Variability In Outcomes Research Articles

Construction and analysis of a lysosome-dependent cell death score-based prediction model for non-small cell lung cancer

BackgroundNon-small cell lung cancer (NSCLC) is the most common type of tumor globally and the leading cause of cancer-related deaths. Although treatment strategies such as immune checkpoint inhibitors and chemotherapy have advanced, the heterogeneity among NSCLC patients results in significant variability in treatment outcomes. Studies have shown that certain patients respond poorly to immune checkpoint inhibitors, indicating that treatment response is closely related to multiple factors. Therefore, it is necessary to develop predictive models to stratify patients based on gene expression and clinical characteristics, aiming for precision therapy.ObjectiveThis study aims to construct a stratified prognostic model for NSCLC patients based on lysosome-dependent cell death (LDCD) scoring by integrating single-cell RNA sequencing (scRNA-seq) and bulk RNA sequencing data. By analyzing the immune-related characteristics of high-risk and low-risk groups, we further explored the impact of cell death patterns on lung cancer and identified potential therapeutic targets.MethodsThis study obtained single-cell RNA sequencing data and gene expression data of NSCLC patients and normal lung tissues from the GEO and TCGA databases. We used R packages such as Seurat and CellChat for data preprocessing and analysis, and performed dimensionality reduction and visualization through Principal Component Analysis (PCA) and UMAP algorithms. LASSO regression analysis was used to construct the predictive model, followed by cross-validation and ROC curve analysis. The model’s effectiveness was validated through survival analysis and immune microenvironment analysis.ResultsThe study showed a significant increase in the proportion of monocytes in NSCLC tissues, suggesting their important role in cancer progression. Cell communication analysis indicated that macrophages, smooth muscle cells, and myeloid cells exhibit strong intercellular communication during cancer progression. Using the constructed prognostic model based on 12 LDCD-related genes, we found significant differences in overall survival and immune microenvironment between the high-risk and low-risk groups.

Ketamine Analgo-sedation for Mechanically Ventilated Critically Ill Adults: A Rapid Practice Guideline from the Saudi Critical Care Society and the Scandinavian Society of Anesthesiology and Intensive Care Medicine.

This Rapid Practice Guideline (RPG) aimed to provide evidence‑based recommendations for ketamine analgo-sedation (monotherapy and adjunct) versus non-ketamine sedatives or usual care in adult intensive care unit (ICU) patients on invasive mechanical ventilation (iMV) and to identify knowledge gaps for future research. The RPG panel comprised 23 multinational multidisciplinary panelists, including a patient representative. An up-to-date systematic review and meta-analysis constituted the evidence base. The Grading Recommendations, Assessment, Development, and Evaluation approach, and the evidence-to-decision framework were used to assess the certainty of evidence and to move from evidence to decision/recommendation. The panel provided input on the balance of the desirable and undesirable effects, certainty of evidence, patients' values and preferences, costs, resources, equity, feasibility, acceptability, and research priorities. Data from 17 randomized clinical trials (n=898) and 9 observational studies (n=1934) were included. There was considerable uncertainty about the desirable and undesirable effects of ketamine monotherapy for analgo-sedation. The evidence was very low certainty and downgraded for risk of bias, indirectness, and inconsistency. Uncertainty or variability in values and preferences were identified. Costs, resources, equity, and acceptability were considered varied. Adjunctive ketamine therapy had no effect on mortality (within 28 days) (relative risk [RR] 0.99; 95% confidence interval [CI] 0.76 to 1.27; low certainty), and may slightly reduce iMV duration (days) (mean difference [MD] -0.05 days; 95% CI -0.07 to -0.03; low certainty), and uncertain effect on the cumulative dose of opioids (mcg/kg/h morphine equivalent) (MD -11.6; 95% CI -20.4 to -2.7; very low certainty). Uncertain desirable effects (cumulative dose of sedatives and vasopressors) and undesirable effects (adverse event rate, delirium, arrhythmia, hepatotoxicity, hypersalivation, use of physical restraints) were also identified. A possibility of important uncertainty or variability in patient-important outcomes led to a balanced effect that favored neither the intervention nor the comparison. Cost, resources, and equity were considered varied. The RPG panel provided two conditional recommendations and suggested (1) against using ketamine as monotherapy analgo-sedation in critically ill adults on iMV when other analgo-sedatives are available; and (2) using ketamine as an adjunct to non-ketamine usual care sedatives (e.g., opioids, propofol, dexmedetomidine) or continuing with non-ketamine usual care sedatives alone. Large-scale trials should provide additional evidence.

Prognostic factors for tube feeding in type I SMA patients treated with disease-modifying therapies: a cohort study

The aim of this study was to assess the need for tube feeding in a cohort of treated infants with type I SMA and to identify predictive factors. All patients were classified at baseline, when treatment started, and at follow-up according to their functional level and the need for tube feeding. Fisher’s exact test was used to examine the associations between the outcome at the last follow-up and SMA type, SMN2 copy number, and baseline nutritional status. ANOVA was performed to compare CHOP INTEND scores and age at treatment initiation with outcomes. The cohort includes 75 type I SMA infants treated between 0.1 and 5 years of age. At the last follow-up, 34 had no need for tube feeding, 9 had tube feeding but were also able to be fed by mouth, and 32 had tube feeding and were unable to be fed by mouth. Thirty of the 41 infants with tube feeding at follow-up already had feeding difficulties when treatment was started. The need for tube feeding at follow-up was associated with the level of feeding involvement at baseline and with CHOP INTEND scores [p < 0.001] but not with SMN2 copy number, SMA type 1 subtypes or age at treatment. The results of this study suggest that the need for tube feeding is not frequent in treated infants with type I SMA and, when occurring, can be predicted by the level of feeding involvement and low CHOP INTEND scores at baseline.What is Known:• The advent of disease-modifying therapies is increasingly changing the approach to swallowing and nutritional management in type I SMA.• Clinical trials and real-world data using all three disease-modifying therapies report a rather wide variability of feeding outcome and need for tube feeding that is often related to different cohorts that makes comparison between studies very difficult.What is New:• The real-world findings of this study, including all the children treated since treatments became available, confirmed that the need for tube feeding is not an invariable finding.• The level of feeding involvement at baseline appears to be a reliable prognostic indicator of bulbar outcome.• The results highlight the need for interventional studies with structured Speech and Language Therapist protocols that will help to better understand the extent to which bulbar function can be maintained or regained even in children requiring tube feeding.

Ketamine analgo-sedation for mechanically ventilated critically ill adults: A rapid practice guideline from the Saudi Critical Care Society and the Scandinavian Society of Anesthesiology and Intensive Care Medicine.

This Rapid Practice Guideline (RPG) aimed to provide evidence-based recommendations for ketamine analgo-sedation (monotherapy and adjunct) versus non-ketamine sedatives or usual care in adult intensive care unit (ICU) patients on invasive mechanical ventilation (iMV) and to identify knowledge gaps for future research. The RPG panel comprised 23 multinational multidisciplinary panelists, including a patient representative. An up-to-date systematic review and meta-analysis constituted the evidence base. The Grading Recommendations, Assessment, Development, and Evaluation approach, and the evidence-to-decision framework were used to assess the certainty of evidence and to move from evidence to decision/recommendation. The panel provided input on the balance of the desirable and undesirable effects, certainty of evidence, patients' values and preferences, costs, resources, equity, feasibility, acceptability, and research priorities. Data from 17 randomized clinical trials (n = 898) and nine observational studies (n = 1934) were included. There was considerable uncertainty about the desirable and undesirable effects of ketamine monotherapy for analgo-sedation. The evidence was very low certainty and downgraded for risk of bias, indirectness, and inconsistency. Uncertainty or variability in values and preferences were identified. Costs, resources, equity, and acceptability were considered varied. Adjunctive ketamine therapy had no effect on mortality (within 28 days) (relative risk [RR] 0.99; 95% confidence interval [CI] 0.76 to 1.27; low certainty), and may slightly reduce iMV duration (days) (mean difference [MD] -0.05 days; 95% CI -0.07 to -0.03; low certainty), and uncertain effect on the cumulative dose of opioids (mcg/kg/h morphine equivalent) (MD -11.6; 95% CI -20.4 to -2.7; very low certainty). Uncertain desirable effects (cumulative dose of sedatives and vasopressors) and undesirable effects (adverse event rate, delirium, arrhythmia, hepatotoxicity, hypersalivation, use of physical restraints) were also identified. A possibility of important uncertainty or variability in patient-important outcomes led to a balanced effect that favored neither the intervention nor the comparison. Cost, resources, and equity were considered varied. The RPG panel provided two conditional recommendations and suggested (1) against using ketamine as monotherapy analgo-sedation in critically ill adults on iMV when other analgo-sedatives are available; and (2) using ketamine as an adjunct to non-ketamine usual care sedatives (e.g., opioids, propofol, dexmedetomidine) or continuing with non-ketamine usual care sedatives alone. Large-scale trials should provide additional evidence.

Development and clinical implementation of an LC-HRMS method for ivacaftor, lumacaftor, tezacaftor and elexacaftor in human plasma and breast milk.

The four cystic fibrosis (CF) transmembrane conductance regulator (CFTR) modulators, ivacaftor, lumacaftor, tezacaftor, and elexacaftor, have revolutionised the treatment of CF by direct action on the protein target behind the disease's development. The aim was to develop and validate a quantification method for these CFTR modulators in plasma and breast milk to better understand inter-patient variability in pharmacokinetics and treatment outcome, including the risk of adverse drug reactions. The ability to monitor CFTR modulators in breast milk enables the estimation of the exposure of breastfed infant, with a potential concern for CFTR modulator-induced liver injury. The analysis was performed on a Thermo Vanquish Flex Binary UHPLC system coupled to a high-resolution mass spectrometer (HRMS), Thermo Q Exactive. The analytes were detected using positive electrospray ionisation in full scan mode. After sample preparation by protein precipitation, the supernatant was injected onto the LC system and the analytes were separated using a Zorbax SB-C18 Rapid Res HPLC column (3.5µm, 4.6 × 75mm). This is the first published method for CFTR modulators in breast milk. The validated quantification range for ivacaftor is 0.0050-10µg/mL with a coefficient of variation < 6% and a mean accuracy of 97-106%; for lumacaftor, tezacaftor, and elexacaftor, the validated quantification range is 0.050-100µg/mL with a coefficient of variation < 8% and a mean accuracy 93-106%. A simple and sensitive quantification method for CFTR modulators has been developed and used for routine analysis of human plasma and breast milk samples since 2022.

Obstetric Outcomes of Nighttime Versus Daytime Delivery with Labor Epidural: An Observational Retrospective Study.

Background: Variability in obstetric outcomes in terms of the number and type of deliveries related to the day-night cycle has been described in previous studies. This 11-year retrospective analysis explores the effects of nighttime versus daytime delivery with labor epidural on obstetric outcomes. Methods: Data on deliveries performed between 1 October 2008 and 1 October 2019 were collected and differentiated into daytime, occurring from 8:00 a.m. to 7:59 p.m., and nighttime deliveries, occurring from 8:00 p.m. to 7:59 a.m. of the following day. The data collected included the patient history and maternal and neonatal outcomes. Results: A total of 29831 patients were included in the analysis. A positive and statistically significant correlation between the number of cesarean sections (Odds Ratio 1.35; 95% confidence interval = 1.26-1.44; p < 0.001) and the number of vaginal operative deliveries (Odds Ratio 1.21; 95% confidence interval = 1.01-1.44; p < 0.05) in patients who did not receive an epidural at nighttime was reported. Regarding the labor epidurals, a significantly greater incidence of accidental dural punctures with needles (0,4%; p < 0.05) in the nighttime versus daytime was reported. Conclusions: The absence of labor epidurals was associated with a significant increase in the number of cesarean sections and vaginal operative deliveries occurring at nighttime, without significant differences in labor duration. The incidence of anesthesiologic complications was greater in deliveries performed at nighttime.

Evaluating the Effectiveness of Physical Therapy in Patients Post-Arthroscopic Partial Meniscectomy for Traumatic Meniscal Tears.

ABSTRACT Background: Meniscal tears are among the most common knee injuries, often resulting from sports-related activities or trauma. The menisci are vital for maintaining knee health and function, and a tear can lead to pain, swelling, and impaired mobility. Arthroscopic partial meniscectomy (APM) is a common surgical intervention aimed at alleviating symptoms by removing the damaged portion of the meniscus. Despite the benefits, postoperative challenges such as pain, reduced knee function, and prolonged recovery times are common, making rehabilitation a critical component of recovery. Objective: This study aims to evaluate the effectiveness of physical therapy in patients who have undergone APM for traumatic meniscal tears. The objective is to determine the impact of structured rehabilitation on pain levels, knee function, and overall quality of life compared to standard postoperative care without intensive physical therapy. Methods: A retrospective cross-sectional study was conducted with a sample size of under 50 participants from various private and public orthopedic clinics in Karachi. The study involved patients who had undergone APM and were assessed using the Visual Analog Scale (VAS) and Lysholm scoring scale. The exclusion criteria included patients with meniscal tears less than 10mm, non-traumatic meniscal tears, other knee surgeries, and pre-existing conditions that might interfere with physical therapy outcomes. Results: The average age of participants was approximately 36 years, with a mean body weight of 69 kg. Sports-related trauma was the leading cause of meniscal tears (41.9%), followed by accidents (34.9%) and age-related degeneration (23.3%). Physical therapy led to significant improvements in knee function, with 76.7% of participants reporting good functionality and 93% noting reduced pain and swelling. However, challenges such as difficulty with stair climbing (51.2%) and muscle soreness (27.9%) were also reported. Conclusion: Physical therapy plays a crucial role in the postoperative rehabilitation of patients following APM. The findings indicate that structured rehabilitation significantly improves functional outcomes, reduces pain, and enhances the quality of life. However, variability in patient outcomes suggests the need for further research to optimize rehabilitation protocols, considering individual factors such as the extent of the injury, pre-existing conditions, and patient adherence.

Cohort profile: study design and baseline characteristics of an observational longitudinal weight loss cohort and biorepository of patients undergoing sleeve gastrectomy in the USA

PurposeWe developed a comprehensive sleeve gastrectomy (SG) weight loss study cohort and biorepository to uncover mechanisms, biomarkers and predictive factors of weight loss, weight maintenance and amelioration of obesity-related comorbidities....

Teacher–community nexus and rural schools as community knowledge hubs: a program implementation in Western Nigeria

PurposeThis study explores a program to transform rural schools in Kwara State, Western Nigeria, into community knowledge hubs by leveraging local networks and community-based workshops. It aims to demonstrate how local resources are utilized to enhance educational outcomes and community engagement in rural settings.Design/methodology/approachEmploying a qualitative research methodology, the study analyzes the implementation of this program through interviews with 13 teachers and in-field participation, examining the perspective of local teachers.FindingsThe findings reveal that this program has significantly enriched community engagement with practical skills both for students and the adult population, fostering collaboration between community and schools. Local teachers, leveraging their rural networks and knowledge, have been central to mobilizing networks and integrating practical education that addresses community-specific issues.Research limitations/implicationsThe critical role of participatory educational strategies is highlighted, designing interventions for the distinct needs of communities. It notes the variability in potential outcomes due to the self-designed networks by local teachers, suggesting a need for exploration into how these networks’ configurations are developed in different places.Practical implicationsThis study advocates for the creation of comprehensive programs including all local stakeholders in developing a dedicated support community network. It emphasizes non-formal education to offer a variety of learning experiences, which may be more effective in fostering community-wide educational engagement.Originality/valueThis study contributes to the academic literature by highlighting the critical role of local networks in African rural education settings. It provides a novel perspective on how rural schools can serve as hubs for community development and lifelong learning for the whole community, extending beyond traditional educational outcomes only for students.

Evaluating the Protective Role of Vitamin A Supplementation in Periodontal Health: A Comprehensive Systematic Review and Meta-Analysis.

Background: Recent studies suggest a potential role for vitamin A supplementation in improving periodontal health, though evidence remains inconclusive. This systematic review and meta-analysis aimed to evaluate the protective role of vitamin A supplementation on periodontal health, focusing on outcomes such as gingival inflammation, pocket depth reduction, and alveolar bone preservation. Methods: A literature search was conducted in PubMed, Scopus, and Web of Science up until May 2024, adhering to strict inclusion criteria that required studies to involve human participants diagnosed with periodontal diseases and to assess the impact of vitamin A through dietary intake or supplementation. This review excluded studies not explicitly focused on vitamin A and those lacking clear, quantifiable outcomes. The risk of bias was assessed using the Newcastle-Ottawa Scale for observational studies and the Cochrane Collaboration's tool for randomized controlled trials. Meta-analysis was performed to synthesize data and quantify the effectiveness of vitamin A on periodontal health outcomes. Results: A total of six studies were included in the final analysis with a total of 50,722 participants. The meta-analysis revealed a pooled odds ratio (OR) of 0.97 (95% CI: 0.94-1.00) for the association between vitamin A supplementation and periodontal health, indicating a slight protective effect. Notably, two high-quality studies reported ORs of 0.92 (95% CI: 0.85-1.00) and 0.83 (95% CI: 0.69-1.00), respectively, suggesting a potential reduction in periodontal disease risk with sufficient vitamin A levels. However, high heterogeneity (I2 = 86.93%) across studies indicates variability in outcomes, possibly influenced by demographic and lifestyle factors. Conclusions: Vitamin A supplementation may offer a marginal protective effect against periodontal disease, although results vary significantly across different populations and study designs. Further research is needed to clarify these relationships and to explore the mechanisms through which vitamin A influences periodontal health, considering the high degree of observed heterogeneity.

Evaluating the Value of a Geology Degree: An Economic and Societal Analysis

In an era where the economic returns on investment in higher education are increasingly scrutinized, the question arises: Is a geology degree worth it? This paper tends to provide answers to this inquiry through comprehensive economic analysis to evaluate the financial viability and broader benefits of obtaining a geology degree. The analysis begins by examining the economic landscape for geologists, including their earning potential, employment opportunities, and career advancement trajectories. Data from national labor statistics, industry reports, and academic studies are synthesized to provide a nuanced understanding of the financial outcomes associated with a geology degree. Factors such as geographic location, industry specialization, and level of education are considered to capture the variability in economic outcomes among geology graduates. This paper also explores the non-monetary benefits of a geology degree, such as job satisfaction, intellectual fulfilment, and contributions to societal challenges like natural resource management, environmental conservation, and hazard mitigation. These aspects contribute to a holistic evaluation of the degree's value proposition, balancing economic returns with intrinsic rewards. Furthermore, the analysis addresses trends in the geology job market, including the impacts of technological advancements, environmental regulations, and global economic shifts on career opportunities for geologists. Insights into emerging fields within geology, such as geotechnical engineering, hydrogeology, and environmental consulting, are also discussed to illuminate evolving career pathways and specialization opportunities. Through this multidimensional examination, the paper aims to provide valuable insights to prospective students contemplating a geology degree, educators shaping curricula, and policymakers concerned with higher education and workforce development. By integrating economic principles with empirical data and qualitative perspectives, this study offers a robust framework for understanding a geology degree's economic implications and broader societal contributions in contemporary contexts.

Pericardiocentesis, Chest Tube Insertion, and Needle Thoracostomy During Resuscitation of Nontraumatic Adult In-Hospital Cardiac Arrest: A Retrospective Cohort Study.

In-hospital cardiac arrest (IHCA) is a significant public health burden. Rates of return of spontaneous circulation (ROSC) have been improving, but the best way to care for patients after the initial resuscitation remains poorly understood, and improvements in survival to discharge are stagnant. Existing North American cardiac arrest databases lack comprehensive data on the postresuscitation period, and we do not know current post-IHCA practice patterns. To address this gap, we developed the Discover IHCA study, which will thoroughly evaluate current post-IHCA care practices across a diverse cohort. Our study collects granular data on post-IHCA treatment practices, focusing on temperature control and prognostication, with the objective of describing variation in current post-IHCA practices. This is a multicenter, prospectively collected, observational cohort study of patients who have suffered IHCA and have been successfully resuscitated (achieved ROSC). There are 24 enrolling hospital systems (23 in the United States) with 69 individuals enrolling in hospitals (39 in the United States). We developed a standardized data dictionary, and data collection began in October 2023, with a projected 1000 total enrollments. Discover IHCA is endorsed by the Society of Critical Care Medicine. The study collects data on patient characteristics, including prearrest frailty, arrest characteristics, and detailed information on postarrest practices and outcomes. Data collection on post-IHCA practice was structured around current American Heart Association and European Resuscitation Council guidelines. Among other data elements, the study captures postarrest temperature control interventions and postarrest prognostication methods. The majority of participating hospital systems are large, academic, tertiary care centers serving urban populations. The analysis will evaluate variations in practice and their association with mortality and neurologic function. We expect this study, Discover IHCA, to identify variability in practice and outcomes following IHCA and be a vital resource for future investigations into best practices for managing patients after IHCA.

Unveiling the Quest: Crafting an Enzyme-Linked Immunosorbent Assay (ELISA) Technique to Uncover COVID-19 Antibodies.

The COVID-19 pandemic, caused by the novel coronavirus SARS-CoV-2, has had a profound impact on global health. Rapid and accurate diagnostic tools are crucial for effective disease control and management. The enzyme-linked immunosorbent assay (ELISA) has emerged as a reliable and widely used method for detecting COVID-19 antibodies in patients, which develop in response to SARS-CoV-2 infection. While the ELISA technique is effective in identifying the presence of antibodies and thus confirming exposure to the virus, its role in predicting the clinical course and severity of the disease is limited. ELISA primarily confirms prior exposure to the virus or vaccination status, but it does not directly correlate antibody levels with the severity or progression of the disease. The variability in clinical outcomes is influenced by factors such as viral load, patient co-morbidities, genetic predispositions, and the timing of the immune response. ELISA has diverse applications in epidemiology, vaccination assessment, and therapeutic development. It determines antibody prevalence, aids in surveillance, and evaluates vaccine effectiveness and antibody protection duration. ELISA quantitatively measures antibody levels, providing insights into the immune response and treatment efficacy. Challenges include specialized facilities and personnel, cross-reactivity, and false results. Multiplex assays and integration with other diagnostics are future directions. In summary, ELISA is an essential tool in COVID-19 diagnostics, enabling precise assessment of the immune response and contributing to effective strategies. The development of point-of-care devices that integrate ELISA technology could enable rapid and accessible testing in various settings. Additionally, integrating ELISA with other diagnostic platforms could enhance the overall diagnostic capabilities for COVID-19. Despite challenges, ongoing advancements in ELISA technology, and its integration with other diagnostic approaches, hold promise for further improving COVID-19 diagnostics and management strategies.

Influencing factors for surgical treatment in neonatal necrotizing enterocolitis: a systematic review and meta-analysis

BackgroundNecrotizing enterocolitis (NEC) is a complex disease characterized by gastrointestinal inflammation and is one of the most common gastrointestinal emergencies in neonates. Mild to moderate cases of NEC require medical treatment, whereas severe cases necessitate surgical intervention. However, evidence for surgical indications is limited and largely dependent on the surgeon’s experience, leading to variability in outcomes. The primary aim of this study is to identify the risk factors for surgical intervention in neonatal NEC, which will aid in predicting the optimal timing for surgical intervention.MethodsA literature search was conducted in PubMed, Embase, and Web of Science databases for case-control studies exploring risk factors for NEC requiring surgical intervention. The search was completed on June 16, 2024, and data analysis was performed using R Studio 4.3.2.Results18 studies were included, comprising 1,104 cases in the surgery group and 1,686 in the medical treatment group. The meta-analysis indicated that high C-reactive protein (CRP) levels [OR = 1.42, 95% CI (1.01, 1.99)], lower gestational age [OR = 0.52, 95% CI (0.3, 0.91)], sepsis [OR = 2.94, 95% CI (1.87, 4.60)], coagulation disorder [OR = 3.45, 95% CI (1.81, 6.58)], lack of enteral feeding [OR = 3.18, 95% CI (1.37, 7.35)], and hyponatremia [OR = 1.22, 95% CI (1.07, 1.39)] are significant risk factors for surgical treatment in neonatal NEC.ConclusionsHigh CRP levels, coagulation disorders, sepsis, lower gestational age, lack of enteral feeding, and hyponatremia are significant risk factors for surgical intervention in neonatal NEC. These findings have potential clinical significance for predicting surgical risk.

Probabilistic Refinement of Focused Ultrasound Thalamotomy Targeting for Parkinson's Disease Tremor.

There remains high variability in clinical outcomes when the same magnetic resonance image-guided focused ultrasound (MRgFUS) thalamotomy target is used for both essential tremor (ET) and tremor-dominant Parkinson's disease (TDPD). Our goal is to refine the MRgFUS thalamotomy target for TDPD versus ET. We retrospectively performed voxel-wise efficacy and structural connectivity mapping using 3-12-month post-procedure hand tremor scores for a multicenter cohort of 32 TDPD patients and a previously published cohort of 79 ET patients, and 24-hour T1-weighted post-MRgFUS brain images. We validated our findings using Unified Parkinson's Disease Rating Scale part III scores for an independent cohort of nine TDPD patients. The post-MRgFUS clinical improvements were 45.9% ± 35.9%, 55.5% ± 36%, and 46.1% ± 18.6% for ET, multicenter TDPD and validation TDPD cohorts, respectively. The TDPD and ET efficacy maps differed significantly (ppermute < 0.05), with peak TDPD improvement (87%) at x = -13.5; y = -15.0; z = 1.5, ~3.5 mm anterior and 3 mm dorsal to the ET target. Discriminative connectivity projections were to the motor and premotor regions in TDPD, and to the motor and somatosensory regions in ET. The disorder-specific voxel-wise efficacy map could be used to estimate outcome in TDPD patients with high accuracy (R = 0.8; R2 = 0.64; P < 0.0001). The model was validated using the independent cohort of nine TDPD patients (R = 0.73; R2 = 0.53; P = 0.025-voxel analysis). We demonstrated that the most effective MRgFUS thalamotomy target in TDPD is in the ventral intermediate nucleus/ventralis oralis posterior border region. This finding offers new insights into the thalamic regions instrumental in tremor control, with pivotal implications for improving treatment outcomes. © 2024 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Age-Related Blood Pressure Gradients Are Associated With Blood Pressure Control and Global Population Outcomes.

The strong relationship between blood pressure (BP) and age is well known. Limited evidence suggests that a steeper age-BP slope may be associated with an increased risk of adverse outcomes. The May Measurement Month campaign enables an investigation of geographic, socioeconomic, and sex differences in age-related BP gradients and their association with public-health outcomes. Cross-sectional, annual global BP May Measurement Month screening data were analyzed. Average systolic BP and age-related BP slopes across different age groups were calculated to assess regional, socioeconomic, and sex-stratified variations. The association of BP slopes derived from adjusted linear regression models with country-level health metrics was investigated. Age-related systolic BP gradients differed distinctly across global geographic regions, income levels, and between sexes. The steepest age gradients of BP were observed in populations from Africa and Europe. Women had lower BP levels than men at younger ages (20s and 30s) but subsequently experienced more pronounced age-related BP gradients. Geographically divergent age-related BP gradients were significantly associated with major national public health indicators. Globally, steeper age-related BP slopes were associated with poor BP control, increased disability-adjusted life years, and death rates. A steeper population age-BP slope of 1 mm Hg per 10 years was associated with a decrease in life expectancy of 3.3 years in this population (95% CI, -5.1 to -1.4; P=0.0007). Age-related BP gradients vary considerably across global populations and are associated with variability in BP-related risks and adverse outcomes across regions. Effective public health strategies may require region-specific targeting of adverse BP gradients to improve health outcomes.

Cortical and Subjective Measures of Individual Noise Tolerance Predict Hearing Outcomes with Varying Noise Reduction Strength

Noise reduction (NR) algorithms are employed in nearly all commercially available hearing aids to attenuate background noise. However, NR processing also involves undesirable speech distortions, leading to variability in hearing outcomes among individuals with different noise tolerance. Leveraging 30 participants with normal hearing engaged in speech-in-noise tasks, the present study examined whether the cortical measure of neural signal-to-noise ratio (SNR)—the amplitude ratio of auditory evoked responses to target speech onset and noise onset—could predict individual variability in NR outcomes with varying strength, thus serving as a reliable indicator of individual noise tolerance. In addition, we also measured subjective ratings of noise tolerance to see if these measures could capture different perspectives on individual noise tolerance. Results indicated a significant correlation between neural SNR and NR outcomes that intensified with increasing strength of NR processing. While subjective ratings of noise tolerance were not correlated with the neural SNR, noise-tolerance ratings could predict outcomes with stronger NR processing and account for additional variance in the regression model, although the effect was limited. Our findings underscore the importance of accurately assessing an individual’s noise tolerance characteristics in predicting perceptual benefits from various NR processing methods and suggest the advantage of incorporating both cortical and subjective measures in the relevant methodologies.

Determinants of Health Outcomes of Patients Presenting with Massive Traumatic Bleeding in the Emergency Department in Selected Hospitals in Kiambu County, Kenya

Purpose: The study sought to identify the determinants of the health outcomes of patients presenting with massive traumatic bleeding in the emergency department of selected hospitals in Kiambu County, Kenya. Methods: The research employed an analytical cross-sectional study design, utilizing quantitative data. Data was collected using a questionnaire, an observation checklist, and extraction of secondary data from patient records. A census sampling was done. The collected data underwent analysis using IBM SPSS version 26. Simple linear regression and multiple logistic regression analysis was used to analyze the data. Results: Regarding the health outcomes of patients presenting with massive traumatic bleeding, three outcomes were observed: 68.39% of the patients were discharged in fair general condition (FGC), 21.70% were referred and 9.90% were deceased. The experience of the healthcare workers, 11.6% of the variability of the health outcome of the patient is explained by experience of healthcare workers (p-value = 0.0138). Comparing the health outcomes in the two facilities, there was no difference in health outcome (p&lt;0.001). According to the multinomial logistic regression the results indicate that age is a significant predictor of the deceased outcome (B=0.064, p=0.014). Therefore, age is the most significant predictor of the health outcomes of patients presenting with massive traumatic bleeding. Unique Contribution to Theory, Policy and Practice: To reduce poor health outcomes of pediatric and geriatric patients, it is recommended that a specific area in the emergency department should be set aside for the trauma patients in these age categories. Due to adding special areas in the emergency department, more staff and resources will need to be allocated to the emergency department.

Neocortical cholinergic pathology after neonatal brain injury is increased by Alzheimer's disease-related genes in mice

Hypoxic-ischemic encephalopathy (HIE) in neonates causes mortality and neurologic morbidity, including poor cognition with a complex neuropathology. Injury to the cholinergic basal forebrain and its rich innervation of cerebral cortex may also drive cognitive pathology. It is uncertain whether genes associated with adult cognition-related neurodegeneration worsen outcomes after neonatal HIE. We hypothesized that neocortical damage caused by neonatal HI in mice is ushered by persistent cholinergic innervation and interneuron (IN) pathology that correlates with cognitive outcome and is exacerbated by genes linked to Alzheimer's disease. We subjected non-transgenic (nTg) C57Bl6 mice and mice transgenically (Tg) expressing human mutant amyloid precursor protein (APP-Swedish variant) and mutant presenilin (PS1-ΔE9) to the Rice-Vannucci HI model on postnatal day 10 (P10). nTg and Tg mice with sham procedure were controls. Visual discrimination (VD) was tested for cognition. Cortical and hippocampal cholinergic axonal and IN pathology and Aβ plaques, identified by immunohistochemistry for choline acetyltransferase (ChAT) and 6E10 antibody respectively, were counted at P210. Simple ChAT+ axonal swellings were present in all sham and HI groups; Tg mice had more than their nTg counterparts, but HI did not affect the number of axonal swellings in APP/PS1 Tg mice. In contrast, complex ChAT+ neuritic clusters (NC) occurred only in Tg mice; HI increased that burden. The abundance of ChAT+ clusters in specific regions correlated with decreased VD. The frequency of attritional ChAT+ INs in the entorhinal cortex (EC) was increased in Tg shams relative to their nTg counterparts, but HI obviated this difference. Cholinergic IN pathology in EC correlated with NC number. The Aβ deposition in APP/PS1 Tg mice was not exacerbated by HI, nor did it correlate with other metrics. Adult APP/PS1 Tg mice have significant cortical cholinergic axon and EC ChAT+ IN pathologies; some pathology was exacerbated by neonatal HI and correlated with VD. Mechanisms of neonatal HI induced cognitive deficits and cortical neuropathology may be modulated by genetic risk, perhaps accounting for some of the variability in outcomes.

Soluble fms-like tyrosine kinase-1/placental growth factor ratio at 36 weeks’ gestation: association with spontaneous onset of labor and intrapartum fetal compromise in low-risk pregnancies

Previous evidence showed that placental dysfunction triggers spontaneous preterm or term births and intrapartum fetal compromise and often requires urgent delivery, thereby exposing both the fetus and the mother to significant risks. Predicting spontaneous labor onset and intrapartum fetal compromise could improve obstetrical management and outcomes, but this is currently difficult, particularly in low-risk populations. The objective of this study was to examine whether placental dysfunction, as assessed at 36 weeks' gestation by the soluble fms-like tyrosine kinase-1 to placental growth factor ratio, is associated with the interval to spontaneous onset of labor and intrapartum fetal compromise that requires cesarean delivery in a routinely examined population. This was a retrospective analysis of prospectively collected data of women with singleton pregnancies who underwent routine assessment at 35+0 to 36+6 weeks' gestation at the King's College Hospital (London, England). Using a general linear model, the study examined the outcomes related to the soluble fms-like tyrosine kinase-1/placental growth factor ratio, including the time interval from testing to spontaneous onset of labor and the subsequent rate of fetal compromise that required a cesarean delivery. Patients who underwent induction of labor or prelabor cesarean deliveries were excluded from the study. Competing risks regression and Cox regression models were used to estimate the cumulative incidence and the risk of the outcomes of interest. In the screened population of 45,375 patients, 23,831 (52.5%) had spontaneous onset of labor and were included in the analysis. Cases with an soluble fms-like tyrosine kinase-1/placental growth factor ratio >50 delivered about 1 week earlier than those with a ratio of ≤50 (39.2 vs 40.0 weeks' gestation; P<.001). The general linear model showed that a larger soluble fms-like tyrosine kinase-1/placental growth factor ratio was associated with earlier spontaneous onset of labor (P<.001), particularly among multiparous women. The soluble fms-like tyrosine kinase-1/placental growth factor ratio was significantly associated, as expected, with cases of preeclampsia and advanced maternal age. The cumulative incidence of spontaneous onset of labor was significantly higher in cases with an soluble fms-like tyrosine kinase-1/placental growth factor ratio >50 than in those with a ratio 50 (P<.001). Cox regression showed that the risk for spontaneous onset of labor increased with an soluble fms-like tyrosine kinase-1/placental growth factor ratio >50 (hazard ratio, 1.424; 95% confidence interval, 1.253-1.618; P<.001) and, as expected, the risk was mitigated over time from when the soluble fms-like tyrosine kinase-1/placental growth factor ratio was measured to spontaneous labor onset (P<.001). Cases with intrapartum fetal compromise had a higher mean soluble fms-like tyrosine kinase-1/placental growth factor ratio than those without intrapartum fetal compromise (21.79 vs 17.67; P<.001). Qualitative addition of fetal compromise to the general linear model showed a higher soluble fms-like tyrosine kinase-1/placental growth factor ratio in cases with fetal compromise than in those without fetal compromise (P=.014). Competing risks regression showed a positive dose-response effect for fetal compromise with increasing soluble fms-like tyrosine kinase-1/placental growth factor ratios (P<.001). Above and below the optimal cutoff of 50, the quoted cumulative incidences were 6.7% and 4.7%, respectively (P<.001). The effect of the soluble fms-like tyrosine kinase-1/placental growth factor ratio remained significant even after adjusting for preeclampsia, which is a well-known major risk factor for fetal compromise. Finally, the proportion of cases with intrapartum fetal compromise who had an soluble fms-like tyrosine kinase-1/placental growth factor ratio >50 decreased from 35% to 0% with advancing gestation. This study showed that an increased soluble fms-like tyrosine kinase-1/placental growth factor ratio at 36 weeks' gestation is associated with an earlier gestational age at spontaneous onset of labor and higher rates of intrapartum fetal compromise. There are 2 major implications, namely an soluble fms-like tyrosine kinase-1/placental growth factor ratio >50 indicates imminent labor onset with about a 40% mean risk increase and immediate clinical translation for term pregnancy monitoring. In addition, an increased soluble fms-like tyrosine kinase-1/placental growth factor ratio increases the risk for intrapartum fetal compromise, although outcome variability indicates reassessment within multimarker models.