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BJPsych Bulletin Jun 2024Clozapine remains the gold standard intervention for treatment-resistant schizophrenia; however, it remains underused, especially for some minority groups. A significant... (Review)
Review
Clozapine remains the gold standard intervention for treatment-resistant schizophrenia; however, it remains underused, especially for some minority groups. A significant impediment is concern about propensity to neutropenia. The aim of this article is to provide an update on current knowledge relating to: the pattern and incidence of severe blood dyscrasias; the effectiveness of current monitoring regimes in reducing harm; the mechanisms of and the distinctions between clozapine-induced neutropenia and agranulocytosis; benign ethnic neutropenia; and changes to the monitoring thresholds in the USA and other international variations. These all have implications for the practical use of clozapine; specifically, how barriers to initiating, maintaining and restarting clozapine can be understood and in many cases overcome, especially for patients from minority groups, potentially with simpler approaches than the use of lithium or G-CSF.
PubMed: 38828731
DOI: 10.1192/bjb.2024.38 -
Australasian Psychiatry : Bulletin of... May 2024This paper critiques the haematological monitoring guidelines for clozapine. It describes the history of clozapine, as well as the pathophysiology and epidemiology of...
OBJECTIVES
This paper critiques the haematological monitoring guidelines for clozapine. It describes the history of clozapine, as well as the pathophysiology and epidemiology of clozapine-induced neutropenia (CIN) and agranulocytosis (CIA). The paper appraises the extant literature on mandatory clozapine haematological monitoring.
CONCLUSION
Contemporary Australian protocols for clozapine haematological monitoring are not consistent with the current evidence base. CIN and CIA are rare occurrences, and the associated risk of death is low. Potential modifications to existing guidelines include changing neutrophil thresholds for patients with benign ethnic neutropenia and reducing the frequency or removing haematological monitoring after two years of clozapine treatment.
PubMed: 38820548
DOI: 10.1177/10398562241258764 -
Oncology Letters Jul 2024Myeloid sarcoma (MS) is a rare extramedullary tumor mass that carries a high risk of progression to acute myeloid leukemia (AML), and patients with MS are commonly...
Myeloid sarcoma (MS) is a rare extramedullary tumor mass that carries a high risk of progression to acute myeloid leukemia (AML), and patients with MS are commonly treated with the AML regimen. However, MS is frequently misdiagnosed due to its lack of clinical specificity. Patients with MS who harbor tumor protein p53 (TP53) mutations and complex karyotypes are considered to have a poorer prognosis. The present study reports a case of lymph node MS with TP53 (V173G)-related myelodysplastic syndrome (MDS). The mass was first considered to be a lymphoma and treated as such. However, following immunohistochemical analysis, which revealed cells positive for CD43, myeloperoxidase and CD117, the patient was later diagnosed with MS combined with MDS. The patient went into complete remission after the first cycle of chemotherapy, and showed a decrease in platelet, red blood cell and white blood cell counts following the second cycle of chemotherapy. After the third chemotherapy, agranulocytosis occurred, leading to refractory pneumonia and eventually death due to respiratory failure. MS with TP53-related MDS has a low incidence rate, a poor prognosis and a short survival time. The clinical manifestations of MS are non-specific and easy to misdiagnose, leading to delayed diagnosis and treatment, and ultimately worsening the prognosis of the patients. Therefore, a lymph node biopsy should be performed as soon as possible for patients with lymph node enlargement, and early treatment should be carried out to prolong the survival period.
PubMed: 38807682
DOI: 10.3892/ol.2024.14458 -
Andes Pediatrica : Revista Chilena de... Apr 2024Bacteremia is a major cause of morbidity and mortality in patients with cancer and episodes of high-risk febrile neutropenia (HRFN).
UNLABELLED
Bacteremia is a major cause of morbidity and mortality in patients with cancer and episodes of high-risk febrile neutropenia (HRFN).
OBJECTIVE
To identify the frequency of microorganisms isolated from blood cultures (BC) and their antimicrobial resistance (R) profile in children with HRFN, compared with the same data from previous studies of the same group.
METHOD
Prospective, multicenter, epidemiological surveillance study of microorganisms isolated from BC in patients under 18 years of age, from 7 PINDA network hospitals, between 2016 and 2021.
RESULTS
284 episodes of HRFN with positive BC were analyzed out of 1091 enrolled episodes (26%). Median age 7.2 years [3.0-12.3]. The main isolates were gram-negative bacilli (GNB) 49.2%, gram-positive cocci (GPC) 43.8%, and fungi 3.6%. The most frequently isolated microorganisms were viridans group Streptococci (VGS) (25.8%), Escherichia coli (19.8%), Pseudomonas spp. (11.2%), Klebsiella spp. (10.9%), and coagulase negative Staphylococci (CoNS) (10.9%). There was an increase in R to third-generation cephalosporins (p = 0.011) in GNB and to oxacillin in CoNS (p = 0.00), as well as a decrease in R to amikacin in non-fermenting GNB (p = 0.02) and to penicillin in VGS (p = 0.04).
CONCLUSION
VGS is the main agent isolated in BC from pediatric patients with cancer and episodes of HRFN, followed by E. coli, Pseudomonas spp., and Klebsiella spp. Having epidemiological surveillance of microorganisms isolated from BC and their antimicrobial R profile is essential to favor the rational use of antimicrobials.
Topics: Humans; Child; Neoplasms; Prospective Studies; Child, Preschool; Febrile Neutropenia; Chile; Bacteremia; Female; Male; Blood Culture; Anti-Bacterial Agents; Drug Resistance, Bacterial; Microbial Sensitivity Tests; Adolescent; Gram-Negative Bacteria
PubMed: 38801361
DOI: 10.32641/andespediatr.v95i2.5012 -
Supportive Care in Cancer : Official... May 2024Febrile neutropenia (FN) is a known side effect of chemotherapy, often requiring hospitalization. Economic burden increases with an FN episode and estimates of cost per...
PURPOSE
Febrile neutropenia (FN) is a known side effect of chemotherapy, often requiring hospitalization. Economic burden increases with an FN episode and estimates of cost per episode should be updated from real-world data.
METHODS
A retrospective claims analysis of FN episodes in patients with non-myeloid malignancies from 2014 to 2021 was performed in IQVIA PharMetrics® Plus database. FN episodes were defined as having same-day claims for neutropenia and fever or infection, plus antibiotic in outpatient settings, following a claim for chemotherapy; index date was defined as the first claim for neutropenia/fever/infection. Patients receiving bone marrow/stem cell transplant and CAR-T therapy were excluded, as were select hematologic malignancies or COVID-19. Healthcare utilization and costs were evaluated and described overall, by episode type (w/wo hospitalization), index year, malignancy type, NCI comorbidity score, and age group.
RESULTS
7,033 FN episodes were identified from 6,825 patients. Most episodes had a hospitalization (91.2%) and 86% of patients had ≥1 risk factor for FN. Overall, FN episodes had a mean (SD) FN-related cost of $25,176 ($39,943). Episodes with hospitalization had higher average FN-related costs versus those without hospitalization ($26,868 vs $7,738), and costs increased with comorbidity score (NCI=0: $23,095; NCI >0-2: $26,084; NCI ≥2: $26,851).
CONCLUSIONS
FN continues to be associated with significant economic burden, and varied by cancer type, comorbidity burden, and age. In this analysis, most FN episodes were not preceded by GCSF prophylaxis. The results of this study highlight the opportunity to utilize GCSF in appropriate oncology scenarios.
Topics: Humans; Retrospective Studies; Male; Middle Aged; Female; United States; Adult; Aged; Chemotherapy-Induced Febrile Neutropenia; Neoplasms; Patient Acceptance of Health Care; Health Care Costs; Hospitalization; Young Adult; Adolescent; Antineoplastic Agents; Insurance, Health; Health Resources
PubMed: 38777864
DOI: 10.1007/s00520-024-08492-5 -
ACG Case Reports Journal May 2024Randomized controlled trials demonstrate a significant decline in hospital admissions and length of stay following the initiation of clozapine in individuals with...
Randomized controlled trials demonstrate a significant decline in hospital admissions and length of stay following the initiation of clozapine in individuals with bipolar disorder and schizophrenia, along with an increase in quality-adjusted life years. The morbidity and mortality associated with clozapine-induced gastrointestinal hypomotility (CIGH) is greater than agranulocytosis. Despite this, we only have clozapine risk evaluation and mitigation strategies by the US Food and Drug Administration for white cell count monitoring, but none exists for CIGH. Our case highlights CIGH due to multiple factors and recommendations to prevent it and enhance clozapine compliance by conducting a thorough literature review.
PubMed: 38764552
DOI: 10.14309/crj.0000000000001351 -
Transplant Infectious Disease : An... Jun 2024Infective endocarditis (IE) is a serious complication of bloodstream infections (BSIs) that occurs at variable rates depending on the pathogen and clinical setting....
BACKGROUND
Infective endocarditis (IE) is a serious complication of bloodstream infections (BSIs) that occurs at variable rates depending on the pathogen and clinical setting. There is a paucity of data describing the risk of IE in patients with hematologic malignancy who develop bacteremia while neutropenic.
METHODS
Adult patients on the hematology ward from January 2018 to December 2020 with hematologic malignancy and bacteremia were evaluated retrospectively for endocarditis by applying the 2023 Duke-ISCVID criteria. Charts of possible cases were evaluated 90 days after the initial BSI for new infectious complications that could indicate missed IE. Descriptive statistics compared patients admitted for hematopoietic stem cell transplantation (HSCT) to those admitted for alternative reasons (non-HSCT).
RESULTS
Among the 1005 positive blood cultures initially identified, there were 66 episodes in 65 patients with hematologic malignancy and at least grade 3 neutropenia for a mean duration of 11.4 days during their admission. Transthoracic echocardiography (TTE) was performed in 34.8% of BSIs, and transesophageal echocardiography (TEE) in 6.1%. There were no new infectious complications in possible cases 90 days after their initial BSI. No cases of endocarditis were identified.
CONCLUSIONS
Endocarditis is rare amongst patients with hematologic malignancy, bacteremia, and neutropenia, and no cases were identified in this cohort. The use of routine TTE in this setting seems unwarranted, and the addition of TEE is unlikely to improve patient-centered outcomes.
Topics: Humans; Neutropenia; Male; Female; Middle Aged; Hematologic Neoplasms; Retrospective Studies; Bacteremia; Hematopoietic Stem Cell Transplantation; Adult; Endocarditis; Aged; Echocardiography; Echocardiography, Transesophageal
PubMed: 38761053
DOI: 10.1111/tid.14302 -
Advances in Therapy Jul 2024A target trough concentration (C) of teicoplanin ≥ 15-20 mg/L between the fourth and sixth day has been suggested for severe infections or management of febrile...
INTRODUCTION
A target trough concentration (C) of teicoplanin ≥ 15-20 mg/L between the fourth and sixth day has been suggested for severe infections or management of febrile neutropenia (FN). Owing to no reports discussing the impact of early target attainment on treatment outcomes, this study aimed to evaluate the dose-C relationship and clinical outcome and estimate the optimal early target C for FN in patients with hematological malignancies.
METHODS
This single-center, prospective study enrolled patients with hematological malignancies who were treated with teicoplanin either as an empirical antibiotic for FN or as targeted treatment for Gram-positive bacteria. Blood samples were collected on day three (48 h) post-loading doses, day 5 (96 h), and day 8 (when applicable) and determined by ultrahigh-pressure liquid chromatography-triple quadruple mass spectrometry. A total of 117 samples from 47 patients with FN (27 men, 20 women) were consecutively analyzed. A two-tailed α value of 0.05 was considered statistically significant.
RESULTS
The mean C values at 48 h, 96 h, and on day 8 were 23.4, 21.4, and 27.8 mg/L, respectively. The patients achieving C ≥ 20 mg/L at 48 h had a higher likelihood of treatment success. The areas under the receiver operating characteristic curves were 0.71 for clinical efficacy and the cutoff value of C at 48 h was 18.85 mg/L (95% confidence interval 0.55-0.87; P = 0.018).
CONCLUSIONS
The C of teicoplanin after completion of loading doses could predict the treatment response, with a target concentration ≥ 18.85 mg/L.
Topics: Humans; Teicoplanin; Male; Female; Hematologic Neoplasms; Middle Aged; Anti-Bacterial Agents; Drug Monitoring; Prospective Studies; Aged; Adult; Febrile Neutropenia; Dose-Response Relationship, Drug; Treatment Outcome; Young Adult
PubMed: 38743241
DOI: 10.1007/s12325-024-02884-z -
Molecular Genetics and Metabolism Jun 2024Empagliflozin has been successfully repurposed for treating neutropenia and neutrophil dysfunction in patients with glycogen storage disease type 1b (GSD 1b), however,...
Empagliflozin has been successfully repurposed for treating neutropenia and neutrophil dysfunction in patients with glycogen storage disease type 1b (GSD 1b), however, data in infants are missing. We report on efficacy and safety of empagliflozin in infants with GSD 1b. This is an international retrospective case series on 21 GSD 1b infants treated with empagliflozin (total treatment time 20.6 years). Before starting empagliflozin (at a median age of 8.1 months with a median dose of 0.3 mg/kg/day) 12 patients had clinical signs and symptoms of neutrophil dysfunction. Six of these previously symptomatic patients had no further neutropenia/neutrophil dysfunction-associated findings on empagliflozin. Eight patients had no signs and symptoms of neutropenia/neutrophil dysfunction before start and during empagliflozin treatment. One previously asymptomatic individual with a horseshoe kidney developed a central line infection with pyelonephritis and urosepsis during empagliflozin treatment. Of the 10 patients who were treated with G-CSF before starting empagliflozin, this was stopped in four and decreased in another four. Eleven individuals were never treated with G-CSF. While in 17 patients glucose homeostasis remained stable on empagliflozin, four showed glucose homeostasis instability in the introductory phase. In 17 patients, no other side effects were reported, while genital (n = 2) or oral (n = 1) candidiasis and skin infection (n = 1) were reported in the remaining four. Empagliflozin had a good effect on neutropenia/neutrophil dysfunction-related signs and symptoms and a favourable safety profile in infants with GSD 1b and therefore qualifies for further exploration as first line treatment.
Topics: Humans; Glycogen Storage Disease Type I; Neutropenia; Male; Female; Infant; Benzhydryl Compounds; Retrospective Studies; Neutrophils; Glucosides; Sodium-Glucose Transporter 2 Inhibitors; Treatment Outcome; Granulocyte Colony-Stimulating Factor
PubMed: 38733639
DOI: 10.1016/j.ymgme.2024.108486