FRONTIER1: a partially randomized phase 2 study assessing the safety, pharmacokinetics, and pharmacodynamics of Mim8, a factor VIIIa mimetic.

BACKGROUND: Mim8 (denecimig) is a factor VIII (FVIII) mimetic bispecific antibody in development for the treatment of hemophilia. Data from the phase 1 part of FRONTIER1 (EudraCT: 2019-000465-20, NCT04204408, and NN7769-4513) suggested that Mim8 was well tolerated in healthy participants and exhibited pharmacokinetic (PK) properties consistent with dose proportionality. OBJECTIVES: The partially randomized, phase 2, multiple ascending dose (MAD) part of FRONTIER1 aimed to evaluate the safety, PK, pharmacodynamics (PD), and exploratory efficacy of Mim8 in participants with hemophilia A with or without FVIII inhibitors. METHODS: The MAD part of FRONTIER1 consisted of 42 participants, assigned to 5 cohorts, with participants in cohorts 3 and 4 randomized 1:1 to dosing weekly or every 4 weeks, respectively. Four of the 42 participants (9.5%) had FVIII inhibitors prior to study enrolment. The primary endpoint was treatment-emergent adverse events (TEAEs). PK and PD were evaluated by Mim8 plasma concentration and thrombin generation, respectively. Exploratory efficacy was assessed via the number of treated bleeds. Safety and PD parameters were also evaluated from an exploratory cohort treated with emicizumab. RESULTS: Mim8 was well tolerated, with 1 serious TEAE (anxiety-related chest pain) deemed unrelated to Mim8. There was no dose dependency on the number, causality, type, or severity of TEAEs. PK/PD properties supported weekly to monthly dosing approaches, and few participants experienced treated bleeds beyond the lowest dose cohort (1 in cohorts 2 and 3, and 3 in cohort 5). CONCLUSION: These data support the continued clinical development of Mim8, and FRONTIER1 has proceeded onto an extension phase.

Strengthening Privacy and Data Security in Biomedical Microelectromechanical Systems by IoT Communication Security and Protection in Smart Healthcare.

Biomedical Microelectromechanical Systems (BioMEMS) serve as a crucial catalyst in enhancing IoT communication security and safeguarding smart healthcare systems. Situated at the nexus of advanced technology and healthcare, BioMEMS are instrumental in pioneering personalized diagnostics, monitoring, and therapeutic applications. Nonetheless, this integration brings forth a complex array of security and privacy challenges intrinsic to IoT communications within smart healthcare ecosystems, demanding comprehensive scrutiny. In this manuscript, we embark on an extensive analysis of the intricate security terrain associated with IoT communications in the realm of BioMEMS, addressing a spectrum of vulnerabilities that spans cyber threats, data manipulation, and interception of communications. The integration of real-world case studies serves to illuminate the direct repercussions of security breaches within smart healthcare systems, highlighting the imperative to safeguard both patient safety and the integrity of medical data. We delve into a suite of security solutions, encompassing rigorous authentication processes, data encryption, designs resistant to attacks, and continuous monitoring mechanisms, all tailored to fortify BioMEMS in the face of ever-evolving threats within smart healthcare environments. Furthermore, the paper underscores the vital role of ethical and regulatory considerations, emphasizing the need to uphold patient autonomy, ensure the confidentiality of data, and maintain equitable access to healthcare in the context of IoT communication security. Looking forward, we explore the impending landscape of BioMEMS security as it intertwines with emerging technologies such as AI-driven diagnostics, quantum computing, and genomic integration, anticipating potential challenges and strategizing for the future. In doing so, this paper highlights the paramount importance of adopting an integrated approach that seamlessly blends technological innovation, ethical foresight, and collaborative ingenuity, thereby steering BioMEMS towards a secure and resilient future within smart healthcare systems, in the ambit of IoT communication security and protection.

Expert opinion paper on the treatment of hemophilia B with albutrepenonacog alfa.

Introduction: Current guidelines recommend prophylactic treatment of hemophilia B with the missing coagulation factor IX, either with standard half-life or extended half-life products. Extended half-life products have half-lives three to six times longer than the former, allowing a reduction in the number of weekly injections and therefore, potentially impacting on treatment adherence and quality of life. Albutrepenonacog alfa is an extended half-life fusion protein of coagulation factor IX with recombinant human albumin, indicated for both on-demand and prophylactic treatment for bleeding in patients with hemophilia B of all ages.Areas covered: The authors review the clinical and pharmacokinetic characteristics of albutrepenonacog alfa, as well as the available information regarding trough levels and real-world evidence. Given the availability of other factor IX products in the market, indirect comparisons of clinical and pharmacokinetic characteristics are presented.Expert opinion: The authors exhibit their expert opinion on which patient profiles are candidates for prophylactic treatment with albutrepenonacog alfa, and on the management of patients in terms of dosing, regimens of administration and protocols for switching the treatment.

Incidence, characteristics and clinical profile of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection in patients with pre-existing primary immune thrombocytopenia (ITP) in Spain.

Infections are one of the well-known precipitating factors for relapses in patients with immune thrombocytopenia (ITP). Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection can sometimes lead to or be associated with thrombocytopenia due to an increase in peripheral platelet destruction from inflammatory hyperactivation. Currently, we do not know if SARS-CoV-2 infection modifies the natural evolution of chronic or persistent ITP or if previous immunosuppression of patients with ITP influences the incidence and severity of coronavirus disease 2019 (COVID-19) in this group. The present study was an observational, multicentre, national series of 32 adult patients with pre-existing ITP and subsequent SARS-CoV-2 infection, collected by the Spanish ITP Group [Grupo Español de Trombocitopenia Inmune (GEPTI)].

[Evaluation of the bone mass in the different types of menopause ]. / Evaluación de la masa ósea en los diferentes tipos de menopausia.

OBJECTIVE: To evaluate the bone mass condition in the different types of menopause and know if there is difference between the groups. DESIGN: Case reports. MATERIAL AND METHODS: From September through November 2001 at the Specialties Hospital No. 1, we studied 184 patients with menopause. They were divided in 5 groups: 74 regular menopause, 31 surgical menopause and oophorectomy unilateral, 43 surgical menopause and bilateral oophorectomy, 32 premature menopause, and 4 post-radiotherapy menopause, analyzing the bone mass with a densitometry. The statistical analysis was by descriptive statistics and t student to find the difference between the groups. RESULTS: We observed 45% with osteopenia y 8% with osteoporosis in regular menopause. In surgical menopause and oophorectomy unilateral group, we found 26% with osteopenia and 6% with osteoporosis. There were 42% with ostepenia and 14% with osteopososis in surgical menopause and bilateral oophorectomy group. In premature menopause, we found 47% with osteopenia and 12% with osteoporosis. In post-radiotherapy menopause, we found 75% with osteopenia and 25% with osteoporosis. All of them with predominance in femur. We did not observe any significant difference between the surgical and the premature menopause groups. CONCLUSIONS: In a half of patients with menopause we found bone mass decrease with predominance in femur, like osteopenia. There was no significant difference between the surgical and the premature menopause groups.

Uso del captopril y estradiol-medroxiprogesterona en pacientes hipertensas premenopáusicas / Use of captopril and estradiol -medroxyprogesterone in premenopausal hipertensive patients

Introducción. La premenopausia se refiere a la parte del climaterio que precede a la menopausia, donde se presenta una disminución de las hormonas ováricas, que conduce a enfermedades cardiovasculares como hipertensión arterial, infarto agudo del miocardio y accidente cerebrovascular. Objetivo. Evaluar la respuesta antihipertensiva del estradiolmedroxiprogesterona, para reducir la presión arterial en la paciente premenopáusica. Material y métodos. En un ensayo clínico del primero de marzo de 1997 al 30 septiembre de 1998, se evaluaron 106 pacientes con hipertensión arterial, hipoestrogenismo clínico y estradiol inferior a 30 pg/mL, se asignaron al azar a dos grupos con seguimiento de seis meses. Grupo A: 53 con captopril, Grupo B: 53 con estradiolmedroxiprogesterona, antes y después del tratamiento se analizaron la presión arterial, colesterol, triglicéridos e hipoestrogenismo clínico. (El análisis estadístico fue con prueba para diferencias de medias). Resultados. Se observó una disminución de la presión arterial con estradiol igual que con captopril, con una p < 0.05. La disminución del colesterol y triglicéridos fue más significativa en el grupo estradiol con una p < 0.05. Existió una mayor atenuación de la sintomatología del hipoestrogenismo en el grupo con estradiol. Conclusiones. La respuesta antihipertensiva con estradiol fue igual que con captopril en las pacientes hipertensivas premenopáusicas.