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Aim: Electronic prescribing has allowed for the collection of prescription data in real time in Greece for the first time. Hence, the aim of the current study was to present the characteristics of prescriptions for the Greek population during the period from 2015 to 2021. Methods: This retrospective study was based on data extracted from the nationwide Greek electronic prescription database between January 2015 and December 2021. Descriptive statistics methods were used for the needs of the study. As the basic figures examined depend on the size of the population, in order for the results to be comparable, we estimated the corresponding measures per inhabitant, using population data from the Greek Statistical Authority. Appropriate indicators for the comparison of consumption and expenditure over time were estimated. A study of the trend was also carried out using time series and linear regression models. In order to facilitate the design and implementation of specialized policies, it is useful to identify the drug categories with the highest consumption and expenditure, as well as the geographical areas that present similar characteristics. For the first, ABC analysis was used, which helps to identify the most popular categories of drugs, while for the second, cluster analysis was carried out. Agglomerative clustering was used to divide the regions into similar groups. This hierarchical clustering algorithm classifies the population into several clusters, with areas in the same cluster being more similar, and areas in different clusters being dissimilar. The Ward linkage method with Euclidean distance was used. Results: The analysis of prescription drug consumption and expenditure from 2015 to 2021 revealed significant fluctuations and trends across various drug categories, age groups, and geographical areas. Notably, the quantity of prescriptions increased by 20% since 2015, while expenditure surged by over 30%, with significant spikes following the end of the MoU in 2019 and the onset of the pandemic in 2020. In terms of expenditure, antineoplastic and immunomodulation agents (category L) held the largest share, driven by the introduction of new, costly drugs. The expenditure per inhabitant revealed gender and age disparities, with older populations, particularly women, incurring higher costs. Geographically, drug expenditure, and consumption varied significantly, with distinct regional clusters identified. These clusters, while showing some overlap in consumption and expenditure patterns, also highlighted unique regional characteristics. Conclusions: The insights into prescription drug consumption and expenditure trends offer a valuable basis for developing targeted interventions aimed at optimizing healthcare resource allocation. Moreover, the findings underscore the importance of addressing regional and demographic disparities in pharmaceutical use, thereby contributing to more equitable and cost-effective healthcare strategies. More specifically, the age distribution of prescriptions shows the increase in younger ages, which, as a result, anticipates the overall increase in prescriptions. The knowledge of the most convex categories of medicine, as well as the percentages of the use of generic drugs, shows where interventions should be made, with financial incentives and information through new information channels. The geographic disparities recorded should lead to policies that help the residents of hard-to-reach areas to access prescriptions. In addition, the present study provides a strategic framework for policymakers and healthcare managers to guide future studies and inform decision-making processes. [ABSTRACT FROM AUTHOR]

Background: Autoimmune hemolytic anemia (AIHA) is a rare disease due to increased destruction of erythrocytes by autoantibodies, with or without complement activation. Summary: AIHA is usually classified in warm AIHA (wAIHA) and cold agglutinin disease (CAD), based on isotype and thermal amplitude of the autoantibody. The direct antiglobulin test (DAT) or Coombs test is the cornerstone of AIHA diagnosis, as it is positive with anti-IgG in wAIHA, and with anti-C3d/IgM antisera plus high titer cold agglutinins in CAD. Therapy is quite different, as steroids and rituximab are effective in the former, but have a lower response rate and duration in the latter. Splenectomy, which is still a good option for young/fit wAIHA, is contraindicated in CAD, and classic immunosuppressants are moving to further lines. Several new drugs are increasingly used or are in trials for relapsed/refractory AIHAs, including B-cell (parsaclisib, ibrutinib, rilzabrutinib), and plasma cell target therapies (bortezomib, daratumumab), bispecific agents (ianalumab, obexelimab, povetacicept), neonatal Fc receptor blockers (nipocalimab), and complement inhibitors (sutimlimab, riliprubart, pegcetacoplan, iptacopan). Clinically, AIHAs are highly heterogeneous, from mild/compensated to life-threatening/fulminant, and may be primary or associated with infections, neoplasms, autoimmune diseases, transplants, immunodeficiencies, and drugs. Along with all these variables, there are rare forms like mixed (wAIHA plus CAD), atypical (IgA or warm IgM driven), and DAT negative, where the diagnosis and clinical management are particularly challenging. Key Messages: This article covers the classic clinical features, diagnosis, and therapy of wAIHA and CAD, and focuses, with the support of clinical vignettes, on difficult diagnosis and refractory/relapsing cases requiring novel therapies. [ABSTRACT FROM AUTHOR]

Background • Cerebral infarction (CI) is one of the leading causes of death in middle-aged and elderly people, and there is a need to focus on overall rehabilitation during the recovery period of CI in the clinic, to provide a more reliable guarantee for the health of patients. Objective • To observe the therapeutic efficacy of Getong Tongluo Capsule (GTC) plus Clopidogrel hydrogen sulfate tablets (CHST) therapy assisted by home rehabilitation guidance in convalescents from CI, to provide clinical reference and evidence for future CI management. Methods • CI convalescents who visited the Fourth People’s Hospital of Haikou City between 2016 and 2021 were selected as the research participants. Based on the assistance of home rehabilitation guidance, 44 patients receiving CHST treatment and 56 patients receiving GTC + CHST treatment were assigned to a control group (CG) and research group (RG), respectively. The blood viscosity of the two groups was compared before and after treatment. In addition, patients were assessed by the National Institutes of Health Stroke Scale (NIHSS), Mini-Mental State Examination (MMSE), Fugl-Meyer Assessment (FMA), Modified Barthel index (MBI), and Self-rating Anxiety/Depression Scale (SAS/SDS) scores. Finally, the adverse reaction rate was counted. Results • The post-treatment blood viscosity decreased in both cohorts and was lower in RG compared with CG (P < .001). Regarding various scale scores, NIHSS, SAS, and SDS were lower in RG than CG, while MMSE, FMA, and MBI were higher (P < .001). The adverse reaction rate was not significantly different between groups (P = .587). Conclusion • GTC + CHST therapy assisted by home rehabilitation guidance is effective in the treatment of CI patients in the convalescent stage and is worth recommending. [ABSTRACT FROM AUTHOR]

Background: High-dose cytarabine (HDAC) is commonly used for consolidation therapy in young acute myeloid leukemia (AML) patients, but the dosage of cytarabine is still controversial in the clinic due to its obvious post-chemotherapy adverse effects. The aim of this study was to contrast the efficacy in different dose groups of cytarabine after consolidation therapy in Chinese AML patients. Methods: AML patients treated with cytarabine consolidation at Qilu Hospital, Shandong University from January 2010 to September 2022 were retrospectively analyzed, from which 346 AML patients with relatively complete follow-up data were selected for this study. We compared the patients' overall survival (OS) rate, relapse-free survival (RFS) rate, and hematologic adverse events in terms of their general characteristics, cytarabine consolidation therapy dose, consolidation course, 2022 European Leukemia Net (ELN) risk stratification, and transplantation. Results: In AML patients under 60 years of age, the 5-year RFS rate with high-dose cytarabine consolidation therapy was superior to that of small-dose cytarabine (P = 0.024), while the 5-year RFS rate was comparable in the high-dose and intermediate-dose groups, and there was no obvious difference among the three groups in the 5-year OS rate (P > 0.05). OS and RFS of those given more than 3 courses of cytarabine consolidation therapy were better than those in the 1–2 courses group (P = 0.060, P = 0.040). OS and RFS were better in patients with cumulative dose of cytarabine ≥ 36g than in patients with cumulative dose < 36g (P < 0.05), but cumulative dose ≥ 54g was comparable in OS and RFS with ≥ 36–< 54g group (P > 0.05). There was no significant difference in hematologic adverse effects among the three treatment groups. In the latest ELN risk stratification favorable-risk group, the cumulative dose of cytarabine ≥ 36g had a better 5-year RFS rate than the < 36g group (P = 0.038), and in the intermediate-risk group the 5-year OS rate and RFS rate were better in the ≥ 36g group than the < 36g group (P = 0.012, 0.025). In addition, the prognosis of transplanted patients was better than that of non-transplanted patients, whereas in non-transplanted patients, consolidation therapy with ≥ 36g cytarabine can effectively improve outcomes. Multivariate analysis indicated that age, fibrinogen (FIB) and the cumulative dose of cytarabine of ≥ 36–< 54g were predictors of OS, while age, white blood cell (WBC) and HDAC were predictors of RFS. Conclusion: The results of the study showed that consolidation therapy with cytarabine up to a cumulative dose of ≥ 36–< 54g in AML patients who did not undergo transplantation significantly improved patient prognosis. In the latest ELN risk stratification, cumulative doses of cytarabine ≥ 36g had a better prognosis in favorable and intermediate-risk patients. [ABSTRACT FROM AUTHOR]

Cirsium japonicum Fisch. ex DC. (CF) and Cirsium setosum (Willd.) MB (CS) are commonly used clinically to stop bleeding and eliminate carbuncles. Still, CF is mainly used for treating inflammation, while CS favors hemostasis. Therefore, the present study used UHPLC-MS to analyze the main chemical constituents in CF-CS extract. We optimized the extraction process using single-factor experiments and response surface methodology. Afterward, the hemostatic and anti-inflammatory effects of CF-CS extract were investigated by determining the clotting time in vitro, the bleeding time of rabbit trauma, and the induction of rabbit inflammation using xylene and lipopolysaccharide. The study of hemostatic and anti-inflammatory effects showed that the CF-CS, CF, and CS extract groups could significantly shorten the coagulation time and bleeding time of rabbits compared with the blank group (p < 0.01); compared with the model group, it could dramatically inhibit xylene-induced ear swelling in rabbits and the content of TNF-α, IL-6, and IL-1β in the serum of rabbits (p < 0.01). The results showed that combined CF and CS synergistically increased efficacy. CF-CS solved the problem of the single hemostatic and anti-inflammatory efficacy of a single drug, which provided a new idea for the research and development of natural hemostatic and anti-inflammatory medicines. [ABSTRACT FROM AUTHOR]

Akihiko Akamine,1 Yuya Nagasaki,2 Atsushi Tomizawa,2 Katsuya Otori2,3 1Department of Pharmacy, Doujin Hospital, Okinawa, Japan; 2Department of Pharmacy, Kitasato University Hospital, Kanagawa, Japan; 3Research and Education Center for Clinical Pharmacy, Division of Clinical Pharmacy, Laboratory of Pharmacy Practice and Science 1, Kitasato University School of Pharmacy, Tokyo, JapanCorrespondence: Akihiko Akamine, Department of Pharmacy, Doujin Hospital, 1-37-12 Gusukuma, Urasoe, Okinawa, 901-2133, Japan, Tel +81-98-876-2212, Fax +81-98-874-7034, Email a-aka@kitasato-u.ac.jpPurpose: The risk factors for non-adherence to pharmacist or non-pharmacist explanations of preoperative medication discontinuation are unknown. The primary outcome of this study was to determine whether the final explainer’s occupation was a risk factor for non-adherence. The secondary outcomes were to determine the risk factors for non-adherence after limiting the departments or adjusting for age.Patients and Methods: We retrospectively examined the data (including patient age, sex, prescription medications, comorbidities, presence of roommate, and number of days between receiving explanation and surgery) of 1132 patients on medications that could affect surgery at a Japanese university hospital between April 1, 2017, and March 31, 2020. The primary endpoint was whether the occupation of the last person explaining medication discontinuation to the patient was an independent risk factor for non-adherence (age ≥ 65 years vs < 65 years). Secondary endpoints included subgroup analyses in urological, gastrointestinal, and otolaryngological areas, as well as a sensitivity analysis (age as a continuous variable) to confirm the validity of the primary endpoint results. A multivariate binary logistic regression identified independent non-adherence risk factors.Results: The main analysis showed that discontinuing two or more medications was a risk factor for non-adherence (adjusted odds ratio (AOR): 1.67; 95% confidence interval (CI): 1.13– 2.47; p = 0.01). However, in analyses coordinated by department (urological, gastrointestinal, and otolaryngological), ≥ 65 (versus < 65) years of age was determined as a risk factor for increased nonadherence (AOR: 2.27, 95% CI: 1.11– 4.63; p=0.024). Age-adjusted analysis (continuous variables) showed similar results to the primary endpoint (AOR: 1.68, 95% CI: 1.14– 2.49, p = 0.009).Conclusion: Two or more medications, and not the final explainer’s occupation, were associated with pre-surgery medication non-adherence. To prevent non-adherence, pharmacists and non-pharmacists should educate patients about preoperative medication discontinuation. These findings could help identify high-risk non-adherence patients.Plain Language Summary: At Kitasato University Hospital, pharmacists and non-pharmacists explain before surgery that patients scheduled for surgery should discontinue medications that could affect surgery. However, there are patients who fail to follow these explanations precisely, but the risk factors have not yet been identified. This study examined risk factors for patients who failed to comply with explanations from a pharmacist or non-pharmacist regarding the use of medications that could affect surgery. Risk factors were examined using a statistical method for identifying risk factors by considering patients’ age ≥ 65 (versus < 65) years, sex, the job title that explained the instructions to the patient, number of medications to be discontinued before surgery, and number of days between instructions and surgery as risk factors. Based on pharmacist/non-pharmacist explanations, the statistical analysis revealed that patients taking two or more medications that could affect surgery may be a risk factor for non-adherence to medications that should be discontinued before surgery. To improve medication adherence, pharmacists and non-pharmacists should be aware of the patient’s non-adherence risk factors, repeatedly explain them to the patient, and help the patient understand that failure to comply with the explanation increases surgical cancelation and intraoperative bleeding risks.Keywords: medication adherence, hematologic agents, pharmaceutical service

Background : in the field of rare diseases (RDs) most of the European studies on budget impact analysis of drugs that have been conducted often lay on theoretical assumptions and focus only on Orphan drugs (ODs). Objectives : we aimed to estimate the budget impact of specific drugs for non-oncological RDs, both ODs and non-ODs, using real-world data about patients residing in Veneto Region (Italy) and to describe its expenditure structure and dynamics. Methods : a population-based multi-source observational study was conducted using data from Regional administrative databases; an ad-hoc drugs' list specific for RDs including both ODs and non-ODs and classifying them by ATC codes has been created. Results : In 2019, the total expenditure for drugs specific for RDs was EUR 97.2 million (6.6% of the total Regional budget). The RD drug list included 58 ATC codes, of which 15 ATC had an annual budget impact over EUR 1 million ("blockbuster drugs"). The most expensive treatment was a non-OD drug (Coagulation factor VIII). The two most represented therapeutical areas were the metabolic and the hematological ones. Conclusions : Cost analyses on RD high-cost drugs expenditure should consider any specific RD drug, not only ODs. Expenditure dynamics for RD drugs are peculiar showing "blockbuster drugs". Some therapeutical areas seem to be lacking in the drug research field. [ABSTRACT FROM AUTHOR]

Zeolite‐based hemostatic agents are considered as an outstanding material to achieve rapid and definitive hemostasis in pre‐hospital management. However, developing a safer zeolitic hemostat that avoids the potential thrombotic risk caused by tiny zeolite residue in bleeding wounds remains a critical challenge. In this research, we employ an in situ biosynthesis process to fabricate a sandwich‐like structured bacterial cellulose/zeolite (BC/zeolite) hybrid hemostat. Zeolite particles were firmly bonded into the BC membranes with <1% leaching after 24 soaking. This hemostat displays effective hemostatic performance after calcium ion‐exchange process. The BC/zeolite‐Ca hemostat can significantly decrease in vitro blood clotting time from 7.5 ± 0.3 min to 2.2 ± 0.3 min. This work achieves a low‐cost, eco‐friendly, and low‐risk approach through in situ biosynthesis in the preparation of BC‐ and zeolite‐based hybrid for pre‐hospital hemostasis applications. [ABSTRACT FROM AUTHOR]

Background: Whether combination therapy has higher hemostatic efficacy than epinephrine injection monotherapy in different Forrest classifications is not clear. This study aimed to compare hemostatic efficacy between epinephrine injection monotherapy (MT) and combination therapy (CT) based on different Forrest classifications. Methods: We retrospectively analyzed peptic ulcer bleeding (PUB) patients who underwent endoscopic epinephrine injections or epinephrine injections combined with a second therapy between March 2014 and June 2022 in our center, and the patients were divided into MT group or CT group. Subsequently, a propensity score matching analysis (PSM) was performed and rebleeding rates were calculated according to Forrest classifications via a stratified analysis. Results: Overall, 605 patients who met the inclusion criteria were included, and after PSM, 173 patients in each of the CT and MT groups were included. For PUB patients with nonbleeding visible vessels (FIIa), the rebleeding rates by Days 3, 7, 14, and 30 after PSM were 8.8%, 17.5%, 19.3%, and 19.3% in the MT group, respectively, and rates were 0%, 4.1%, 5.5%, and 5.5% in the CT group, respectively, with significant differences observed between the two groups by Days 3, 7, 14, and 30 (P = 0.015, P = 0.011, P = 0.014, and P = 0.014, respectively). However, for PUB patients with oozing bleeding (FIb), the rebleeding rates by Days 3, 7, 14, and 30 after PSM were 14.9%, 16.2%, 17.6%, and 17.6% in the MT group, respectively, and rates were 13.2%, 14.7%, 14.7%, and 16.2% in the CT group, respectively, with no significant differences observed between the two groups by Days 3, 7, 14, and 30 (P = 0.78, P = 0.804, P = 0.644 and P = 0.825). Conclusion: Combined therapy has higher hemostatic efficacy than epinephrine injection monotherapy for PUB patients with visible blood vessel (FIIa) ulcers. However, epinephrine injection monotherapy is equally as effective as combined therapy for PUB patients with oozing blood (FIb) ulcers. [ABSTRACT FROM AUTHOR]

This guidance document has been prepared on behalf of the International Council for Standardisation in Hematology. The aim of the document is to provide guidance and recommendations on the measurement of factor VIII (FVIII) and factor IX (FIX) inhibitors. After an introduction on the clinical background and relevance of factor VIII and factor IX inhibitor testing, the following aspects of laboratory testing are included: screening for inhibitors, assay principle, sample requirements, testing requirements and interpretation, quality assurance, interferences and recent developments. This guidance document focusses on recommendations for a standardised procedure for the laboratory measurement of FVIII and FIX type I inhibitors. The recommendations are based on published data in peer‐reviewed literature and expert opinion. [ABSTRACT FROM AUTHOR]

In vitro potency is one of the important parameters representing efficacy potential of drugs and commonly used as benchmark of efficacious exposure at early clinical development. There are limited numbers of studies which systematically investigate on how predictive in vitro potency is to estimate therapeutic drug exposure, especially those focusing on targeted anticancer agents despite the recent increase in approvals. This study aims to fill in such knowledge gaps. A total of 87 small molecule targeted drugs approved for oncology indication between 2001 and 2020 by the US Food and Drug Administration (FDA) were identified; relevant preclinical and clinical data were extracted from the public domain. Relationships between the in vitro potency and the therapeutic dose or exposure (unbound average drug concentration [Cu,av] as the primary exposure metrics) were assessed by descriptive analyses. The Spearman's rank correlation test showed slightly better correlation of the Cu,av (ρ = 0.232, p = 0.041) rather than the daily dose (ρ = 0.186, p = 0.096) with the in vitro potency. Better correlation was observed for the drugs for hematologic malignancies compared with those for solid tumors (root mean square error: 140 [n = 28] versus 297 [n = 59]). The present study shows that in vitro potency is predictive to estimate the therapeutic drug exposure to some extent, whereas the general trend of overexposure was observed. The results suggested that in vitro potency alone is not sufficient and robust enough to estimate the clinically efficacious exposure of molecularly targeted small molecule oncology drugs. The totality of data, including both nonclinical and clinical, needs to be considered for dose optimization. [ABSTRACT FROM AUTHOR]

Background and Hypothesis Treatment response to specific antipsychotic medications is difficult to predict on clinical grounds alone. The current study hypothesizes that the baseline complement pathway activity predicts the treatment response and investigates the relationship between baseline plasma biomarkers with treatment response to antipsychotic medications. Study Design Baseline plasma samples were collected from first episode of psychosis patients (n = 243) from a multi-center clinical trial. The participants were treated with amisulpride for 4 weeks. Levels of complement and coagulation proteins at baseline were measured using both data-dependent and data-independent mass spectrometry approaches. The primary outcome was remission status at 4 weeks and the secondary outcomes included change in psychotic and functional symptoms over the period of treatment. In addition, immunoassays were performed at baseline for complement C1R, as well as for activation markers C4a and sC5b-9. Study Results The plasma level of complement variant C4A was significantly associated with remission at 4 weeks. Moreover, higher levels of several complement and coagulation pathway proteins were associated with a reduction in psychotic symptoms and an improvement in functioning. Immunoassays showed an association of baseline levels of C1R and C4a as well as complement activation marker sC5b-9 levels with treatment response. Conclusion The results demonstrated that the response to antipsychotic treatment might be related to pre-treatment levels of plasma complement and coagulation pathway proteins. This is consistent with independent evidence associating immune dysfunction with the pathophysiology of psychosis. Moreover, these results inform the development of novel therapeutic approaches that target the complement system for psychosis. [ABSTRACT FROM AUTHOR]

Aim: Since suboptimal vitamin D3 levels may be associated with anemia and several disorders, the study presented here investigated hematological indices state at patients with vitamin D3 deficiency. Methods: This cross-sectional study performed in Isfahan, Iran between 2017 and 2019. Initially, patient vitamin D3 level was determined. Based on vitamin D3 reference ranges them were divided into two vitamin D3-deficient (vitamin D3<25ng/mL) and control groups (>25ng/mL). Completed blood count was measured by hematology analyzer. Alkaline phosphatase (ALK) level was also measured and the results were statistically analyzed. Results: Of 1925 studied patients, 621 (32.3%) patients were male and 1274 (67.7%) females. 909 patients have an abnormal levels of vitamin D3 (<25ng/mL) and 1016 patients have sufficient vitamin D3 level. A weak correlation observed between white cell count and mean cell volume and low level of vitamin D3 (beta = 0.11). We also found a significant difference in mean age of patients with vitamin D3-deficient compared to control (p = 0.003). Moreover, we found no significant change in serum ALK levels between patients with vitamin D3 deficiency and control as well as subgroups of vitamin D3 deficiency. Conclusions: Vitamin D3 deficiency may not have significant impact on red cell count and indices, differential white blood cell count, and platelet count. It is suggested that a prospective cohort study be conducted in the future. [ABSTRACT FROM AUTHOR]

Since the recognition of BRAF V600E mutations in the majority of cases of hairy cell leukaemia, Erdheim–Chester disease and Langerhans cell histiocytosis, the targeted oral kinase inhibitors dabrafenib and vemurafenib have been adapted for their treatment. Like other targeted agents, these drugs produce high response rates and predictable but unique side effects. Physician familiarity is essential for the effective use of these agents. We review the Australian experience of BRAF/MEK inhibitor therapy in these rare haematological cancers. [ABSTRACT FROM AUTHOR]

Introduction: Abnormal uterine bleeding (AUK) is a term used for changes in menstrual bleeding pattern, duration, or amount. In adolescent girls, it is associated with the immature hypothalamo-pituitary-ovarian axis, bleeding disorders, infections, endocrine disorders, systemic diseases, vagina-cervix-uterus and problems related to the ovary and drugs. There are different approaches between different disciplines in this assessment. In our study, we aimed to share our results and contribute to the hematological approach to these cases by retrospectively evaluating the abnormal uterine bleeding examination and treated cases in Afyon Health Sciences University Department of Pediatric Hematology. Materials and Methods: Between July 2016 and September 2019, patients over 12 years admitted to the Afyonkarahisar University of Health Sciences Department of Pediatric Hematology who had hemoglobin value <12 grams/dL and 60-80 mL bleeding in normal menstrual period (3-6 pads/day or 10-15 pads/cycle), menstrual cycle lasting longer than 8 days, and menstrual cycle repeated more than 21-28 days were included in the study and their records were analyzed retrospectively. The demographic features, admittion complaints, consultations, treatments applied and the results were documented and evaluated. Results: A total of 39 subjects were enrolled in the study. The mean age of the patients was 16.2±1.5 (13.2-21.5), the mean age at menarche was 12.4±1.1 (8-14). Hb <8 g/dL in 53.8% (n=21) of patients, hb 8-10 g/dL in 23% (n=9) and 10-12 g/dL in 23% (n=9) and von Willebrand Type 1 was detected in one patient. Conclusion: Abnormal uterine bleeding is an important cause of anemia in adolescent girls. It is necessary to conduct investigations for etiology and bleeding disorders especially von Willebrand disease, in differential diagnosis. The communication of different disciplines and the knowledge of other disciplines about the approach to the subject for effective treatment of abnormal uterine bleeding plays an important role in decreasing hospital admissions and increasing the success of treatment. [ABSTRACT FROM AUTHOR]

Background Neurointerventionists lack guidelines for the use of antithrombotic therapies in their clinical practice; consequently, there is likely to be significant heterogeneity in antithrombotic use between centers. Through a nationwide survey, we aimed to obtain an exhaustive cross-sectional overview of antithrombotic use in neurointerventional procedures in France. Methods In April 2021, French neurointerventional surgery centers were invited to participate in a nationwide 51-question survey disseminated through an active traineeled research collaborative network (the JENI-RC). Results All 40 centers answered the survey. Fifty-one percent of centers reported using ticagrelor and 43% used clopidogrel as premedication before intracranial stenting. For flow diversion treatment, dual antiplatelet therapy was maintained for 3 or 6 months in 39% and 53% of centers, respectively, and aspirin was prescribed for 12 months or more than 12 months in 63% and 26% of centers, respectively. For unruptured aneurysms, the most common heparin bolus dose was 50 IU/kg (59%), and only 35% of centers monitored heparin activity for dose adjustment. Tirofiban was used in 64% of centers to treat thromboembolic complications. Fifteen percent of these comprehensive stroke centers reported using tenecteplase to treat acute ischemic strokes. Cangrelor appeared as an emergent drug in specific indications. Conclusion This nationwide survey highlights the important heterogeneity in clinical practices across centers. There is a pressing need for trials and guidelines to further evaluate and harmonize antithrombotic regimens in the neurointerventional field. [ABSTRACT FROM AUTHOR]

An analysis of the range of antioxidant and hemostatic preparations registered in the Republic of Uzbekistan was carried out on the basis of information from the State Registers of Medicines, Medical Devices and Medical Equipment: 2019 No. 23, 2020 No. 24, 2021 No. 25. The sales volume of hemostatic drugs in the Uzbek market in 2019-2021 was studied based on DRUG AUDIT data. [ABSTRACT FROM AUTHOR]

Venetoclax is a novel agent used in hematologic malignancies. Although no long-term studies have directly implicated venetoclax, few studies show possible association with electrolyte abnormalities. Severe derangements in serum electrolyte levels can cause cardiac dysrhythmias, which can be potentially fatal. We present a case of venetoclax in association with the other medications causing life-threatening arrhythmias. Hypothesized mechanisms include damage to the distal tubules causing loss of potassium and magnesium. Our patient required modification of his medications and aggressive repletion of electrolytes with good outcomes. For patients on venetoclax, especially those with polypharmacy, caution should be exercised to prevent severe electrolyte derangements, which can lead to life-threatening arrhythmias. [ABSTRACT FROM AUTHOR]

Hematologic malignancies are lethal diseases arising from accumulated leukemic cells with substantial genetic or epigenetic defects in their natural development. Epigenetic modifications, including DNA methylation and histone modifications, are critical in hematologic malignancy formation, propagation, and treatment response. Both mutations and aberrant recruitment of epigenetic modifiers are reported in different hematologic malignancies, which regarding the reversible nature of epigenetic regulations, make them a potential target for cancer treatment. Here, we have first outlined a comprehensive overview of current knowledge related to epigenetic regulation's impact on the development and prognosis of hematologic malignancies. Furthermore, we have presented an updated overview regarding the current status of epigenetic-based drugs in hematologic malignancies treatment. And finally, discuss current challenges and ongoing clinical trials based on the manipulation of epigenetic modifies in hematologic malignancies. • HMAs like 5-azacytidine and Decitabine treat MDS and AML by causing DNA hypomethylation, but responses vary by dosage and mutations. • HDACis like Panobinostat, vorinostat, and valproic acid treat hematologic malignancies by promoting cell differentiation and apoptosis. • Combining epigenetic drugs with BCL2 inhibitors or HDACis with immune checkpoint inhibitors enhances treatment response in AML and lymphoma. • Targeting bromodomain proteins like BRD4 with BET inhibitors downregulates oncogenes, inducing apoptosis in various hematologic malignancies. [ABSTRACT FROM AUTHOR]

Erythropoietin (EPO) acts on erythroid progenitor cells to promote their survival and differentiation to mature erythrocytes. Along with this canonical role, EPO is also reported to modulate energy metabolism, resulting in improved glucose tolerance and insulin sensitivity. EPO also stimulates the production of the hormone erythroferrone (ERFE) which acts to suppress hepcidin production, thus increasing dietary iron absorption and mobilizing stored iron for use in erythropoiesis. ERFE (initially termed myonectin) was also reported have an effect on systemic lipid metabolism by promoting the clearance of nonesterifed fatty acids (NEFA) from circulation. As increased levels of circulating NEFA blunt insulin sensitivity and impair glucose tolerance, ERFE-induced clearance of NEFA after EPO administration would have a beneficial effect on glucose metabolism. The aim of this study was to determine if the known metabolic effect of EPO treatment on glucose homeostasis is mediated by ERFE, produced in response to EPO. Mice lacking Erfe did not differ from wild-type mice in blood lipid parameters, blood glucose, and glucose or insulin tolerance at baseline or after chronic EPO treatment. Additionally, hepcidin suppression and the response of erythrocyte parameters to chronic EPO treatment were unaffected by the absence of Erfe. These findings suggest that the known beneficial effects of EPO on glucose metabolism are not attributable to an accompanying increase in ERFE production, and that Erfe is dispensable for normal glucose homeostasis. Furthermore, our data indicate that ERFE-independent mechanisms can suppress hepcidin in response to chronically elevated EPO levels.

Marzeptacog alfa (activated) (MarzAA) is an activated recombinant human FVII (rFVIIa) variant developed as subcutaneous (s.c.) administration for the treatment or prevention of bleeding episodes in patients with hemophilia A (HA) or hemophilia B (HB) with inhibitors and other rare bleeding disorders. Population pharmacokinetic (PK) modeling was applied for dose selection for a pivotal phase III clinical trial evaluating s.c. MarzAA for episodic treatment of spontaneous or traumatic bleeding episodes. The population PK model used MarzAA intravenous and s.c. data from previously completed clinical trials in patients with HA/HB with or without inhibitors. Based on the model, clinical trial simulations were performed to predict MarzAA exposure after different dosing regimens. The exposure target was identified using an exposure‐matching strategy with a wild‐type rFVIIa but adjusting for the difference in potency between the two compounds. Simulations demonstrated a sufficient absorption rate and prolonged exposure following a single 60 μg/kg dose leading to 51% and 70% of the population reaching levels above the target after 3 and 6 h, respectively. According to the phase III protocol, if a second dose was required after 3 h because of a lack of efficacy, 90% of the population was observed to be above target 6 h after the initial dose. The model‐informed drug development approach integrated information from several trials and guided dose selection in the pivotal phase III clinical trial for episodic treatment of an acute bleeding event in individuals with HA or HB with inhibitors without the execution of a phase II trial for that indication. [ABSTRACT FROM AUTHOR]

Certaines situations fréquentes comme l'exploration d'une splénomégalie ou d'une lymphocytose ou plus rares comme une anémie hémolytique auto-immune, une maladie des agglutinines froides ou une cryoglobulinémie ont pour point commun de pouvoir conduire au diagnostic de lymphome splénique. Les lymphomes spléniques sont rares, généralement des lymphomes non-hodgkiniens et regroupent des entités très différentes dans leur présentation clinique et biologique allant d'un lymphome agressif comme le lymphome T hépatosplénique à un lymphome B indolent ne nécessitant parfois pas de traitement en première intention comme le lymphome splénique de la zone marginale, le plus fréquent des lymphomes spléniques. Ces lymphomes sont parfois difficiles à diagnostiquer et à différencier. Dans cette revue nous présentons les manifestations cliniques et biologiques pouvant conduire à suspecter un lymphome splénique ainsi que la démarche diagnostique et les différentes entités pouvant être rattachées à ce cadre nosologique. Nous étendons volontairement la définition stricte du lymphome splénique (lymphome ayant pour seule atteinte d'organe la rate) aux lymphomes pouvant être révélés ou évoluer vers une atteinte splénique. Cela permettra également d'aborder les diagnostics différentiels non hématologiques qu'il faut évoquer devant une splénomégalie. Some common clinical situations, such as splenomegaly or lymphocytosis, or less common, such as autoimmune hemolytic anemia, cold agglutinin disease, or cryoglobulinemia can lead to the diagnosis of splenic lymphoma. Splenic lymphoma is rare, mainly of non-hodgkinian origin, encompassing very different hematological entities in their clinical and biological presentation from an aggressive form such as hepato-splenic lymphoma to indolent B-cell lymphoma not requiring treatment such as marginal zone lymphoma, the most frequent form of splenic lymphoma. These entities can be challenging to diagnose and differentiate. This review presents different clinical and biological manifestations suspicious of splenic lymphoma and proposes a diagnosis work-up. We extended the strict definition of splenic lymphoma (lymphoma exclusively involving the spleen) to lymphoma thant can be revealed by a splenomegaly and we discuss the differential diagnosis of splenomegaly. [ABSTRACT FROM AUTHOR]

What Is Known and Objective: Eltrombopag is an orally bioavailable drug developed as a second‐line treatment for immune thrombocytopenia. However, there are limited reports on thrombotic events related to eltrombopag use. This study aimed to assess the relationship between eltrombopag and thrombotic events in a large population extracted from the Food and Drug Administration Adverse Event Reporting System (FAERS) database. Methods: A total of 525 FAERS reports on thrombotic events associated with eltrombopag alone and 59 on those associated with the simultaneous use of eltrombopag and glucocorticoids, from Q1 2004 to Q3 2021, were included. Reports of thrombotic events were analysed using the following algorithms: reporting odds ratio (ROR), proportional reporting ratio (PRR), Bayesian confidence propagation neural network (BCPNN), and multi‐item gamma Poisson shrinker (MGPS). The time to onset and outcomes of thrombotic events between the two groups were also analysed. Results and Discussion: A total of 525 reports of thrombotic events with eltrombopag were identified. Compared with eltrombopag alone, the concomitant use of eltrombopag and glucocorticoids was associated with a higher incidence of thrombotic events based on higher ROR (9.92, 95% two‐sided CI 7.58–12.97 vs. 3.46, 95% two‐sided CI 3.17–3.77), PRR (9.06, χ2 = 427.37 vs. 3.37, χ2 = 881.55), IC (3.18, 95% one‐sided CI = 2.43 vs. 1.75, 95% one‐sided CI = 1.6), and EBGM (9.06, 95% one‐sided CI = 7.23, vs 3.36, 95% one‐sided CI = 3.13). What Is New and Conclusion: Our findings support an association between thrombotic events and eltrombopag use. Moreover, concomitant use of eltrombopag and glucocorticoids appeared to result in an even higher incidence of thrombotic events. [ABSTRACT FROM AUTHOR]

Thrombocytopenia is a common and unsolved problem in myelodysplastic syndrome (MDS) patients; we aimed to summarize the evidence of TPO-RA treatment for heath-related quality of life (HRQoL) and platelet transfusion burden of MDS patients. We searched Pubmed, Web of Science, EMBASE, and CENTRAL for randomized clinical trials (RCTs) comparing TPO-RA to placebo in MDS published until July 31, 2021. A random-effect model was used. Eight RCTs with 908 patients were identified. Only three RCTs involving eltrombopag reported HRQoL, and all three studies treated HRQoL as a secondary outcome. In these three RCTs, the HRQoL instruments used in each study were different. However, this outcome cannot be meta-analyzed because some studies did not provide complete data. Subsequent clinical trials should pay more attention to this. Compared to placebo, TPO-RA did not affect platelet transfusion incidence 0.83 (95% CI 0.60-1.15). There was no evidence for subgroup differences in the analyses of different types of TPO-RA, different additional agent, and different types of MDS risk groups. However, platelet transfusion units (RR = 0.68, 95% CI 0.53 to 0.84) were significantly decreased. The RR of patients who did not require platelet transfusion for 56 or more consecutive days was not different between groups (RR = 0.98, 95% CI 0.41 to 2.34). TPO-RA may decrease platelet transfusion units in MDS patients with thrombocytopenia. But the significance of this finding should be interpreted with caution, because too few studies were meta-analyzed. [ABSTRACT FROM AUTHOR]

Objectives: We primarily aimed to investigate the hematologic inflammatory parameters such as mean platelet volume (MPV), neutrophil-lymphocyte ratio (NLR), and platelet-lymphocyte ratio (PLR) in patients with acromegaly. We also aimed to reveal the importance of these parameters in determining disease activity. Methods: The medical data of 535 patients with acromegaly were retrospectively reviewed. The sociodemographic characteristics, presence of comorbid disease, acromegaly-related clinical and medical treatment characteristics, insulinlike growth factor-1 and growth hormone levels at diagnosis, postoperative 3rd month and last visit, and hematologic inflammatory markers and indices at last visit were obtained from the patients' medical charts. The patients were divided into age-, sex-, and comorbid disease-matched four groups according to their last remission status: active disease, remission with only surgery, remission with medication, and discordant disease. Finally, a total of 290 patients were included. Results: We examined a total of 290 patients with acromegaly after primary therapy; 36 had active disease, 77 were in remission with only surgery, 129 were in remission with medication, and 48 had a discordant disease. When the patients were categorized by last remission status, the median MPV was higher in patients with discordant disease than in the remission group with only surgery, and there were no differences in terms of the NLR and PLR between groups. When the participants were divided into two groups according to the presence of remission at the postoperative 3rd month, patients who had remission had lower MPV levels than those who had not. However, the groups had similar features for the NLR and PLR. Conclusion: Our results, particularly those that reveal positive association between MPV and remission status, indicate that subclinical inflammation may play a role in increased mortality and morbidity. Therefore, in addition to patients with active disease, patients with discordant disease should be followed closely for cardiovascular risks. [ABSTRACT FROM AUTHOR]

C. odorata L. is considered to be a plant weed that is scattered in various climates. As a weed, this plant contains a variety of beneficial secondary metabolites. Several studies have shown the benefits of C. odorata L. leaf extract. This study reviews the metabolite content and the pharmacological activities of C. odorata L. leaf extract. A literature search was carried out to obtain various studies related to the use of this plant extract. Secondary metabolites identified in C. odorata L. are alkaloids, flavonoids, tannins, saponins, and steroids. Several reports have also shown that even though it is considered a weed, C. odorata L. leaf extract also provides many benefits due to its pharmacological activities. Various pharmacological activities include anti-inflammatory, anti-microbial, antioxidant, antidyslipidemia, hematologic agent, anti-diabetic and anti-cataract, analgesic and antipyretic, wound healing, anti-malaria, mosquito larvicidal, anti-hypercholesterolemia, and antifungal. [ABSTRACT FROM AUTHOR]

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Importance: Sickle cell disease (SCD) is an inherited disorder of hemoglobin, characterized by formation of long chains of hemoglobin when deoxygenated within capillary beds, resulting in sickle-shaped red blood cells, progressive multiorgan damage, and increased mortality. An estimated 300 000 infants are born annually worldwide with SCD. Most individuals with SCD live in sub-Saharan Africa, India, the Mediterranean, and Middle East; approximately 100 000 individuals with SCD live in the US.Observations: SCD is diagnosed through newborn screening programs, where available, or when patients present with unexplained severe atraumatic pain or normocytic anemia. In SCD, sickling and hemolysis of red blood cells result in vaso-occlusion with associated ischemia. SCD is characterized by repeated episodes of severe acute pain and acute chest syndrome, and by other complications including stroke, chronic pain, nephropathy, retinopathy, avascular necrosis, priapism, and leg ulcers. In the US, nearly all children with SCD survive to adulthood, but average life expectancy remains 20 years less than the general population, with higher mortality as individuals transition from pediatric to adult-focused health care systems. Until 2017, hydroxyurea, which increases fetal hemoglobin and reduces red blood cell sickling, was the only disease-modifying therapy available for SCD and remains first-line therapy for most individuals with SCD. Three additional therapies, L-glutamine, crizanlizumab, and voxelotor, have been approved as adjunctive or second-line agents. In clinical trials, L-glutamine reduced hospitalization rates by 33% and mean length of stay from 11 to 7 days compared with placebo. Crizanlizumab reduced pain crises from 2.98 to 1.63 per year compared with placebo. Voxelotor increased hemoglobin by at least 1 g/dL, significantly more than placebo (51% vs 7%). Hematopoietic stem cell transplant is the only curative therapy, but it is limited by donor availability, with best results seen in children with a matched sibling donor. While SCD is characterized by acute and chronic pain, patients are not more likely to develop addiction to pain medications than the general population.Conclusions and Relevance: In the US, approximately 100 000 people have SCD, which is characterized by hemolytic anemia, acute and chronic pain, acute chest syndrome; increased incidence of stroke, nephropathy, and retinopathy; and a life span that is 20 years shorter than the general population. While hydroxyurea is first-line therapy for SCD, L-glutamine, crizanlizumab, and voxelotor have been approved in the US since 2017 as adjunctive or second-line treatments, and hematopoietic stem cell transplant with a matched sibling donor is now standard care for severe disease. [ABSTRACT FROM AUTHOR]

Tooth removal, particularly for patients with severe periodontitis, can frequently cause massive bleeding, postoperative infection, and bone resorption, resulting in a dry socket. Thus, developing bio-multifunctional materials with excellent antibacterial, hemostatic, and osteogenic characteristics for the prevention of dry sockets after tooth removal is highly desirable in clinical applications. Herein, chitosan-CaP microflowers (CM) and metronidazole (MD) loaded calcium alginate (CA) sponges (CA@CM/MD) with enhanced antibacterial, hemostatic, and osteogenic properties were developed via Ca2+ crosslinking, lyophilization, and electrostatic interaction for the prevention of dry socket after tooth removal. The fabricated CM particles display 3-dimensional, relatively homogeneous, and flower-shaped architectures. The CA@CM/MD composite sponges were facilely shaped into the tooth root as well as exhibit interconnected porous and lamellar structures with remarkable porosity, suitable maximum swelling ratio, as well as excellent compressive and hemostatic performance. Besides, the in vitro cellular assessment demonstrates that the prepared CA@CM/MD composite sponges possess satisfactory cytocompatibility. Importantly, the designed sponges significantly suppress the growth of S. aureus and E. coli , as well as promote cellular osteogenic differentiation by upregulating the formation of alkaline phosphatase. Our findings indicate that the tooth root-shaped composite sponges hold great promise for wound management after tooth removal. [ABSTRACT FROM AUTHOR]