Subjective cognitive complaints (SCC) can precede cognitive decline and are associated with demographic, exposure, lifestyle, and psychological factors. Prevalences of SCC and their correlates in individuals with repetitive head impacts (RHI) are poorly understood. This study characterized SCC in former elite American football players by frequency, mood and behavioral correlates, concordance with informant reports, and associations with neuropsychological test performance, cerebrospinal fluid (CSF), and magnetic resonance imaging (MRI) markers of neurodegeneration.

Former American football players (n = 180) completed measures of global and domain-specific SCC, neuropsychiatric symptom questionnaires, neuropsychological testing, lumbar puncture, and MRI. Elastic net regression evaluated the relative importance of potential SCC correlates. Intraclass correlation coefficients measured concordance between self and informant reports. Multiple linear regressions tested associations between SCC and verbal memory and executive functioning scores. CSF Aβ1-42, p-tau181, t-tau, neurofilament light (NfL), hippocampal volume, and regional cortical thickness were examined for their potential associations with SCC.

Rates of SCC ranged from 43 to 77% depending on the domain. Symptoms of depression, impulsivity, and anxiety were strongly associated with SCC. Self- and informant-reported SCC showed moderate inter-rater agreement. Adjusting for age, race, education, APOE ϵ4 carrier status, and depressive symptoms, SCC were associated with lower objective verbal memory and executive functioning performance. SCC were associated with lower parahippocampal cortical thickness but not with hippocampal volume or any of the measured CSF tests.

SCC are strongly associated with neuropsychiatric factors in former American football players. SCC may also be a marker of cognitive decline and neurodegeneration.

Recruitment for rare disease studies is challenging due to small eligible populations. Traditional clinical research management systems often lack tools to track recruitment contacts prior to enrollment. The NET-PRO study, focused on neuroendocrine tumors (NETs), implemented a participation monitoring system to enhance recruitment efficiency and representativeness.

NET-PRO is a multicenter cohort study of 2538 adults diagnosed with gastroenteropancreatic (GEP) or lung NETs between January 2018 and September 2024. Recruitment occurred from January 2022 to February 2025 across 14 U.S. medical centers. Sites used flexible recruitment methods (email, mail, phone, in-clinic) and tracked contacts using REDCap-based tools. Participant characteristics were analyzed by enrollment mode (online or mail) and recruitment difficulty (number of contacts required prior to enrollment) using standardized mean differences, chi-square tests, and ANOVA.

Of 9279 contacted patients, 2675 consented (28.8%) and 2538 enrolled (27.4%). Most enrolled online (83.2%), while 16.8% enrolled by mail. Mail respondents were older, had lower education and income, and more comorbidities. Among those enrolled, recruitment difficulty was associated with older age, lower education and income, but not comorbidity. Over half of the most difficult-to-recruit participants enrolled online. Contact methods varied by attempt, with email dominating early contacts and phone/mail used more in later attempts.

A participation monitoring tool supported flexible, multimodal recruitment and improved sample representativeness in a rare cancer study. Tracking recruitment contacts enabled adaptive strategies and may reduce bias in observational research by enabling better outreach to harder-to-reach populations.

To evaluate car seat tolerance screening failure rate in infants with CHD, clinical factors associated with test failure, and the impact of a failed test.

Single-centre retrospective study of 193 infants with CHD discharged from a general cardiology service between November 2020 and November 2024. Characteristics were compared between patients who passed and failed car seat testing using Wilcoxon-Mann–Whitney tests for continuous variables, and chi-square or Fisher’s exact tests for categorical variables.

Car seat test failure rate was 6.2% (12 of 193 patients). Neither median birthweight (3.2 kg vs. 3.3 kg, p = 0.68) nor the rate of prematurity (13.8% vs. 16.7%, p = 0.68) differed significantly between passing and failing groups. There was no relationship between cardiac physiology and car seat test failure (p = 0.39). There were no differences in rates of seizure (p = 0.29), stroke (p = 1.00), gastroesophageal reflux disease (p = 0.84), vocal cord dysfunction (p = 1.00), or pulmonary hypertension (p = 1.00) between passing and failing groups. Infants who failed had significantly higher rates of DiGeorge Syndrome (25.0%) compared to those who passed (2.2%) (p = 0.006). Readmission within 30 days of discharge was not different between failing (16.7%) and passing (17.1%) groups (p = 1.00). A failed test delayed discharge by a median of 1.5 days [IQR: 1.0–2.5 days].

The car seat test failure rate of our CHD cohort is higher than the published failure rate for premature infants. There was no relationship between cardiac physiology and test failure. DiGeorge Syndrome was the only comorbidity associated with increased failure rate. Failed car seat tests delay hospital discharge.

Distinguishing viral versus bacterial lower respiratory tract infection (LRTI) is challenging. We previously developed a rapid, host response-based test (Biomeme HR-B/V assay) using peripheral blood samples to identify viral versus bacterial infection. We assessed the performance of this assay when using nasopharyngeal (NP) samples.

Patients with LRTI were enrolled, and a NP swab sample was run using the HR-B/V assay (assessing 24 gene targets) on the FranklinTM platform. The performance of the prior classifier at identifying viral versus bacterial infection was assessed. A novel predictive model was generated for NP samples using the same 24 targets. Results were validated using external datasets with nasal/NP RNA sequence data.

Nineteen patients (median age 62 years, 52.1% male) were included. When using the prior HR-B/V classifier on NP samples of 19 patients with LRTI (12 viral, 7 bacterial), the area under the receiver operator curve (AUC) for viral versus bacterial infection was 0.786 (0.524–1), with accuracy 0.79 (95% CI 0.57–0.91), positive percent agreement (PPA) 0.43 (95% CI 0.16–0.75), and negative percent agreement (NPA) 1.00 (95% CI 0.76–1). The novel model had AUC 0.881 (95% CI 0.726–1), accuracy 0.84 (95% CI 0.62–0.94), PPA 0.86 (95% CI 0.49–0.97), and NPA 0.83 (95% CI 0.55–0.95) for bacterial infection. Validation in two external datasets showed AUC of 0.932 (95% CI 0.90–0.96) and 0.915 (95% CI 0.88–0.95).

We show that host response in the nasopharynx can distinguish viral versus bacterial LRTI. These findings need to be replicated in larger cohorts with diverse LRTI etiologies.

Genetic research on nicotine dependence has utilized multiple assessments that are in weak agreement.

We conducted a genome-wide association study (GWAS) of nicotine dependence defined using the Diagnostic and Statistical Manual of Mental Disorders (DSM-NicDep) in 61,861 individuals (47,884 of European ancestry [EUR], 10,231 of African ancestry, and 3,746 of East Asian ancestry) and compared the results to other nicotine-related phenotypes.

We replicated the well-known association at the CHRNA5 locus (lead single-nucleotide polymorphism [SNP]: rs147144681, p = 1.27E−11 in EUR; lead SNP = rs2036527, p = 6.49e−13 in cross-ancestry analysis). DSM-NicDep showed strong positive genetic correlations with cannabis use disorder, opioid use disorder, problematic alcohol use, lung cancer, material deprivation, and several psychiatric disorders, and negative correlations with respiratory function and educational attainment. A polygenic score of DSM-NicDep predicted DSM-5 tobacco use disorder criterion count and all 11 individual diagnostic criteria in the independent National Epidemiologic Survey on Alcohol and Related Conditions-III sample. In genomic structural equation models, DSM-NicDep loaded more strongly on a previously identified factor of general addiction liability than a “problematic tobacco use” factor (a combination of cigarettes per day and nicotine dependence defined by the Fagerström Test for Nicotine Dependence). Finally, DSM-NicDep showed a strong genetic correlation with a GWAS of tobacco use disorder as defined in electronic health records (EHRs).

Our results suggest that combining the wide availability of diagnostic EHR data with nuanced criterion-level analyses of DSM tobacco use disorder may produce new insights into the genetics of this disorder.

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.

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).

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).

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.

Guideline-based tobacco treatment is infrequently offered. Electronic health record-enabled patient-generated health data (PGHD) has the potential to increase patient treatment engagement and satisfaction.

We evaluated outcomes of a strategy to enable PGHD in a medical oncology clinic from July 1, 2021 to December 31, 2022. Among 12,777 patients, 82.1% received a tobacco screener about use and interest in treatment as part of eCheck-in via the patient portal.

We attained a broad reach (82.1%) and moderate response rate (30.9%) for this low-burden PGHD strategy. Patients reporting current smoking (n = 240) expressed interest in smoking cessation medication (47.9%) and counseling (35.8%). As a result of patient requests via PGHD, most tobacco treatment requests by patients were addressed by their providers (40.6–80.3%). Among patients with active smoking, those who received/answered the screener (n = 309 ) were more likely to receive tobacco treatment compared with usual care patients who did not have the patient portal (n = 323) (OR = 2.72, 95% CI = 1.93–3.82, P < 0.0001) using propensity scores to adjust for the effect of age, sex, race, insurance, and comorbidity. Patients who received yet ignored the screener (n = 1024) compared with usual care were also more likely to receive tobacco treatment, but to a lesser extent (OR = 2.20, 95% CI = 1.68–2.86, P < 0.0001). We mapped observed and potential benefits to the Translational Science Benefits Model (TSBM).

PGHD via patient portal appears to be a feasible, acceptable, scalable, and cost-effective approach to promote patient-centered care and tobacco treatment in cancer patients. Importantly, the PGHD approach serves as a real world example of cancer prevention leveraging the TSBM.

Viloxazine ER (extended-release capsules; Qelbree®) is a nonstimulant medication, FDA-approved for ADHD in children (≥6 years) and adults. Efficacy and safety for children and adolescents were evaluated in one phase 2 [NCT02633527]and four phase 3 [NCT03247517, NCT03247556, NCT03247530, and NCT03247543], double-blind (DB), placebo-controlled trials that fed into a long-term, open-label extension (OLE) trial [NCT02736656]. Here we report the findings from this OLE trial.

Participants completing the DB trials were eligible for the OLE. Viloxazine ER was initiated at 100 mg/day (children) or 200 mg/day (adolescents) and adjusted (if needed) over a 12-week Dose-Optimization Period (up to 400 mg/day [children] or 600 mg/day [adolescents]). Maintenance treatment then continued up to 72 months. Safety assessments included adverse events (AEs), clinical laboratory tests, vital signs, ECG (12-lead), and the Columbia Suicide Severity Rating Scale (C-SSRS). Efficacy assessments included the ADHD Rating Scale, 4th (Phase 2) or 5th (Phase 3) Edition (ADHD-RS-IV/5), and the Clinical Global Impression-Improvement (CGI-I) scale. Efficacy was assessed relative to DB baseline at study visits ˜ 3 months apart. Two response measures, 50% improvement in ADHD-RS-IV/5 Total score and CGI-I score of 1-2, were also evaluated.

1100 individuals (646 children; 454 adolescents; 66.5% male/33.5% female) received treatment. Median (range) exposure to viloxazine ER was 260 (1 to 1896) days. AEs were reported by 57.3% participants, most commonly (≥5%) nasopharyngitis (9.7%), somnolence (9.5%), headache (8.9%) decreased appetite (6.0%), and fatigue (5.7%). AEs were mostly mild or moderate in severity (3.9% reported any severe AE); AEs led to viloxazine ER discontinuation for 8.2%. The mean (SD) changes from DB baseline in ADHD-RS IV/5 Total score were -17.0 (14.18) (viloxazine ER) and -11.2 (13.19) (placebo) at the last DB study visit, 24.3 (11.96) at OLE Month 3, and 22.4 (13.62) at participants’ last OLE study visit. ADHD-RS-IV/5 and CGI-I responder rates each exceeded 65% at all OLE visits following Dose-Optimization.

The safety and efficacy of viloxazine ER were maintained with long-term use in children and adolescents with ADHD. No new safety concerns emerged, and efficacy results suggested potential for continued improvement over that seen during DB treatment.

Supernus Pharmaceuticals, Inc.

There are no contemporary data on the burden of healthcare-associated infections (HAIs) in New Zealand.

To estimate the economic burden of HAIs in adults in New Zealand public hospitals by number and monetary value of bed days lost; number of deaths, number of life years lost, and the monetary value (in NZ dollars); Accident Compensation Commission (ACC) HAI treatment injury payments; and disability-adjusted life years (DALYs).

The annual incidence rate was calculated from the observed prevalence of HAIs in New Zealand, and length of patient stays. Total HAIs for 2021 were estimated by multiplying adult admissions by incidence rates. The excess length of stay and mortality risk attributed to those with HAI was calculated using a multistate model. Payments for treatment injuries were obtained from the ACC. DALYs for HAIs were estimated from the literature.

The incidence rate of HAI was 4.74%, predicting 24,191 HAIs for 2021, resulting in 76,861 lost bed days, 699 deaths, with 9,371 years of life lost (YoLL). The annual economic burden was estimated to be $955m comprised of $121m for lost bed days, $792m for cost of YoLL, and $43m ACC claims. There were 24,165 DALY which is greater than many other measured injuries in New Zealand, eg motor vehicle traffic crashes with 20,328 DALY.

HAIs are a significant burden for patients, their families, and the public health system. Preventive guidelines for many HAIs exist and a strategic plan is needed to reduce HAIs in New Zealand.