Suchergebnisse

ABSTRACT Objective: To assess compliance with recommendations for empiric antibiotic therapy for febrile neutropenia, as outlined in the 1997 guidelines of the Infectious Diseases Society of America (IDSA), and to compare selected outcomes of episodes for which treatment was or was not in compliance with these guidelines.Methods: A concurrent, noninterventional chart review was conducted for 50 consecutive episodes of febrile neutropenia that occurred in 44 patients between January and May 1999 at a university-affiliated, tertiary care referral oncology centre. Empiric antibiotic therapy was assessed for compliance with IDSA guidelines. Episodes treated with compliant and noncompliant treatment regimens were compared for defervescence at 72 h and other selected clinical outcomes. Infection and response to therapy were assessed according to previously published criteria.Results: An empiric antibiotic regimen that was in compliance with the guidelines was prescribed in 28 (56%) of the 50 episodes. Patients who received such therapy were more likely than those receiving noncompliant therapy to be male (71% and 41%, p = 0.03) and to have a hematological malignancy (75% and 50%, p = 0.07). There were no significant differences between groups with respect to defervescence at 72 h, overall response to therapy, number of modifications to the antibiotic regimen, duration of empiric and total antibiotic therapy, adverse drug reactions, consultation to the infectious disease service, admission to the intensive care unit, or mortality rate.Conclusion: Because outcomes were similar in patients receiving compliant and noncompliant therapy, it appears unnecessary to implement a prescriptive policy enforcing compliance for all episodes of febrile neutropenia at this oncology centre. RÉSUMÉ Objectif : Évaluer la conformité aux recommandations en matière d'antibiothérapie empirique pour le traitement de la neutropénie fébrile, telles que décrites dans les lignes directrices de 1997 de l'Infectious Diseases Society of America (IDSA), et comparer des résultats thérapeutiques choisis pour les épisodes pour lesquels les lignes directrices avaient ou n'avaient pas été observées.Méthodes : Une analyse simultanée non expérimentale a été menée sur les données de 50 épisodes consécutifs de neutropénie fébrile qui sont survenus chez 44 patients, entre janvier et mai 1999 à un centre de références de soins tertiaires oncologiques affilié à une université. L'antibiothérapie empirique a été évaluée pour observer le résultat de la conformité aux lignes directrices de l'IDSA. Les épisodes pour lesquels le schéma thérapeutique était ou non conforme avec les lignes directrices ont été comparés, à la recherche de signes de défervescence 72 heures après le traitement et d'autres résultats cliniques choisis. L'infection et la réaction au traitement ont aussi été évaluées conformément à des critères déjà publiés.Résultats : L'antibiothérapie empirique conforme aux lignes directrices a été prescrite dans 28 (56 %) des 50 épisodes. Les patients qui ont reçu cette antibiothérapie étaient pour la plupart, contrairement à ceux qui ont reçu une antibiothérapie non conforme aux lignes directrices, des hommes (71 % vs 41 %, p = 0,03) et présentaient une affection hématologique (75 % vs 50 %, p = 0,07). Aucune différence notable entre les deux groupes n'a été observée au chapitre de la défervescence à 72 heures, de la réponse globale au traitement, du nombre de modifications de schéma thérapeutique, de la durée du traitement antibiotique empirique et généralisé, des réactions médicamenteuses indésirables, des consultations au service des maladies infectieuses, des admissions à l'unité des soins intensifs, ou de la mortalité.Conclusion : Étant donné que les résultats étaient semblables pour les patients qui recevaient ou non l'antibiothérapie conformément aux lignes directrices, il semble donc inutile de mettre en oeuvre une politique normative obligeant l'observance des lignes directrices pour tous les épisodes de neutropénie fébrile dans ce centre de soins oncologiques.

Abstract Background The primary objective was to describe the total direct inpatient costs among solid tumor and lymphoma patients with chemotherapy-induced febrile neutropenia (FN) and the factors that were associated with higher direct cost. The secondary objective was to describe the out-of-pocket patient payments and the factors that were associated with higher out-of-pocket patient payments. Methods This was a single-center observational study conducted at the largest cancer center in Singapore. All of the adult cancer patients hospitalized due to FN from 2009 to 2012 were studied. The primary outcomes were the total hospital cost and the out-of-pocket patient payments (adjusted by government subsidy) per FN episode. Univariate analysis and multiple linear regression were conducted to identify the factors associated with higher FN costs. Results Three hundred and sixty seven adult cancer patients were documented with FN-related hospitalizations. The mean total hospital cost was US$4,193 (95% CI: US$3,779-4,607) and the mean out-of-pocket patient payment was US$2,230 (95% CI: US$1,976-2,484), per FN episode. The factors associated with a higher total hospital cost were longer length of stay, severe sepsis, and lymphoma as underlying cancer. The out-of-pocket patient payment was positively associated with longer length of stay, severe sepsis, lymphoma diagnosed as underlying cancer, the therapeutic use of granulocyte colony-stimulating factor (GCSF), the private ward class, and younger patients. Conclusions The total hospital cost and out-of-pocket patient payments of FN management in lymphoma cases were substantial compared with other solid tumors. Factors associated with a higher FN management cost may be useful for developing appropriate strategies to reduce the cost of FN for cancer patients.

BackgroundThe primary objective was to describe the total direct inpatient costs among solid tumor and lymphoma patients with chemotherapy-induced febrile neutropenia (FN) and the factors that were associated with higher direct cost. The secondary objective was to describe the out-of-pocket patient payments and the factors that were associated with higher out-of-pocket patient payments.MethodsThis was a single-center observational study conducted at the largest cancer center in Singapore. All of the adult cancer patients hospitalized due to FN from 2009 to 2012 were studied. The primary outcomes were the total hospital cost and the out-of-pocket patient payments (adjusted by government subsidy) per FN episode. Univariate analysis and multiple linear regression were conducted to identify the factors associated with higher FN costs.ResultsThree hundred and sixty seven adult cancer patients were documented with FN-related hospitalizations. The mean total hospital cost was US$4,193 (95% CI: US$3,779-4,607) and the mean out-of-pocket patient payment was US$2,230 (95% CI: US$1,976-2,484), per FN episode. The factors associated with a higher total hospital cost were longer length of stay, severe sepsis, and lymphoma as underlying cancer. The out-of-pocket patient payment was positively associated with longer length of stay, severe sepsis, lymphoma diagnosed as underlying cancer, the therapeutic use of granulocyte colony-stimulating factor (GCSF), the private ward class, and younger patients.ConclusionsThe total hospital cost and out-of-pocket patient payments of FN management in lymphoma cases were substantial compared with other solid tumors. Factors associated with a higher FN management cost may be useful for developing appropriate strategies to reduce the cost of FN for cancer patients.

BackgroundThe primary objective was to describe the total direct inpatient costs among solid tumor and lymphoma patients with chemotherapy-induced febrile neutropenia (FN) and the factors that were associated with higher direct cost. The secondary objective was to describe the out-of-pocket patient payments and the factors that were associated with higher out-of-pocket patient payments.MethodsThis was a single-center observational study conducted at the largest cancer center in Singapore. All of the adult cancer patients hospitalized due to FN from 2009 to 2012 were studied. The primary outcomes were the total hospital cost and the out-of-pocket patient payments (adjusted by government subsidy) per FN episode. Univariate analysis and multiple linear regression were conducted to identify the factors associated with higher FN costs.ResultsThree hundred and sixty seven adult cancer patients were documented with FN-related hospitalizations. The mean total hospital cost was US$4,193 (95% CI: US$3,779-4,607) and the mean out-of-pocket patient payment was US$2,230 (95% CI: US$1,976-2,484), per FN episode. The factors associated with a higher total hospital cost were longer length of stay, severe sepsis, and lymphoma as underlying cancer. The out-of-pocket patient payment was positively associated with longer length of stay, severe sepsis, lymphoma diagnosed as underlying cancer, the therapeutic use of granulocyte colony-stimulating factor (GCSF), the private ward class, and younger patients.ConclusionsThe total hospital cost and out-of-pocket patient payments of FN management in lymphoma cases were substantial compared with other solid tumors. Factors associated with a higher FN management cost may be useful for developing appropriate strategies to reduce the cost of FN for cancer patients.

Objective: Febrile neutropenia (FN) is viewed as the most decimating oncological crisis particularly inchemotherapy-incited patients. The primary objective of the study was to identify the total directexpenditure of patients during febrile neutropenia with clinical consequences and the secondary aim wasto find out the factors associated with higher cost. Materials and Method: This was a single-centered hospital-based study in the largest and only specializedcancer care centre in Bangladesh in the government sector. This prospective study was done in theinpatients' department of the National Institute of Cancer Research and Hospital from April 2020 toJanuary 2021. The primary outcome was the out-of-pocket patient payments (adjusted by governmentsubsidy) per FN episode. Univariate analysis and multiple linear regression were conducted to identifythe factors associated with higher costs. Results and Discussions: A total of 101 patients were enrolled in the study. The mean (SD) age was33.49 (±15.79) years. Of the 101 participants, 63.4% were male. Among the patients, 13.9% died during theepisode and 86.1% recovered. Having co-morbidities and COVID-19 were associated with an increasedrisk of death. The mean cost was US$ 999.44 (±499.05) and the mean length of hospital stay was 21.98(±9.3) days. The longer hospital stay was significantly associated with higher costs. Conclusion: This study will help to ascertain the hospital cost and clinical outcome of FN whichultimately can help in policymaking strategy. J MEDICINE 2022; 23: 48-53

Cornelius F WallerFreiburg University Medical Center, Department of Hematology/Oncology, Freiburg, GermanyAbstract: Recombinant granulocyte colony-stimulating factor (filgrastim) stimulates the proliferation and differentiation of hematopoietic stem and progenitor cells committed to neutrophil and granulocyte lineages. Filgrastim has been used as an adjunct to chemotherapy for ameliorating neutropenia, one of the major side effects of chemotherapy in cancer patients. Its use has led to reduction of infections and hospital admissions for patients with cancer undergoing chemotherapy. In addition, filgrastim has multiple other indications in hematology and oncology. Following the European Union patent expiry of Neupogen® (filgrastim; Amgen Inc) in 2006, a biosimilar filgrastim has been developed (Nivestim™; Hospira). In accordance with the requirements of the European Medicines Agency, Nivestim has been studied in a development program that included preclinical studies, two Phase I clinical trials, and one Phase III clinical study. Preclinical studies showed pharmacodynamic as well as pharmacokinetic bioequivalence with the original product, Neupogen. Two randomized, single-center, Phase I trials compared both the pharmacokinetic, pharmacodynamic, and safety profiles of Nivestim and Neupogen in healthy volunteers. In both studies, 90% confidence intervals for the primary endpoints were within the predefined range (0.80–1.25) necessary to demonstrate bioequivalence. Nivestim was well tolerated, with no additional safety concerns over Neupogen. Bioequivalence was demonstrated in a randomized, double-blind multicenter Phase III trial of 279 patients with breast cancer receiving myelosuppressive chemotherapy. The mean duration of severe neutropenia in cycle 1, the primary endpoint, was similar between Nivestim (1.6 days, n = 165) and Neupogen (1.3 days, n = 85), meeting predefined criteria for bioequivalence. Secondary endpoints supporting bioequivalence included the mean time to recovery of absolute neutrophil count and incidence of febrile neutropenia. The most common treatment-related adverse event with Nivestim was grade 1–2 bone pain. As a result of these preclinical and clinical trials, Nivestim was approved by the European Medicines Agency and in Australia for prevention of febrile neutropenia and treatment of neutropenia in cancer patients treated with cytotoxic chemotherapy (except in patients with myelodysplastic syndromes and chronic myelogenous leukemia). Nivestim is also indicated for the treatment of myelosuppression after bone marrow transplantation, of neutropenia in patients with human immunodeficiency virus, and of severe congenital, cyclic, or idiopathic neutropenia.Keywords: filgrastim, biosimilar, granulocyte colony-stimulating factor, neutropenia, Nivestim™

International audience ; Nivestim™ (filgrastim) is a follow-on biologic agent licensed in the EU for the treatment of neutropenia and febrile neutropenia induced by myelosuppressive chemotherapy. Nivestim™ has been studied in phase 2 and 3 clinical trials where its efficacy and safety was found to be similar to its reference product, Neupogen®. Follow-on biologics continue to be scrutinised for safety. We present a design for two observational phase IV studies that are evaluating the safety profile of Nivestim™ for the prevention and treatment of febrile neutropenia (FN) in patients treated with cytotoxic chemotherapy in general clinical practice. The NEXT (Tolérance de Nivestim chez les patiEnts traités par une chimiothérapie anticancéreuse cytotoXique en praTique courante) and VENICE (VErträglichkeit von NIvestim unter zytotoxischer Chemotherapie in der Behandlung malinger Erkrankungen) trials are multicentre, prospective, longitudinal, observational studies evaluating the safety profile of Nivestim™ in 'real-world' clinical practice. Inclusion criteria include patients undergoing cytotoxic chemotherapy for malignancy and receiving Nivestim as primary or secondary prophylaxis (NEXT and VENICE), or as treatment for ongoing FN (NEXT only). In accordance with European Union pharmacovigilance guidelines, the primary objective is to evaluate the safety of Nivestim™ by gathering data on adverse events in all system organ classes. Secondary objectives include obtaining information on patient characteristics, efficacy of Nivestim™ therapy (including chemotherapy dose intensity), patterns of use of Nivestim™, and physician knowledge regarding filgrastim prescription and the reasons for choosing Nivestim™. Data will be gathered at three visits: 1. At the initial inclusion visit, 2. At a 1-month follow-up visit, and 3. At the end of chemotherapy.Recruitment for VENICE commenced in July 2011 and in November 2011 for NEXT. VENICE completed recruitment in July 2013 with 407 patients, and NEXT in September 2013 with 2123 ...

International audience ; Nivestim™ (filgrastim) is a follow-on biologic agent licensed in the EU for the treatment of neutropenia and febrile neutropenia induced by myelosuppressive chemotherapy. Nivestim™ has been studied in phase 2 and 3 clinical trials where its efficacy and safety was found to be similar to its reference product, Neupogen®. Follow-on biologics continue to be scrutinised for safety. We present a design for two observational phase IV studies that are evaluating the safety profile of Nivestim™ for the prevention and treatment of febrile neutropenia (FN) in patients treated with cytotoxic chemotherapy in general clinical practice. The NEXT (Tolérance de Nivestim chez les patiEnts traités par une chimiothérapie anticancéreuse cytotoXique en praTique courante) and VENICE (VErträglichkeit von NIvestim unter zytotoxischer Chemotherapie in der Behandlung malinger Erkrankungen) trials are multicentre, prospective, longitudinal, observational studies evaluating the safety profile of Nivestim™ in 'real-world' clinical practice. Inclusion criteria include patients undergoing cytotoxic chemotherapy for malignancy and receiving Nivestim as primary or secondary prophylaxis (NEXT and VENICE), or as treatment for ongoing FN (NEXT only). In accordance with European Union pharmacovigilance guidelines, the primary objective is to evaluate the safety of Nivestim™ by gathering data on adverse events in all system organ classes. Secondary objectives include obtaining information on patient characteristics, efficacy of Nivestim™ therapy (including chemotherapy dose intensity), patterns of use of Nivestim™, and physician knowledge regarding filgrastim prescription and the reasons for choosing Nivestim™. Data will be gathered at three visits: 1. At the initial inclusion visit, 2. At a 1-month follow-up visit, and 3. At the end of chemotherapy.Recruitment for VENICE commenced in July 2011 and in November 2011 for NEXT. VENICE completed recruitment in July 2013 with 407 patients, and NEXT in September 2013 with 2123 ...

International audience ; Nivestim™ (filgrastim) is a follow-on biologic agent licensed in the EU for the treatment of neutropenia and febrile neutropenia induced by myelosuppressive chemotherapy. Nivestim™ has been studied in phase 2 and 3 clinical trials where its efficacy and safety was found to be similar to its reference product, Neupogen®. Follow-on biologics continue to be scrutinised for safety. We present a design for two observational phase IV studies that are evaluating the safety profile of Nivestim™ for the prevention and treatment of febrile neutropenia (FN) in patients treated with cytotoxic chemotherapy in general clinical practice. The NEXT (Tolérance de Nivestim chez les patiEnts traités par une chimiothérapie anticancéreuse cytotoXique en praTique courante) and VENICE (VErträglichkeit von NIvestim unter zytotoxischer Chemotherapie in der Behandlung malinger Erkrankungen) trials are multicentre, prospective, longitudinal, observational studies evaluating the safety profile of Nivestim™ in 'real-world' clinical practice. Inclusion criteria include patients undergoing cytotoxic chemotherapy for malignancy and receiving Nivestim as primary or secondary prophylaxis (NEXT and VENICE), or as treatment for ongoing FN (NEXT only). In accordance with European Union pharmacovigilance guidelines, the primary objective is to evaluate the safety of Nivestim™ by gathering data on adverse events in all system organ classes. Secondary objectives include obtaining information on patient characteristics, efficacy of Nivestim™ therapy (including chemotherapy dose intensity), patterns of use of Nivestim™, and physician knowledge regarding filgrastim prescription and the reasons for choosing Nivestim™. Data will be gathered at three visits: 1. At the initial inclusion visit, 2. At a 1-month follow-up visit, and 3. At the end of chemotherapy.Recruitment for VENICE commenced in July 2011 and in November 2011 for NEXT. VENICE completed recruitment in July 2013 with 407 patients, and NEXT in September 2013 with 2123 ...

International audience ; Nivestim™ (filgrastim) is a follow-on biologic agent licensed in the EU for the treatment of neutropenia and febrile neutropenia induced by myelosuppressive chemotherapy. Nivestim™ has been studied in phase 2 and 3 clinical trials where its efficacy and safety was found to be similar to its reference product, Neupogen®. Follow-on biologics continue to be scrutinised for safety. We present a design for two observational phase IV studies that are evaluating the safety profile of Nivestim™ for the prevention and treatment of febrile neutropenia (FN) in patients treated with cytotoxic chemotherapy in general clinical practice. The NEXT (Tolérance de Nivestim chez les patiEnts traités par une chimiothérapie anticancéreuse cytotoXique en praTique courante) and VENICE (VErträglichkeit von NIvestim unter zytotoxischer Chemotherapie in der Behandlung malinger Erkrankungen) trials are multicentre, prospective, longitudinal, observational studies evaluating the safety profile of Nivestim™ in 'real-world' clinical practice. Inclusion criteria include patients undergoing cytotoxic chemotherapy for malignancy and receiving Nivestim as primary or secondary prophylaxis (NEXT and VENICE), or as treatment for ongoing FN (NEXT only). In accordance with European Union pharmacovigilance guidelines, the primary objective is to evaluate the safety of Nivestim™ by gathering data on adverse events in all system organ classes. Secondary objectives include obtaining information on patient characteristics, efficacy of Nivestim™ therapy (including chemotherapy dose intensity), patterns of use of Nivestim™, and physician knowledge regarding filgrastim prescription and the reasons for choosing Nivestim™. Data will be gathered at three visits: 1. At the initial inclusion visit, 2. At a 1-month follow-up visit, and 3. At the end of chemotherapy.Recruitment for VENICE commenced in July 2011 and in November 2011 for NEXT. VENICE completed recruitment in July 2013 with 407 patients, and NEXT in September 2013 with 2123 patients. Last patient, last visit for each study will be December 2013 and March 2014 respectively. The NEXT and VENICE studies will provide long-term safety, efficacy and practice pattern data in patients receiving Nivestim™ to support myelosuppressive chemotherapy in real world clinical practice. These data will improve our understanding of the performance of Nivestim™ in patients encountered in the general patient population. NEXT NCT01574235, VENICE NCT01627990.

International audience ; Nivestim™ (filgrastim) is a follow-on biologic agent licensed in the EU for the treatment of neutropenia and febrile neutropenia induced by myelosuppressive chemotherapy. Nivestim™ has been studied in phase 2 and 3 clinical trials where its efficacy and safety was found to be similar to its reference product, Neupogen®. Follow-on biologics continue to be scrutinised for safety. We present a design for two observational phase IV studies that are evaluating the safety profile of Nivestim™ for the prevention and treatment of febrile neutropenia (FN) in patients treated with cytotoxic chemotherapy in general clinical practice. The NEXT (Tolérance de Nivestim chez les patiEnts traités par une chimiothérapie anticancéreuse cytotoXique en praTique courante) and VENICE (VErträglichkeit von NIvestim unter zytotoxischer Chemotherapie in der Behandlung malinger Erkrankungen) trials are multicentre, prospective, longitudinal, observational studies evaluating the safety profile of Nivestim™ in 'real-world' clinical practice. Inclusion criteria include patients undergoing cytotoxic chemotherapy for malignancy and receiving Nivestim as primary or secondary prophylaxis (NEXT and VENICE), or as treatment for ongoing FN (NEXT only). In accordance with European Union pharmacovigilance guidelines, the primary objective is to evaluate the safety of Nivestim™ by gathering data on adverse events in all system organ classes. Secondary objectives include obtaining information on patient characteristics, efficacy of Nivestim™ therapy (including chemotherapy dose intensity), patterns of use of Nivestim™, and physician knowledge regarding filgrastim prescription and the reasons for choosing Nivestim™. Data will be gathered at three visits: 1. At the initial inclusion visit, 2. At a 1-month follow-up visit, and 3. At the end of chemotherapy.Recruitment for VENICE commenced in July 2011 and in November 2011 for NEXT. VENICE completed recruitment in July 2013 with 407 patients, and NEXT in September 2013 with 2123 patients. Last patient, last visit for each study will be December 2013 and March 2014 respectively. The NEXT and VENICE studies will provide long-term safety, efficacy and practice pattern data in patients receiving Nivestim™ to support myelosuppressive chemotherapy in real world clinical practice. These data will improve our understanding of the performance of Nivestim™ in patients encountered in the general patient population. NEXT NCT01574235, VENICE NCT01627990.

AbstractParoxysmal nocturnal hemoglobinuria (PNH) is a hematological disorder that affects hematopoietic stem cells. An association with other hematological diseases, such as hemolytic anemia and neutropenia, is observed with a high occurrence of aplastic anemia. The aim of the present study is to report a case of dental infection in a patient with PNH exhibiting exuberant gingival involvement. A 45‐year‐old male patient sought the Federal University of Ceara reporting severe toothache associated with tooth 24. Clinical examination revealed that the tooth was associated with an apparent fistula and a yellowish lesion with smooth surface located in the palate. The patient had interrupted the medication to control PNH. Blood transfusion was requested due to deficient hematological parameters. Tooth extraction and excisional biopsy were performed under antibiotic coverage. In the postoperative period, low‐level laser therapy (LLLT) was performed. Histopathological examination revealed connective tissue showing extensive necrotic areas, accumulation of basophilic material, numerous cyst‐like cavities, and degenerated cells. Histopathological findings were compatible with the initial clinical diagnosis of gingival necrosis. The patient evolved with febrile neutropenia, requiring hospitalization for 1 month. Improvement in the overall health was observed after the administration of antibiotics, eculizumab, and weekly LLLT at the biopsy site.

Treatment of individuals exposed to potentially lethal doses of radiation is of paramount concern to health professionals and government agencies. We evaluated the efficacy of filgrastim to increase survival of nonhuman primates (NHP) exposed to an approximate mid-lethal dose (LD50/60) (7.50 Gy) of LINAC-derived photon radiation. Prior to total-body irradiation (TBI), nonhuman primates were randomized to either a control (n =22) or filgrastim-treated (n =24) cohorts. Filgrastim (10 μg/kg/d) was administered beginning 1 day after TBI and continued daily until the absolute neutrophil count (ANC) was >1,000/μL for 3 consecutive days. All nonhuman primates received medical management as per protocol. The primary end point was all cause overall mortality over the 60 day in-life study. Secondary end points included mean survival time of decedents and all hematologic-related parameters. Filgrastim significantly (P < 0.004) reduced 60 day overall mortality [20.8% (5/24)] compared to the controls [59.1% (13/22)]. Filgrastim significantly decreased the duration of neutropenia, but did not affect the absolute neutrophil count nadir. Febrile neutropenia (ANC <500/μL and body temperature ≥103°F) was experienced by 90.9% (20/22) of controls compared to 79.2% (19/24) of filgrastim-treated animals (P = 0.418). Survival was significantly increased by 38.3% over controls. Filgrastim, administered at this dose and schedule, effectively mitigated the lethality of the hematopoietic subsyndrome of the acute radiation syndrome.

Part I. Admitting Orders -- Philosophy -- Components -- Part II. Pre- and Post-Procedure Orders -- Safe and Effective Handoffs -- Effective Discharge Planning -- Cardiovascular Disease -- ST-Elevation Myocardial Infarction -- Unstable Angina (UA) and Non-ST Elevation Myocardial -- Infarction (NSTEMI) -- Atrial Fibrillation -- Congestive Heart Failure -- Syncope -- Hypertensive Emergency -- Aortic Dissection -- Endocrine Disease -- Adult Diabetic Ketoacidosis -- Hyperosmolar Hyperglycemic State -- Gastrointestinal Disease -- Upper Gastrointestinal Bleed -- Lower GI Bleed -- Complications of Cirrhosis -- Diverticulitis -- Acute Pancreatitis -- Acute Hepatitis and Acute Liver Failure -- Small Bowel Obstruction -- Inflammatory Bowel Disease -- Cholecystitis -- Cholangitis -- Gastroparesis -- Geriatrics -- Delirium -- Falls -- Hip Fracture -- Hematology and Oncology -- Cancer, Admit for Chemotherapy -- Febrile Neutropenia -- Infectious Diseases -- Bacterial Endocarditis -- Cellulitis -- Fever in Injection Drug Use -- Meningitis -- Osteomyelitis -- Diabetic Foot Infection -- Pyelonephritis -- Acute Arthritis -- Severe Sepsis and Septic Shock -- Pulmonary Tuberculosis -- Central Line Infection -- Fever of Unknown Origin -- Neurologic Diseases -- Seizure -- Acute Ischemic Stroke -- Alcohol Withdrawal -- Renal and Electrolyte -- Acute Renal Failure -- Hyperkalemia -- Hyponatremia -- Nephrolithiasis -- Prevention of Contrast Nephropathy -- Pulmonary Disease -- Deep Vein Thrombosis and Pulmonary Embolism -- Community-Acquired Pneumonia in -- Immunocompetent Adults -- Chronic Obstructive Pulmonary Disease Exacerbation -- Asthma Exacerbation -- Common Orders in Hospitalized Patients -- Diabetes Management -- Acute Pain Management -- Comfort Care -- Transfusion -- Venous Thromboembolism Prophylaxis.

On 18 September 2017, a marketing authorisation valid through the European Union (EU) was issued for midostaurin in combination with standard daunorubicin and cytarabine induction and high-dose cytarabine consolidation chemotherapy and for patients in complete response followed by midostaurin single agent maintenance therapy, for adult patients with newly diagnosed acute myeloid leukaemia (AML) who are Fms-like tyrosine kinase 3 mutation positive and as monotherapy for the treatment of adult patients with aggressive systemic mastocytosis (ASM), systemic mastocytosis with associated haematological neoplasm (SM-AHN) or mast cell leukaemia (MCL). The recommended dose of midostaurin is 50 mg orally twice daily for AML and 100 mg orally twice daily for ASM, SM-AHN and MCL. Midostaurin was evaluated in two pivotal studies. Study A2301 (RATIFY) included 717 patients with AML. Overall survival (OS) was statistically significantly different between the two groups, and the median OS was 74.7 months in the midostaurin+daunorubicin+cytarabine group and 25.6 months in the placebo+daunorubicin+cytarabine group (HR 0.774; 95% CI 0.629 to 0.953; p=0.0078). Study D2201 included 116 patients with ASM, SM-AHN or MCL. An overall response rate, by IWG-MRT/ECNM (international working group – myelofibrosis research and treatment/European competence network on mastocytosis) criteria of 28.3% was observed in all patients and 60.0%, 20.8% and 33.3% in patients with ASM, SM-AHN and MCL respectively. The most common adverse drug reactions (ADRs) with midostaurin treatment in AML were febrile neutropenia, nausea, exfoliative dermatitis, vomiting, headache, petechiae and fever. In ASM, SM-AHN, MCL the most common ADRs were nausea, vomiting, diarrhoea, peripheral oedema and fatigue. The objective of this paper is to summarise the scientific review of the application leading to regulatory approval in the EU.