Disentangling periodic and aperiodic resting EEG correlates of personality.

Previous studies of resting electroencephalography (EEG) correlates of personality traits have conflated periodic and aperiodic sources of EEG signals. Because these are associated with different underlying neural dynamics, disentangling them can avoid measurement confounds and clarify findings. In a large sample (n = 300), we investigated how disentangling these activities impacts findings related to two research programs within personality neuroscience. In Study 1 we examined associations between Extraversion and two putative markers of reward sensitivity-Left Frontal Alpha asymmetry (LFA) and Frontal-Posterior Theta (FPT). In Study 2 we used machine learning to predict personality trait scores from resting EEG. In both studies, power within each EEG frequency bin was quantified as both total power and separate contributions of periodic and aperiodic activity. In Study 1, total power LFA and FPT correlated negatively with Extraversion (r ∼ -0.14), but there was no relation when LFA and FPT were derived only from periodic activity. In Study 2, all Big Five traits could be decoded from periodic power (r ∼ 0.20), and Agreeableness could also be decoded from total power and from aperiodic indices. Taken together, these results show how separation of periodic and aperiodic activity in resting EEG may clarify findings in personality neuroscience. Disentangling these signals allows for more reliable findings relating to periodic EEG markers of personality, and highlights novel aperiodic markers to be explored in future research.

Entospletinib with decitabine in acute myeloid leukemia with mutant TP53 or complex karyotype: A phase 2 substudy of the Beat AML Master Trial.

BACKGROUND: Patients with acute myeloid leukemia (AML) who have tumor protein p53 (TP53) mutations or a complex karyotype have a poor prognosis, and hypomethylating agents are often used. The authors evaluated the efficacy of entospletinib, an oral inhibitor of spleen tyrosine kinase, combined with decitabine in this patient population. METHODS: This was a multicenter, open-label, phase 2 substudy of the Beat AML Master Trial (ClinicalTrials.gov identifier NCT03013998) using a Simon two-stage design. Eligible patients aged 60 years or older who had newly diagnosed AML with mutations in TP53 with or without a complex karyotype (cohort A; n = 45) or had a complex karyotype without TP53 mutation (cohort B; n = 13) received entospletinib 400 mg twice daily with decitabine 20 mg/m2 on days 1-10 every 28 days for up to three induction cycles, followed by up to 11 consolidation cycles, in which decitabine was reduced to days 1-5. Entospletinib maintenance was given for up to 2 years. The primary end point was complete remission (CR) and CR with hematologic improvement by up to six cycles of therapy. RESULTS: The composite CR rates for cohorts A and B were 13.3% (95% confidence interval, 5.1%-26.8%) and 30.8% (95% confidence interval, 9.1%-61.4%), respectively. The median duration of response was 7.6 and 8.2 months, respectively, and the median overall survival was 6.5 and 11.5 months, respectively. The study was stopped because the futility boundary was crossed in both cohorts. CONCLUSIONS: The combination of entospletinib and decitabine demonstrated activity and was acceptably tolerated in this patient population; however, the CR rates were low, and overall survival was short. Novel treatment strategies for older patients with TP53 mutations and complex karyotype remain an urgent need.

Olanzapine within steroid-sparing antiemetic regimen to prevent chemotherapy-induced nausea and vomiting in patients with acute leukemia receiving multi-day intensive chemotherapy.

INTRODUCTION: Olanzapine use for chemotherapy-induced nausea and vomiting (CINV) in hematological malignancies, for multi-day chemotherapy, and with a steroid-sparing antiemetic strategy is poorly understood. This study investigated if olanzapine is associated with improved prevention of CINV when added to a steroid-sparing antiemetic regimen in patients with acute leukemia receiving intensive, moderately emetogenic, multi-day chemotherapy. METHODS: This was a single-center, retrospective cohort study in patients with acute leukemia. Patients who received olanzapine for CINV prevention were compared to those who did not. All patients received a 5-HT3 antagonist. Adult patients receiving moderately emetogenic, multi-day, intensive chemotherapy for acute leukemia were included. Patients were excluded if they received steroids greater than physiological doses during the study period. The primary endpoint was the complete response of CINV (no emesis or rescue antiemetic usage). RESULTS: This study included 58 patients, 12 patients received olanzapine and 46 patients were in the control group. Baseline demographics were similar. In the study population, 89.7% had acute myeloid leukemia, median age was 54 (interquartile range 42-63) years, 34.5% were female, 27.6% had prior CINV. Complete response of CINV was similar between groups, 4 (33.3%) and 15 (32.6%) patients in the olanzapine and control groups, respectively. Safety events were similar between groups. CONCLUSION: Patients with acute leukemia receiving multi-day intensive chemotherapy are at high risk for CINV. The limited data in this study suggests that olanzapine use within a steroid-sparing antiemetic regimen was well tolerated and associated with similar incidence and severity of CINV compared to the control group.

Lowering platelet count threshold to 10,000/µL for peripherally inserted central catheter placement safely conserves blood products.

Despite the low risk of peripherally inserted central catheter (PICC) insertion-related bleeding, the practice of administering prophylactic platelets varies greatly. Limiting unnecessary blood product transfusions reduces transfusion-related adverse events, financial cost, and delays in care. We assessed the impact of lowering prophylactic platelet administration threshold on blood product utilization patterns and bleeding events. This quasi-experimental study was conducted in an urban academic tertiary medical center. The study population included patients with platelet counts ≥ 10,000/µL and < 50,000/µL undergoing PICC placement in 2018 and 2019 when the minimum platelet thresholds were 50,000/µL and 10,000/µL, respectively. The primary outcome was blood product utilization and the secondary outcome was PICC insertion-related bleeding complications. Thirty-five patients using the 10,000/µL (10 K) platelet threshold and 46 patients using the 50,000/µL (50 K) platelet threshold were enrolled. The 50 K group received more platelets before PICC insertion (0.870 ± 0.885 and 0.143 ± 0.430 pools of platelets-per-person, p < 0.001). No patients experienced clinically significant bleeding. Immediately following PICC insertion, minor bleeding occurred in five patients (two [4.3%] and three [8.6%] in the 50 K and 10 K groups, respectively). Bleeding rates between the two cohorts did not differ (p = 0.647). Lowering the minimum platelet threshold from 50,000/µL to 10,000/µL resulted in less prophylactic platelet and total blood product administration with no appreciable difference in PICC insertion-related bleeding.

Arsenic trioxide dose capping to decrease toxicity in the treatment of acute promyelocytic leukemia.

Arsenic trioxide (ATO) and all-trans retinoic acid (ATRA) combination therapy yields high complete remission and disease-free survival rates in acute promyelocytic leukemia (APL). ATO is dosed on actual body weight and high ATO doses in overweight patients may contribute to increased toxicity. We performed a retrospective, two-center study comparing toxicities in patients who received the Lo-Coco et al ATRA/ATO regimen with capped ATO, ≤10 mg/dose, and non-capped ATO, >10 mg/dose. A total of 44 patients were included; 15 received doses ≤10 mg and 29 received >10 mg. During induction, there was no difference in the incidence of grade ≥3 hepatotoxicity, grade ≥3 QTc prolongation, neurotoxicity, and cardiac toxicity between groups. In consolidation, patients receiving >10 mg/dose experienced a greater incidence of neurotoxicity (66.7% vs 22.2%; p = 0.046). Capping doses saved $24634.37/patient and reduced waste of partially-used vials. At a median follow-up of 27 months, no disease relapses occurred in either group. This represents an opportunity to improve the safety profile of this highly effective regimen.

A Prospective Study of Peritransplant Sorafenib for Patients with FLT3-ITD Acute Myeloid Leukemia Undergoing Allogeneic Transplantation.

FLT3-ITD-mutated acute myeloid leukemia (AML) remains a therapeutic challenge. FLT3 inhibition in the setting of minimal residual disease and a new immune system via allogeneic transplantation offers a promise of improved survival for these patients. We performed a prospective study of patients with FLT3-ITD AML undergoing allogeneic transplant that was conducted to evaluate the safety, tolerability, and outcome of sorafenib administered peritransplant. Sorafenib dosing was individualized, starting at 200 mg twice a day (BID), and titrated based on tolerability or toxicities until a tolerable dose was identified. Forty-four patients, with a median age of 52 years, undergoing allogeneic transplant were started on sorafenib in the peritransplant period (21 pretransplant). The median duration of post-transplant follow-up was 27.6 months (range, 5.2 to 60.4). Overall survival was 76% at both 24 and 36 months. Event-free survival at 24 and 36 months was 74% and 64%, respectively. Ten patients died in the post-transplant period, with 6 deaths due to relapsed leukemia and 4 from transplant-associated toxicity. Tolerable doses ranged from 200 mg every other day to 400 mg BID with similar exposure. Correlative studies evaluating FLT3 inhibition via a plasma inhibitory activity assay showed consistent inhibition of FLT3 at all tolerability-determined dosing levels. Sorafenib is well tolerated in the peritransplant setting irrespective of the conditioning intensity or the donor source. Our findings indicate that sorafenib dosing can be individualized in the post-transplantation setting according to patient tolerability. This approach results in effective in vivo FLT3 inhibition and yields encouraging survival results.

A phase 1 study of the antibody-drug conjugate brentuximab vedotin with re-induction chemotherapy in patients with CD30-expressing relapsed/refractory acute myeloid leukemia.

BACKGROUND: Outcomes for patients with relapsed/refractory acute myeloid leukemia (R/R AML) remain poor. Novel therapies specifically targeting AML are of high interest. Brentuximab vedotin (BV) is an antibody-drug conjugate that is specific for human CD30. In this phase 1 dose escalation study, the authors evaluated the safety of BV combined with mitoxantrone, etoposide, and cytarabine (MEC) re-induction chemotherapy for patients with CD30-expressing R/R AML. METHODS: Using a standard dose escalation design, the authors evaluated 3 dose levels of BV (0.9 mg/kg, 1.2 mg/kg, and 1.8 mg/kg) administered once on day 1 followed by MEC on days 3 through 7. RESULTS: There were no dose-limiting toxicities noted and the maximum tolerated dose was not reached. The recommended phase 2 dose of BV was determined to be 1.8 mg/kg when combined with MEC. The side effect profile was similar to that expected from MEC chemotherapy alone, with the most common grade ≥3 toxicities being febrile neutropenia, thrombocytopenia, and anemia (toxicities were graded using the National Cancer Institute Common Terminology Criteria for Adverse Events [version 4.0]). Among the 22 patients enrolled on the trial, the composite response rate was 36%, with a composite response rate of 42% noted among those who received the highest dose of BV. The median overall survival was 9.5 months, with a median disease-free survival of 6.8 months observed among responders. Approximately 55% of patients were able to proceed with either allogeneic hematopoietic stem cell transplantation or donor lymphocyte infusion. CONCLUSIONS: The combination of BV with MEC was found to be safe in patients with CD30-expressing R/R AML and warrants further study comparing this combination with the use of MEC alone in this population (ClinicalTrials.gov identifier NCT01830777). LAY SUMMARY: The outcomes for patients with relapsed/refractory acute myeloid leukemia (R/R AML) are exceptionally poor. New and emerging treatment combinations are actively being studied in an effort to improve outcomes. The authors examined the combination of brentuximab vedotin, an antibody product that recognizes a marker called CD30, with mitoxantrone, etoposide, and cytarabine (MEC), a common chemotherapy regimen, in patients with R/R AML that expressed the CD30 marker. The authors found that the combination was safe and well tolerated. Future studies comparing this new combination with the use of MEC alone can help to inform its effectiveness for this patient population.

Peripheral blood blast rate of clearance is an independent predictor of clinical response and outcomes in acute myeloid leukaemia.

The day 14 bone marrow aspirate and biopsy (D14BM) is regularly used to predict achievement of complete remission (CR) with induction chemotherapy in acute myeloid leukemia (AML), however its utility has been questioned. Clearance of peripheral blood blasts (PBB) may serve as an early measure of chemosensitivity. PBB rate of clearance (PBB-RC) was calculated for treatment-naive AML patients (n = 164) undergoing induction with an anthracycline and cytarabine (7+3) and with detectable PBB at diagnosis. PBB-RC was defined as the percentage of the absolute PBB count on the day of diagnosis that was cleared with each day of therapy, on average, until D14 or day of PBB clearance. Each 5% increase in PBB-RC approximately doubled the likelihood of D14BM clearance (OR = 1·81; 95% CI: 1·24-2·64, P < 0·005). PBB-RC was also associated with improved CR rates (OR per 5% = 1·97; 95% CI: 1·27-3·01, P < 0·005) and overall survival (OS) [hazard ratio (HR) per 5% = 0·67; 95% CI: 0·52-0·87]. African American patients had poorer OS adjusted for PBB-RC (HR = 2·18; 95% CI: 1·13-4·23), while race was not associated with D14BM or CR rate. PBB-RC during induction chemotherapy is predictive of D14BM clearance, CR, and OS, and can therefore serve as a prognostic marker for clinical outcomes in AML.

Genomic Serotyping, Clinical Manifestations, and Antimicrobial Resistance of Nontyphoidal Salmonella Gastroenteritis in Hospitalized Children in Ho Chi Minh City, Vietnam.

Nontyphoidal Salmonella (NTS) are among the most common etiological agents of diarrheal diseases worldwide and have become the most commonly detected bacterial pathogen in children hospitalized with diarrhea in Vietnam. Aiming to better understand the epidemiology, serovar distribution, antimicrobial resistance (AMR), and clinical manifestation of NTS gastroenteritis in Vietnam, we conducted a clinical genomics investigation of NTS isolated from diarrheal children admitted to one of three tertiary hospitals in Ho Chi Minh City. Between May 2014 and April 2016, 3,166 children hospitalized with dysentery were recruited into the study; 478 (∼15%) children were found to be infected with NTS by stool culture. Molecular serotyping of the 450 generated genomes identified a diverse collection of serogroups (B, C1, C2 to C3, D1, E1, G, I, K, N, O, and Q); however, Salmonella enterica serovar Typhimurium was the most predominant serovar, accounting for 41.8% (188/450) of NTS isolates. We observed a high prevalence of AMR to first-line treatments recommended by WHO, and more than half (53.8%; 242/450) of NTS isolates were multidrug resistant (MDR; resistant to ≥3 antimicrobial classes). AMR gene detection positively correlated with phenotypic AMR testing, and resistance to empirical antimicrobials was associated with a significantly longer hospitalization (0.91 days; P = 0.04). Our work shows that genome sequencing is a powerful epidemiological tool to characterize the serovar diversity and AMR profiles in NTS. We propose a revaluation of empirical antimicrobials for dysenteric diarrhea and endorse the use of whole-genome sequencing for sustained surveillance of NTS internationally.

Novel multiplex real-time PCR assays reveal a high prevalence of diarrhoeagenic Escherichia coli pathotypes in healthy and diarrhoeal children in the south of Vietnam.

BACKGROUND: Diarrhoeagenic Escherichia coli (DEC) infections are common in children in low-middle income countries (LMICs). However, detecting the various DEC pathotypes is complex as they cannot be differentiated by classical microbiology. We developed four multiplex real-time PCR assays were to detect virulence markers of six DEC pathotypes; specificity was tested using DEC controls and other enteric pathogens. PCR amplicons from the six E. coli pathotypes were purified and amplified to be used to optimize PCR reactions and to calculate reproducibility. After validation, these assays were applied to clinical samples from healthy and diarrhoeal Vietnamese children and associated with clinical data. RESULTS: The multiplex real-time PCRs were found to be reproducible, and specific. At least one DEC variant was detected in 34.7% (978/2815) of the faecal samples from diarrhoeal children; EAEC, EIEC and atypical EPEC were most frequent Notably, 41.2% (205/498) of samples from non-diarrhoeal children was positive with a DEC pathotype. In this population, only EIEC, which was detected in 34.3% (99/289) of diarrhoeal samples vs. 0.8% (4/498) non-diarrhoeal samples (p < 0.001), was significantly associated with diarrhoea. Multiplex real-time PCR when applied to clinical samples is an efficient and high-throughput approach to DEC pathotypes. CONCLUSIONS: This approach revealed high carriage rates of DEC pathotypes among Vietnamese children. We describe a novel diagnostic approach for DEC, which provides baseline data for future surveillance studies assessing DEC burden in LMICs.

Favorable outcomes of acute leukemias of ambiguous lineage treated with hyperCVAD: a multi-center retrospective study.

Acute leukemias of ambiguous lineage (ALAL) are rare hematologic malignancies with poor outcomes. Retrospective studies have suggested that acute lymphoblastic leukemia (ALL) regimens are more effective than acute myeloid leukemia (AML) regimens. We retrospectively examined the effectiveness of the widely-used adult ALL regimen hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone (hyperCVAD) as initial therapy in patients with ALAL at five academic institutions. Twenty-five patients were identified, including 23 with mixed phenotype acute leukemia (MPAL) and two with acute undifferentiated leukemia. Five of 8 tested (63%) had FLT3-ITD and 3 of 25 (12%) were Philadelphia chromosome-positive. The complete remission (CR) rate was 76%, with CR with incomplete count recovery (CRi) in an additional 8%, for an overall response rate of 84%. Median number of cycles to CR/CRi was 1. There were no deaths in the first 30 days. Of the 21 patients achieving CR or CRi, 14 (66%) proceeded to allogeneic hematopoietic stem cell transplantation. With a median follow-up time of 31.6 months, median overall survival for the entire cohort was not reached, and the estimated 2-year survival was 63%. HyperCVAD can be considered an effective and tolerable front-line regimen for patients with ALAL, and warrants further prospective study.

Optimizing pegylated asparaginase use: An institutional guideline for dosing, monitoring, and management.

The incorporation of L-asparaginase and pegylated asparaginase into pediatric-inspired regimens has conferred a survival advantage in treatment of adults with acute lymphoblastic leukemia. Use of asparaginase products requires careful prevention, monitoring, and management of adverse effects including hypersensitivity, hepatotoxicity, pancreatitis, coagulopathy, and thrombosis. Currently, there is limited published literature to offer guidance on management of these toxicities. At the University of Maryland Marlene and Stewart Greenebaum Comprehensive Cancer Center, a standard of practice guideline was created to prevent and manage asparaginase-related adverse events. By sharing our long-term experience with asparaginase products and clinical management of asparaginase-induced toxicities, this article aims to improve patient safety and optimize treatment outcomes.

The Role of Maternally Acquired Antibody in Providing Protective Immunity Against Nontyphoidal Salmonella in Urban Vietnamese Infants: A Birth Cohort Study.

Background: Nontyphoidal Salmonella (NTS) organisms are a major cause of gastroenteritis and bacteremia, but little is known about maternally acquired immunity and natural exposure in infant populations residing in areas where NTS disease is highly endemic. Methods: We recruited 503 pregnant mothers and their infants (following delivery) from urban areas in Vietnam and followed infants until they were 1 year old. Exposure to the dominant NTS serovars, Salmonella enterica serovars Typhimurium and Enteritidis, were assessed using lipopolysaccharide (LPS) O antigen-specific antibodies. Antibody dynamics, the role of maternally acquired antibodies, and NTS seroincidence rates were modeled using multivariate linear risk factor models and generalized additive mixed-effect models. Results: Transplacental transfer of NTS LPS-specific maternal antibodies to infants was highly efficient. Waning of transplacentally acquired NTS LPS-specific antibodies at 4 months of age left infants susceptible to Salmonella organisms, after which they began to seroconvert. High seroincidences of S. Typhimurium and S. Enteritidis LPS were observed, and infants born with higher anti-LPS titers had greater plasma bactericidal activity and longer protection from seroconversion. Conclusions: Although Vietnamese infants have extensive exposure to NTS, maternally acquired antibodies appear to play a protective role against NTS infections during early infancy. These findings suggest that prenatal immunization may be an appropriate strategy to protect vulnerable infants from NTS disease.

Systematic review and meta-analysis of the effect of iron chelation therapy on overall survival and disease progression in patients with lower-risk myelodysplastic syndromes.

The impact of iron chelation therapy (ICT) on overall survival (OS) and progression to acute myeloid leukemia (AML) in patients with iron overload and International Prognostic Scoring System low- or intermediate-risk myelodysplastic syndromes (MDS) is not well understood. We conducted a systematic review and meta-analysis of published studies of ICT in patients with MDS to better elucidate these relationships. We searched PubMed, EMBASE, Cochrane databases, and the World Health Organization Clinical Trial Registry for studies reporting the impact of ICT on OS in patients with low- or intermediate-risk MDS. Studies were examined for demographics, effect measures, and potential bias risk. Fixed and random-effects models were used to calculate adjusted OS and adjusted hazards ratio (aHR) estimates, respectively, among the different studies. Nine observational studies (four prospective and five retrospective) were identified. For patients with MDS, ICT was associated with an overall lower risk of mortality compared with no ICT (aHR 0.42; 95% confidence interval (CI) 0.28-0.62; P < 0.01); however, there was significant heterogeneity across the studies. In studies reporting progression to AML, ICT was not associated with decreased risk of progression (odds ratio 0.68; 95% CI 0.31-1.43; P < 0.030). This systematic review and meta-analysis of nine nonrandomized trials demonstrated significant reduction in risk of mortality in patients with iron overload and low- or intermediate-risk MDS treated with ICT; however, a causal relationship cannot be established. Randomized, controlled trials are needed to more definitively evaluate the relationship between ICT and survival in patients with iron overload and low- or intermediate-risk MDS.

Relapsed Philadelphia Chromosome-Positive Pre-B-ALL after CD19-Directed CAR-T Cell Therapy Successfully Treated with Combination of Blinatumomab and Ponatinib.

Adults with relapsed or refractory (R/R) B-cell acute lymphoblastic leukemia (B-ALL) treated with conventional chemotherapy have dismal outcomes. Novel immunotherapies targeting CD19, including the bispecific T-cell engager blinatumomab and chimeric antigen-receptor T (CAR-T) cells, have revolutionized the treatment of R/R B-ALL. Robust response rates to CAR-T cell therapy after blinatumomab have recently been reported, but it is unknown whether blinatumomab can be effective following failure of anti-CD19 CAR-T cell therapy. Herein, we describe a patient with Philadelphia chromosome-positive B-ALL who relapsed after CD19-directed CAR-T therapy, but subsequently responded to the combination of blinatumomab and the tyrosine kinase inhibitor ponatinib, with the achievement of a complete remission lasting 12 months.

No Clinical Benefit of Empirical Antimicrobial Therapy for Pediatric Diarrhea in a High-Usage, High-Resistance Setting.

Background: Pediatric diarrheal disease presents a major public health burden in low- to middle-income countries. The clinical benefits of empirical antimicrobial treatment for diarrhea are unclear in settings that lack reliable diagnostics and have high antimicrobial resistance (AMR). Methods: We conducted a prospective multicenter cross-sectional study of pediatric patients hospitalized with diarrhea containing blood and/or mucus in Ho Chi Minh City, Vietnam. Clinical parameters, including disease outcome and treatment, were measured. Shigella, nontyphoidal Salmonella (NTS), and Campylobacter were isolated from fecal samples, and their antimicrobial susceptibility profiles were determined. Statistical analyses, comprising log-rank tests and accelerated failure time models, were performed to assess the effect of antimicrobials on disease outcome. Results: Among 3166 recruited participants (median age 10 months; interquartile range, 6.5-16.7 months), one-third (1096 of 3166) had bloody diarrhea, and 25% (793 of 3166) were culture positive for Shigella, NTS, or Campylobacter. More than 85% of patients (2697 of 3166) were treated with antimicrobials; fluoroquinolones were the most commonly administered antimicrobials. AMR was highly prevalent among the isolated bacteria, including resistance against fluoroquinolones and third-generation cephalosporins. Antimicrobial treatment and multidrug resistance status of the infecting pathogens were found to have no significant effect on outcome. Antimicrobial treatment was significantly associated with an increase in the duration of hospitalization with particular groups of diarrheal diseases. Conclusions: In a setting with high antimicrobial usage and high AMR, our results imply a lack of clinical benefit for treating diarrhea with antimicrobials; adequately powered randomized controlled trials are required to assess the role of antimicrobials for diarrhea.

Quantifying antimicrobial access and usage for paediatric diarrhoeal disease in an urban community setting in Asia.

Objectives: Antimicrobial-resistant infections are a major global health issue. Ease of antimicrobial access in developing countries is proposed to be a key driver of the antimicrobial resistance (AMR) epidemic despite a lack of community antimicrobial usage data. Methods: Using a mixed-methods approach (geospatial mapping, simulated clients, healthcare utilization, longitudinal cohort) we assessed antimicrobial access in the community and quantified antimicrobial usage for childhood diarrhoea in an urban Vietnamese setting. Results: The study area had a pharmacy density of 15.7 pharmacies/km2 (a pharmacy for every 1316 people). Using a simulated client method at pharmacies within the area, we found that 8% (3/37) and 22% (8/37) of outlets sold antimicrobials for paediatric watery and mucoid diarrhoea, respectively. However, despite ease of pharmacy access, the majority of caregivers would choose to take their child to a healthcare facility, with 81% (319/396) and 88% (347/396) of responders selecting a specialized hospital as one of their top three preferences when seeking treatment for watery and mucoid diarrhoea, respectively. We calculated that at least 19% (2688/14427) of diarrhoea episodes in those aged 1 to <5 years would receive an antimicrobial annually; however, antimicrobial usage was almost 10 times greater in hospitals than in the community. Conclusions: Our data question the impact of community antimicrobial usage on AMR and highlight the need for better education and guidelines for all professionals with the authority to prescribe antimicrobials.

The prognostic value of circulating myeloblasts in patients with myelodysplastic syndromes.

The prognostic value of peripheral blasts (PB) is not well-studied in patients with myelodysplastic syndromes (MDS). We evaluated the impact of PB on overall survival (OS) and transformation to acute myeloid leukemia (AML) in a large cohort. The MDS database at the Moffitt Cancer Center was retrospectively reviewed to identify patients with ≥ 1% PB (PB-MDS) and those without PB (BM-MDS). We also assessed the correlation between PB and gene mutations. One thousand seven hundred fifty-eight patients were identified, among whom 13% had PB near the time of diagnosis. PB-MDS patients were more likely to be younger with trilineage cytopenia, complex karyotype, higher-risk disease, transfusion dependence, and therapy-related MDS. The rate of AML transformation was 49 vs. 26% (p < 0.005) and median OS was 16.5 vs. 45.8 months (p < 0.005) in the PB-MDS and BM-MDS groups, respectively. In Cox regression analysis, the presence of PB was an independent prognostic covariate for OS, HR 1.57 (95% CI 1.2-2). Among 51 patients with an available gene panel, the rate of ≥ 1 gene mutation in the PB-MDS group (n = 4) was 100% compared to 81% in the BM-MDS group (n = 47). The presence of PB in MDS is an adverse independent prognostic variable that refines prognostic discrimination.

The effect of iron chelation therapy on overall survival in sickle cell disease and ß-thalassemia: A systematic review.

Red blood cell transfusions have become standard of care for the prevention of life-threatening anemia in patients with ß-thalassemia and sickle cell disease (SCD). However, frequent transfusions can lead to accumulation of iron that can result in liver cirrhosis, diabetes mellitus, arthritis, arrhythmias, cardiomyopathy, heart failure, and hypogonadotropic hypogonadism. Iron chelation therapy has been shown to reduce serum ferritin levels and liver iron content, but limitations of trial design have prevented any demonstration of improved survival. The objective of this systematic review was to investigate the impact of iron chelation therapy on overall and event-free survival in patients with ß-thalassemia and SCD. Eighteen articles discussing survival in ß-thalassemia and 3 in SCD were identified. Overall iron chelation therapy resulted in better overall survival, especially if it is instituted early and compliance is maintained. Comparative studies did not show any significant differences between available iron chelation agents, although there is evidence that deferiprone is better tolerated than deferoxamine and that compliance is more readily maintained with the newer oral drugs, deferiprone and deferasirox. Iron chelation therapy, particularly the second-generation oral agents, appears to be associated with improved overall and event-free survival in transfusion-dependent patients with ß-thalassemia and patients with SCD.