a set of 30 new H i absorption lines that were robustly detected in the Pilot Surveys, almost doubling the number of known H i absorption systems at $0.4\lt z\lt1$. The detected lines span a wide range in H i optical depth, including three lines with a peak optical depth $\tau\gt1$, and appear to be a mixture of intervening and associated systems. Interestingly, around two-thirds of the lines found in this untargeted sample are detected against sources with a peaked-spectrum radio continuum, which are only a minor (5–20%) fraction of the overall radio-source population. The detection rate for H i absorption lines in the Pilot Surveys (0.3 to 0.5 lines per 40 deg$^2$ ASKAP field) is a factor of two below the expected value. One possible reason for this is the presence of a range of spectral-line artefacts in the Pilot Survey data that have now been mitigated and are not expected to recur in the full FLASH survey. A future paper in this series will discuss the host galaxies of the H i absorption systems identified here.

Parkinson’s disease (PD) is a severe neurodegenerative disorder characterized by prominent motor and non-motor (e.g., cognitive) abnormalities. Notwithstanding Food and Drug Administration (FDA)-approved treatments (e.g., L-dopa), most persons with PD do not adequately benefit from the FDA-approved treatments and treatment emergent adverse events are often reasons for discontinuation. To date, no current therapy for PD is disease modifying or curative. Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are central nervous system (CNS) penetrant and have shown to be neuroprotective against oxidative stress, neuroinflammation, and insulin resistance, as well as promoting neuroplasticity. Preclinical evidence suggests that GLP-1RAs also attenuate the accumulation of α-synuclein. The cellular and molecular effects of GLP-1RAs provide a basis to hypothesize putative therapeutic benefit in individuals with PD. Extant preclinical and clinical trial evidence in PD provide preliminary evidence of clinically meaningful benefit in the cardinal features of PD. Herein, we synthesize extant preclinical and early-phase clinical evidence, suggesting that GLP-1RAs may be beneficial as a treatment and/or illness progression modification therapeutic in PD.

Suicide accounts for over 700,000 deaths per year globally and remains a public health priority. Evidence suggests that sleep-related interventions may be effective in reducing depressive symptom severity and suicidal thoughts in patients diagnosed with depression and comorbid insomnia. This study aims to systematically review the efficacy of sedative-hypnotics and/or cognitive behavioral therapy for insomnia (CBT-I) on measures of suicidality.

In accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, PubMed, Medline, Cochrane Library, Embase, Scopus, and Web of Science were searched from inception to July 30, 2024. Studies were included if they (1) were randomized controlled trials (RCTs) and (2) reported on suicide-related measures associated with sleep interventions as a primary outcome, secondary outcome, or a safety measure. We endeavored to define and operationalize suicidality as suicidal ideation (SI), suicide attempts (SA), and suicide completion (SC). In cases where study authors failed to separate these three dimensions, the term “suicidality” was applied.

Eighteen studies were identified meeting inclusion criteria, comprised of studies investigating benzodiazepines (n = 2), Z-drugs (n=4), orexin receptor antagonists (ORAs) (n=8), and CBT-I (n=4). Zolpidem reduces SI as well as insomnia (linear association = 0.12, p<0.05) as evidenced by improvement on both the Columbia-Suicide Severity Rating Scale (C-SSRS) and the Scale for Suicide Ideation (SSI). ORAs were not associated with either an increase or decrease in suicidality. CBT-I alleviates SI in patients with insomnia (t = −3.35, p<0.05).

Effectively treating insomnia is associated with reduced SI. Available evidence suggests that Food and Drug Administration (FDA)-approved sedative-hypnotics do not increase the risk of suicidality.

The scatter in global atomic hydrogen (Hi) scaling relations is partly attributed to differences in how Hi and stellar properties are measured, with Hi reservoirs typically extending beyond the inner regions of galaxies where star formation occurs. Using pilot observations from the Widefield ASKAP L-band Legacy All-sky Blind Survey (WALLABY), we present the first measurements of Hi mass enclosed within the stellar-dominated regions of galaxies for a statistical sample of 995 local gas-rich systems, investigating the factors driving its variation. We examine how global Hi scaling relations change when measurements are restricted to $R_{\text{25}}$ and $R_{\text{24}}$ – the isophotal radii at 25 and 24 mag arcsec$^{-2}$ in the i-band – and explore how the fraction of Hi mass and Hi surface density within these radii correlate with other galaxy properties. On average, 68% of the total Hi mass is enclosed within $R_{\text{25}}$ and 54% within $R_{\text{24}}$, though significant variation exists between galaxies, ranging from $\sim$20% to 100%. The fraction of Hi mass within $R_{\text{25}}$ shows a mild correlation with stellar properties, with galaxies of higher stellar mass, greater stellar surface density, or redder colours enclosing a larger fraction of their Hi reservoirs. These correlations do not significantly strengthen when considering $R_{\text{24}}$. Conversely, global Hi surface densities show no significant correlation with stellar mass or stellar surface density, but trends start emerging when these are measured within the inner regions of galaxies. The strongest correlation is observed with optical colour, with bluer galaxies having higher average Hi surface densities within $R_{\text{25}}$. This trend of the average Hi surface density with optical colour strengthens when we restrict from $R_{\text{25}}$ to $R_{\text{24}}$, suggesting a closer connection between inner Hi reservoirs and star formation. This study underscores the value of (at least marginally) resolved Hi surveys of statistical samples for advancing our understanding of the gas-star formation cycle in galaxies.

Glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) receptor agonists (RAs) mimic naturally occurring GLP-1 and GIP and are highly effective anti-diabetic and anti-obesity agents. In addition to their robust acute and long-term effects on weight, metabolism, and blood pressure, these agents also reduce cardiovascular mortality as well as stroke risk and associated consequences. A replicated and convergent body of preclinical evidence also indicates that incretin receptor agonists activate molecular effectors critical to neuroplasticity, neuroprotection, and anti-apoptosis. Herein, we propose that GLP-1 RAs and GIP RAs are promising transdiagnostic mechanistically informed therapeutics in the treatment and prevention of multiple domains of psychopathology, including general cognitive, reward, and motivation systems and mental disorders. Major neurocognitive disorders (eg, Alzheimer’s Disease, Parkinson’s Disease), alcohol and substance use disorders, traumatic brain injury, and depressive disorders are near-term therapeutic targets. In addition, GLP-1 RAs and GIP RAs have robust effects on comorbidities that differentially affect persons with mental disorders (eg, cardiovascular, cerebrovascular, and metabolic disorders) and psychotropic drug-related weight gain.

Item response theory (IRT) model applications extend well beyond cognitive ability testing, and various patient-reported outcomes (PRO) measures are among the more prominent examples. PRO (and like) constructs differ from cognitive ability constructs in many ways, and these differences have model fitting implications. With a few notable exceptions, however, most IRT applications to PRO constructs rely on traditional IRT models, such as the graded response model. We review some notable differences between cognitive and PRO constructs and how these differences can present challenges for traditional IRT model applications. We then apply two models (the traditional graded response model and an alternative log-logistic model) to depression measure data drawn from the Patient-Reported Outcomes Measurement Information System project. We do not claim that one model is “a better fit” or more “valid” than the other; rather, we show that the log-logistic model may be more consistent with the construct of depression as a unipolar phenomenon. Clearly, the graded response and log-logistic models can lead to different conclusions about the psychometrics of an instrument and the scaling of individual differences. We underscore, too, that, in general, explorations of which model may be more appropriate cannot be decided only by fit index comparisons; these decisions may require the integration of psychometrics with theory and research findings on the construct of interest.

Studies with sensitive questions should include a sufficient number of respondents to adequately address the research interest. While studies with an inadequate number of respondents may not yield significant conclusions, studies with an excess of respondents become wasteful of investigators’ budget. Therefore, it is an important step in survey sampling to determine the required number of participants. In this article, we derive sample size formulas based on confidence interval estimation of prevalence for four randomized response models, namely, the Warner’s randomized response model, unrelated question model, item count technique model and cheater detection model. Specifically, our sample size formulas control, with a given assurance probability, the width of a confidence interval within the planned range. Simulation results demonstrate that all formulas are accurate in terms of empirical coverage probabilities and empirical assurance probabilities. All formulas are illustrated using a real-life application about the use of unethical tactics in negotiation.