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1.
PM R ; 2024 Jul 05.
Article in English | MEDLINE | ID: mdl-38967454

ABSTRACT

INTRODUCTION: The timely translation of evidence-based programs into real-world clinical settings is a persistent challenge due to complexities related to organizational context and team function, particularly in inpatient settings. Strategies are needed to promote quality improvement efforts and implementation of new clinical programs. OBJECTIVE: This study examines the role of CONNECT, a complexity science-based implementation intervention to promote team readiness, for enhancing implementation of the 'Assisted Early Mobility for Hospitalized Older Veterans' program (STRIDE), an inpatient, supervised walking program. DESIGN: We conducted a stepped-wedge cluster randomized trial using a convergent mixed-methods design. Within each randomly assigned stepped-wedge sequence, Veterans Affairs Medical Centers (VAMCs) were randomized to receive standardized implementation support only or additional training via the CONNECT intervention. Data for the study were obtained from hospital administrative and electronic health records, surveys, and semi-structured interviews with clinicians before and after implementation of STRIDE. SETTING: Eight U.S. VAMCs. PARTICIPANTS: Three hundred fifty-three survey participants before STRIDE implementation and 294 surveys after STRIDE implementation. Ninety-two interview participants. INTERVENTION: CONNECT, a complexity-science-based intervention to improve team function. MAIN OUTCOME MEASURES: The implementation outcomes included STRIDE reach and fidelity. Secondary outcomes included validated measures of team function (i.e., team communication, coordination, role clarity). RESULTS: At four VAMCs randomized to CONNECT, reach was higher (mean 12.4% vs. 3.8%), and fidelity was similar to four non-CONNECT VAMCs. VAMC STRIDE delivery teams receiving CONNECT reported improvements in team function domains, similar to non-CONNECT VAMCs. Qualitative findings highlight CONNECT's impact and the influence of team characteristics and contextual factors, including team cohesion, leadership support, and role clarity, on reach and fidelity. CONCLUSION: CONNECT may promote greater reach of STRIDE, but improvement in team function among CONNECT VAMCs was similar to improvement among non-CONNECT VAMCs. Qualitative findings suggest that CONNECT may improve team function and implementation outcomes but may not be sufficient to overcome structural barriers related to implementation capacity.

2.
Clin Transl Sci ; 17(7): e13870, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38952168

ABSTRACT

The AIDA randomized clinical trial found no significant difference in clinical failure or survival between colistin monotherapy and colistin-meropenem combination therapy in carbapenem-resistant Gram-negative infections. The aim of this reverse translational study was to integrate all individual preclinical and clinical pharmacokinetic-pharmacodynamic (PKPD) data from the AIDA trial in a pharmacometric framework to explore whether individualized predictions of bacterial burden were associated with the trial outcomes. The compiled dataset included for each of the 207 patients was (i) information on the infecting Acinetobacter baumannii isolate (minimum inhibitory concentration, checkerboard assay data, and fitness in a murine model), (ii) colistin plasma concentrations and colistin and meropenem dosing history, and (iii) disease scores and demographics. The individual information was integrated into PKPD models, and the predicted change in bacterial count at 24 h for each patient, as well as patient characteristics, was correlated with clinical outcomes using logistic regression. The in vivo fitness was the most important factor for change in bacterial count. A model-predicted growth at 24 h of ≥2-log10 (164/207) correlated positively with clinical failure (adjusted odds ratio, aOR = 2.01). The aOR for one unit increase of other significant predictors were 1.24 for SOFA score, 1.19 for Charlson comorbidity index, and 1.01 for age. This study exemplifies how preclinical and clinical anti-infective PKPD data can be integrated through pharmacodynamic modeling and identify patient- and pathogen-specific factors related to clinical outcomes - an approach that may improve understanding of study outcomes.


Subject(s)
Acinetobacter baumannii , Anti-Bacterial Agents , Meropenem , Microbial Sensitivity Tests , Humans , Acinetobacter baumannii/drug effects , Acinetobacter baumannii/isolation & purification , Meropenem/pharmacokinetics , Meropenem/administration & dosage , Meropenem/pharmacology , Middle Aged , Female , Male , Anti-Bacterial Agents/pharmacokinetics , Anti-Bacterial Agents/administration & dosage , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/therapeutic use , Colistin/pharmacokinetics , Colistin/administration & dosage , Adult , Aged , Animals , Treatment Outcome , Mice , Acinetobacter Infections/drug therapy , Acinetobacter Infections/microbiology , Translational Research, Biomedical , Drug Therapy, Combination/methods , Models, Biological
3.
Clin Infect Dis ; 2024 Jul 24.
Article in English | MEDLINE | ID: mdl-39045871

ABSTRACT

There is an unmet need for developing drugs for the treatment of gonorrhea, due to rapidly evolving resistance of Neisseria gonorrhoeae against antimicrobial drugs used for empiric therapy, an increase in globally reported multidrug resistant cases, and the limited available therapeutic options. Furthermore, few drugs are under development. Development of antimicrobials is hampered by challenges in clinical trial design, limitations of available diagnostics, changes in and varying standards of care, lack of robust animal models, and clinically relevant pharmacodynamic targets. On April 23, 2021, the U.S. Food and Drug Administration; Centers for Disease Control and Prevention; and National Institute of Allergy and Infectious Diseases, National Institutes of Health co-sponsored a workshop with stakeholders from academia, industry, and regulatory agencies to discuss the challenges and strategies, including potential collaborations and incentives, to facilitate the development of drugs for the treatment of gonorrhea. This article provides a summary of the workshop.

4.
Contemp Clin Trials ; : 107637, 2024 Jul 20.
Article in English | MEDLINE | ID: mdl-39038701

ABSTRACT

BACKGROUND: Chronic graft-versus-host disease (GVHD) is a leading cause of late morbidity and mortality after allogeneic hematopoietic cell transplantation. Despite significant progress in chronic GVHD therapies, challenges remain in understanding pleomorphic phenotypes and varying response to treatment. The goal of the Predicting the Quality of Response to Specific Treatments (PQRST) in chronic GVHD study is to identify predictors of treatment response. This report describing the study design seeks to raise awareness and invite collaborations with investigators who wish to access clinical data and research samples from this study. METHODS: This is a prospective, observational cohort study involving data collection from patients who are beginning first-, second-, or third-line systemic therapy for chronic GVHD with defined agents. Evaluable participants will have baseline assessments and research samples prior to starting the index therapy, and 1 month after starting treatment. Response assessments occur at 3 and 6 months after start of treatment, or if a new systemic therapy is started before 6 months. Target enrollment is approximately 200 patients at 8 institutions, with at least 6 months of follow up to determine response to index therapy. RESULTS: Enrollment started in July 2020 and was delayed due to the COVID-19 pandemic; as of 3/1/2024, 137 evaluable participants have been enrolled. DISCUSSION: The Chronic GVHD Consortium "PQRST" is a large longitudinal cohort study that aims to investigate predictors of treatment response by identifying biologically and clinically defined patient subgroups. We welcome investigators to collaborate in the use of these data. TRIAL REGISTRATION: NCT04431479.

5.
Crit Care Explor ; 6(7): e1122, 2024 Jul 01.
Article in English | MEDLINE | ID: mdl-39023121

ABSTRACT

IMPORTANCE: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has evolved through multiple phases in the United States, with significant differences in patient centered outcomes with improvements in hospital strain, medical countermeasures, and overall understanding of the disease. We describe how patient characteristics changed and care progressed over the various pandemic phases; we also emphasize the need for an ongoing clinical network to improve the understanding of known and novel respiratory viral diseases. OBJECTIVES: To describe how patient characteristics and care evolved across the various COVID-19 pandemic periods in those hospitalized with viral severe acute respiratory infection (SARI). DESIGN: Severe Acute Respiratory Infection-Preparedness (SARI-PREP) is a Centers for Disease Control and Prevention Foundation-funded, Society of Critical Care Medicine Discovery-housed, longitudinal multicenter cohort study of viral pneumonia. We defined SARI patients as those hospitalized with laboratory-confirmed respiratory viral infection and an acute syndrome of fever, cough, and radiographic infiltrates or hypoxemia. We collected patient-level data including demographic characteristics, comorbidities, acute physiologic measures, serum and respiratory specimens, therapeutics, and outcomes. Outcomes were described across four pandemic variant periods based on a SARS-CoV-2 sequenced subsample: pre-Delta, Delta, Omicron BA.1, and Omicron post-BA.1. SETTING: Multicenter cohort of adult patients admitted to an acute care ward or ICU from seven hospitals representing diverse geographic regions across the United States. PARTICIPANTS: Patients with SARI caused by infection with respiratory viruses. MAIN OUTCOMES AND RESULTS: Eight hundred seventy-four adult patients with SARI were enrolled at seven study hospitals between March 2020 and April 2023. Most patients (780, 89%) had SARS-CoV-2 infection. Across the COVID-19 cohort, median age was 60 years (interquartile range, 48.0-71.0 yr) and 66% were male. Almost half (430, 49%) of the study population belonged to underserved communities. Most patients (76.5%) were admitted to the ICU, 52.5% received mechanical ventilation, and observed hospital mortality was 25.5%. As the pandemic progressed, we observed decreases in ICU utilization (94% to 58%), hospital length of stay (median, 26.0 to 8.5 d), and hospital mortality (32% to 12%), while the number of comorbid conditions increased. CONCLUSIONS AND RELEVANCE: We describe increasing comorbidities but improved outcomes across pandemic variant periods, in the setting of multiple factors, including evolving care delivery, countermeasures, and viral variants. An understanding of patient-level factors may inform treatment options for subsequent variants and future novel pathogens.


Subject(s)
COVID-19 , SARS-CoV-2 , Humans , COVID-19/epidemiology , Male , Female , Middle Aged , United States/epidemiology , Longitudinal Studies , Aged , Pandemics , Adult , Hospitalization/statistics & numerical data , Intensive Care Units , Cohort Studies
7.
Postgrad Med ; : 1-9, 2024 Jul 24.
Article in English | MEDLINE | ID: mdl-39045637

ABSTRACT

Current evidence for medical therapies for diabetic kidney disease (DKD) is largely based on large-scale clinical trials. These trials, however, often exhibit heterogeneity in participant characteristics and baseline kidney function. These differences may lead to misinterpretation in clinical practice, such that treatment effects from different trials are directly compared and generalized to broader populations beyond the population in which each trial was conducted. This is particularly relevant if comparisons on efficacy and safety are made when the underlying study populations are distinctly different. Indeed, key clinical trials evaluating sodium-glucose transport protein-2 inhibitors (SGLT2i), non-steroidal mineralocorticoid receptor antagonist (nsMRA), and glucagon-like peptide-1 receptor agonist (GLP-1RA) differed in recruitment requirements (inclusion/exclusion criteria), resulting in differences in the severity of the underlying kidney disease as well as risk factor profiles. Moreover, these trials defined their primary and secondary outcomes differently. Collectively, these factors lead to distinct study populations with different baseline risks for DKD progression in the placebo arm in each clinical trial. Consequently, a direct head-to-head comparison of the treatment effect between treatments using relative risk measures from placebo-controlled clinical trials alone is not recommended. In addition, healthcare professionals should be equipped to understand the specific target population of clinical trials to avoid over-generalization when drawing conclusions from these trials.


The medicines approved to help people with compromised kidney function were developed based on clinical trials that differed in many ways. There is a risk that clinical trials may be incorrectly compared and generalized by healthcare providers. In this review, the authors highlight the importance of interpreting clinical trial results cautiously while being mindful of the study population features. Key clinical trials for the treatment of diabetic kidney disease had different recruitment requirements for participants, a wide range of kidney disease severity, and different risks of disease progression in the comparison arm that did not receive the treatment during the trial. The conclusion of this review is to highlight the inappropriateness of comparing these medicines with each other using the results of clinical trials alone. It is important for the medical community to understand the specific types of patients that were involved in the clinical trials, to avoid unjustified conclusions.

8.
Essays Biochem ; 2024 Jun 28.
Article in English | MEDLINE | ID: mdl-38939918

ABSTRACT

NUAK1 and NUAK2 belong to a family of kinases related to the catalytic α-subunits of the AMP-activated protein kinase (AMPK) complexes. Despite canonical activation by the tumour suppressor kinase LKB1, both NUAKs exhibit a spectrum of activities that favour tumour development and progression. Here, we review similarities in structure and function of the NUAKs, their regulation at gene, transcript and protein level, and discuss their phosphorylation of specific downstream targets in the context of the signal transduction pathways and biological activities regulated by each or both NUAKs.

9.
Metab Eng ; 84: 145-157, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38936762

ABSTRACT

Biological conversion of lignin from biomass offers a promising strategy for sustainable production of fuels and chemicals. However, aromatic compounds derived from lignin commonly contain methoxy groups, and O-demethylation of these substrates is often a rate-limiting reaction that influences catabolic efficiency. Several enzyme families catalyze aromatic O-demethylation, but they are rarely compared in vivo to determine an optimal biocatalytic strategy. Here, two pathways for aromatic O-demethylation were compared in Pseudomonas putida KT2440. The native Rieske non-heme iron monooxygenase (VanAB) and, separately, a heterologous tetrahydrofolate-dependent demethylase (LigM) were constitutively expressed in P. putida, and the strains were optimized via adaptive laboratory evolution (ALE) with vanillate as a model substrate. All evolved strains displayed improved growth phenotypes, with the evolved strains harboring the native VanAB pathway exhibiting growth rates ∼1.8x faster than those harboring the heterologous LigM pathway. Enzyme kinetics and transcriptomics studies investigated the contribution of selected mutations toward enhanced utilization of vanillate. The VanAB-overexpressing strains contained the most impactful mutations, including those in VanB, the reductase for vanillate O-demethylase, PP_3494, a global regulator of vanillate catabolism, and fghA, involved in formaldehyde detoxification. These three mutations were combined into a single strain, which exhibited approximately 5x faster vanillate consumption than the wild-type strain in the first 8 h of cultivation. Overall, this study illuminates the details of vanillate catabolism in the context of two distinct enzymatic mechanisms, yielding a platform strain for efficient O-demethylation of lignin-related aromatic compounds to value-added products.


Subject(s)
Pseudomonas putida , Pseudomonas putida/genetics , Pseudomonas putida/metabolism , Metabolic Engineering , Bacterial Proteins/genetics , Bacterial Proteins/metabolism , Demethylation , Directed Molecular Evolution
10.
J Clin Med ; 13(12)2024 Jun 07.
Article in English | MEDLINE | ID: mdl-38929897

ABSTRACT

Background: Gender-affirming mastectomy (GAM) improves the psychosocial functioning and quality of life of transgender and non-binary (TGNB) individuals. However, the perioperative period is often marked by emotional stress, concerns about surgical outcomes, and physical discomfort. While inpatient procedures provide multiple opportunities to engage with and educate patients, outpatient surgeries, such as GAM, pose a unique challenge as patients are followed for <24 h postoperatively. Given the heightened emotional and psychological distress related to gender dysphoria TGNB individuals often experience, addressing these gaps can significantly improve outcomes. This study aims to characterize patient and surgical characteristics associated with patient-initiated communication (PIC) frequency in this population. Methods: A single-center retrospective review of TGNB patients undergoing GAM from February 2018 to November 2022 was conducted. Demographics, surgical characteristics, and frequency of and reasons for perioperative PIC (30 days before and after surgery) were recorded. The primary outcome was the incidence of perioperative PIC. The secondary outcomes included (1) the rationale for PIC and (2) patient and surgical characteristics associated with PIC. Results: A total of 352 patients were included. Of these, 285 (74.6%) initiated communication in the perioperative period, totaling 659 PICs. The median age was 25.0 (interquartile range [IQR]: 9.0) years. The median body mass index (BMI) was 28.5 (IQR: 8.5) kg/m2. The mean number of PICs was 0.7 ± 1.3 preoperatively and 1.3 ± 1.7 postoperatively (p < 0.001). The most frequent preoperative PIC subjects were administrative issues (AI; n = 66, 30.7%), preoperative requirements (n = 43, 20.0%), and cost and insurance (n = 33, 15.0%). The most frequent postoperative PIC subjects were wound care (n = 77, 17.3%), AI (n = 70, 15.0%), activity restrictions (n = 60, 13.5%), drainage (n = 56, 12.6%), and swelling (n = 37, 8.3%). Collectively, older patients (ß = 0.234, p = 0.001), those with a history of major depressive disorder or generalized anxiety disorder (2.4 ± 3.0 vs. 1.7 ± 1.9; p = 0.019), and those without postoperative drains (n = 16/17, 94.1% vs. n = 236/334, 70.7%; p = 0.025) engaged in higher levels of PIC. There were no significant associations between other patient characteristics, perioperative details, or complications and PIC frequency. Conclusions: Perioperative PIC is prevalent among the majority of GAM patients at our institution, with age, psychiatric diagnosis, and postoperative drain use identified as significant predictors. To mitigate PIC frequency, it is crucial to ensure adequate support staffing and provide comprehensive postoperative instructions, particularly concerning activity restrictions and drainage management. These interventions may reduce PICs in high-volume centers. Further research should investigate targeted interventions to further support TGNB patients during the perioperative period.

12.
Article in English | MEDLINE | ID: mdl-38858818

ABSTRACT

BACKGROUND AND HYPOTHESIS: Finerenone, a non-steroidal mineralocorticoid receptor antagonist, improved kidney, and cardiovascular outcomes in patients with CKD and T2D in two Phase 3 outcome trials. The FIND-CKD study investigates the effect of finerenone in adults with CKD without diabetes. METHODS: FIND-CKD (NCT05047263 and EU CT 2023-506897-11-00) is a randomized, double-blind, placebo-controlled Phase 3 trial in patients with CKD of non-diabetic aetiology. Adults with a urinary albumin-creatinine ratio (UACR) of ≥ 200 to ≤3500 mg/g and eGFR ≥ 25 to <90 mL/min/1.73 m2 receiving a maximum tolerated dose of a renin-angiotensin-system (RAS) inhibitor were randomized 1:1 to once daily placebo or finerenone 10 or 20 mg depending on eGFR above or below 60 mL/min/1.73 m2. The primary efficacy outcome is total eGFR slope, defined as the mean annual rate of change in eGFR from baseline to Month 32. Secondary efficacy outcomes include a combined cardiorenal composite outcome comprising time to kidney failure, sustained ≥57% decrease in eGFR, hospitalization for heart failure, or cardiovascular death, as well as separate kidney and cardiovascular composite outcomes. Adverse events are recorded to assess tolerability and safety. RESULTS: Across 24 countries, 3231 patients were screened and 1584 were randomized to study treatment. The most common causes of CKD were chronic glomerulonephritis (57.0%) and hypertensive/ischaemic nephropathy (29.0%). Immunoglobulin A nephropathy was the most common glomerulonephritis (26.3% of the total population). At baseline, mean eGFR and median UACR were 46.7 mL/min/1.73 m2 and 818.9 mg/g, respectively. Diuretics were used by 282 participants (17.8%), statins by 851 (53.7%), and calcium channel blockers by 794 (50.1%). SGLT2 inhibitors were used in 16.9% of patients; these individuals had a similar mean eGFR (45.6 vs 46.8 mL/min/1.73 m2) and slightly higher median UACR (871.9 vs 808.3 mg/g) compared to those not using SGLT2 inhibitors at baseline. CONCLUSIONS: FIND-CKD is the first Phase 3 trial of finerenone in patients with CKD of non-diabetic aetiology.

13.
J Am Coll Emerg Physicians Open ; 5(3): e13187, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38846102

ABSTRACT

This article provides a report of a case of organ dysfunction, myonecrosis, rhabdomyolysis, multifocal ischemic cerebral infarcts, and cerebral edema after a patient's use of xylazine and fentanyl. Within the US opioid epidemic, xylazine is emerging as a troubling national sub-story. The prevalence of xylazine within illicitly manufactured opioids and the proportion of opioid-involved overdose deaths with detected xylazine are rising dramatically, the latter increasing 276% between 2019 and 2022. A 27-year-old woman with opioid use disorder, active intravenous drug use, and prior bacteremia presented to our institution's emergency department (ED) with left lower extremity pain and associated weakness, new acute bilateral hearing loss, multiple electrolyte derangements, and cerebral infarcts followed by cerebral edema, leading to an emergent sub-occipital decompressive craniectomy and placement of an external ventricular drain. A definitive mechanism was not determined; however, we hypothesized that xylazine toxicity played a role in her clinical presentation, which could have future clinical implications, including the possibility to incorporate xylazine as part of toxicology screens.

14.
Skin Health Dis ; 4(3): e381, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38846703

ABSTRACT

In this pilot study, participants with symptomatic lymphocytic primary cicatricial alopecia applied 6% topical gabapentin solution twice daily to affected areas for 12 weeks. There was a significant reduction in symptoms, but no pronounced effect on nerve fibre density or neuropeptide expression.

15.
Cardiol Rev ; 2024 Jun 04.
Article in English | MEDLINE | ID: mdl-38833498

ABSTRACT

Robert Gross performed the first repair of a patent ductus arteriosus in 1938. His life and career were dedicated to the advancement of vascular, cardiac, pediatric surgery, and the unrelenting care of his patients.

16.
Clin Anat ; 2024 Jun 06.
Article in English | MEDLINE | ID: mdl-38845390

ABSTRACT

Learning 2D sectional anatomy facilitates the comprehension of 3D anatomical structures, anatomical relationships, and radiological anatomy. However, the efficacy of technology-enhanced collaborative instructional activities in sectional anatomy remains unclear, especially if theoretical frameworks, namely the Cognitive Theory of Multimedia Learning (CTML), are applied in instructional design. Thus, this study compared the educational impact of distinct 45-min-long technology-enhanced collaborative learning tasks in sectional anatomy. A sample of 115 first-year medical students was randomly divided into three experimental groups that used different supporting technologies to learn the sectional anatomy of the chest: IMAIOS e-learning platform and Microsoft Surface Hub (n = 37); anatomage table (n = 38); anatomage table with CTML-based presets (n = 40). Prelearning and postlearning tests revealed that significant knowledge gains in sectional anatomy were obtained by all groups even though no inter-group differences were found. Moreover, a five-point Likert scale questionnaire showed that the learning session was highly valued by all participants and that users of the anatomage with CTML-based presets reported higher enjoyment than users of the IMAIOS system (mean difference = 0.400; p = 0.037). In addition, students using the IMAIOS system and the anatomage with CTML-based presets provided System Usability Scale (SUS) scores of 67.64 and 67.69, respectively, reaching the benchmark of usability. By contrast, students using the anatomage table without presets awarded a SUS score of 64.14. These results suggest that the integration of multimedia technologies in anatomy teaching and learning should be grounded on CTML principles of instructional design. Otherwise, students' perceptions of ed-tech usability are potentially hindered.

17.
Metabolism ; : 155931, 2024 Jun 04.
Article in English | MEDLINE | ID: mdl-38852020

ABSTRACT

The spectrum of cardiorenal and metabolic diseases comprises many disorders, including obesity, type 2 diabetes (T2D), chronic kidney disease (CKD), atherosclerotic cardiovascular disease (ASCVD), heart failure (HF), dyslipidemias, hypertension, and associated comorbidities such as pulmonary diseases and metabolism dysfunction-associated steatotic liver disease and metabolism dysfunction-associated steatohepatitis (MASLD and MASH, respectively, formerly known as nonalcoholic fatty liver disease and nonalcoholic steatohepatitis [NAFLD and NASH]). Because cardiorenal and metabolic diseases share pathophysiologic pathways, two or more are often present in the same individual. Findings from recent outcome trials have demonstrated benefits of various treatments across a range of conditions, suggesting a need for practice recommendations that will guide clinicians to better manage complex conditions involving diabetes, cardiorenal, and/or metabolic (DCRM) diseases. To meet this need, we formed an international volunteer task force comprising leading cardiologists, nephrologists, endocrinologists, and primary care physicians to develop the DCRM 2.0 Practice Recommendations, an updated and expanded revision of a previously published multispecialty consensus on the comprehensive management of persons living with DCRM. The recommendations are presented as 22 separate graphics covering the essentials of management to improve general health, control cardiorenal risk factors, and manage cardiorenal and metabolic comorbidities, leading to improved patient outcomes.

18.
Epilepsy Behav ; 157: 109867, 2024 Jun 01.
Article in English | MEDLINE | ID: mdl-38824751

ABSTRACT

BACKGROUND: Seizure clusters are underresearched and associated with adverse outcomes in patients with epilepsy. This study was a noninterventional, retrospective claims-based analysis using the Wisconsin Health Information Organization (WHIO) All-Payer Claims Database to characterize the epilepsy population in Wisconsin, with a focus on prevalence, treatment patterns, and healthcare resource utilization (HCRU) in patients with seizure clusters prior to the introduction of nasal spray rescue medications. This timeframe allows characterization of a historical baseline for future comparisons with newer treatments. METHODS: Four cohorts were defined: (1) all-epilepsy (all patients with epilepsy); and subcohorts of: (2) patients receiving a monotherapy antiseizure medication (ASM); (3) patients receiving ASM polytherapy; and (4) patients treated for seizure clusters (ie, those taking rescue medications and ≥ 1 ASM). Primary outcomes were HCRU over a 12-month follow-up period, which were descriptively analyzed. RESULTS: Between 2017 and 2019, 16,384 patients were included in the all-epilepsy cohort; 11,688 (71.3 %) were on monotherapy, 3,849 (23.5 %) were on polytherapy, and 526 (3.2 %) were treated for seizure clusters. Twelve-month retentions to the ASM treatments were 46.7 % (7,895/16,904) in the all-epilepsy cohort, and 40.0 % (4,679/11,688) and 40.1 % (1,544/3,849) in the monotherapy and polytherapy subcohorts, respectively. Rescue medication prescriptions were obtained 1,029 times by the 526 patients in the treated seizure cluster subcohort, with infrequent refill rates (mean 1.6-1.9 times/year). A higher proportion of patients in the treated seizure cluster subcohort had epilepsy-related outpatient visits (89.7 %), other visits (71.3 %), and hospitalizations (25.3 %) than patients in the monotherapy (72.2 %, 50.2 %, 19.3 %, respectively) and polytherapy (83.3 %, 63.3 %, 22.8 %, respectively) subcohorts. Mean (standard deviation) all-cause ($114,717 [$231,667]) and epilepsy-related ($76,134 [$204,930]) costs over 12 months were higher in the treated seizure cluster subcohort than the monotherapy ($89,324 [$220,181] and $30,745 [$145,977], respectively) and polytherapy ($101,506 [$152,931] and $49,383 [$96,285], respectively) subcohorts. CONCLUSIONS: Patients treated for seizure clusters incurred higher all-cause and epilepsy-related costs and epilepsy-related HCRU than other subcohorts and had infrequent rescue medication refills. The findings of this analysis highlight the need for appropriate treatment for those patients with epilepsy experiencing seizure clusters. The effect of newer rescue medications to alter these findings will be explored in a follow-up study. Regardless, specialist providers with expertise in treating refractory epilepsy and seizure cluster patients may help to reduce the burden of seizure clusters.

19.
Sci Rep ; 14(1): 13175, 2024 Jun 07.
Article in English | MEDLINE | ID: mdl-38849398

ABSTRACT

Recent behavioral evidence suggests that the semantic relationships between isolated objects can influence attentional allocation, with highly semantically related objects showing an increase in processing efficiency. This semantic influence is present even when it is task-irrelevant (i.e., when semantic information is not central to the task). However, given that objects exist within larger contexts, i.e., scenes, it is critical to understand whether the semantic relationship between a scene and its objects continuously influence attention. Here, we investigated the influence of task-irrelevant scene semantic properties on attentional allocation and the degree to which semantic relationships between scenes and objects interact. Results suggest that task-irrelevant associations between scenes and objects continuously influence attention and that this influence is directly predicted by the perceived strength of semantic associations.

20.
Am J Ophthalmol ; 2024 Jun 15.
Article in English | MEDLINE | ID: mdl-38880374

ABSTRACT

PURPOSE: To develop a patient-reported outcome measure to assess the impact of glaucoma and treatment, including minimally invasive glaucoma surgery (MIGS). DESIGN: Observational study before and after concomitant cataract and Food and Drug Administration-approved implantable MIGS device surgery. SETTING: Survey administration was on a computer, iPad, or similar device. PATIENT POPULATION: 184 adults completed the baseline survey, 124 a survey 3 months after surgery, and 106 the 1-month test-retest reliability survey. The age range was 37 to 89 (average age = 72). Most were female (57%), non-Hispanic White (81%), and had a college degree (56%). MAIN OUTCOME MEASURES: The Glaucoma Outcomes Survey (GOS) assesses functional limitations (27 items), vision-related symptoms (7 items), psychosocial issues (7 items), and satisfaction with microinvasive glaucoma surgery (1 item). These multiple-item scales were scored on a 0 to 100 range, with a higher score indicating worse health. RESULTS: Internal consistency reliability estimates ranged from 0.75 to 0.93, and 1-month test-retest intraclass correlations ranged from 0.83 to 0.92 for the GOS scales. Product-moment correlations among the scales ranged from 0.56 to 0.60. Improvement in visual acuity in the study eye from baseline to the 3-month follow-up was significantly related to improvements in GOS functional limitations (r = 0.18, P = .0485), vision-related symptoms (r = 0.19, P = .0386), and psychosocial concerns (r = 0.18, P = .0503). Responders to treatment ranged from 17% for vision-related symptoms to 48% for functional limitations. CONCLUSIONS: This study supports using the GOS for ophthalmic procedures such as MIGS. Further evaluation of the GOS in different patient subgroups and clinical settings is needed.

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