Prospective Outcome Research Articles

Loneliness mediates the association between trait social anxiety and cardiovascular reactivity to acute psychological stress.

The primary aims of the current study are (1) to examine the association between trait social anxiety and cardiovascular reactivity to acute psychological stress, and (2) to identify if loneliness significantly mediates the association between trait social anxiety and cardiovascular reactivity. A sample of 658 participants completed a cardiovascular reactivity protocol consisting of a resting baseline and stressor phase (mental arithmetic and Stroop), with systolic blood pressure (SBP), diastolic blood pressure (DBP) and heart rate (HR) monitored throughout. Participants also completed self-reported measures assessing social anxiety and loneliness. Social anxiety was associated with increased self-reported stress. However, no significant associations between social anxiety and measures of cardiovascular reactivity were observed in regression analyses. Loneliness was significantly associated with lower SBP and DBP reactivity. Additionally, loneliness significantly mediated the association between trait social anxiety and both SBP reactivity and DBP reactivity. Here, trait social anxiety predicted greater levels of loneliness, which in turn was associated with diminished cardiovascular reactivity. No significant associations emerged for HR reactivity. These blunted blood pressure responses to acute stress may indicate a potential mechanism leading to adverse prospective health outcomes.

BRAF inhibitor monotherapy in BRAFV600E-mutated pediatric low-grade glioma: a single center's experience.

Pediatric low-grade gliomas (pLGGs) have an overall survival of over 90%; however, patients harboring a BRAFV600E alteration may have worse outcomes, particularly when treated with classic chemotherapy. Combined BRAF/MEK inhibition following incomplete resection demonstrated improved outcome in BRAFV600E altered pLGG compared to combined carboplatin/vincristine chemotherapy and is now considered the standard FDA-approved treatment for this group of tumors. The aim herein was to investigate the efficacy and tolerability of single agent BRAF inhibitor treatment in BRAFV600E altered pLGG. A single institution retrospective chart review analysis was performed on patients, 0 to 21 years of age, with newly diagnosed and/or progressive BRAFV600E mutated pLGGs (WHO Grade 1 or 2) at Children's Healthcare of Atlanta treated off-study with BRAF inhibitor monotherapy between 2013-2023. 2-year progression free survival (PFS) and objective tumor response was evaluated. All toxicities possibly associated with BRAF inhibition therapy were evaluated and described according to Common Terminology Criteria for Adverse Events version 5 (CTCAEv5). MRI brain imaging data at baseline and best response wasevaluated to identify patterns that may predict response to BRAF inhibition monotherapy. Fifteen patients diagnosed with BRAFV600E mutated pLGG, treated with monotherapy BRAF inhibition, were identified. Median age of diagnosis: 3.8 years (0.2 -18.1). Histologic diagnosis: pilocytic astrocytoma (PA) (N=4); ganglioglioma (GGL) (N=3); GGL, atypical (N=3); pleomorphic xanthroastrocytoma (PXA) (N=2); low-grade neuroepithelial tumor (N=1); infiltrating glioma (N=1); and LGG (NOS) (N=1). Tumor locations included: hypothalamus/optic chiasm (N=6); brainstem (N=4); third ventricle/thalamus (N=2); parietal/temporal lobe (N=2); and spinal cord (N=1). Mean duration of BRAF inhibitor monotherapy: 38.41 months (range 3.9-83.7). Median follow-up: 32.6 months (16 - 78.1). Two-year PFS for patients on BRAFi monotherapy for at least 10 months: 90% (95% CI: 73.2%-100%). Objective Response (OR) for 15 evaluable patients on BRAF inhibitor (BRAFi) therapy: 73% (0/15 CR + 6/15 PR + 5/15 MR) with Overall Response Rate (ORR=CR+PR): 40%. Overall, patients tolerated treatment well with Grade 1 rash being the most common toxicity. Two of 15 patients (13%) discontinued therapy due to toxicities, and 2 other patients switched within drug class from vemurafenib to dabrafenib due to toxicities. In this small cohort of incompletely resected BRAFV600E mutated pLGGs, BRAFi monotherapy was effective and well tolerated with an ORR comparable to published prospective outcomes of dual MEK/BRAF inhibitor therapy. This promising monotherapy treatment should be considered when choosing treatment for incompletely resected BRAFV600E-altered pLGGs.

The role of neutrophilia in hyperlactatemia, blood acidosis, impaired oxygen transport, and mortality outcome in critically ill COVID-19 patients.

COVID-19 severity and high in-hospital mortality are often associated with severe hypoxemia, hyperlactatemia, and acidosis, yet the key players driving this association remain unclear. It is generally assumed that organ damage causes toxic acidosis, but since neutrophil numbers in severe COVID-19 can exceed 80% of the total circulating leukocytes, we asked if metabolic acidosis mediated by the glycolytic neutrophils is associated with lung damage and impaired oxygen delivery in critically ill patients. Based on prospective mortality outcome, critically ill COVID-19 patients were divided into ICU- survivors and ICU-non-survivors. Samples were analyzed to explore if correlations exist between neutrophil counts, lung damage, glycolysis, blood lactate, blood pH, hemoglobin oxygen saturation, and mortality outcome. We also interrogated isolated neutrophils, platelets, and PBMCs for glycolytic activities. Arterial blood gas analyses showed remarkable hypoxemia in non-survivors with no consistent differences in PCO2 or [HCO3 -]. The hemoglobin oxygen dissociation curve revealed a right-shift, consistent with lower blood-pH and elevated blood lactate in non-survivors. Metabolic analysis of different blood cells revealed increased glycolytic activity only when considering the total number of neutrophils. This indicates the role of neutrophilia in hyperlactatemia and lung damage, subsequently contributing to mortality outcomes in severe SARS-CoV-2 infection.

Pelvic Regional Control With 25 Gy in 5 Fractions in Stereotactic Radiation Therapy for High-Risk Prostate Cancer: Pooled Prospective Outcomes From the SHARP Consortium.

To evaluate the efficacy of 25 Gy in 5 fractions (25 Gy/5#) prophylactic pelvic nodal irradiation for regional control during stereotactic radiation therapy (SBRT) for high-risk prostate cancer. The multinational SHARP consortium database of patients treated with curative-intent prostate SBRT for high-risk prostate cancer was queried for prophylactic radiation therapy 25 Gy/5# to the pelvic lymph nodes. Details of Phoenix-defined biochemical failure and location of recurrence (local, regional, or distant) were extracted. Five-year biochemical failure-free survival (BFFS), metastasis-free survival, and overall survival were estimated by Kaplan-Meier method. Impact of potential prognostic factors (tumor stage, grade group [GG], prostate radiation therapy dose, and Androgen Deprivation Therapy (ADT) duration) was analyzed using Cox proportional hazards model. A total of 171 patients were eligible for analysis. Two-thirds of the patients had GG 4-5 cancer. Prostate was irradiated to 40 Gy/5# in 51.5% of the cohort, whereas the rest received 35 to 36.25 Gy/5#. Median ADT duration was 15 months (IQR, 9-24). Over a median follow-up of 51 months, biochemical failure was recorded for 19 (11.1%) patients. Restaging with Prostate Specific Membrane Antigen (PSMA)-Positron Emission Tomography Computed Tomography (PETCT) showed recurrence within the pelvic nodes in 3 patients, all with co-occurring distant metastases. Overall pelvic control was 98.2%, with 5-year BFFS and overall survival being 86.1% and 89.3%, respectively. None of the prognostic factors showed a statistically significant impact on BFFS, except GG (adjusted HR 3.6 [95% CI, 0.9-13.0], P = .06). For high-risk prostate cancer treated with SBRT, prophylactic pelvic nodal irradiation with 25 Gy/5# achieved near universal regional control.

CYP2C19 Genotype-Guided Antiplatelet Therapy and Clinical Outcomes in Patients Undergoing a Neurointerventional Procedure.

In neurovascular settings, including treatment and prevention of ischemic stroke and prevention of thromboembolic complications after percutaneous neurointerventional procedures, dual antiplatelet therapy with a P2Y12 inhibitor and aspirin is the standard of care. Clopidogrel remains the most commonly prescribed P2Y12 inhibitor for neurovascular indications. However, patients carrying CYP2C19 no-function alleles have diminished capacity for inhibition of platelet reactivity due to reduced formation of clopidogrel's active metabolite. In patients with cardiovascular disease undergoing a percutaneous coronary intervention, CYP2C19 no-function allele carriers treated with clopidogrel experience a higher risk of major adverse cardiovascular outcomes, and multiple large prospective outcomes studies have shown an improvement in clinical outcomes when antiplatelet therapy selection was guided by CYP2C19 genotype. Similarly, accumulating evidence has associated CYP2C19 no-function alleles with poor clinical outcomes in clopidogrel-treated patients in neurovascular settings. However, the utility of implementing a genotype-guided antiplatelet therapy selection strategy in the setting of neurovascular disease and the clinical outcomes evidence in neurointerventional procedures remains unclear. In this review, we will (1) summarize existing evidence and guideline recommendations related to CYP2C19 genotype-guided antiplatelet therapy in the setting of neurovascular disease, (2) evaluate and synthesize the existing evidence on the relationship of clinical outcomes to CYP2C19 genotype and clopidogrel treatment in patients undergoing a percutaneous neurointerventional procedure, and (3) identify knowledge gaps and discuss future research directions.

Predicting Neck Dysfunction After Open-Door Cervical Laminoplasty - A Prospective Cohort Patient-Reported Outcome Measurement Study.

To analyze the predictive factors for neck pain and cervical spine function after laminoplasty for degenerative cervical myelopathy (DCM) using K-means for longitudinal data (KML). In this prospective cohort study, we collected clinical and radiographic data from patients with DCM who underwent cervical laminoplasty. A novel index of surgical outcome, "neck function," which comprises neck pain and cervical spine function according to the Japanese Orthopedic Association Cervical Myelopathy Evaluation Questionnaire, was proposed. We treated surgical outcomes as longitudinal rather than cross-sectional data and used KML for analysis. Patients were categorized as having good or poor outcomes based on the KML graph of neck pain and cervical spine function. From 2016 to 2020, 104 patients underwent laminoplasty for DCM; however, 35 patients were excluded because of loss to follow-up or incomplete data. The authors found that central canal stenosis (odds ratio [OR], 17.93; 95% confidence interval [CI], 1.26-254.73; p=0.03) and preoperative neck pain (OR per 1 point increase=1.49; 95% CI, 1.12-1.99; p=0.006) were 2 negative predictive factors and that a positive K-line during flexion was a positive predictive factor (OR, 0.11; 95% CI, 0.01-0.87; p=0.036) for neck function after laminoplasty. Central canal stenosis, preoperative neck pain and a K-line during flexion were found to be predictive of postoperative neck pain and cervical spine function after laminoplasty. To achieve better surgical outcomes for neck function, the authors suggest the utilization of these determinants as a guiding framework for the selection of surgical approaches for DCM.

A Commentary on "Predicting Neck Dysfunction After Open-Door Cervical Laminoplasty - A Prospective Cohort Patient-Reported Outcome Measurement Study".

A Commentary on "Predicting Neck Dysfunction After Open-Door Cervical Laminoplasty - A Prospective Cohort Patient-Reported Outcome Measurement Study".

Current Clinical Applications of PSMA-PET for Prostate Cancer Diagnosis, Staging, and Treatment.

Over the past decade, prostate-specific membrane antigen positron emission tomography (PSMA-PET) has revolutionized prostate cancer (PCa) imaging, offering greater sensitivity and specificity compared to conventional imaging modalities such as CT, MRI, and bone scintigraphy. PSMA-PET is particularly valuable in staging newly diagnosed patients with intermediate- and high-risk disease, detecting biochemical recurrence, and evaluating metastatic cases. By utilizing radiotracers that accumulate specifically in PSMA-expressing cells, even small metastases can be detected, offering a detailed assessment of cancer extent and enabling more targeted diagnostic evaluations. Among the most utilized radiotracers, [68Ga]- and [18F]-labeled PSMA tracers enable precise imaging even with low disease burden. This diagnostic precision also supports advanced therapeutic approaches, including metastasis-directed therapy for oligometastatic cases and systemic treatment options, such as radioligand therapy, which presents new treatment perspectives for metastatic, castration-resistant PCa. This review examines the evolution of PSMA-PET in the diagnostics and therapy of PCa while comparing the current recommendations from leading clinical guidelines. The integration of PSMA-PET into clinical practice has redefined the management of PCa, improving diagnostic accuracy and enabling personalized treatment strategies, while lacking prospective long-term outcome data. As PSMA-PET continues to expand in clinical application, this review highlights its significant advancements while critically addressing limitations to ensure balanced and evidence-based implementation in prostate cancer care.

Context changes retrieval of prospective outcomes during decision deliberation.

Foreseeing the future outcomes is the art of decision-making. Substantial evidence shows that, during choice deliberation, the brain can retrieve prospective decision outcomes. However, decisions are seldom made in a vacuum. Context carries information that can radically affect the outcomes of a choice. Nevertheless, most investigations of retrieval processes examined decisions in isolation, disregarding the context in which they occur. Here, we studied how context shapes prospective outcome retrieval during deliberation. We designed a decision-making task where participants were presented with object-context pairs and made decisions which led to a certain outcome. We show during deliberation, likely outcomes were retrieved in transient patterns of neural activity, as early as 3 s before participants decided. The strength of prospective outcome retrieval explains participants' behavioral efficiency, but only when context affects the decision outcome. Our results suggest context imparts strong constraints on retrieval processes and how neural representations are shaped during decision-making.

Prospective Outcomes After Serial Platelet-Rich Plasma (PRP) Injection in Vocal Fold Scar and Sulcus.

Vocal fold scar and sulcus pose significant treatment challenges with no current optimal treatment. Platelet-rich plasma (PRP), an autologous concentration of growth factors, holds promise for regenerating the superficial lamina propria. This study aims to evaluate the potential benefits of serial PRP injections on mucosal wave restoration and vocal function. In a prospective clinical trial across two institutions, patients with vocal fold scar underwent four serial PRP injections, one month apart. Blinded independent laryngologists and expert listeners used pretreatment and one-month post-fourth injection videostroboscopy and CAPE-V assessments to evaluate mucosal wave and voice quality changes, respectively. Additionally, patient reported outcome measures (PROMs) were evaluated. In the study, 15 patients received 55 PRP injections without adverse effects. Eight patients (53.3%) had mild, three patients (20%) had moderate, and four patients (26.7%) had severe scar. There was an average reduction of 8.7 points in post-treatment VHI-10 scores (p = 0.007). The raters observed an improvement in post-treatment voice in 73.4% of cases, and CAPE-V scores showed a reduction of 18.8 points on average (p = 0.036). The videostroboscopic VALI ratings showed an improvement in mucosal wave rating from 2.0 to 4.0. On average, the raters perceived the post-PRP exams to be better in 56.7% of cases. PRP has been validated as a safe autologous option for treatment of vocal fold scar. While results for mucosal wave and voice quality varied, there was a consistent improvement in PROMs. 3: Prospective cohort study, with blinded analysis Laryngoscope, 134:5021-5027, 2024.

Patient/anesthesiologist intersubjective experiences and intravenous supplementation during elective cesarean delivery: A prospective patient-reported outcome study

IntroductionThis prospective, observational study investigated the impact of patient/anesthesiologist interactions and socioeconomic factors on administering intravenous analgesics and anxiolytics during elective Cesarean delivery under spinal anesthesia. The study explored the role of emotional experiences and psychosocial characteristics on intraoperative administration of intravenous adjuncts. MethodsThe study included 502 patient/anesthesiologist dyads from two hospitals in Israel. Patients and anesthesiologists completed questionnaires assessing pain, anxiety, medication requests, and subjective experiences. Logistic regression models were used to analyze associations between variables and medication administration. ResultsOut of 502 patients, 110 (21.9 %) received intravenous supplementation. Only 40.6 % of patients who requested analgesics received them, while anxiolytics were administered four times more often than analgesics. Patients with higher salaries and those speaking the same language as the anesthesiologist were less likely to receive supplementation. Anesthesiologists feeling more attached to or close to patients were more likely to administer medication, while those motivated to protect patients were less likely. ConclusionThe study revealed a substantial gap between patient requests for analgesics and their administration, as well as an overreliance on anxiolysis compared to analgesia. Unconscious attitudes related to patient factors and subjective physician perceptions played a role in medication decisions. The findings emphasize the need for better pain assessment and management training, and awareness of implicit biases in healthcare settings. Future research should investigate optimal communication strategies and address unconscious attitudes to improve patient-centered care.

Ablation Depth-Dependent Survival Analysis of Phototherapeutic Keratectomy for Recurrent Corneal Erosion Syndrome.

Phototherapeutic keratectomy (PTK) is a treatment for recurrent corneal erosion syndrome (RCES). The aim of this study was to investigate whether deeper ablations yielded greater success rates. Retrospective case notes review with prospective patient-reported outcome measures for all patients who had undergone PTK for RCES at a single tertiary referral unit. Patients received treatment with the Schwind Amaris® 750s excimer laser. The primary outcome measure was recurrence-free survival of patients with ablation depth ≥ 15µm compared to < 15µm. Seventy eyes of 63 patients were included for analysis, of whom 39 (56%) had preceding trauma and 20 (29%) had epithelial basement membrane dystrophy (EBMD), with the remaining 11 (15%) of unknown aetiology. Twenty eyes (29%) received an ablation ≥ 15µm (mean ablation depth 16.85 ± 3.4µm) and 50 (71%) received < 15µm (mean ablation depth 9.26 ± 1.5µm). Overall, 65 eyes (93%) reported a subjective improvement in symptoms, with 46 (66%) remaining completely symptom free at the last follow-up [mean follow-up 24 (range, 9-48)months]. Eighty-five per cent of eyes in the ≥ 15µm group remained symptom free compared to 58% of those with < 15µm (p = 0.036). PTK is an effective treatment for RCES, with deeper ablations yielding longer symptom-free survival.

Abstract 4137309: Superior Ventricular Longitudinal Strain Is Linked To Metabolic Adaptations, Protective Ventricular Remodeling Among Older Women And Clinical Outcomes.

Background: Superior left ventricular (LV) systolic function among older women over men has been linked to differences in aging-related ventricular remodeling. Global longitudinal strain (LVGLS) is particularly susceptible to early aging perturbations and may precede systolic failure. Combining cardiovascular magnetic resonance (CMR) with metabolomics, we investigated LVGLS in parallel with markers of myocardial biosynthesis and metabolism pathways to explore the mechanisms and sex dimorphisms of cardiac aging. Methods: Community adults without cardiovascular disease (CVD) underwent serum metabolomics profiling and simultaneous CMR. Prospective clinical outcomes were tracked from 2014 to 2021. Multiple logistic regression adjusted for significant baseline variables. Results: Among 202 participants (46% women, 70.2±8.8 years), participants with better LVGLS were characterized by smaller LV chambers (LVESVi 30.0±14.2 vs 22.0±5.6ml/m 2 , adj. p &lt;0.001; LVEDVi 70.9±19.9 vs 64.0±10.2ml/m 2 , p=0.001 adj. p=0.054) and mass (LVMi 51.5±14.5 vs 43.9±8.8g/m 2 , adj. p=0.008) accompanied by lower levels of several long-chain acylcarnitines species (C12:2-OH/C10:2-DC, C12:1-OH, C12-OH/C10-DC, C14, C16:3-OH/C14:3-DC) independent of sex, diastolic blood pressure, smoking history, and body habitus. Compared to men of similar age, women had superior LVGLS (-21.9±2.6 vs -20.1±2.8%, adj. p=0.024) in tandem with smaller ventricles and less hypertrophy despite similar adjusted LVEF. Higher anaplerotic (methionine, arginine) and proteogenic (phenylalanine, tyrosine) amino acids (AA), together with lower acylcarnitines, distinguished women with better over poorer LVGLS while no AA differences were observed among men. During follow-up, poorer baseline LVGLS was associated with incident composite mortality and hospitalizations (OR=1.12 95%CI 1.01-1.24, p=0.026 adj. p=0.049). Conclusion: Preserved ventricular systolic function among older women was linked to superior LVGLS and favorable remodeling than men. Better LVGLS was accompanied by biomarkers of better mitochondrial oxidation, anaplerosis, and proteogenesis, suggesting enhanced myocardial fuel energetics and biosynthesis with better strain. LVGLS represents a promising quantifiable marker of early systolic aging among older adults without CVD linked to prospective clinical outcomes. Biological insights into the aging-adaptive mechanisms of strain conservation may reveal targets in preventing aging susceptibilities to myocardial dysfunction.

Limited Delamination Modifications to the Extended Deep Plane Rhytidectomy: An Anatomical Basis for Improved Outcomes.

Background: This study introduces variations of a limited delamination approach to the deep plane face- and necklift. Objectives: To report surgeons' perceptions of limited delamination deep plane rhytidectomy, define the anatomical basis to support these modifications, and report complication rates. Methods: This retrospective multi-institutional chart review study of patients undergoing a modified classical deep plane face- and necklift. Surgeons' perception of outcomes and self-reported complications were collected. Results: In total, 3964 patients having undergone face- and necklift with six surgeons being included. Most patients were female (87.9%) with an age range of 31-83 years (mean 58 years). Most were primary procedures (2672/3964; 67.4%) with a median follow-up of 425 days (range 21-5470). Preliminary surgeon experience demonstrated increased ease of flap management, improved biomechanics, smaller perceived rates of skin discoloration, and telangiectasia of the skin and lower revisions rate (n = 11; 0.8%). Complication rates were low for hematoma (n = 24; 1.9%) and seroma requiring needle aspiration (n = 26; 2%) and minor infection (n = 18; 1.4%). Conclusions: A multicenter surgeon experience with the limited delamination extended deep plane rhytidectomy is based on anatomical evidence and demonstrates low complication rates and surgeon-perceived improved long-term outcomes. Prospective comparative outcomes of these evolving techniques are warranted.

The Relationship Between Perceived Discrimination and Reported Nutrient Intake Among Pregnant Individuals of Minoritized Racial and Ethnic Groups

BackgroundImplications of lifelong, perceived discrimination on nutrient intake during the preconception period are unclear. ObjectiveThe objective was to identify associations between perceived discrimination and consumption of specific nutrients associated with risk of adverse pregnancy outcomes. DesignThis is a secondary data analysis of the prospective Nulliparous Pregnancy Outcomes Study: Monitoring Mothers-to-Be cohort. Participants completed a Block food frequency questionnaire assessing diet during the 3 months before pregnancy and a Krieger Experiences of Discrimination Scale assessing personal encounters of discrimination. Participants and settingParticipants were recruited from 8 clinical centers across the United States between 2010 and 2013. Each participant completed the food frequency and Krieger questionnaires and self-identified as belonging to a minoritized racial or ethnic group for this analysis (n = 2457). Main outcome measuresMain outcomes include reported total energy and macronutrient intake, percent of energy from macronutrients, saturated and unsaturated fatty acids, added sugar, sodium, dietary fiber, and Healthy Eating Index-2010 Seafood and Plant Proteins component score. Statistical analyses performedParticipants were grouped as reporting fewer (< 3) or more (≥ 3) circumstances of discrimination on the Krieger scale. Multivariable regression models examined associations between discrimination group and nutrient intake. Variables with nonnormal distributions were log transformed. Associations were adjusted for total energy intake. Primary outcomes underwent false discovery rate correction. ResultsThose reporting 3 or more circumstances of discrimination had higher reported energy intake (P = .002) and higher reported intake of total fat, saturated fat, unsaturated fats, protein, added sugar, and sodium after false discovery rate correction (all P values < .05) compared with those reporting fewer circumstances. After adjustment for total energy intake, reporting 3 or more circumstances was associated with greater reported intake of saturated fat and n-3 polyunsaturated fatty acids, and lower reported intake of dietary fiber (all P values < .05). ConclusionsReporting 3 or more circumstances of discrimination was associated with higher reported total energy intake. After adjustment for total energy, reporting 3 or more circumstances of perceived discrimination was associated with less nutritious intake for some (higher saturated fat and lower dietary fiber) but not all (higher eicosapentaenoic and docosahexaenoic acids) nutrients.

Long-Term Neurologic Outcomes in Pediatric Arterial Ischemic Stroke: The Impact of Age and Lesion Location.

The impact of age-at-stroke on outcome following pediatric arterial ischemic stroke remains controversial. We studied the interaction of age-at-stroke and infarct location and extent with long-term neurological outcomes. We conducted a longitudinal prospective outcome study of children with acute pediatric arterial ischemic stroke diagnosed from 1996 to 2016 at the Hospital for Sick Children, Toronto, Canada. Pediatric Stroke Outcome Measure scores were dichotomized as normal or abnormal (ie, mild, moderate, or severe). Outcomes were analyzed by age-at-stroke (newborn: birth to 28 days; early childhood: 29 days to 5 years; middle/late childhood: >5-18 years), and infarct location, based on each of the following: model 1: circulation (anterior/posterior); model 2: cortical versus subcortical involvement; and model 3: specific arterial territory, including infarct extent (small [<50% arterial territory] or large [≥50%]). Univariable and multivariable logistic regression models were fitted. Among 285 children, the outcome at median 6.1 years was 43.5% abnormal. Controlling for infarct location, increasing age-at-stroke was associated with increasing abnormal outcome. Model 1 demonstrated that, compared with neonates, abnormal outcomes were increased in early childhood (adjusted odds ratio [aOR], 2.91 [95% CI, 1.24-7.05]) and more so in middle/late childhood (aOR, 4.46 [95% CI, 1.71-12.13]). Outcomes were worse for combined locations, including anterior+posterior (model 1: aOR, 15.4 [95% CI, 4.49-64.63]) and cortical+subcortical (model 2: aOR, 10.7 [95% CI, 3.88-32.74]). Abnormal outcomes were also increased for anterior circulation (model 1: aOR, 14.91 [95% CI, 5.29-54.21]) and subcortical locations (model 2: aOR, 4.36 [95% CI, 1.37-14.95]). Among individual arterial territories, outcomes were best for superior division middle cerebral artery (100% normal) and worst for lateral lenticulostriate artery infarcts (47.4% abnormal; model 3: aOR, 14.2 [95% CI, 3.5-67.6]). Among survivors of pediatric stroke, abnormal long-term neurological outcome is increased with increasing age-at-stroke, supporting enhanced plasticity after focal injury to the newborn brain compared with older pediatric ages.

Pear Deck Utilization to Improve Learners' Motivation and Emotional Engagement

Along with the rapid development of technology, many educational platforms nowadays are used to support teaching and learning processes. Among these platforms is Pear Deck. It is an interactive platform that offers benefits to effectively increase students’ motivation and emotional engagement. This study aims to identify students’ motivation and emotional engagement in English lessons by utilizing Pear Deck. This case study revealed that the students feel emotions before the sessions start, all linked to their past experiences (retrospective outcomes). Fear, happiness, and excitement are the emotions the students feel at the beginning of the sessions, and they turn out to be enjoyable and happy at the end of the session. The emotions that the students feel during the sessions can potentially lead to the prospective outcomes of the students, which are success in their future endeavors. Additionally, the choice of suitable materials that will be delivered to the students must be considered by the teachers or educators to encourage and motivate students and uplift students’ emotional engagement with the lesson.

The role of candidate pharmacogenetic variants in determining valproic acid efficacy, toxicity and concentrations in patients with epilepsy.

Antiseizure medications (ASM) exhibit considerable interindividual variability in terms of efficacy and adverse events. Genetic variation is thought to contribute to these differences in clinical outcomes. Specifically, the response to valproic acid (VPA), a widely used ASM, is influenced by multiple pharmacogenetic factors. However, and in contrast to other ASMs such as phenytoin and carbamazepine, there is a paucity of data on the association between VPA and various gene variants. The aim of this study was hence to evaluate the influence of candidate pharmacogenetic variants on VPA efficacy, toxicity and serum concentrations in a homogeneous cohort of patients newly diagnosed with genetic generalized epilepsies (GGE). In this prospective cohort study, demographic, clinical and treatment outcomes of GGE patients were retrieved from their medical records. Whole exome sequencing was performed in collaboration with Epi25. Gene variants associated with VPA efficacy, metabolism and toxicities were retrieved from PharmGKB. An analysis was then conducted to explore potential associations between these gene variants and VPA clinical outcomes. Of the 166 patients included, 60 (36.1%) experienced treatment failure while 106 (63.9%) achieved treatment success. After adjusting for VPA maintenance dose, carriers of the rs3892097 (CYP2D6) variant were 2.5 times more likely to experience treatment failure compared to wildtype (p = 0.026). The rs1057910 variant (CYP2C9*3) was associated with increased serum VPA concentrations (p = 0.034). Moreover, the rs1137101 variant (LEPR gene, a metabolism regulator) was significantly associated with a higher risk of weight gain (regression coefficient of 3.430 [0.674; 6.186], p = 0.015) and a higher frequency of hair loss (OR = 3.394 [1.157; 9.956], p = 0.026), while the rs4480 variant (SOD2 gene, encoding for a mitochondrial scavenging enzyme) was correlated with a lower frequency of hair loss (OR = 0.276 [0.089; 0.858], p = 0.026). These findings highlight the role of genetic factors in VPA treatment and underscore the potential for developing therapeutic strategies to enhance patient outcomes and minimize adverse effects.

Exome sequencing in over 63,000 patients in TIMI trials uncovers pathogenic cardiomyopathy variant carriers with high risk for heart failure and cardiovascular death

Abstract Background Rare genetic variants predisposing to cardiomyopathy (CMP) confer increased risk for adverse events. The prevalence of CMP variants in contemporary cardiovascular (CV) trials and their association with prevalent heart failure (HF) and incident HF hospitalizations (HHF) is not established. Purpose We aimed to identify carriers of rare pathogenic/likely pathogenic (PLP) variants for dilated cardiomyopathy (DCM), hypertrophic cardiomyopathy (HCM), and arrhythmogenic right ventricular cardiomyopathy (ARVC) in well-phenotyped clinical trial cohorts and to evaluate their prognostic significance. Methods Rare variants were identified from high-quality exome sequencing data from 5 large clinical trials (ENGAGE AF-TIMI 48, SAVOR-TIMI 53, PEGASUS-TIMI 54, DECLARE-TIMI 58, FOURIER (TIMI 59)). Putatively pathogenic variants for cardiomyopathy were identified using phenotype- and gene-specific curation of protein-truncating variants and high-confidence variant classifications from ClinVar. We conducted logistic regression for prevalent disease and Cox proportional hazard models for incident HHF, both adjusted by age, sex, trial, and first 10 principal components and using those without CMP variants as the reference. Sensitivity analysis by history of HF at baseline was performed for prospective outcomes. Results In 63,700 participants, we identified 866 CMP variant carriers of which 518 identified as DCM carriers (age 65±9 yrs, male 66%), 194 HCM carriers (65.5±9 yrs, male 69%), and 125 ARVC carriers (66±9 yrs, male 77%). Out of the 518 DCM variant carriers, 402 had a PLP variant in TTN. DCM variant carriers had higher odds of history of HF (Odds ratio [OR] 1.94, 1.57-2.39, p&amp;lt;0.0001) whereas this was not observed for HCM variant carriers (OR 1.18, 0.85-1.65, p=0.33) or ARVC variant carriers (OR 1.23, 0.80-1.90, p=0.35). Over a mean follow-up of 2.5 years, the rate of HHF was significantly higher for DCM variant carriers (Hazard ratio [HR] 1.58, 1.14-2.20, p=0.006), HCM variant carriers (HR 2.78, 1.87-4.13, p&amp;lt;0.001), and ARVC variant carriers (HR 1.89, 1.02-3.53, p=0.04). These associations were, if anything, stronger in patients without HF at baseline (HR 2.06, 1.30-3.25) than in patients with HF at baseline (HR 1.48, 1.12-1.95). DCM variant carriers also had a higher rate of CV death (HR 1.50, 1.05-2.12, p=0.02), which was not observed for HCM (HR 1.10, 0.57-2.11, p=0.78) or ARVC (HR 0.35, 0.09-1.41, p=0.14) variant carriers. Conclusion In 5 contemporary CV trials, CMP variant carriers have an increased rate of HHF, while DCM variant carriers also have a higher rate of CV death. These findings motivate better identification of these high-risk individuals and the incorporation of genetic testing in CV trials.

Associations between symptom-based long COVID clusters and long-term quality of life, work and daily activities among individuals testing positive for SARS-CoV-2 at a national retail pharmacy

BackgroundEvidence on long COVID symptom clustering patterns among patients with COVID-19 is limited. We summarized long COVID symptoms in clusters defined by number of symptoms co-occurring together, and we assessed Health-Related Quality of Life (HQRoL), Work Productivity and Activity Impairment (WPAI) outcomes across these clusters over time. We assessed associations between the clusters and BNT162b2 vaccination status.MethodsA prospective longitudinal patient-reported outcomes (PRO) study recruited laboratory-confirmed symptomatic COVID-19 patients seeking testing from a national retail pharmacy. Long COVID-19 symptoms were self-reported by participants at 4-week, 3-month and 6-month surveys. Patient classes identified via latent class analysis (LCA) with long COVID-19 symptoms were simplified into clusters based on number of symptoms. HRQoL and WPAI outcomes were collected using EQ-ED-5L and WPAI: GH questionnaires. Mixed models for repeated measures analyses were conducted to examine associations between exposure groups and outcomes.ResultsThe study included 328 participants that were segmented into three groups of long COVID-19 symptoms based on LCA and then simplified by the number of symptoms (Cluster 1 low, <2; Cluster 2 moderate, 2–6; and Cluster 3 high, >6 symptoms). The number of long COVID-19 symptoms was negatively associated with HRQoL and WPAI, whereby participants with high symptom burden (>6 symptoms) had the lowest HRQoL and WPAI scores assessed by absenteeism, presenteeism, work productivity loss, activity impairment, and hours worked metrics. Compared with those unvaccinated and not up-to-date with COVID-19 vaccination, subjects boosted with BNT162b2 consistently reported less symptom burden during the follow-up, regardless of their symptom-based cluster.ConclusionThree distinct patient clusters based on frequency of long COVID symptoms experienced different HRQoL and WPAI outcomes over 6 months. The cluster with more concomitant symptoms experienced greater burden than the others. Participants up-to-date with BNT162b2 reported lower symptom burden across all clusters and timeframes.Clinical trial registrationClinicaltrials.gov NCT05160636.