A Journey into the Unknown: An Ethnographic Examination of Drug-Resistant Epilepsy Treatment and Management in the United States

Patients often recognize unmet needs that can improve patient-provider experiences in disease treatment management. These needs are rarely captured and may be hard to quantify in difficult-to-treat disease states such as drug-resistant epilepsy (DRE). To further understand challenges living with and managing DRE, a team of medical anthropologists conducted ethnographic field assessments with patients to qualitatively understand their experience with DRE across the United States. In addition, healthcare provider assessments were conducted in community clinics and Comprehensive Epilepsy Centers to further uncover patient-provider treatment gaps. We identified four distinct stages of the treatment and management journey defined by patients\u27 perceived control over their epilepsy: Gripped in the Panic Zone, Diligently Tracking to Plan, Riding a Rollercoaster in the Dark, and Reframing Priorities to Redefine Treatment Success. We found that patients sought resources to streamline communication with their care team, enhanced education on treatment options beyond medications, and long-term resources to protect against a decline in control over managing their epilepsy once drug-resistant. Likewise, treatment management optimization strategies are provided to improve current DRE standard of care with respect to identified patient-provider gaps. These include the use of digital disease management tools, standardizing neuropsychiatrists into patients\u27 initial care team, and introducing surgical and non-pharmacological treatment options upon epilepsy and DRE diagnoses, respectively. This ethnographic study uncovers numerous patient-provider gaps, thereby presenting a conceptual framework to advance DRE treatment. Further Incentivization from professional societies and healthcare systems to support standardization of the treatment optimization strategies provided herein into clinical practice is needed

Activin Receptor-like Kinase 1 Ligand Trap Reduces Microvascular Density and Improves Chemotherapy Efficiency to Various Solid Tumors

PURPOSE: Antiangiogenic therapy, mostly targeting VEGF, has been applied in cancer patients for the last decade. However, resistance to anti-VEGF therapy and/or no significant benefit as monotherapeutic agent is often observed. Therefore, new antiangiogenic strategies are needed. In the current study, we investigated the therapeutic effect of interfering with the bone morphogenetic protein (BMP)9/activin receptor-like kinase (ALK)1 signaling pathway by using an ALK1-Fc ligand trap. EXPERIMENTAL DESIGN: We analyzed the potential antiangiogenic and antitumor effects of ALK1-Fc protein as monotherapy and in combination with chemotherapy in vivo in mouse models of melanoma, head and neck cancer, and invasive lobular breast carcinomas. ALK1-Fc sequesters BMP9 and 10 and prevents binding of these ligands to endothelial ALK1, which regulates angiogenesis. RESULTS: Treatment of mice with ALK1-Fc strongly decreased the tumors' microvascular density in the three different mouse cancer models. However, this effect was not accompanied by a reduction in tumor volume. An immunohistochemical analysis of the tumor samples revealed that ALK1-Fc treatment increased the pericyte coverage of the remaining tumor vessels and decreased the hypoxia within the tumor. Next, we observed that combining ALK1-Fc with cisplatin inhibited tumor growth in the breast and head and neck cancer models more efficiently than chemotherapy alone. CONCLUSIONS: The addition of ALK1-Fc to the cisplatin treatment was able to enhance the cytotoxic effect of the chemotherapy. Our results provide strong rationale to explore combined targeting of ALK1 with chemotherapy in a clinical setting, especially in the ongoing phase II clinical trials with ALK1-Fc

Puberdade e maturidade sexual em touros jovens da raça Simental, criados sob regime extensivo em clima tropical Puberty and sexual maturity in young Simmental bulls, raised under pasture conditions in a tropical climate

Objetivou-se determinar a idade à puberdade e maturidade sexual e sua relação com peso corporal e mensurações testiculares em tourinhos da raça Simental criados sob regime extensivo em clima tropical. Utilizaram-se 44 tourinhos com 1 a 30 meses de idade. As mensurações corporais e testiculares foram feitas mensalmente e os ejaculados coletados quinzenalmente, a partir dos seis meses de idade, utilizando-se o método de eletroejaculação. Observou-se idade à puberdade aos 13,42 ± 3,02 meses e maturidade sexual aos 21,43 ± 6,6 meses de idade, com peso corporal e perímetro escrotal, respectivamente, de 324,2 ± 23,7 kg e 26,90 ± 1,41 cm para a puberdade e 360 ± 69,04 kg e 34,88 ± 3,9 cm para maturidade sexual. Este estudo revelou idade tardia para a cronologia dos eventos reprodutivos, com relação direta do tipo de manejo adotado.<br>The objective of this study was to determine the age at puberty and sexual maturity and its relationship with body weight and testicular measurements in Simmental young bulls raised under pasture conditions in a tropical climate. Forty-four young bulls at 1 to 30 months of age were used. Body and testicular measurements were made monthly and ejaculates collected fortnightly, from six months of age by using the method of electroejaculation. Age at puberty was 13.42 ± 3.02 months and sexual maturity was observed at 21.43 ± 6.6 months of age, with body weight and scrotal circumference of 324.2 ± 23.7 kg and 26.90 ± 1.41 cm for puberty and 360 ± 69.04 kg and 34.88 ± 3.9 cm to sexual maturity, respectively. This study found late age to the timing of reproductive events, with direct relation to the type of management adopted

Data from: SYNGAP1 encephalopathy: a distinctive generalized developmental and epileptic encephalopathy

Objective. To delineate the epileptology, a key part of the SYNGAP1 phenotypic spectrum, in a large patient cohort. Methods. Patients were recruited via investigators' practices or social media. We included patients with (likely) pathogenic SYNGAP1 variants or chromosome 6p21.32 microdeletions incorporating SYNGAP1. We analysed patients' phenotypes using a standardized epilepsy questionnaire, medical records, EEG, MRI and seizure videos. Results. We included 57 patients (53% male, median age 8 years) with SYNGAP1 mutations (n=53) or microdeletions (n=4). 56/57 patients had epilepsy: generalized in 55, with focal seizures in seven and infantile spasms in one. Median seizure onset age was 2 years. A novel type of drop attack was identified comprising eyelid myoclonia evolving to a myoclonic-atonic (n=5) or atonic (n=8) seizure. Seizure types included eyelid myoclonia with absences (65%), myoclonic seizures (34%), atypical (20%) and typical (18%) absences and atonic seizures (14%), triggered by eating in 25%. Developmental delay preceded seizure onset in 54/56 (96%) patients of whom early developmental history was available. Developmental plateauing or regression occurred with seizures in 56 in the context of developmental and epileptic encephalopathies (DEEs). 55/57 patients had intellectual disability, which was moderate to severe in 50. Other common features included behavioural problems (73%), high pain threshold (72%), eating problems including oral aversion (68%), hypotonia (67%), sleeping problems (62%), autism spectrum disorder (54%) and ataxia or gait abnormalities (51%). Conclusions. SYNGAP1 mutations cause a generalized DEE with a distinctive syndrome combining epilepsy with eyelid myoclonia and myoclonic-atonic seizures, and predilection to seizures triggered by eating

Acute flaccid myelitis: cause, diagnosis, and management

Acute flaccid myelitis (AFM) is a disabling, polio-like illness mainly affecting children. Outbreaks of AFM have occurred across multiple global regions since 2012, and the disease appears to be caused by non-polio enterovirus infection, posing a major public health challenge. The clinical presentation of flaccid and often profound muscle weakness (which can invoke respiratory failure and other critical complications) can mimic several other acute neurological illnesses. There is no single sensitive and specific test for AFM, and the diagnosis relies on identification of several important clinical, neuroimaging, and cerebrospinal fluid characteristics. Following the acute phase of AFM, patients typically have substantial residual disability and unique long-term rehabilitation needs. In this Review we describe the epidemiology, clinical features, course, and outcomes of AFM to help to guide diagnosis, management, and rehabilitation. Future research directions include further studies evaluating host and pathogen factors, including investigations into genetic, viral, and immunological features of affected patients, host-virus interactions, and investigations of targeted therapeutic approaches to improve the long-term outcomes in this population