Tenecteplase has been shown to be non-inferior to alteplase for the treatment of acute ischemic stroke within 4.5 hours of stroke onset. While not formally approved by regulatory authorities, many jurisdictions have transitioned to using tenecteplase for routine stroke treatment because it is simpler to use and has cost advantages.

We report a three-phase time-series analysis over 2.5 years and the process for transition from use of alteplase to tenecteplase for the routine treatment of acute ischemic stroke from a system-wide perspective involving an entire province. The transition was planned and implemented centrally. Data were collected in clinical routine, arising from both administrative sources and a prospective stroke registry, and represent real-world outcome data. Data are reported using standard descriptive statistics.

A total of 1211 patients were treated with intravenous thrombolysis (477 pre-transition using alteplase, 180 transition period using both drugs, 554 post-transition using tenecteplase). Baseline characteristics, adverse events and outcomes were similar between epochs. There were four dosing errors with tenecteplase, including providing the cardiac dose to two patients. There were no instances of major hemorrhage associated with dosing errors.

The transition to using intravenous tenecteplase for stroke treatment was seamless and resulted in identical outcomes to intravenous alteplase.

The best prehospital transport strategy for patients with suspected stroke due to possible large vessel occlusion varies by jurisdiction and available resources. A foundational problem is the lack of a definitive diagnosis at the scene. Rural stroke presentations provide the most problematic triage destination decision-making. In Alberta, Canada, the implementation and 5-year experience with a rural field consultation approach to provide service to rural patients with acute stroke is described.

The protocols established through the rural field consultation system and the subsequent transport patterns for suspected stroke patients during the first 5 years of implementation are presented. Outcomes are reported using home time and data are summarized using descriptive statistics.

From April 2017 to March 2022, 721 patients met the definition for a rural field consultation, and 601 patients were included in the analysis. Most patients (n = 541, 90%) were transported by ground ambulance. Intravenous thrombolysis was provided for 65 (10.8%) of patients, and 106 (17.6%) underwent endovascular thrombectomy. The median time from first medical contact to arterial access was 3.2 h (range 1.3–7.6) in the direct transfers, compared to 6.5 h (range 4.6–7.9) in patients arriving indirectly to the comprehensive stroke center (CSC). Only a small proportion of patients (n = 5, 0.8%) were routed suboptimally to a primary stroke center and then to a CSC where they underwent endovascular therapy.

The rural field consultation system was associated with shortened delays to recanalization and demonstrated that it is feasible to improve access to acute stroke care for rural patients.

Clostridioides difficile infection (CDI) may be misdiagnosed if testing is performed in the absence of signs or symptoms of disease. This study sought to support appropriate testing by estimating the impact of signs, symptoms, and healthcare exposures on pre-test likelihood of CDI.

A panel of fifteen experts in infectious diseases participated in a modified UCLA/RAND Delphi study to estimate likelihood of CDI. Consensus, defined as agreement by >70% of panelists, was assessed via a REDCap survey. Items without consensus were discussed in a virtual meeting followed by a second survey.

All fifteen panelists completed both surveys (100% response rate). In the initial survey, consensus was present on 6 of 15 (40%) items related to risk of CDI. After panel discussion and clarification of questions, consensus (>70% agreement) was reached on all remaining items in the second survey. Antibiotics were identified as the primary risk factor for CDI and grouped into three categories: high-risk (likelihood ratio [LR] 7, 93% agreement among panelists in first survey), low-risk (LR 3, 87% agreement in first survey), and minimal-risk (LR 1, 71% agreement in first survey). Other major factors included new or unexplained severe diarrhea (e.g., ≥ 10 liquid bowel movements per day; LR 5, 100% agreement in second survey) and severe immunosuppression (LR 5, 87% agreement in second survey).

Infectious disease experts concurred on the importance of signs, symptoms, and healthcare exposures for diagnosing CDI. The resulting risk estimates can be used by clinicians to optimize CDI testing and treatment.

We aimed to determine whether automated identification of antibiotic targeting suspected urinary tract infection (UTI) shortened the time to antimicrobial stewardship (AS) intervention.

Retrospective before-and-after study.

Tertiary and quaternary care academic medical center.

Emergency department (ED) or admitted adult patients meeting best practice alert (BPA) criteria during pre- and post-BPA periods.

We developed a BPA to alert AS pharmacists of potential ASB triggered by the following criteria: ED or admitted status, antibiotic order with genitourinary indication, and a preceding urinalysis with ≤ 10 WBC/hpf. We evaluated the median time from antibiotic order to AS intervention and overall percent of UTI-related interventions among patients in pre-BPA (01/2020–12/2020) and post-BPA (04/15/2021–04/30/2022) periods.

774 antibiotic orders met inclusion criteria: 355 in the pre- and 419 in the post-BPA group. 43 (35 UTI-related) pre-BPA and 117 (94 UTI-related) post-BPA interventions were documented. The median time to intervention was 28 hours (IQR 18–65) in the pre-BPA group compared to 16 hours (IQR 2–34) in the post-BPA group (P < 0.01). Despite absent pyuria, there were six cases with gram-negative bacteremia presumably from a urinary source.

Automated identification of antibiotics targeting UTI without pyuria on urinalysis reduced the time to stewardship intervention and increased the rate of UTI-specific interventions. Clinical decision support aided in the efficiency of AS review and syndrome-targeted impact, but cases still required AS clinical review.

Diagnosis of acute ischemia typically relies on evidence of ischemic lesions on magnetic resonance imaging (MRI), a limited diagnostic resource. We aimed to determine associations of clinical variables and acute infarcts on MRI in patients with suspected low-risk transient ischemic attack (TIA) and minor stroke and to assess their predictive ability.

We conducted a post-hoc analysis of the Diagnosis of Uncertain-Origin Benign Transient Neurological Symptoms (DOUBT) study, a prospective, multicenter cohort study investigating the frequency of acute infarcts in patients with low-risk neurological symptoms. Primary outcome parameter was defined as diffusion-weighted imaging (DWI)-positive lesions on MRI. Logistic regression analysis was performed to evaluate associations of clinical characteristics with MRI-DWI-positivity. Model performance was evaluated by Harrel’s c-statistic.

In 1028 patients, age (Odds Ratio (OR) 1.03, 95% Confidence Interval (CI) 1.01–1.05), motor (OR 2.18, 95%CI 1.27–3.65) or speech symptoms (OR 2.53, 95%CI 1.28–4.80), and no previous identical event (OR 1.75, 95%CI 1.07–2.99) were positively associated with MRI-DWI-positivity. Female sex (OR 0.47, 95%CI 0.32–0.68), dizziness and gait instability (OR 0.34, 95%CI 0.14–0.69), normal exam (OR 0.55, 95%CI 0.35–0.85) and resolved symptoms (OR 0.49, 95%CI 0.30–0.78) were negatively associated. Symptom duration and any additional symptoms/symptom combinations were not associated. Predictive ability of the model was moderate (c-statistic 0.72, 95%CI 0.69–0.77).

Detailed clinical information is helpful in assessing the risk of ischemia in patients with low-risk neurological events, but a predictive model had only moderate discriminative ability. Patients with clinically suspected low-risk TIA or minor stroke require MRI to confirm the diagnosis of cerebral ischemia.

Screen time in infancy is linked to changes in social-emotional development but the pathway underlying this association remains unknown. We aim to provide mechanistic insights into this association using brain network topology and to examine the potential role of parent–child reading in mitigating the effects of screen time.

We examined the association of screen time on brain network topology using linear regression analysis and tested if the network topology mediated the association between screen time and later socio-emotional competence. Lastly, we tested if parent–child reading time was a moderator of the link between screen time and brain network topology.

Infant screen time was significantly associated with the emotion processing-cognitive control network integration (p = 0.005). This network integration also significantly mediated the association between screen time and both measures of socio-emotional competence (BRIEF-2 Emotion Regulation Index, p = 0.04; SEARS total score, p = 0.04). Parent–child reading time significantly moderated the association between screen time and emotion processing-cognitive control network integration (β = −0.640, p = 0.005).

Our study identified emotion processing-cognitive control network integration as a plausible biological pathway linking screen time in infancy and later socio-emotional competence. We also provided novel evidence for the role of parent–child reading in moderating the association between screen time and topological brain restructuring in early childhood.

Prior research, largely focused on US male veterans, indicates an increased risk of cardiovascular disease among individuals with post-traumatic stress disorder (PTSD). Data from other settings and populations are scarce. The objective of this study is to examine PTSD as a risk factor for incident major adverse cardiovascular events (MACEs) in South Africa.

We analysed reimbursement claims (2011–2020) of a cohort of South African medical insurance scheme beneficiaries aged 18 years or older. We calculated adjusted hazard ratios (aHRs) for associations between PTSD and MACEs using Cox proportional hazard models and calculated the effect of PTSD on MACEs using longitudinal targeted maximum likelihood estimation.

We followed 1,009,113 beneficiaries over a median of 3.0 years (IQR 1.1–6.0). During follow-up, 12,662 (1.3%) persons were diagnosed with PTSD and 39,255 (3.9%) had a MACE. After adjustment for sex, HIV status, age, population group, substance use disorders, psychotic disorders, major depressive disorder, sleep disorders and the use of antipsychotic medication, PTSD was associated with a 16% increase in the risk of MACEs (aHR 1.16, 95% confidence interval (CI) 1.05–1.28). The risk ratio for the effect of PTSD on MACEs decreased from 1.59 (95% CI 1.49–1.68) after 1 year of follow-up to 1.14 (95% CI 1.11–1.16) after 8 years of follow-up.

Our study provides empirical support for an increased risk of MACEs in males and females with PTSD from a general population sample in South Africa. These findings highlight the importance of monitoring cardiovascular risk among individuals diagnosed with PTSD.

Children with CHD or born very preterm are at risk for brain dysmaturation and poor neurodevelopmental outcomes. Yet, studies have primarily investigated neurodevelopmental outcomes of these groups separately.

To compare neurodevelopmental outcomes and parent behaviour ratings of children born term with CHD to children born very preterm.

A clinical research sample of 181 children (CHD [n = 81]; very preterm [≤32 weeks; n = 100]) was assessed at 18 months.

Children with CHD and born very preterm did not differ on Bayley-III cognitive, language, or motor composite scores, or on expressive or receptive language, or on fine motor scaled scores. Children with CHD had lower ross motor scaled scores compared to children born very preterm (p = 0.047). More children with CHD had impaired scores (<70 SS) on language composite (17%), expressive language (16%), and gross motor (14%) indices compared to children born very preterm (6%; 7%; 3%; ps < 0.05). No group differences were found on behaviours rated by parents on the Child Behaviour Checklist (1.5–5 years) or the proportion of children with scores above the clinical cutoff. English as a first language was associated with higher cognitive (p = 0.004) and language composite scores (p < 0.001). Lower median household income and English as a second language were associated with higher total behaviour problems (ps < 0.05).

Children with CHD were more likely to display language and motor impairment compared to children born very preterm at 18 months. Outcomes were associated with language spoken in the home and household income.

Parkinsonism and Parkinson's disease (PD) have been described as consequences of repetitive head impacts (RHI) from boxing, since 1928. Autopsy studies have shown that RHI from other contact sports can also increase risk for neurodegenerative diseases, including chronic traumatic encephalopathy (CTE) and Lewy bodies. In vivo research on the relationship between American football play and PD is scarce, with small samples, and equivocal findings. This study leveraged the Fox Insight study to evaluate the association between American football and parkinsonism and/or PD Diagnosis and related clinical outcomes.

Fox Insight is an online study of people with and without PD who are 18+ years (>50,000 enrolled). Participants complete online questionnaires on motor function, cognitive function, and general health behaviors. Participants self-reported whether they "currently have a diagnosis of Parkinson's disease, or parkinsonism, by a physician or other health care professional." In November 2020, the Boston University Head Impact Exposure Assessment was launched in Fox Insight for large-scale data collection on exposure to RHI from contact sports and other sources. Data used in this abstract were obtained from the Fox Insight database https://foxinsight-info.michaeljfox.org/insight/explore/insight.jsp on 01/06/2022. The sample includes 2018 men who endorsed playing an organized sport. Because only 1.6% of football players were women, analyses are limited to men. Responses to questions regarding history of participation in organized football were examined. Other contact and/or non-contact sports served as the referent group. Outcomes included PD status (absence/presence of parkinsonism or PD) and Penn Parkinson's Daily Activities Questionnaire-15 (PDAQ-15) for assessment of cognitive symptoms. Binary logistic regression tested associations between history and years of football play with PD status, controlling for age, education, current heart disease or diabetes, and family history of PD. Linear regressions, controlling for these variables, were used for the PDAQ-15.

Of the 2018 men (mean age=67.67, SD=9.84; 10, 0.5% Black), 788 (39%) played football (mean years of play=4.29, SD=2.88), including 122 (16.3%) who played youth football, 494 (66.0%) played high school, 128 (17.1%) played college football, and 5 (0.7%) played at the semi-professional or professional level. 1738 (86.1%) reported being diagnosed with parkinsonism/PD, and 707 of these were football players (40.7%). History of playing any level of football was associated with increased odds of having a reported parkinsonism or PD diagnosis (OR=1.52, 95% CI=1.14-2.03, p=0.004). The OR remained similar among those age <69 (sample median age) (OR=1.45, 95% CI=0.97-2.17, p=0.07) and 69+ (OR=1.45, 95% CI=0.95-2.22, p=0.09). Among the football players, there was not a significant association between years of play and PD status (OR=1.09, 95% CI=1.00-1.20, p=0.063). History of football play was not associated with PDAQ-15 scores (n=1980) (beta=-0.78, 95% CI=-1.59-0.03, p=0.059) among the entire sample.

Among 2018 men from a data set enriched for PD, playing organized football was associated with increased odds of having a reported parkinsonism/PD diagnosis. Next steps include examination of the contribution of traumatic brain injury and other sources of RHI (e.g., soccer, military service).

White matter hyperintensity (WMH) burden is greater, has a frontal-temporal distribution, and is associated with proxies of exposure to repetitive head impacts (RHI) in former American football players. These findings suggest that in the context of RHI, WMH might have unique etiologies that extend beyond those of vascular risk factors and normal aging processes. The objective of this study was to evaluate the correlates of WMH in former elite American football players. We examined markers of amyloid, tau, neurodegeneration, inflammation, axonal injury, and vascular health and their relationships to WMH. A group of age-matched asymptomatic men without a history of RHI was included to determine the specificity of the relationships observed in the former football players.

240 male participants aged 45-74 (60 unexposed asymptomatic men, 60 male former college football players, 120 male former professional football players) underwent semi-structured clinical interviews, magnetic resonance imaging (structural T1, T2 FLAIR, and diffusion tensor imaging), and lumbar puncture to collect cerebrospinal fluid (CSF) biomarkers as part of the DIAGNOSE CTE Research Project. Total WMH lesion volumes (TLV) were estimated using the Lesion Prediction Algorithm from the Lesion Segmentation Toolbox. Structural equation modeling, using Full-Information Maximum Likelihood (FIML) to account for missing values, examined the associations between log-TLV and the following variables: total cortical thickness, whole-brain average fractional anisotropy (FA), CSF amyloid ß42, CSF p-tau181, CSF sTREM2 (a marker of microglial activation), CSF neurofilament light (NfL), and the modified Framingham stroke risk profile (rFSRP). Covariates included age, race, education, APOE z4 carrier status, and evaluation site. Bootstrapped 95% confidence intervals assessed statistical significance. Models were performed separately for football players (college and professional players pooled; n=180) and the unexposed men (n=60). Due to differences in sample size, estimates were compared and were considered different if the percent change in the estimates exceeded 10%.

In the former football players (mean age=57.2, 34% Black, 29% APOE e4 carrier), reduced cortical thickness (B=-0.25, 95% CI [0.45, -0.08]), lower average FA (B=-0.27, 95% CI [-0.41, -.12]), higher p-tau181 (B=0.17, 95% CI [0.02, 0.43]), and higher rFSRP score (B=0.27, 95% CI [0.08, 0.42]) were associated with greater log-TLV. Compared to the unexposed men, substantial differences in estimates were observed for rFSRP (Bcontrol=0.02, Bfootball=0.27, 994% difference), average FA (Bcontrol=-0.03, Bfootball=-0.27, 802% difference), and p-tau181 (Bcontrol=-0.31, Bfootball=0.17, -155% difference). In the former football players, rFSRP showed a stronger positive association and average FA showed a stronger negative association with WMH compared to unexposed men. The effect of WMH on cortical thickness was similar between the two groups (Bcontrol=-0.27, Bfootball=-0.25, 7% difference).

These results suggest that the risk factor and biological correlates of WMH differ between former American football players and asymptomatic individuals unexposed to RHI. In addition to vascular risk factors, white matter integrity on DTI showed a stronger relationship with WMH burden in the former football players. FLAIR WMH serves as a promising measure to further investigate the late multifactorial pathologies of RHI.

Despite associations between hypoglycemia and cognitive performance using cross-sectional and experimental methods (e.g., Insulin clamp studies), few studies have evaluated this relationship in a naturalistic setting. This pilot study utilizes an EMA study design in adults with T1D to examine the impact of hypoglycemia and hyperglycemia, measured using CGM, on cognitive performance, measured via ambulatory assessment.

Twenty adults with T1D (mean age 38.9 years, range 26-67; 55% female; 55% bachelor’s degree or higher; mean HbA1c = 8.3%, range 5.4% - 12.5%), were recruited from the Joslin Diabetes Center at SUNY Upstate Medical University. A blinded Dexcom G6 CGM was worn during everyday activities while completing 3-6 daily EMAs using personal smartphones. EMAs were delivered between 9 am and 9 pm, for 15 days. EMAs included 3 brief cognitive tests developed by testmybrain.org and validated for brief mobile administration (Gradual Onset CPT d-prime, Digit Symbol Matching median reaction time, Multiple Object Tracking percent accuracy) and self-reported momentary negative affect. Day-level average scores were calculated for the cognitive and negative affect measures. Hypoglycemia and hyperglycemia were defined as the percentage of time spent with a sensor glucose value <70 mg/dL or > 180 mg/dL, respectively. Daytime (8 am to 9 pm) and nighttime (9 pm to 8 am) glycemic excursions were calculated separately. Multilevel models estimated the between- and within-person association between the night prior to, or the same day, time spent in hypoglycemia or hyperglycemia and cognitive performance (each cognitive test was modeled separately). To evaluate the effect of between-person differences, person-level variables were calculated as the mean across the study and grand-mean centered. To evaluate the effect of within-person fluctuations, day-level variables were calculated as deviations from these person-level means.

Within-person fluctuations in nighttime hypoglycemia were associated with daytime processing speed. Specifically, participants who spent a higher percentage of time in hypoglycemia than their average percentage the night prior to assessment performed slower than their average performance on the processing speed test (Digit Symbol Matching median reaction time, b = 94.16, p = 0.042), while same day variation in hypoglycemia was not associated with variation in Digit Symbol Matching performance. This association remained significant (b = 97.46, p = 0.037) after controlling for within-person and between-person effects of negative affect. There were no significant within-person associations between time spent in hyperglycemia and Digit Symbol Matching, nor day/night hypoglycemia or hyperglycemia and Gradual Onset CPT or Multiple Object Tracking.

Our findings from this EMA study suggest that when individuals with T1D experience more time in hypoglycemia at night (compared to their average), they have slower processing speed the following day, while same day hypoglycemia and hyperglycemia does not similarly impact processing speed performance. These results showcase the power of intensive longitudinal designs using ambulatory cognitive assessment to uncover novel determinants of cognitive variation in real world settings that have direct clinical applications for optimizing cognitive performance. Future research with larger samples is needed to replicate these findings.

Neurocognitive impairment and quality of life are two important long-term challenges for patients with complex CHD. The impact of re-interventions during adolescence and young adulthood on neurocognition and quality of life is not well understood.

In this prospective longitudinal multi-institutional study, patients 13–30 years old with severe CHD referred for surgical or transcatheter pulmonary valve replacement were enrolled. Clinical characteristics were collected, and executive function and quality of life were assessed prior to the planned pulmonary re-intervention. These results were compared to normative data and were compared between treatment strategies.

Among 68 patients enrolled from 2016 to 2020, a nearly equal proportion were referred for surgical and transcatheter pulmonary valve replacement (53% versus 47%). Tetralogy of Fallot was the most common diagnosis (59%) and pulmonary re-intervention indications included stenosis (25%), insufficiency (40%), and mixed disease (35%). There were no substantial differences between patients referred for surgical and transcatheter therapy. Executive functioning deficits were evident in 19–31% of patients and quality of life was universally lower compared to normative sample data. However, measures of executive function and quality of life did not differ between the surgical and transcatheter patients.

In this patient group, impairments in neurocognitive function and quality of life are common and can be significant. Given similar baseline characteristics, comparing changes in neurocognitive outcomes and quality of life after surgical versus transcatheter pulmonary valve replacement will offer unique insights into how treatment approaches impact these important long-term patient outcomes.

Cost-effective treatments are needed to reduce the burden of depression. One way to improve the cost-effectiveness of psychotherapy might be to increase session frequency, but keep the total number of sessions constant.

To evaluate the cost-effectiveness of twice-weekly compared with once-weekly psychotherapy sessions after 12 months, from a societal perspective.

An economic evaluation was conducted alongside a randomised controlled trial comparing twice-weekly versus once-weekly sessions of psychotherapy (cognitive–behavioural therapy or interpersonal psychotherapy) for depression. Missing data were handled by multiple imputation. Statistical uncertainty was estimated with bootstrapping and presented with cost-effectiveness acceptability curves.

Differences between the two groups in depressive symptoms, physical and social functioning, and quality-adjusted life-years (QALY) at 12-month follow-up were small and not statistically significant. Total societal costs in the twice-weekly session group were higher, albeit not statistically significantly so, than in the once-weekly session group (mean difference €2065, 95% CI −686 to 5146). The probability that twice-weekly sessions are cost-effective compared with once-weekly sessions was 0.40 at a ceiling ratio of €1000 per point improvement in Beck Depression Inventory-II score, 0.32 at a ceiling ratio of €50 000 per QALY gained, 0.23 at a ceiling ratio of €1000 per point improvement in physical functioning score and 0.62 at a ceiling ratio of €1000 per point improvement in social functioning score.

Based on the current results, twice-weekly sessions of psychotherapy for depression are not cost-effective over the long term compared with once-weekly sessions.

Twice weekly sessions of cognitive behavioral therapy (CBT) and interpersonal psychotherapy (IPT) for major depressive disorder (MDD) lead to less drop-out and quicker and better response compared to once weekly sessions at posttreatment, but it is unclear whether these effects hold over the long run.

Compare the effects of twice weekly v. weekly sessions of CBT and IPT for depression up to 24 months since the start of treatment.

Using a 2 × 2 factorial design, this multicentre study randomized 200 adults with MDD to once or twice weekly sessions of CBT or IPT over 16–24 weeks, up to a maximum of 20 sessions. Main outcome measures were depression severity, measured with the Beck Depression Inventory-II and the Longitudinal Interval Follow-up Evaluation. Intention-to-treat analyses were conducted.

Compared with patients who received once weekly sessions, patients who received twice weekly sessions showed a significant decrease in depressive symptoms up through month 9, but this effect was no longer apparent at month 24. Patients who received CBT showed a significantly larger decrease in depressive symptoms up to month 24 compared to patients who received IPT, but the between-group effect size at month 24 was small. No differential effects between session frequencies or treatment modalities were found in response or relapse rates.

Although a higher session frequency leads to better outcomes in the acute phase of treatment, the difference in depression severity dissipated over time and there was no significant difference in relapse.