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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.

ABSTRACTThis study evaluated the oral health‐related quality of life (OHQoL) in children with neutropenia. Twenty‐seven children with neutropenia were compared to 33 healthy, age‐matched control subjects. Previously validated age‐specific, multidimensional and self‐reporting child OHQoL questionnaires were used. Overall and subscale scores were compared between the two groups. Respondents in the group of children with neutropenia reported that their disease had a significant impact on their oral health in terms of oral symptoms (p<0.0001), functional limitations (p<0.0001), and social well‐being (p<0.0001). In global ratings, they rated their oral health to be markedly worse than that of the healthy subjects (p<0.0001). However, there was no difference between the groups in the extent to which their oral condition affected their lives overall. These results, along with responses to individual measures of social and emotional well‐being, suggest that children in this group with neutropenia have psychologically adapted to the oral health challenges they experience because of their condition.

ABSTRACTThe purpose of this cross‐sectional study was to assess and compare the oral health of children with neutropenia, who are under the active care of a hematologist in a designated marrow failure and myelodysplasia program, to a healthy control group. Children aged 6–18 with neutropenia attending the Marrow Failure and Myelodysplasia Program at SickKids Hospital and controls attending the Children's Clinic, Faculty of Dentistry, University of Toronto were asked to participate in the study consisting of a patient questionnaire followed by a dental and radiographic examination. Fifteen patients with neutropenia (mean age 12.14 ± 4.04 years) and 26 healthy controls (mean age 11.61 ± 3.82 years) participated in this study. Patients with neutropenia reported significantly increased mouth sores (p < .008) and bleeding gums while brushing (p < .001). The dmft/t score was significantly lower for the neutropenia group (p < .009). The clinical examination also showed that there were no statistically significant differences with respect to ulcerations, gingival recession, tooth mobility, gingival inflammation, periodontal bone loss, DMFT/T scores, plaque, and calculus levels. Preliminary data demonstrates that pediatric patients who are under the active care of a hematologist do not present with an increased risk of oral diseases.

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.

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™

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.

Background Data on the haematological outcomes of patients who continue clozapine treatment following neutropenia are very rare as even mild neutropenia results in mandatory discontinuation of clozapine in most countries. However, in Iceland where clozapine monitoring is less stringent allows an observational study to be done on the risk of agranulocytosis and neutropenia during treatment with clozapine compared with other antipsychotics among patients with schizophrenia. Methods The present study is a part of a wider ongoing longitudinal study of schizophrenia in Iceland. We identified 201 patients with schizophrenia treated with clozapine and 410 patients with schizophrenia who had never been on clozapine by searching the electronic health records of Landspitali, the National University Hospital. Neutrophil counts were searched in electronic databases to identify patients who developed neutropenia/agranulocytosis and the frequency of neutrophil measurements was examined as well. Results The median number of days between neutrophil measurements during the first 18 weeks of clozapine treatment was 25 days but after the first 18 weeks on the drug the median became 124 days. Thirty four cases of neutropenia were identified during clozapine treatment with an average follow up time of 9.2 years. The majority, 24 individuals developed mild neutropenia (1500–1900 neutrophils/mm3). None of these progressed to agranulocytosis. The remaining 10 patients developed neutropenia in the range 500–1400 /mm3 of whom one developed agranulocytosis, three stopped clozapine use and 6 patients continued on clozapine for at least a year without developing agranulocytosis. Unexpectedly, schizophrenia patients on other antipsychotics had an equal risk of developing neutropenia as those on clozapine. Conclusions Neutropenia is common both in patients with schizophrenia on clozapine treatment and in those never on clozapine. Therefore a large part of neutropenia during clozapine treatment is probably not caused by clozapine. These findings have implications in assessing the balance between the risk of progression from neutropenia to agranulocytosis against the morbidity resulting from the premature discontinuation of clozapine under the current monitoring regulations in the US and in most of Europe. ; This project received funding from the European Union's Seventh Framework Programme for research, technological development and demonstration under grant agreement no. 279227 (Crestar). Dr MacCabe receives salary support from the National Institute for Health Research (NIHR) Mental Health Biomedical Research Centre at South London and Maudsley NHS Foundation Trust and King's College London. Our funders had no further role in study design; in the collection, analysis and interpretation of data; in the writing of the report; and in the decision to submit the paper for publication. The views expressed are those of the authors and not necessarily those of the European Union, the NHS, the NIHR or the UK Department of Health. ; Peer Reviewed

In young patients with abnormal loosening of teeth and periodontal breakdown, dental professionals should consider a wide range of etiological factors/diseases, analyze differential diagnoses, and make appropriate referrals. The long‐term oral and dental follow‐up of a female patient diagnosed in early infancy with cyclic neutropenia is reviewed, and recommendations for care are discussed.

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

Obiettivo tesi Lo studio si propone di analizzare l'utilizzo dei fattori di crescita e delle eritropoietine nel trattamento della neutropenia e dell'anemia nel paziente onco-ematologico, verificandone l'aderenza o meno alle linee guida AIOM 2010. Ciò acquista un particolare significato anche in considerazione dell'attuale congiuntura economica che interessa il Servizio Sanitario Nazionale che vede da una parte una minore disponibilità di risorse e dall'altra una crescente richiesta di terapie ad alto costo; questo è particolarmente rilevante in ambito oncologico. In considerazione del fatto che i farmaci di cui trattiamo incidono in modo significativo sulla spesa farmaceutica risulta importante adottare tutti gli strumenti di conoscenza affinchè il loro uso sia appropriato e possa rispettare i profili di costo/efficacia. Partendo dall'idea della figura del "Farmacista di Dipartimento", che propone l'inserimento di questa figura professionale in reparto quale ausilio nella valutazione delle scelte terapeutiche, per favorire una corretta politica di Governo clinico che tenga conto sia dell'appropriatezza che del miglior utilizzo delle risorse, si è cercato di fissare i dati una prima esperienza di osservazione diretta sulle scelte di terapia nel paziente neutropenico/anemico post trattamento chemioterapico. Questo potrebbe essere un punto di partenza per la definizione di linee guida di indirizzo e per la pianificazione di possibili strumenti di monitoraggio per la sorveglianza dei trattamenti in uso, per ottenere una condivisione con gli specialisti ed elaborare delle raccomandazioni e degli indicatori per evidenziare l'aderenza o meno alle stesse.

Funding Information: The authors thank all participants, clinicians and researchers for making this study possible. This CRESTAR project has received funding from the European Union's Seventh Framework Programme for research, technological development and demonstration under grant agreement #279227. M.P. wishes to thank the MRC Centre for Drug Safety Science (grant code MR/L006758/1) for support. A.F.P. acknowledges support by a "Springboard" award (ref: SBF005 \1083) from the Academy of Medical Sciences. J.T.R.W. and M.C.O. acknowledge support by a collaborative research grant from Takeda (Takeda played no part in the conception, design, implementation or interpretation of this study). Genome-wide data of CIAC used for identifying overlapping individuals were obtained from NIMH Repository & Genomics Resource, a centralized national biorepository for genetic studies of psychiatric disorders (www.nimhgenetics. org). The collection of data and biomaterials for this study was supported by funding provided by R01 MH080403 (PIs: P.F.S., Edwin J.C.G. van den Oord) from the US National Institute of Mental Health via the American Recovery and Reinvestment Act of 2009. Dr. Denis Fourches and Dr. Alexander Tropsha acknowledge the support from National Science Foundation grant ABI 10-567. The study was led by P.F.S., L. Fredrik Jarskog, Jeffrey A. Lieberman, J.L.K. and Mark J. Daly. Dr. Thomas Lehner (NIMH) and Dr. David Goldstein (Duke University) were also involved in assisting with this project. The authors acknowledge the assistance of Dr. Michael Karukin (Teva Pharmaceuticals) and Dr. Rafael Muniz and Dr. Vinod Kumar (Novartis) for help in accessing US national clozapine registries. Dr. Stanton Gerson (Department of Hematology, Case Western Reserve), Dr. Armond Goldman (Department of Immunology, University of Texas Galveston) and Dr. Nancy Berliner (Department of Hematology, Harvard University) provided input on mechanisms of agranulocytosis. Publisher Copyright: © 2021, The Author(s). ; The atypical antipsychotic ...

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 ...