BAY 81‐8973 prophylaxis and pharmacokinetics in haemophilia A: Interim results from the TAURUS study

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Psychosis secondary to COVID‐19 in pediatric sickle cell disease

Key Clinical Message COVID‐19 psychosis is a potential long‐term sequela of COVID‐19. Vulnerable populations, such as individuals with sickle cell disease, are at high risk for psychosis. Given the limited number of cases, more investigations in the etiopathology and management of this new disease is needed. Abstract We report a case of a 15‐year‐old female with a past medical history of depression who developed psychosis post‐SARS‐CoV‐2 infection (COVID‐19). After an initial moderate COVID‐19 infection, the patient appeared to recover and was discharged home. Four weeks later, she presented with symptoms of psychosis and symptoms of cognitive impairment. Imaging studies did not show any evidence of stroke and toxicology studies were negative. She was treated with antipsychotics and required inpatient neuropsychiatric rehabilitation. Acute psychotic syndrome resolved after 3 weeks, antipsychotics were weaned, and an antidepressant was initiated. Mild cognitive impairment with significant memory loss persisted for about 1 year. Thereafter, she returned to her baseline but remains on an antidepressant. Some studies have previously reported the occurrence of psychosis in individuals with COVID‐19. This report is the first outline of severe prolonged post‐COVID‐19 psychosis in a child with sickle cell disease. Given the neurologic vulnerability of children with sickle cell disease, these individuals should be monitored for neuropsychiatric symptoms post COVID‐19

Dietary agent, benzyl isothiocyanate inhibits signal transducer and activator of transcription 3 phosphorylation and collaborates with sulforaphane in the growth suppression of PANC-1 cancer cells

<p>Abstract</p> <p>The Signal Transducer and Activator of Transcription (STAT) proteins comprise a family of latent transcription factors with diverse functions. STAT3 has well established roles in cell proliferation, growth and survival, and its persistent activation has been detected with high frequency in many human cancers. As constitutive activation of STAT3 appears to be vital for the continued survival of these cancerous cells, it has emerged as an attractive target for chemotherapeutics. We examined whether the inhibitory activities of bioactive compounds from cruciferous vegetables, such as Benzyl isothiocyanate (BITC) and sulforaphane, extended to STAT3 activation in PANC-1 human pancreatic cancer cells. BITC and sulforaphane were both capable of inhibiting cell viability and inducing apoptosis in PANC-1. Sulforaphane had minimal effect on the direct inhibition of STAT3 tyrosine phosphorylation, however, suggesting its inhibitory activities are most likely STAT3-independent. Conversely, BITC was shown to inhibit the tyrosine phosphorylation of STAT3, but not the phosphorylation of ERK1/2, MAPK and p70S6 kinase. These results suggest that STAT3 may be one of the targets of BITC-mediated inhibition of cell viability in PANC-1 cancer cells. In addition, we show that BITC can prevent the induction of STAT3 activation by Interleukin-6 in MDA-MB-453 breast cancer cells. Furthermore, combinations of BITC and sulforaphane inhibited cell viability and STAT3 phosphorylation more dramatically than either agent alone. These findings suggest that the combination of the dietary agents BITC and sulforaphane has potent inhibitory activity in pancreatic cancer cells and that they may have translational potential as chemopreventative or therapeutic agents.</p

BAY 81-8973 prophylaxis and pharmacokinetics in haemophilia A: Interim results from the TAURUS study

Objectives: To report interim data from TAURUS, a study assessing real-world prophylactic treatment with unmodified, full-length recombinant FVIII BAY 81-8973 (Kovaltry®; Bayer) indicated for haemophilia A. Methods: TAURUS (NCT02830477) is an international, open-label, prospective, non-interventional, single-arm study with a one-year observation period (target N = 350). Patients have moderate or severe haemophilia A (FVIII ≤5% or ≤1%) and ≥50 exposure days to any FVIII product. Clinician- and patient-reported outcomes are captured on previous product use, changes in prophylaxis dose and dosing frequency, FVIII consumption, reported bleeding rates, treatment satisfaction and adherence, pharmacokinetic (PK) data (if available) and safety data. Results: At cut-off, baseline data were available from 160 patients (89 had ≥6 months of follow-up data). Most patients had severe haemophilia A (85%), infused BAY 81-8973 ≥ 3×/wk (59%) and experienced a median number of total bleeds of 2.0 (non-annualised; 246 days median documentation period). Good levels of treatment satisfaction (Hemo-SATA,P) and adherence (VERITAS-Pro) were maintained. TAURUS demonstrated a favourable PK profile of BAY 81-8973 in comparison with other standard half-life rFVIIIs and supported the WAPPS PopPK model. No patients developed inhibitors. Conclusions: TAURUS data demonstrate effective prophylaxis with BAY 81-8973 in the real world without compromising patient satisfaction or adherence.SCOPUS: ar.jDecretOANoAutActifinfo:eu-repo/semantics/publishe

Efficacy and safety in patients with haemophilia A switching to octocog alfa (BAY 81-8973) : final results of the global real-world study, TAURUS

To report the final results of the 2-year TAURUS study, assessing weekly prophylaxis dosing regimens of octocog alfa (Kovaltry®/BAY 81-8973) used in standard clinical practice in patients with moderate-to-severe haemophilia A. TAURUS (NCT02830477) is a phase 4, multinational, prospective, non-interventional, single-arm study in patients of any age with moderate or severe haemophilia A (≤5% factor [F]VIII activity). TAURUS was designed to primarily investigate weekly prophylaxis dosing regimens used in standard clinical practice. Annualised bleeding rates (ABRs), treatment satisfaction and adherence, and safety were also assessed. Of 302 patients included in the full analysis set, 84.4% (n = 255) maintained their octocog alfa prophylaxis baseline regimen throughout the study, with a majority of patients (76.5%, n = 231) on two times or three times weekly regimens at the end of the observation period (≥1-≤2 years). ABRs, treatment satisfaction, and adherence remained stable during the observation period. Octocog alfa was well tolerated and there were no new or unexpected adverse events. These data show that a smooth transition is observed when switching to octocog alfa from a previous FVIII treatment, with no safety issues and stable bleeding rates in a real-world setting of patients with moderate-to-severe haemophilia A

Therapy-related myeloid neoplasms resembling juvenile myelomonocytic leukemia: a case series and review of the literature.

Therapy-related myeloid neoplasms (t-MN) are a distinct subgroup of myeloid malignancies with a poor prognosis that include cases of therapy-related myelodysplastic syndrome (t-MDS), therapy-related myeloproliferative neoplasms (t-MPN) and therapy-related acute myeloid leukemia (t-AML). Here, we report a series of patients with clinical features consistent with juvenile myelomonocytic leukemia (JMML), an overlap syndrome of MDS and myeloproliferative neoplasms that developed after treatment for another malignancy

Organ iron accumulation in chronically transfused children with sickle cell anaemia: baseline results from the TWiTCH trial

Sweden is undergoing energy transition to become a zero-carbon economy with electricity production aims at 100% from renewable resources by 2040. Sweden also has a national goal to have fossil-free vehicle fleet by 2030. The increasing share of intermittent renewable resources creates growth in mismatches between electricity supply and demand. Demand flexibility provides solution to imbalances in power system where the prosumers can regulate their energy consumption. Demand response (DR) mechanism could be beneficial to power gird stability. Electric heat pumps serve as a pool of flexible load meanwhile the thermal inertia of the residential buildings serves as thermal energy storage. In this thesis, a techno-economic analysis of demand flexibility from heat pumps for residential buildings located in central Örebro is carried out with assistance of building energy simulations. This thesis aims to improve the intelligence of this existing buildings by comprehending the size of thermal inertia availability according to different heat demand, building envelope materials, ventilation systems, weather conditions and user behaviors. Two multi-family residential buildings, Klockarängsvägen and Pärllöken, are selected for case study and compared in terms of thermal inertia and avoided peak power fees in avoided peak power fee from flexible heat pump loads. Both buildings use heat pumps for space heating and domestic hot water supply. Electricity billings are subscribed to power tariff scheme, which makes peak power shifting more profitable. On the coldest day scenario when the ambient temperature is -20°C, Pärllöken’s indoor temperature drops from 21°C to 19.1°C if heat pump is turned off for an hour. Klockarängsvägen’s indoor temperature drops from 21°C to 16.6°C if heat pump is turned off for an hour. At the lowest indoor temperature setpoint of 18°C, Pärllöken demonstrates a maximum power-shift capacity of 25 kW and heatshift capacity of 75 kWh on the coldest day. That of Klockarängsvägen is a maximum power-shift capacity of 20 kW and heat-shift capacity of 20 kWh. With larger building thermal inertia and more power-shift capacity, Pärllöken is undoubtedly the winner thanks to concrete wall materials, heavier building thermal mass, balanced ventilation, heat recovery system, and higher window class. In economic analysis, based on the proposed energy models, two control strategy options in Pärllöken are considered. Economic analysis focuses on winter season from October to March. Option 1 operates heat pump in variable capacity control mode at part load capacity. Option 2 operates in fixed capacity on/off -4- control. In winter season, Pärllöken saves 1 646 SEK in Option 1 and 2 273 SEK in Option 2. Klockarängsvägen only considers Option 1 for economic analysis, which results in 20 948 SEK avoided peak power fee. Option 2 for Klockarängsvägen exceeds indoor temperature setpoint very quickly mainly due to poorer building envelope insulation in which conserves lower thermal inertia.Sverige genomgår en energitransformation för att bli en fossilfri ekonomi som siktar på att ha en elproduktion från 100% förnybara resurser år 2040. Sverige har också ett nationellt mål att ha en fossilfri fordonsflotta till 2030. Den ökande andelen av intermittenta förnybara resurser bidrar till ökning av obalans mellan produktion och efterfråga av elektricitet. Efterfrågeflexibilitet ger en lösning på problemet med obalanser i energisystemet där prosumenter kan reglera sin energiförbrukning. Efterfrågeflexibilitet kan vara fördelaktigt för kraft- och nätstabilitet. Elektriska värmepumpar kan agera som en stor flexibel last samtidigt som fastighetens termiska tröghet fungerar som värmeenergilagring. I denna avhandling utförs en teknisk-ekonomisk analys av efterfrågeflexibilitet från värmepumpar för två bostadshus beläget i centrala Örebro med hjälp av energisimuleringar av fastigheten. Genom denna avhandling syftar författaren på att höja intelligensen av de befintliga fastigheterna genom att undersöka storleken av den termiska trögheten som finns tillgänglig med avseende på olika värmescenario, byggnadsmaterial, ventilationssystem, väderförhållanden och användarbeteenden. Två flerfamiljshus, Klockarängsvägen och Pärllöken, väljs för jämförelse med avseende på den termisk tröghet som bidrar mest till efterfrågeflexibiliteten. De två utvalda fastigheterna använder värmepumpar för värme och varmvatten. Båda fastigheterna faktureras enligt effektabonnemang, vilket gör effektutjämning mer lönsamt. I det kallaste scenariot, när omgivningstemperaturen är -20°C, faller Pärllökens inomhustemperatur från 21°C till 19,1°C och Klockarängsvägens inomhustemperatur sjunker till 16,6°C om värmetillförseln stängs av i en timme. Under det lägsta börvärdet för inomhustemperatur på 18°C visar Pärllöken en maximal effektförskjutningskapacitet på 25 kW och för Klockarängsvägen-byggnader 20 kW. Med hänsyn till fastighetens termiska tröghet är Pärllöken utan tvekan vinnaren på grund av betong som väggsmaterial, högre termisk massa, balanserad ventilation, värmeåtervinningssystem och högre energiklass på fönsterglasen. Ovanstående skäl gör att Pärllökens termiska tidskonstant är minst tre gånger längre innan temperaturen når det lägsta börvärdet på 18°C, jämfört med Klockarängsvägen. Detta ger att Pärllöken har en högre förskjutningskapacitet av värme på 75 kWh jämfört med Klockarängsvägens maximala förskjutningskapacitet på 20 kWh. I en ekonomisk analys, baserat på författarens framtagna energimodeller, beaktas två styrstrategier i Pärllöken. Den ekonomiska analysen fokuserar på vintersäsongen från oktober till mars. Alternativ 1 driver värmepumpen med partiell kapacitet enligt reglerbar effekt. Alternativ 2 stänger av värmepumpen helt. Under vintersäsongen sparar Pärllöken 1 646 SEK med Alternativ 1 och 2 273 SEK med Alternativ 2. Klockarängsvägen använder sig endast av Alternativ 1 för en ekonomisk analys, vilket resulterar i en kostnadsbesparing på 20 948 SEK. En förstudie med värmepump i kombination med andra förnybara tekniker så som solceller på Klockarängsvägen genomförs för att undersöka potentialen av energibesparing. Kombinationen ger dock inte en positiv effekt på grund av den låga solinstrålningen under vintertid

Double-blind, randomized, multicenter phase 2 study of SC411 in children with sickle cell disease (SCOT trial)

Key Points SC411 increases DHA in blood cell membranes and reduces home-managed SCD pain crisis and analgesic and opioid use at home to treat SCD pain. The rate of sickle cell crisis was 53% lower for the pooled active groups vs placebo