A fast algorithm for the two-dimensional Helmholtz transmission problem with large multiple scattering configurationsa).

We develop an efficient three-stage algorithm for simulating multiple acoustic scattering by two-dimensional configurations comprising large numbers of penetrable scatterers. Our approach is based on a boundary integral equation reformulation of the Helmholtz transmission partial differential equation, and a reduction of the boundary integral system for computationally efficient evaluation of wave interactions between scatterers. A key ingredient of our algorithm is to represent the interactions between scatterers using expansions of cylindrical wavefunctions. For large numbers of scatterers, this approach facilitates the application of the fast multipole method, leading to linear complexity of the algorithm with respect to the number of scatterers. Numerical results demonstrate the efficiency of our algorithm for configurations containing a few hundred to hundreds of thousands of individual scatterers.

The Influence of Personality Traits on Driving Behaviors in Preclinical Alzheimer Disease.

INTRODUCTION: Alzheimer disease (AD) has a long preclinical phase in which AD pathology is accumulating without detectable clinical symptoms. It is critical to identify participants in this preclinical phase as early as possible since treatment plans may be more effective in this stage. Monitoring for changes in driving behavior, as measured with GPS sensors, has been explored as a low-burden, easy-to-administer method for detecting AD risk. However, driving is a complex, multifaceted process that is likely influenced by other factors, including personality traits, that may change in preclinical AD. METHODS: We examine the moderating influence of neuroticism and conscientiousness on longitudinal changes in driving behavior in a sample of 203 clinically normal older adults who are at varying risk of developing AD. RESULTS: Neuroticism moderated rates of change in the frequency of speeding as well as the number of trips taken at night. Conscientiousness moderated rates of change in typical driving space. CONCLUSIONS: Personality traits change in early AD and also influence driving behaviors. Studies that seek to utilize naturalistic driving behavior to establish AD risk need to accommodate interpersonal differences, of which personality traits are one of many possible factors. Future studies should explicitly establish how much benefit is provided by including personality traits in predictive models of AD progression.

Disparities in Surgical Intervention and Health-Related Quality of Life Among Racial/Ethnic Groups With Degenerative Lumbar Spondylolisthesis.

BACKGROUND AND OBJECTIVES: Racial and socioeconomic disparities in spine surgery for degenerative lumbar spondylolisthesis persist in the United States, potentially contributing to unequal health-related quality of life (HRQoL) outcomes. This is important as lumbar spondylolisthesis is one of the most common causes of surgical low back pain, and low back pain is the largest disabler of individuals worldwide. Our objective was to assess the relationship between race, socioeconomic factors, treatment utilization, and outcomes in patients with lumbar spondylolisthesis. METHODS: This cohort study analyzed prospectively collected data from 9941 patients diagnosed with lumbar spondylolisthesis between 2015 and 2020 at 5 academic hospitals. Exposures were race, socioeconomic status, health coverage, and HRQoL measures. Main outcomes and measures included treatment utilization rates between racial groups and the association between race and treatment outcomes using logistic regression, adjusting for patient characteristics, socioeconomic status, health coverage, and HRQoL measures. RESULTS: Of the 9941 patients included (mean [SD] age, 67.37 [12.40] years; 63% female; 1101 [11.1%] Black, Indigenous, and People of Color [BIPOC]), BIPOC patients were significantly less likely to use surgery than White patients (odds ratio [OR] = 0.68; 95% CI, 0.62-0.75). Furthermore, BIPOC race was associated with significantly lower odds of reaching the minimum clinically important difference for physical function (OR = 0.74; 95% CI, 0.60; 0.91) and pain interference (OR = 0.77; 95% CI, 0.62-0.97). Medicaid beneficiaries were significantly less likely (OR = 0.65; 95% CI, 0.46-0.92) to reach a clinically important improvement in HRQoL when accounting for race. CONCLUSION: This study found that BIPOC patients were less likely to use spine surgery for degenerative lumbar spondylolisthesis despite reporting higher pain interference, suggesting an association between race and surgical utilization. These disparities may contribute to unequal HRQoL outcomes for patients with lumbar spondylolisthesis and warrant further investigation to address and reduce treatment disparities.

Traumatic Brain Injury, Seizures, and Cognitive Impairment Among Older Adults.

Importance: Traumatic brain injury (TBI), seizures, and dementia increase with age. There is a gap in understanding the associations of TBI, seizures, and medications such as antiseizure and antipsychotics with the progression of cognitive impairment across racial and ethnic groups. Objective: To investigate the association of TBI and seizures with the risk of cognitive impairment among cognitively normal older adults and the role of medications in moderating the association. Design, Setting, and Participants: This multicenter cohort study was a secondary analysis of the Uniform Data Set collected between June 1, 2005, and June 30, 2020, from the National Alzheimer's Coordination Center. Statistical analysis was performed from February 1 to April 3, 2024. Data were collected from participants from 36 Alzheimer's Disease Research Centers in the US who were 65 years or older at baseline, cognitively normal at baseline (Clinical Dementia Rating of 0 and no impairment based on a presumptive etiologic diagnosis of AD), and had complete information on race and ethnicity, age, sex, educational level, and apolipoprotein E genotype. Exposure: Health history of TBI, seizures, or both conditions. Main Outcomes and Measures: Progression to cognitive impairment measured by a Clinical Dementia Rating greater than 0. Results: Among the cohort of 7180 older adults (median age, 74 years [range, 65-102 years]; 4729 women [65.9%]), 1036 were African American or Black (14.4%), 21 were American Indian or Alaska Native (0.3%), 143 were Asian (2.0%), 332 were Hispanic (4.6%), and 5648 were non-Hispanic White (78.7%); the median educational level was 16.0 years (range, 1.0-29.0 years). After adjustment for selection basis using propensity score weighting, seizure was associated with a 40% higher risk of cognitive impairment (hazard ratio [HR], 1.40; 95% CI, 1.19-1.65), TBI with a 25% higher risk of cognitive impairment (HR, 1.25; 95% CI, 1.17-1.34), and both seizure and TBI were associated with a 57% higher risk (HR, 1.57; 95% CI, 1.23-2.01). The interaction models indicated that Hispanic participants with TBI and seizures had a higher risk of cognitive impairment compared with other racial and ethnic groups. The use of antiseizure medications (HR, 1.23; 95% CI, 0.99-1.53), antidepressants (HR, 1.32; 95% CI, 1.17-1.50), and antipsychotics (HR, 2.15; 95% CI, 1.18-3.89) was associated with a higher risk of cognitive impairment, while anxiolytic, sedative, or hypnotic use (HR, 0.88; 95% CI, 0.83-0.94) was associated with a lower risk. Conclusions and Relevance: This study highlights the importance of addressing TBI and seizures as risk factors for cognitive impairment among older adults. Addressing the broader social determinants of health and bridging the health divide across various racial and ethnic groups are essential for the comprehensive management and prevention of dementia.

Adult intussusception: a systematic review of current literature.

BACKGROUND: Intussusception in adults is a rare condition characterized by a low incidence, which complicates the establishment of standardized management protocols unlike those readily available for pediatric cases. This study presents a case series from our institution alongside a systematic review of existing literature. The objective is to delineate effective management strategies for adult intussusception. METHODS: A systematic search of databases was conducted covering the period from January 2000 to May 2024. The study focused on adult patients diagnosed with intussusception either pre-operatively or intraoperatively and managed with either surgical intervention or conservative methods. The analysis also included retrospective review of patient records from our institution, specifically targeting individuals over 18 years of age, to determine the predominant types of intussusception and identify any pathological lead points associated with these cases. RESULTS: In our study, a total of 1,902 patients were included from 59 selected articles, with a mean age of 52.13 ± 14.95 years. Among them, 1,920 intussusceptions were diagnosed, with 98.3% of cases identified preoperatively. Computed tomography (CT) scan was the primary diagnostic modality used in 88.5% of cases. Abdominal pain was the predominant presenting symptom, observed in 86.23% of cases. Only 29 out of 1,920 cases underwent attempted reduction, while the majority required surgical resection due to the high incidence of malignancy in adult cases. The most common type of intussusception identified was colocolic (16.82%), followed by enteric (13.28%), ileocolic (4.89%), and ileocaecal (0.78%) types. A pathological lead point was observed in 302 out of 673 patients (44.84%), with a notably higher frequency of malignancy associated with colocolic intussusception. CONCLUSION: Surgical management remains the cornerstone in treating adult intussusception, particularly in cases involving the colocolic type, where there is a significant risk of underlying malignancy. Attempts at reduction are generally avoided due to the potential risk of tumor dissemination, which could adversely impact patient outcomes. Contrast-enhanced computed tomography (CECT) of the abdomen is pivotal for accurately diagnosing intussusceptions and guiding appropriate management strategies. It is imperative to adhere strictly to oncological principles during surgical interventions to ensure optimal patient care and outcomes.

Population Pharmacokinetic Modeling of Adavosertib (AZD1775) in Patients with Solid Tumors.

Adavosertib (AZD1775) is a potent small-molecule inhibitor of Wee1 kinase. This analysis utilized pharmacokinetic data from 8 Phase I/II studies of adavosertib to characterize the population pharmacokinetics of adavosertib in patients (n = 538) with solid tumors and evaluate the impact of covariates on exposure. A nonlinear mixed-effects modeling approach was employed to estimate population and individual parameters from the clinical trial data. The model for time dependency of apparent clearance (CL) was developed in a stepwise manner and the final model validated by visual predictive checks (VPCs). Using an adavosertib dose of 300 mg once daily on a 5 days on/2 days off dosing schedule given 2 weeks out of a 3-week cycle, simulation analyses evaluated the impact of covariates on the following exposure metrics at steady state: maximum concentration during a 21-day cycle, area under the curve (AUC) during a 21-day cycle, AUC during the second week of a treatment cycle, and AUC on day 12 of a treatment cycle. The final model was a linear 2-compartment model with lag time into the dosing compartment and first-order absorption into the central compartment, time-varying CL, and random effects on all model parameters. VPCs and steady-state observations confirmed that the final model satisfied all the requirements for reliable simulation of randomly sampled Phase I and II populations with different covariate characteristics. Simulation-based analyses revealed that body weight, renal impairment status, and race were key factors determining the variability of drug-exposure metrics.

Laparoscopic versus open pancreaticoduodenectomy: Long-term outcome from a tertiary care centre.

INTRODUCTION: Laparoscopic Whipple's pancreaticoduodenectomy (WPD) is one of the most advanced minimally invasive procedures. In recent years, with advancements in minimally invasive surgery, laparoscopic WPD has been increasingly adopted as a safe and feasible technique. This study aims to compare the short-term and long-term outcomes of laparoscopic WPD to open WPD in resectable ampullary, periampullary and head of pancreas malignancies. PATIENTS AND METHODS: A retrospective analysis of a prospectively maintained database of patients who underwent WPD from January 2015 to January 2021 at the department of surgical gastroenterology in a tertiary care medical college hospital was conducted. Patient demographics and pre-operative details, intraoperative parameters (operating time and blood loss), post-operative length of hospital stay, median intensive care unit (ICU) stay, time to resume oral diet, post-operative complications, interventional procedures, mortality, 3-year survival, 3 year recurrence-free survival and overall survival were analysed. RESULTS: Forty-two patients underwent WPD during our study period; 14 patients underwent laparoscopic WPD and 28 patients underwent open WPD. None required conversion. The majority of the patients had periampullary carcinoma in both the groups. Laparoscopic WPD showed a trend towards shorter ICU stays, hospital stays and surgical site infections (SSIs) compared to open WPD. The median operating time was significantly longer in the laparoscopic WPD group (380 min) compared to the open group (285 min). However, median blood loss was significantly lower in the laparoscopic group (250 mL vs. 300 mL). The pancreas-specific post-operative complications like delayed gastric emptying, post-operative pancreatic fistula or post-operative pancreatic haemorrhage did not differ significantly between the groups. All patients had R0 resection and the mean lymph node yield was comparable between the two groups (14.92 vs. 13.42). The reoperation rate or mortality rate did not show any statistical significance between the two groups. The overall survival was 46 months in the open group and 48 months in the laparoscopic group. Three-year survival was 74.1% in the open WPD group and 69.2% in the laparoscopic group. Three-year recurrence-free survival was 55.5% in the open group and 69.23% in the laparoscopic group. CONCLUSION: Laparoscopic WPD appears to be safe and feasible, with similar short-term and long-term survival outcomes. With a trend favouring laparoscopic WPD in terms of blood loss, hospital and ICU stay and post-operative SSIs, it should be offered to selected patients when the expertise is available.

Corrigendum to "Multidimensional poverty is associated with dementia among adults in Afghanistan" [eClinicalMedicine 58(2023) 101906].

[This corrects the article DOI: 10.1016/j.eclinm.2023.101906.].

Cognition Mediates the Association Between Cerebrospinal Fluid Biomarkers of Amyloid and P-Tau and Neuropsychiatric Symptoms.

Background: Neuropsychiatric symptoms (NPS) can be an early manifestation of Alzheimer's disease (AD). However, the associations among NPS, cognition, and AD biomarkers across the disease spectrum are unclear. Objective: We analyzed cross-sectional mediation pathways between cerebrospinal fluid (CSF) biomarkers of AD (Aß1-42, p-tau181), cognitive function, and NPS. Methods: Primary models included 781 participants from the National Alzheimer's Coordinating Center (NACC) data set who had CSF analyzed for AD biomarkers using Lumipulse. NPS were assessed with the Neuropsychiatric Inventory Questionnaire (NPI-Q). We assessed cognition with the harmonized MMSE/MoCA, as well as neuropsychological tests sensitive to AD pathology: story recall, naming, animal fluency, and Trails B. The Clinical Dementia Rating (CDR®) scale assessed dementia severity. Mediation models were estimated with Kemeny metric covariance in a structural equation model framework, controlling for age, education, sex, and APOEɛ4. Results: The sample was older adults (M = 73.85, SD = 6.68; 49.9% male, 390; 27.9% dementia, 218) who were predominantly white (n = 688, 88.1%). Higher p-tau181/Aß1-42 ratio predicted higher NPI-Q, which was partially mediated by the MMSE/MoCA and, in a second model, story recall. No other pathway was statistically significant. Both the MMSE/MoCA and NPI-Q independently mediated the association between p-tau181/Aß1-42 ratio and CDR global impairment. With dementia excluded, p-tau181/Aß1-42 ratio was no longer associated with the NPI-Q. Conclusions: NPS may be secondary to cognitive impairment and AD pathology through direct and indirect pathways. NPS independently predict dementia severity in AD. However, AD pathology likely plays less of a role in NPS in samples without dementia.

Impact of cognitive impairment on driving behaviour and route choices of older drivers: a real-world driving study.

Maintaining driving independence is important for older adults. However, cognitive decline, a common issue in older populations, can impair older adults' driving abilities and overall safety on the roads. This study explores how cognitive impairment influences driving patterns and driving choices among older adults. We analyzed real-world driving patterns of 246 older adults using GPS dataloggers. Our sample included 230 cognitively normal older adults (CN; Clinical Dementia Rating R [CDR] = 0) and 16 older adults with incident cognitive impairment (ICI; CDR = 0.5). The CN group had an average age of 68.2 years, with 46% females and an average of 16.5 years of education, while the ICI group's average age was 69.2 years, with 36% females and an average of 16.0 years of education. We employed spatial clustering and hashing algorithms to evaluate driving behaviours. Significant differences emerged: The ICI group used fewer distinct routes to their most common destination. These differences can be leveraged to develop driving as a digital biomarker for the early detection and continuous monitoring of cognitive impairment.

Rapid Tumor DNA Analysis of Cerebrospinal Fluid Accelerates Treatment of Central Nervous System Lymphoma.

Delays and risks associated with neurosurgical biopsies preclude timely diagnosis and treatment of central nervous system (CNS) lymphoma and other CNS neoplasms. We prospectively integrated targeted rapid genotyping of cerebrospinal fluid (CSF) into the evaluation of 70 patients with CNS lesions of unknown etiology. Participants underwent genotyping of CSF-derived DNA using a qPCR-based approach for parallel detection of single-nucleotide variants in the MYD88, TERT promoter, IDH1, IDH2, BRAF and H3F3A genes within 80 minutes of sample acquisition. Canonical mutations were detected in 42% of patients with neoplasms, including cases of primary and secondary CNS lymphoma, glioblastoma, IDH-mutant brainstem glioma and H3K27M-mutant diffuse midline glioma. Genotyping results eliminated the need for surgical biopsies in 7/33 (21.2%) cases of newly diagnosed neoplasms, resulting in significantly accelerated initiation of disease-directed treatment (median 3 vs 12 days; p = 0.027). This assay was then implemented in a Clinical Laboratory Improvement Amendments (CLIA) environment, with 2-day median turnaround for diagnosis of central nervous system lymphoma from 66 patients across 4 clinical sites. Our study prospectively demonstrates that targeted rapid CSF genotyping influences oncologic management for suspected CNS tumors.

Predicting Driving Cessation Among Cognitively Normal Older Drivers: The Role of Alzheimer Disease Biomarkers and Clinical Assessments.

BACKGROUND AND OBJECTIVES: With the aging US population and increasing incidence of Alzheimer disease (AD), understanding factors contributing to driving cessation among older adults is crucial for clinicians. Driving is integral for maintaining independence and functional mobility, but the risk factors for driving cessation, particularly in the context of normal aging and preclinical AD, are not well understood. We studied a well-characterized community cohort to examine factors associated with driving cessation. METHODS: This prospective, longitudinal observation study enrolled participants from the Knight Alzheimer Disease Research Center and The DRIVES Project. Participants were enrolled if they were aged 65 years or older, drove weekly, and were cognitively normal (Clinical Dementia Rating [CDR] = 0) at baseline. Participants underwent annual clinical, neurologic, and neuropsychological assessments, including ß-amyloid PET imaging and CSF (Aß42, total tau [t-Tau], and phosphorylated tau [p-Tau]) collection every 2-3 years. The primary outcome was time from baseline visit to driving cessation, accounting for death as a competing risk. The cumulative incidence function of driving cessation was estimated for each biomarker. The Fine and Gray subdistribution hazard model was used to examine the association between time to driving cessation and biomarkers adjusting for clinical and demographic covariates. RESULTS: Among the 283 participants included in this study, there was a mean follow-up of 5.62 years. Driving cessation (8%) was associated with older age, female sex, progression to symptomatic AD (CDR ≥0.5), and poorer performance on a preclinical Alzheimer cognitive composite (PACC) score. Aß PET imaging did not independently predict driving cessation, whereas CSF biomarkers, specifically t-Tau/Aß42 (hazard ratio [HR] 2.82, 95% CI 1.23-6.44, p = 0.014) and p-Tau/Aß42 (HR 2.91, 95% CI 1.28-6.59, p = 0.012) ratios, were independent predictors in the simple model adjusting for age, education, and sex. However, in the full model, progression to cognitive impairment based on the CDR and PACC score across each model was associated with a higher risk of driving cessation, whereas AD biomarkers were not statistically significant. DISCUSSION: Female sex, CDR progression, and neuropsychological measures of cognitive functioning obtained in the clinic were strongly associated with future driving cessation. The results emphasize the need for early planning and conversations about driving retirement in the context of cognitive decline and the immense value of clinical measures in determining functional outcomes.

Exploring Holistic Cancer Care and Survivorship in India Through the Kerala Model of Palliative Care: Role of Community Nurse and Outpatient Meetings.

Support groups and meetings are self-help gatherings that provide a unique sense of community, unconditional acceptance, and information on cancer and its treatment. This cross-sectional study examined 12 outpatient meetings within the Kerala model of palliative care, a community-based service provided to patients irrespective of disease, stage, or prognosis starting from the time of diagnosis. The study focused on the pivotal role of community nurses in facilitating these meetings, with participants including cancer patients and survivors. Using in-depth interviews (n = 52) and participant observations, this research used a qualitative approach and explored the dynamics and outcomes of outpatient meetings. Findings highlight the indispensable contributions of these community nurses serving as linchpins in providing support, guiding discussions, and offering crucial education. Outpatient meetings effectively addressed psychosocial concerns, combatted stigmas associated with cancer, and promoted informed decision making in cancer care. The study emphasizes the need for recognizing the role played by community nurses in improving psychosocial support and diminishing stigma, and ultimately the quality of life of patients and survivors through the palliative cancer care within the Kerala model. We also underscore the need for policy initiatives, resource allocation, and training programs tailored to support these frontline health care providers effectively.

A systematic review/meta-analysis of prevalence and incidence rates illustrates systemic underrepresentation of individuals racialized as Asian and/or Asian-American in ADRD research.

We investigate Alzheimer's disease and related dementia (ADRD) prevalence, incidence rate, and risk factors in individuals racialized as Asian and/or Asian-American and assess sample representation. Prevalence, incidence rate, risk factors, and heterogeneity of samples were assessed. Random-effects meta-analysis was conducted, generating pooled estimates. Of 920 records across 14 databases, 45 studies were included. Individuals racialized as Asian and/or Asian-American were mainly from Eastern and Southern Asia, had higher education, and constituted a smaller sample relative to non-Hispanic white cohorts. The average prevalence was 10.9%, ranging from 0.4% to 46%. The average incidence rate was 20.03 (12.01-33.8) per 1000 person-years with a range of 75.19-13.59 (12.89-14.33). Risk factors included physiological, genetic, psychological, behavioral, and social factors. This review underscores the systemic underrepresentation of individuals racialized as Asian and/or Asian-American in ADRD research and the need for inclusive approaches accounting for culture, language, and immigration status. HIGHLIGHTS: There is considerable heterogeneity in the prevalence of ADRD among studies of Asian-Americans. There is limited data on group-specific risk factors for ADRD among Asian-Americans. The average prevalence of (ADRD) among Asian-Americans was found to be 7.4%, with a wide range from 0.5% to 46%.

Recruiting a prospective community cohort to study Alzheimer's disease and structural and social determinants of health among adults racialized as Black: The ARCHES cohort.

INTRODUCTION: This ongoing, prospective study examines the effectiveness of methods used to successfully recruit and retain 238 Black older adults in a longitudinal, observational Alzheimer's disease (AD) study. METHODS: Recruitment strategies included traditional media, established research registries, speaking engagements, community events, and snowball sampling. Participants were asked to complete an annual office testing session, blood-based biomarker collection, optional one-time magnetic resonance imaging (MRI) scan, and community workshop. RESULTS: Within the first 22 months of active recruitment, 629 individuals expressed interest in participating, and 238 enrolled in the ongoing study. Of the recruitment methods used, snowball sampling, community events, and speaking engagements were the most effective. DISCUSSION: The systemic underrepresentation of Black participants in AD research impacts the ability to generalize research findings and determine the effectiveness and safety of disease-modifying treatments. Research to slow, stop, or prevent AD remains a top priority but requires diversity in sample representation. Highlights: Provide flexible appointments in the evening or weekends, offering transportation assistance, and allowing participants to complete study visits at alternative locations, such as senior centers or community centers.Continuously monitor and analyze recruitment data to identify trends, challenges, and opportunities for improvement.Implement targeted strategies to recruit participants who are underrepresented based on sex, gender, or education to increase representation.Diversify the research team to include members who reflect the racial and cultural backgrounds of the target population, to enhance trust and rapport with prospective participants.

Oncological Surgical Wound Care: A Comparison of Theruptor NXT Non-adherent Dressing and the Current Standard of Care.

Background Oncological surgeries pose an elevated risk of surgical site infections (SSIs) due to their complexity and various associated treatments, impacting patient outcomes and healthcare costs. This has prompted a focus on advanced wound dressings that provide microbial protection, exudate absorption, and improved product performance, enhancing patient satisfaction. Our study aimed to compare the efficacy and safety of Theruptor NXT with the current standard of care (SOC) practice involving cotton/povidone/micropore dressings in the postoperative wound management of oncological surgeries. Methodology A total of 102 patients who underwent oncological surgeries in the Department of Surgical Oncology, Vydehi Institute of Medical Sciences and Research Centre, Bengaluru, India between May and September 2023 were randomized to Theruptor NXT and SOC dressing groups (51 patients each). The incidence of SSIs, wound pain score, cosmetic appearance of the wound, and adverse events were assessed in the two groups at various intervals, i.e., post-surgery day 2 ± 1, day of discharge, and post-surgery day 30 ± 7. Further, the subject satisfaction and product usage were evaluated on post-surgery day 2 ± 1. Results The baseline characteristics were found to be comparable in both groups, i.e., Theruptor NXT and SOC groups. Further, the SSI rates, scar outcomes, and physiological parameters were also similar between the Theruptor NXT and SOC groups, indicating a similar safety profile of both dressings (p > 0.05). However, the product usage assessment revealed statistically significant differences, favoring Theruptor NXT in terms of superior ease of application, stretchability, exudate management, breathability, and non-adherence properties (p < 0.05). Conclusions Our findings suggest that Theruptor NXT wound dressing is a promising, effective, and user-friendly alternative to SOC wound dressing in diverse clinical settings.

Radical surgical resection with molecular margins is associated with improved survival in IDH wildtype GBM.

BACKGROUND: Survival is variable in patients with glioblastoma IDH wild-type (GBM), even after comparable surgical resection of radiographically-detectable disease, highlighting the limitations of radiographic assessment of infiltrative tumor anatomy. The majority of post-surgical progressive events are failures within 2cm of the resection margin, motivating supramaximal resection strategies to improve local control. However, which patients benefit from such radical resections remains unknown. METHODS: We developed a predictive model to identify which IDH wild-type GBM are amenable to radiographic gross total resection (GTR). We then investigated whether GBM survival heterogeneity following GTR is correlated with microscopic tumor burden a by analyzing tumor cell content at the surgical margin with a rapid qPCR-based method for detection of TERT promoter mutation. RESULTS: Our predictive model for achievable GTR, developed on retrospective radiographic and molecular data of GBM patients undergoing resection, had an AUC of 0.83, sensitivity of 62%, and specificity of 90%. Prospective analysis of this model in 44 patients found 89% of patients were correctly predicted to achieve a RV<4.9cc. Of the 44 prospective patients undergoing rapid qPCR TERT promoter mutation analysis at the surgical margin, 7 had undetectable TERT mutation, of which 5 also had a gross total resection (RV<1cc). In these 5 patients at 30 months follow up, 75% showed no progression, compared to 0% in the group with TERT mutations detected at the surgical margin (p=0.02). CONCLUSIONS: These findings identify a subset of patients with GBM that may derive local control benefit from radical resection to undetectable molecular margins.

Is Multidimensional Poverty Associated to Dementia Risk? The Case of Older Adults in Pakistan.

Background and Objectives: Multidimensional poverty is associated with dementia. We aimed at establishing this association in Pakistan. Research Design and Methods: A cross-sectional study was conducted in Punjab and Sindh, Pakistan, between March 30, 2002, and August 22, 2022, among adults aged 50 and older. Multidimensional poverty measures were composed of 6 dimensions and 15 indicators. Poverty was compared between adults with and without dementia using the Rowland Universal Dementia Assessment Scale, adjusting for sex, age, marital status, and household size. Associations between dementia and poverty were investigated using a multivariate logistic regression model. Results: We found that 594 (72.7%), 171 (20.9%), and 52 (6.4%) had no, mild, and moderate-to-severe dementia, respectively. More women than men had dementia (11.4% vs 2.9%). Approximately 40.4% of adults with dementia were found to be deprived in 4 or more dimensions compared to 8.9% without dementia, and the difference in multidimensional poverty between them was 348.6%. Education, health, living conditions, and psychological well-being were the main contributors to poverty. Poverty in 4 or more dimensions was strongly associated with dementia (odds ratio [OR], 5.02; 95% confidence interval [CI], 2.07-12.16) after adjusting for sex, marital status, age, and household size, with greater odds for older women (OR, 2.02; 95% CI, 1.41-2.90). Discussion and Implications: Our findings suggest that early improvement in social determinants of health through targeted structural policies may prevent dementia later in life. Improving access to free, quality education, health care including mental health care and basic living standards, and employment should reduce the collective risk of dementia.

In-silico simulations to study the effects of ankle-joint misalignments in Ankle-Foot-Orthoses during level walking.

Exoskeletons and orthotic devices are commonly used in physical rehabilitation. However, these devices, fitting intimately with the human body, often lead to skin-related issues amongst users. Misalignments between orthotic and anatomical joints cause relative sliding motion between the limb and orthosis and also cause pressure points on the limb, which may contribute to these skin problems. This research quantifies the effects of sagittal plane ankle-joint misalignments for an ankle-foot orthosis (AFO) user during walking. A 2D mathematical model that simulates the effects of sagittal plane ankle-joint misalignments in terms of relative motion between the limb and the orthosis was developed using MATLAB software. The orthotic ankle-joint was systematically misaligned against the anatomical ankle-joint to generate various misalignment conditions. Published gait data of 5 healthy subjects was used to generate walking kinematics which was then superimposed with an articulated AFO. The simulations showed that Anterior-Posterior misalignments resulted in greater pistoning motion than Proximal-Distal misalignments. Combined misalignments (Posterior-Distal, Anterior-Proximal, Posterior-Proximal, and Anterior-Distal) resulted in higher overall relative motions between the limb and AFO. The model also predicted pressure points on the shank and foot caused by misalignments. This study demonstrates that misaligned ankle-joints in AFOs lead to relative sliding motion and pressure points during walking.

Emerging Strategies and Effective Prevention Measures for Investigating the Association Between Stroke and Sudden Cardiac Fatality.

Stroke-related cardiac death is a significant concern for patients with stroke and their healthcare providers. It is a complex and multifaceted condition that requires careful management of both modifiable and non-modifiable risk factors. This review provides an overview of the pathophysiology, risk factors, and prevention strategies for stroke-related cardiac death. The review highlights the importance of identifying and managing modifiable risk factors such as hypertension, diabetes, and lifestyle factors, as well as non-modifiable risk factors such as age and genetics. Additionally, the review explores emerging strategies for prevention, including the use of wearable devices and genetic testing to identify patients at risk, stem cell therapy and gene therapy for cardiac dysfunction, and precision medicine for personalized treatment plans. Despite some limitations to this review, it provides valuable insights into the current understanding of stroke-related cardiac death and identifies important areas for future research. Ultimately, the implementation of evidence-based prevention strategies and personalized treatment plans has the potential to improve outcomes for patients with stroke and reduce the burden of stroke-related cardiac death in the population.