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ObjectivesWe aimed to evaluate the side effects seen in adolescents with clozapine use followed up in an inpatient clinic and the approaches to the treatment of side effects in a naturalistic pattern.Materials and MethodsSociodemographic data, International Statistical Classification of Diseases and Related Health Problems-10 diagnosis, side effects, management and outcomes, prophylactic treatments for side effects, time to initiation of clozapine and clinical observation scores were recorded.ResultsThe most commonly reported side effects were extrapyramidal system side effects (n=91, 62.8%), followed by sialorrhea (n=57, 39.3%), fasciculation (n=55, 37.9%), sedation (n=43, 29.7%) and constipation (n=40, 27.4%). Of the serious side effects, seizures occurred in 5 patients (3.4%), neutropenia occurred in 5 patients (3.5%); ileus and myocarditis were not observed. The mean clozapine discharge dose was 323.9 (±124.45) mg/g. The mean number of antipsychotics used before clozapine was 3, and the mean duration from the first treatment initiation, due to a serious psychiatric diagnosis (schizophrenia, bipolar disorder), to clozapine initiation was 18.4 (±24) weeks. Valproic acid was initiated in 108 patients (74%) and topiramate in 4 patients (2.7%) for seizure prophylaxis, as seizures are one of the serious side effects of clozapine. Five patients (3.5%) developed neutropenia. The most common reason for discontinuation of clozapine treatment was non-compliance (n=8, 14%), while five patients (9.4%) were discontinued due to serious side effects or risk of these side effects.ConclusionIn the adolescent population, it is possible to effectively intervene with different options for side effects that may affect treatment adherence due to clozapine treatment; thus preventing discontinuation of treatment and contributing to improving prognosis by reducing the time without effective symptomatic improvement.

BackgroundABN immunoglobulin (Ig) guidelines advise routine FBC and U and E monitoring with every treatment episode and screening for IgA deficiency. AimsWe audited compliance in inflammatory neuropathy patients on longterm treatment in two UK Neurology departments. We looked for evidence of clinically relevant haematological or AKI Ig-related events.MethodsData was collected from Nov 2015 to Nov 2017. Accepted definitions for clinically and/or biochemically significant haemolysis, neutropenia, thrombocytopenia and AKI were used.Results1919 treatment episodes in 90 patients were analysed. Mean age (SD)=57.6 (14.4)years, 69.1% male, 74% CIDP (26% MMN), 94% IVIg (6% SCIg). Mean dose=1.57 (0.74) g/kg/month or 97.1 (37.3) g/infusion. No clinically significant episodes of haemolysis, neutropenia, thrombocytopenia or AKI occurred in relation to Ig treatment. An asymptomatic drop of >10 g/L Hb occurred in 68/1919 episodes in 38 individuals (3.5%); mean reduction 17.7 g/L, lowest Hb 99 g/L. Two patients with CRF (stage 3) received 28 (IV) and 104 (SC) infusions respectively without impact on eGFR. Two individuals with relative IgA deficiency (0.38 g/L, 0.4 g/L) received 16 infusions over 1.5 years without complications.ConclusionsNo clinically significant Ig-related events were identified in this representative cohort. We suggest annual screening or clinically indicated testing as safe and more appropriate in longterm IVIg use.

•This was an observational real-world study to validate and compare existing prediction models in order to identify suitable models for breast cancer patients receiving chemotherapy.•Our results found that using only pretreatment hematology values had low sensitivity and positive predictive value for predicting febrile neutropenia.•The results of this study provide important information for clinicians when selecting models to identify patients at high-risk of febrile neutropenia. Breast cancer patients receiving chemotherapy may develop a serious complication called febrile neutropenia (FN). We aimed to validate and compare three existing FN prediction models for breast cancer patients receiving chemotherapy in Taiwan. This was a retrospective observational real-world study. Data were acquired from the clinical research databases of three study hospitals. Breast cancer patients who have received at least one antineoplastic chemotherapy drug were chosen for the analysis. For evaluating the occurrence of FN, we used both broad (a body temperature above 38°C with an absolute neutrophil count (ANC) below 0.5 × 109/L or a body temperature above 38°C with a diagnosis of neutropenia) and narrow definitions (having both fever and neutropenia diagnoses or having both neutropenia and infection diagnoses). Sensitivity, specificity, accuracy, positive predictive value (PPV), and negative predictive value (NPV) were calculated for each selected FN model. Among the 1903 patients identified, when the broad and narrow definitions of FN were applied, 70 (3.7%) and 60 (3.2%) patients developed FN in the first cycle, respectively. Using the broad FN definition, Aagaard's model was the highest in sensitivity (90.0%), followed by Chantharakhit's (40.0%) and Chen's (7.2%); in specificity, Chen's (93.6%) was the highest. In addition, the accuracy was highest with the Chen model (90.4%). All three models’ PPVs were low, ranging from 0.5% to 4.2%, but all three models’ NPVs were over 96.3%. When the narrow FN definition was used, Chantharakhit's model showed a relatively high improvement in sensitivity (53.3%) and PPV (3.9%) while negligible increases or even slight decreases were seen in the other two models and in the other performance indicators of Chantharakhit's model. The results of this study provide important information for clinicians when selecting models to identify patients at high-risk of FN. As the model performance observed was less than satisfactory, improving the prediction ability of the models is needed.

Background and importanceUnderreporting in oncology practice is a known phenomenon linked to the predictable toxicity of these drugs. Reporting indicators are often calculated on very large catchment areas and this limits the capacity for self-assessment of the performances in each hospital.Aim and objectivesThe purpose of the study was to evaluate the feasibility of the underreporting rate index in a single cancer centre as a process indicator.Material and methodsReports of adverse drug reactions (ADRs), from 1 January 2018 to 31 January 2019 in our institute (230), were collected in a database. The nine most active ingredients reported were subjected to an indepth analysis and their reporting rates were calculated using the formula (number of drug reports X/number of patients treated with drug X)×100 and (number of drug reports X/number of drug administrations X)×100. The expected value was evaluated using the formula (expected frequency×number of patients treated with the drug X)/100, where the expected frequency was calculated by the summary of product characteristics. The rate of underreporting was calculated as a ratio (missing episodes/expected episodes)×100. Only the results of paclitaxel (the most reported drug) are reported in this abstract as an example.ResultsIn the period January 2018 to January 2019, paclitaxel related ADRs were 51 in 412 patients treated (3293 total administrations). The reporting rate for the number of patients treated was 12.4% while the reporting rate by number of administrations was 1.5%. Severe neutropenia represented the main toxicity with an expected incidence of 39%, while the reported incidence was 6.41%.The underreporting rate of ADRs related to paclitaxel were: neutropenia 82.17%, febrile neutropenia 97.22%, transaminite 94.49%, thrombocytopenia 98.46% and diarrhoea 91.02%. Some gastrointestinal and musculoskeletal system reactions were very common reactions (≥1/10) but there were no reports.Conclusion and relevanceThe indicator allowed better identification of the area of underreporting over time in a more precise way than the absolute number of reports. It is feasible, but when the expected frequency of the event decreases to below 10%, the indicator loses reliability for samples <1000 patients. It is therefore mainly a quantitative indicator of frequent events.References and/or acknowledgementsNo conflict of interest.

Background. Neutropenia is a common laboratory finding in children, therefore it is a common referral reason to pediatric hematology units. This study hypothesizes that most neutropenic children do not require pediatric hematology consultation, and that key clinical indicators can guide the need for referral. Methods. Medical records of 180 patients who were admitted to a tertiary reference center, were evaluated in terms of demographical data, physical examination findings, laboratory findings, and outcome measures. The patients enrolled in the study had newly diagnosed or incidental neutropenia and did not meet the criteria for chronic neutropenia. Neutropenia was classified based on absolute neutrophil count (ANC) as follows: mild (1000–1499/mm³), moderate (500–999/mm³), severe (200–499/mm³), and very severe (

Background Chemotherapy-induced neutropenia (CIN) and febrile neutropenia (FN) pose significant risks in patients with non-myeloid malignancies. This study aimed to evaluate the efficacy and safety of telpegfilgrastim in CIN prevention. Methods This multicentre retrospective study enrolled 110 patients with high-/medium-risk non-myeloid malignancies receiving chemotherapy and telpegfilgrastim prophylaxis, and divided them into 2nd day (83 patients) and 3rd day (27 patients) groups. The primary outcome was the incidence of grade 3/4 CIN, whereas the secondary outcomes included FN incidence, antibiotic usage, and infection rate. Subgroup analyses were conducted for absolute neutrophil counts (ANC), primary/secondary prophylaxis, and single-/multicycle medication. Results The incidence of grade 3/4 CIN was 5.59% in the 2nd day group and 8.89% in the 3rd day group. The 2nd day group reported no cases of FN, whereas the 3rd day group exhibited an incidence of 2.22%. Antibiotic usage and the incidence of infection were relatively lower in the 2nd day group. In the 2nd day group, ANC significantly increased to the normal level in the first cycle and remained higher than baseline after multiple cycles; however, the 3rd day group showed no significant change. In primary prophylaxis, the incidence of grade 3/4 CIN was 2.82% in the 2nd day group and 4.17% in the 3rd day group; in secondary prophylaxis, it was 7.78% and 14.29%, respectively, with an incidence rate ratio of 0.35 ( P  = 0.028) comparing primary to secondary prophylaxis. Bone pain was reported in one patient in each group, with no serious adverse events overall. Conclusions Telpegfilgrastim administered on the 2nd and 3rd day after chemotherapy effectively reduced the risk of CIN and FN. Besides this, primary prophylaxis is more beneficial.

Background Febrile neutropenia (FN) is a prevalent and potentially life-threatening complication in patients with lymphoma receiving myelosuppressive chemotherapy. Pegfilgrastim is more effective than filgrastim as prophylaxis for FN. However, its usage has been limited because of its higher cost. Pegfilgrastim’s value for money remains unclear. Objective To systematically review the cost-effectiveness of pegfilgrastim compared to filgrastim as a primary or secondary prophylaxis for chemotherapy-induced FN among patients with lymphoma. Methods A systematic literature search was conducted in PubMed, EMBASE, Cochrane Library databases, and Google Scholar. The most widely used economic evaluations (cost-effectiveness analysis, cost-utility analysis and cost-benefit analysis) were included in the review. Data extraction was guided by the Consolidated Health Economic Evaluation Reporting Standards checklist, and the quality of reviewed articles was assessed using the Joanna Briggs Institute (JBI) checklist. Cost-effectiveness data were rigorously summarized and synthesized narratively. Costs were adjusted to US$ 2020. Results We identified eight economic evaluation studies (two cost-utility analyses, three cost-effectiveness analyses, and three studies reporting both cost-effectiveness and cost-utility analyses). Half of these studies were from Europe ( n  = 4), the other half were from Iran, USA, Canada, and Singapore. Six studies met > 80% of the JBI quality assessment criteria. Cost-effectiveness estimates in the majority ( n  = 6) of these studies were for Non-Hodgkin Lymphoma patients receiving myelosuppressive chemotherapy with high-risk of FN ( > 20%). The studies considered a wide range of baseline FN risk (17–97.4%) and mortality rates (5.8–8.9%). Reported incremental cost-effectiveness ratios ranged from US$ 2199 to US$ 8,871,600 per quality-adjusted life-year (QALY) gained, dominant to US$ 44,358 per FN averted, and US$ 4261- US$ 7251 per life-years gained. The most influential parameters were medication and hospitalization costs, the relative risk of FN, and assumptions of mortality benefit. Conclusions Most studies showed that pegfilgrastim is cost-effective compared to filgrastim as primary and secondary prophylaxis for chemotherapy-induced FN among patients with lymphoma at a cost-effectiveness threshold of US$ 50,000 per QALY gained. The findings could assist clinicians and healthcare decision-makers to make informed decisions regarding resource allocation for the management of chemotherapy-induced FN in settings similar to those studied.

Upadacitinib, an oral selective Janus kinase (JAK) inhibitor, is under investigation for the treatment of Crohn's disease. In two phase 3 induction trials (U-EXCEL and U-EXCEED), we randomly assigned patients with moderate-to-severe Crohn's disease to receive 45 mg of upadacitinib or placebo (2:1 ratio) once daily for 12 weeks. Patients who had a clinical response to upadacitinib induction therapy were randomly assigned in the U-ENDURE maintenance trial to receive 15 mg of upadacitinib, 30 mg of upadacitinib, or placebo (1:1:1 ratio) once daily for 52 weeks. The primary end points for induction (week 12) and maintenance (week 52) were clinical remission (defined as a Crohn's Disease Activity Index score of <150 [range, 0 to 600, with higher scores indicating more severe disease activity]) and endoscopic response (defined as a decrease in the Simple Endoscopic Score for Crohn's Disease [SES-CD; range, 0 to 56, with higher scores indicating more severe disease] of >50% from baseline of the induction trial [or for patients with an SES-CD of 4 at baseline, a decrease of ≥2 points from baseline]). A total of 526 patients underwent randomization in U-EXCEL, 495 in U-EXCEED, and 502 in U-ENDURE. A significantly higher percentage of patients who received 45-mg upadacitinib than those who received placebo had clinical remission (in U-EXCEL, 49.5% vs. 29.1%; in U-EXCEED, 38.9% vs. 21.1%) and an endoscopic response (in U-EXCEL, 45.5% vs. 13.1%; in U-EXCEED, 34.6% vs. 3.5%) (P<0.001 for all comparisons). At week 52 in U-ENDURE, a higher percentage of patients had clinical remission with 15-mg upadacitinib (37.3%) or 30-mg upadacitinib (47.6%) than with placebo (15.1%), and a higher percentage had an endoscopic response with 15-mg upadacitinib (27.6%) or 30-mg upadacitinib (40.1%) than with placebo (7.3%) (P<0.001 for all comparisons). Herpes zoster infections occurred more frequently in the 45-mg and 30-mg upadacitinib groups than in the respective placebo groups, and hepatic disorders and neutropenia were more frequent in the 30-mg upadacitinib group than in the other maintenance groups. Gastrointestinal perforations developed in 4 patients who received 45-mg upadacitinib and in 1 patient each who received 30-mg or 15-mg upadacitinib. Upadacitinib induction and maintenance treatment was superior to placebo in patients with moderate-to-severe Crohn's disease. (Funded by AbbVie; U-EXCEL, U-EXCEED, and U-ENDURE ClinicalTrials.gov numbers, NCT03345849, NCT03345836, and NCT03345823.).

Autoimmune cytopenias (AIC) are rare complications of allogeneic hematopoietic stem cell transplantation (HSCT). Autoimmune neutropenia (AIN) is the least common type of AIC, and data on its incidence, risk factors and prognosis are scarce. This study aims to describe the incidence of AIN, its potential risk factors, and its clinical outcomes. This retrospective study included children who underwent a first allogeneic HSCT between 2015 and 2022. Patients with primary graft rejection were excluded. The primary endpoint was the incidence of AIN. Secondary endpoints included secondary graft failure (GF), overall survival (OS), and event-free survival (EFS). A total of 208 patients were included, 30 of whom were diagnosed with AIN. The median time from HSCT to AIN diagnosis was 104 days, with a cumulative incidence of 8.73% (95%CI, 5.6-13.51) at 6 months and 14.74% (95%CI, 10.47-20.55) at 2 years after HSCT. No risk factors were found to be associated with AIN. The cumulative incidence of secondary GF at 2 years was 13.75% (95%CI, 5.38-32.68) in patients with AIN compared to 4.73% (95%CI, 2.39-9.25) in patients without AIN (p=0.06). There were no differences in terms of OS or EFS between patients with AIN and patients without AIN, with 3-year OS of 82.9% (95%CI, 63.6-92.5) vs 81.8% (95%CI, 75.26-86.77) (p=0.64) and 3-year EFS of 72.8% (95%CI, 52.8-85.4) vs 79% (95%CI, 72.2-84.31) (p=0.67). We identified two patients with specific human neutrophil alloantigen antibodies (anti-HNA), one of whom had a secondary graft failure. AIN may be a more frequent complication in post-HSCT pediatric patients than previously reported. Patients with AIN may be at a higher risk of secondary GF, but whether the risk of secondary GF is an important issue in patients with AIN needs to be explored in larger cohorts of patients. The study of specific anti-HNA in high-risk AIN patients should be considered.