ABSTRACT
Weekly paclitaxel (WP) is a chemotherapeutic cornerstone in the management of patients with platinum-resistant ovarian carcinoma. Multiple WP dosing regimens have been used clinically and studied individually. However, no formal comparison of these regimens is available to provide objective guidance in clinical decision making. The primary objective of this study was to compare the cumulative dose of paclitaxel delivered using 80 mg/m2/week, administered using either a 3 weeks out of 4 (WP3) or a 4 weeks out of 4 (WP4) regimen. The secondary objective was to evaluate the clinical outcomes associated with both regimens, including efficacy and toxicity parameters. Our retrospective cohort comprised 149 patients harboring platinum-resistant ovarian cancer treated at the CHU de Québec from January 2012 to January 2023. WP3 and WP4 reached a similar cumulative dose (1353.7 vs. 1404.2 mg/m2; p = 0.29). No significant differences in the clinical outcomes were observed. The frequency of dose reduction was significantly higher for WP4 than WP3 (44.7% vs. 4.9%; p < 0.01), mainly due to treatment intolerance from toxicity (34.0% vs. 3.9%; p < 0.01). Our data suggest that a WP3 regimen delivers a similar cumulative dose to WP4, hence offering a better efficacy profile without compromising efficacy.
Subject(s)
Drug Resistance, Neoplasm , Ovarian Neoplasms , Paclitaxel , Humans , Female , Paclitaxel/therapeutic use , Paclitaxel/administration & dosage , Retrospective Studies , Ovarian Neoplasms/drug therapy , Middle Aged , Aged , Adult , Neoplasm Recurrence, Local/drug therapy , Drug Administration Schedule , Antineoplastic Agents, Phytogenic/therapeutic use , Aged, 80 and overABSTRACT
The transition to parenthood is marked by increased potential stressors and relationship satisfaction declines among new parents. Recently, it has been suggested that people with greater mindfulness perceived their environment as less stressful during difficult times in life, which in turn, is associated with greater relationship satisfaction. Accordingly, this dyadic diary study evaluated if perceived stress explains the link between new parents' mindfulness and relationship satisfaction. A total of 78 new parent couples (N = 156 participants; M = 6 months postpartum) provided ecologically valid perceived stress and relationship satisfaction data by responding to a questionnaire on their smartphones, between 7 p.m. and midnight, for 14 consecutive days. Data were analyzed using Actor-Partner Interdependence Mediation Model (APIMeM). Results revealed that parents with higher mindfulness reported lower perceived stress, which in turn was associated with them reporting higher relationship satisfaction. In addition, one's mindfulness was directly positively associated with their partner's relationship satisfaction. Lastly, when all partner effects between mindfulness, perceived stress and relationship satisfaction were tested together without defining specific partner paths, one's mindfulness was positively associated with their partners' relationship satisfaction. Our findings extend current knowledge on the dyadic association between mindfulness and relationship satisfaction during the transition to parenthood by highlighting perceived stress as a key variable underlying this relationship.
ABSTRACT
Objective(s): Blood cultures (BC), when performed in children seen in the emergency department with community-acquired pneumonia (CAP), are most of the time sterile. We described the diagnostic accuracy of white blood cells (WBC), absolute neutrophils count (ANC), C-reactive protein (CRP), and procalcitonin (PCT) to predict blood culture (BC) result in childhood CAP. Study Design: Secondary analysis of a prospective study carried out in eight pediatric emergency departments (France, 2009-2018), including children (≤15 years) with CAP. Analyses involved univariate comparisons and ROC curves. Results: We included 13,752 children with CAP. BC was positive in 137 (3.6%) of the 3,829 children (mean age 3.7 years) in whom it was performed, mostly with Streptococcus pneumoniae (n = 107). In children with bacteremia, ANC, CRP and PCT levels were higher (median 12,256 vs. 9,251/mm3, 223 vs. 72 mg/L and 8.6 vs. 1.0 ng/mL, respectively; p ≤ 0.002), but WBC levels were not. The area under the ROC curve of PCT (0.73 [95%CI 0.64-0.82]) was significantly higher (p ≤ 0.01) than that of WBC (0.51 [0.43-0.60]) and of ANC (0.55 [0.46-0.64]), but not than that of CRP (0.66 [0.56-0.76]; p = 0.21). CRP and PCT thresholds that provided a sensitivity of at least 90% were 30 mg/L and 0.25 ng/mL, respectively, for a specificity of 25.4 and 23.4%, respectively. CRP and PCT thresholds that provided a specificity of at least 90% were 300 mg/L and 20 ng/mL, respectively, for a sensitivity of 31.3 and 28.9%, respectively. Conclusions: PCT and CRP are the best routinely available predictive biomarkers of bacteremia in childhood CAP.
ABSTRACT
Colitis is characterized by colonic inflammation and impaired gut health. Both features aggravate obesity and insulin resistance. Host defense peptides (HDPs) are key regulators of gut homeostasis and generally malfunctioning in above-mentioned conditions. We aimed here to improve bowel function in diet-induced obesity and chemically induced colitis through daily oral administration of lysozyme, a well-characterized HDP, derived from Acremonium alcalophilum.C57BL6/J mice were fed either low-fat reference diet or HFD ± daily gavage of lysozyme for 12 weeks, followed by metabolic assessment and evaluation of colonic microbiota encroachment. To further evaluate the efficacy of intestinal inflammation, we next supplemented chow-fed BALB/c mice with lysozyme during Dextran Sulfate Sodium (DSS)-induced colitis in either conventional or microbiota-depleted mice. We assessed longitudinal microbiome alterations by 16S amplicon sequencing in both models.Lysozyme dose-dependently alleviated intestinal inflammation in DSS-challenged mice and further protected against HFD-induced microbiota encroachment and fasting hyperinsulinemia. Observed improvements of intestinal health relied on a complex gut flora, with the observation that microbiota depletion abrogated lysozyme's capacity to mitigate DSS-induced colitis.Akkermansia muciniphila associated with impaired gut health in both models, a trajectory that was mitigated by lysozyme administration. In agreement with this notion, PICRUSt2 analysis revealed specific pathways consistently affected by lysozyme administration, independent of vivarium, disease model and mouse strain.Taking together, lysozyme leveraged the gut microbiota to curb DSS-induced inflammation, alleviated HFD-induced gastrointestinal disturbances and lowered fasting insulin levels in obese mice. Collectively, these data present A. alcalophilum-derived lysozyme as a promising candidate to enhance gut health.
Subject(s)
Acremonium/enzymology , Colitis/drug therapy , Gastrointestinal Microbiome/drug effects , Muramidase/administration & dosage , Animals , Bacteria/classification , Bacteria/genetics , Bacteria/isolation & purification , Colitis/chemically induced , Colitis/microbiology , Dextran Sulfate/adverse effects , Disease Models, Animal , Female , Humans , Male , Mice , Mice, Inbred BALB C , Mice, Inbred C57BL , Muramidase/metabolismABSTRACT
OBJECTIVE: This randomized controlled trial examined whether KORSA workshops indirectly influence anxiety, depression and stress symptoms among university students through their effect on two second-order psychological flexibility processes: 1) mindfulness and acceptance, and 2) commitment and behavior change. Participants: During the fall 2014 and the winter 2015 semesters, 124 students participated in the study. Methods: They were randomized to either a 4-week intervention group (n = 61) or a wait-list control group (n = 63). They completed measures of anxiety, depression, stress and psychological flexibility before and immediately after the intervention. Results: Bootstrapping-based mediation analyses showed that the intervention indirectly influenced symptoms reduction through its effect on acceptance and mindfulness processes, but not through commitment and behavior change processes. Conclusions: These initial findings suggest that contact with the present moment, acceptance, cognitive defusion and self as context are important processes of change through which KORSA workshops affect the students mental health.
Subject(s)
Acceptance and Commitment Therapy , Mindfulness , Anxiety Disorders , Humans , Students , UniversitiesABSTRACT
Importance: In several countries, 5 years after 13-valent pneumococcal conjugate vaccine (PCV13) implementation, serotype replacement has been reported for invasive pneumococcal disease, which raises concerns about the long-term outcome of PCV13 implementation. The long-term effect of vaccination on community-acquired pneumonia (CAP) remains unknown. Objective: To assess the long-term outcome of PCV13 implementation on CAP in children. Design, Setting, and Participants: This quasi-experimental, population-based, interrupted time-series analysis was based on a prospective multicenter study conducted from June 2009 to May 2017 in 8 French pediatric emergency departments. All patients 15 years and younger with chest radiography-confirmed CAP were included. Exposures: Community-acquired pneumonia. Main Outcomes and Measures: The number of CAP cases per 1000 pediatric emergency department visits over time, analyzed using a segmented regression model, adjusted for influenza-like illness syndromes. Results: We enrolled 12â¯587 children with CAP, including 673 cases of CAP with pleural effusion (5.3%), 4273 cases of CAP requiring hospitalization (33.9%), 2379 cases of CAP with high inflammatory biomarkers (18.9%), and 221 cases of proven pneumococcal CAP (1.8%). The implementation of PCV13 in 2010 was followed by a sharp decrease in the frequency of CAP (-0.8% per month [95% CI, -1.0% to -0.5% per month]), from 6.3 to 3.5 cases of CAP per 1000 pediatric emergency department visits until May 2014, then a slight increase since June 2014 (0.9% per month [95% CI, 0.4%-1.4% per month]), until 3.8 cases of CAP per 1000 pediatric emergency department visits in May 2017. There were marked immediate decreases in cases of CAP with pleural effusion (-48% [95% CI, -84% to -12%]), CAP requiring hospitalization (-30% [95% CI, -56% to -5%]), and CAP with high inflammatory biomarkers (-30% [95% CI, -54% to -6%]), without any rebound thereafter. Conclusions and Relevance: The changes associated with PCV13 use 7 years after implementation remain substantial, especially for CAP with pleural effusion, CAP requiring hospitalization, and CAP with high inflammatory biomarkers. Emerging non-PCV13 serotypes may be less likely involved in severe CAP than invasive pneumococcal disease.
Subject(s)
Community-Acquired Infections/epidemiology , Pneumococcal Vaccines , Pneumonia, Pneumococcal/epidemiology , Vaccination , Adolescent , Child , Child, Preschool , Community-Acquired Infections/prevention & control , Emergency Service, Hospital , Female , France , Humans , Infant , Interrupted Time Series Analysis , Male , Pneumonia, Pneumococcal/prevention & control , Prospective Studies , Time FactorsABSTRACT
OBJECTIVE: Traveller's diarrhoea (TD) is one of the most frequent illnesses affecting children returning from tropical countries. The purpose of this study was to assess the distribution of pathogens associated with TD in children using a multiplex PCR assay on stool samples. DESIGN: All the children admitted for TD in two university hospitals from 1 August to 15October during 2014 and 2015 were included in a prospective study. Stool samples were tested by a multiplex PCR FilmArray GI panel detecting 22 pathogens. Performances for the detection of major enteropathogenic bacteria (Salmonella, Shigella and Campylobacter spp) by multiplex PCR and conventional culture methods were compared. The prevalence of extended spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae was also determined. RESULTS: Fifty-nine children were included. In 58 cases (98%), at least one pathogen was identified, including 9 different enteropathogenic bacteria, 5 viruses and 2 parasites. Multiplex PCR enhanced the enteropathogenic bacteria detection by 25%. The most frequent pathogens were enteroaggregative Escherichia coli (n=32), enteropathogenic E. coli (n=26), enterotoxigenic E. coli (n=19), Salmonella enterica, enteroinvasive E. coli/Shigella (n=16 each), Cryptosporidium, sapovirus (n=11 each), Campylobacter jejuni, norovirus (n=10 each), rotavirus (n=9), Giardia (n=8) and Shiga-toxin-producing E. coli (n=4). Fifty-two coinfections were observed, notably including bacteria and viruses (n=21), multiple bacteria (n=14), or bacteria and parasites (n=10). ESBL were detected in 28 cases. Multiplex PCR could optimise the number of treated patients by 27% compared with stool cultures. CONCLUSION: Multiplex PCR on stools revealed a high prevalence of diverse enteric pathogens and coinfections in children with TD. Major enteropathogenic bacteria were more frequently detected by multiplex PCR compared with conventional culture. Finally, this technique allows the start of appropriate and early antibiotic treatment and seems to optimise the number of correctly treated patients.
Subject(s)
Diarrhea , Multiplex Polymerase Chain Reaction , Travel-Related Illness , Anti-Bacterial Agents/therapeutic use , Bacteria/genetics , Bacteria/isolation & purification , Child , Child, Preschool , Coinfection/diagnosis , Cryptosporidium/genetics , Cryptosporidium/isolation & purification , DNA Viruses/genetics , DNA Viruses/isolation & purification , Diarrhea/microbiology , Diarrhea/parasitology , Diarrhea/virology , Female , France , Giardia/genetics , Giardia/isolation & purification , Hospitals, University , Humans , Infant , Male , Prospective Studies , RNA Viruses/genetics , RNA Viruses/isolation & purificationABSTRACT
We describe here changes in the bacterial causes of pleural empyema before and after implementation of the 13-valent pneumococcal conjugate vaccine (PCV13) program in France (2009-2017). For 220 (39.3%) of 560 children, a bacterial cause was found. The frequency of pneumococcal infection decreased during the study from 79.1% in 2009 to 36.4% in 2017 (P < .001). Group A streptococcus is now the leading cause of documented empyema (45.5%).
Subject(s)
Community-Acquired Infections/microbiology , Empyema, Pleural/microbiology , Pleural Effusion/microbiology , Pneumococcal Vaccines/therapeutic use , Pneumonia/microbiology , Child , Child, Preschool , Emergency Service, Hospital , Female , France/epidemiology , Hospitalization , Humans , Infant , Male , Pediatric Emergency Medicine , Pneumococcal Infections/epidemiology , Pneumococcal Infections/microbiology , Prospective Studies , Streptococcus pneumoniae/isolation & purification , Streptococcus pyogenes/isolation & purification , Vaccines, Conjugate/therapeutic useABSTRACT
Background: Enteric fever in France is primarily travel-associated. Characteristics of paediatric cases are scarce and information from field studies in endemic countries might not be generalizable to non-endemic countries. Methods: In this retrospective study, we reviewed all cases of typhoid and paratyphoid fever treated in a French paediatric tertiary care centre from 1993 to 2015. Results: Fifty cases of enteric fever due to Salmonella enterica serovar Typhi (n = 44) and Paratyphi (n = 6) were identified. Sixty-one percent of the children had travelled to Africa and 34% to the Indian subcontinent. Among travel-associated cases, 85% were visiting friends and relatives (VFR). Ninety-six percent had high fever associated with gastrointestinal symptoms. Anaemia (66%), elevated C-reactive protein (80%), transaminitis (87%) and mild hyponatremia (50%) were the main biological findings. Blood cultures were positive in 90% of cases. Twelve strains (24%) were resistant at least to one antibiotic, and all of them had been isolated since 2003, increasing the resistance rate during this last period to 43% (12/28). Ceftriaxone was administered to 71 patients for a median duration of 6 days (interquartile range (IQR): 4-8). The median time to apyrexia after the onset of treatment was 4 days (IQR: 2-5 days). Complications occurred in nine children with five (10%) presenting neurologic disorders. All 50 patients recovered. Conclusion: In France, paediatric enteric fever is mainly a travel-associated disease and occurs in patients returning from a prolonged stay in an endemic area. Children VFR are at high risk and should be a priority target group for pre-travel preventive measures. The increase in antibiotic resistance reflects the situation in endemic countries and is a major concern.
Subject(s)
Paratyphoid Fever/drug therapy , Paratyphoid Fever/epidemiology , Travel-Related Illness , Travel/statistics & numerical data , Typhoid Fever/diagnosis , Typhoid Fever/epidemiology , Africa , Anti-Bacterial Agents/therapeutic use , Child , Child, Preschool , Female , France , Hospitals, Pediatric , Humans , Indonesia , Male , Paratyphoid Fever/diagnosis , Paratyphoid Fever/microbiology , Retrospective Studies , Risk Factors , Salmonella paratyphi A/isolation & purification , Salmonella typhi/isolation & purification , Tertiary Care Centers , Typhoid Fever/diet therapy , Typhoid Fever/microbiologyABSTRACT
BACKGROUND: The number of trips to the tropics taken by children with chronic health disorders (CHDs) is increasing. METHODS: All of the children with CHDs who attended two international vaccination centres in France before travelling to the tropics were included in a prospective, exposed/unexposed study. Each child was age-matched with two control children and followed for 1â month after returning from the tropics. RESULTS: Fifty-six children with CHDs and 107 control children were included. The children's median age was 6â years old (IQR 2-11). Of the study participants, 127/163 (78%) travelled to West Africa, mainly to visit relatives. The median duration of the stay was 42â days (IQR 31-55). The age of the children, the destination and the duration of the trip were similar between the two groups. Sickle cell disease (23/56) and asthma (16/56) were the most common CHDs. Overall, the children with CHDs experienced more clinical events than the control patients did (p<0.05); however, there was no difference when chronic disease exacerbations were excluded (p=0.64) or when only the period abroad was considered (p=0.24). One child with a recent genetic diagnosis of atypical haemolytic uraemic syndrome died from a first disease exacerbation. CONCLUSIONS: Health problems among children with CHDs travelling abroad are mainly related to chronic disease exacerbations, which mostly occur after the children return. Patients with diseases that require highly specialised care for an exacerbation should avoid travelling to resource-limited tropical countries.
Subject(s)
Chronic Disease/prevention & control , Travel/statistics & numerical data , Case-Control Studies , Child , Child, Preschool , Chronic Disease/epidemiology , Female , France/epidemiology , Health Status , Humans , Male , Patient Compliance/statistics & numerical data , Prospective Studies , Tropical Climate , VaccinationABSTRACT
OBJECTIVE: To evaluate therapeutic education delivered in a pediatric emergency department to improve parents' satisfaction and attitudes about judicious antibiotic use. METHODS: In an emergency department of a tertiary pediatric hospital, children aged 1 month to 6 years and discharged with an oral antibiotic prescription for an acute respiratory or urinary tract infection were randomized to a patient therapeutic education on antibiotic use (intervention group) or fever control (control group) delivered to the parents (in the presence of the children) by a pharmacist trained in therapeutic education. Education consisted in a 30-minute face-to-face session with four components: educational diagnosis, educational contract, education, and evaluation. The main outcome measure was parent satisfaction about information on antibiotics received at the hospital, as assessed by a telephone interview on day 14. The secondary outcome was attitudes about antibiotic use evaluated on day 14 and at month 6. RESULTS: Of the 300 randomized children, 150 per arm, 259 were evaluated on day 14. Parent satisfaction with information on antibiotics was higher in the intervention group (125/129, 96.9%, versus 108/130, 83.0%; P=0.002, exact Fisher test). INTERVENTION: Group parents had higher proportions of correct answers on day 14 to questions on attitudes about judicious antibiotic use than did control-group parents (P=0.017, Mann-Whitney U test). CONCLUSION: Therapeutic education delivered by a clinical pharmacist in the pediatric emergency department holds promise for improving the use of antibiotics prescribed to pediatric outpatients. TRIAL REGISTRATION: ClinicalTrials.gov NCT00948779 http://clinicaltrials.gov/show/NCT00948779.
Subject(s)
Anti-Bacterial Agents/administration & dosage , Health Education , Personal Satisfaction , Attitude , Child , Child, Preschool , Emergency Service, Hospital , Female , Humans , Infant , Male , Parents , Pediatrics , PharmacistsABSTRACT
We performed a cohort study of children who survived bacterial meningitis after the neonatal period at a single pediatric center in France over a 10-year period (1995-2004) to identify predictors of death and long-term neurological deficits in children with bacterial meningitis. We performed multivariate regression to determine independent predictors of death and neurologic deficits. We identified 101 children with bacterial meningitis of which 19 died during initial hospitalization. Need for mechanical ventilation [hazard ratio (HR) 11.5, 95 % confidence interval (CI) 2.4-55.5)] and thrombocytopenia defined as a platelet count <150 × 10(9) per liter (HR 0.6, 95 % CI 0.4-0.9) at presentation were associated with death during initial hospitalization. At final assessment, 42 of the 70 survivors had no neurologic deficits identified; 20 had a single deficit, and eight had multiple deficits. A delay in initiation of antibiotics (HR 1.3, 95 % CI 1.1-1.7) and hydrocephalus on computed tomographic scan (HR 2.6, 95 % CI 1.1-6.0) were associated with having one or more long-term neurologic deficits. Identification of children at risk of death or long-term neurologic sequelae may allow therapeutic interventions to be directed to children at the highest risk.
Subject(s)
Meningitis, Bacterial/complications , Mental Disorders/etiology , Nervous System Diseases/etiology , Cohort Studies , Epilepsy/etiology , Female , Follow-Up Studies , Hearing Loss, Sensorineural/etiology , Hospital Mortality , Hospitalization , Humans , Infant , Intellectual Disability/etiology , Male , Meningitis, Bacterial/diagnosis , Meningitis, Bacterial/mortality , Meningitis, Bacterial/therapy , Migraine Disorders/etiology , Movement Disorders/etiology , Multivariate Analysis , Prognosis , Proportional Hazards Models , Retrospective Studies , Risk Factors , Sleep Wake Disorders/etiology , Treatment OutcomeSubject(s)
Gait Disorders, Neurologic/diagnosis , Gait Disorders, Neurologic/etiology , Humans , Infant , MaleSubject(s)
Headache/diagnosis , Seizures/diagnosis , Vomiting/diagnosis , Anticonvulsants/therapeutic use , Child , Diagnosis, Differential , Diazepam/therapeutic use , Electroencephalography , Headache/etiology , Humans , Magnetic Resonance Imaging , Male , Migraine with Aura/complications , Myoclonus/complications , Seizures/etiology , Syndrome , Tomography, X-Ray Computed , Vomiting/etiologyABSTRACT
MgcRacGAP, a Rho GAP essential to cytokinesis, works both as a Rho GTPase regulator and as a scaffolding protein. MgcRacGAP interacts with MKLP1 to form the centralspindlin complex and associates with the RhoGEF Ect2. The GAP activity of MgcRacGAP is regulated by Aurora B phosphorylation. We have isolated B56epsilon, a PP2A regulatory subunit, as a new MgcRacGAP partner. We report here that (i) MgcRacGAP is phosphorylated by Aurora B and Cdk1, (ii) PP2A dephosphorylates Aurora B and Cdk1 phosphorylated sites and (iii) inhibition of PP2A abrogates MgcRacGAP/Ect2 interaction. Therefore, PP2A may regulate cytokinesis by dephosphorylating MgcRacGAP and its interacting partners.
Subject(s)
CDC2 Protein Kinase/metabolism , GTPase-Activating Proteins/physiology , Mitosis/physiology , Protein Phosphatase 2/metabolism , Protein Serine-Threonine Kinases/metabolism , Animals , Aurora Kinase B , Aurora Kinases , COS Cells , Cell Line, Tumor , Chlorocebus aethiops , Chromatography, High Pressure Liquid , Humans , Phosphorylation , Tandem Mass Spectrometry , Two-Hybrid System TechniquesABSTRACT
The male-germ-cell Rac GTPase-activating protein gene (MgcRacGAP) was initially described as a human RhoGAP gene highly expressed in male germ cells at spermatocyte stage, but exhibits significant levels of expression in most cell types. In somatic cells, MgcRacGAP protein was found to both concentrate in the midzone/midbody and be required for cytokinesis. As a RhoGAP, MgcRacGAP has been proposed to down-regulate RhoA, which is localized to the cleavage furrow and midbody during cytokinesis. Due to embryonic lethality in MgcRacGAP -null mutant mice and to the lack of an in vitro model of spermatogenesis, nothing is known regarding the role and mode of action of MgcRacGAP in male germ cells. We have analysed the expression, subcellular localization and molecular interactions of MgcRacGAP in male germ cells. Whereas MgcRacGAP was found only in spermatocytes and early spermatids, the widespread RhoGTPases RhoA, Rac1 and Cdc42 (which are, to various extents, in vitro substrates for MgcRacGAP activity) were, surprisingly, not detected at these stages. In contrast, Rnd2, a Rho family GTPase-deficient G-protein was found to be co-expressed with MgcRacGAP in spermatocytes and spermatids. MgcRacGAP was detected in the midzone of meiotic cells, but also, unexpectedly, in the Golgi-derived pro-acrosomal vesicle, co-localizing with Rnd2. In addition, a stable Rnd2-MgcRacGAP molecular complex could be evidenced by glutathione S-transferase pull-down and co-immunoprecipitation experiments. We conclude that Rnd2 is a probable physiological partner of MgcRacGAP in male germ cells and we propose that MgcRacGAP, and, quite possibly, other RhoGAPs, may participate in signalling pathways involving Rnd family proteins.