safety and efficacy of fidaxomicin and vancomycin in children and adolescents with clostridioides clostridium difficile infection a phase 3 multicenter randomized single blind clinical trial sunshine

Abstract Background Fidaxomicin, a narrow-spectrum antibiotic approved for Clostridioides (Clostridium) difficile infection (CDI) in adults, is associated with lower rates of recurrence than vancomycin; however, pediatric data are limited. This multicenter, investigator-blind, phase 3, parallel-group trial assessed the safety and efficacy of fidaxomicin in children. Methods Patients aged <18 years with confirmed CDI were randomized 2:1 to 10 days of treatment with fidaxomicin (suspension or tablets, twice daily) or vancomycin (suspension or tablets, 4 times daily). Safety assessments included treatment-emergent adverse events. The primary efficacy end point was confirmed clinical response (CCR), 2 days after the end of treatment (EOT). Secondary end points included global cure (GC; CCR without CDI recurrence) 30 days after EOT (end of study; EOS). Plasma and stool concentrations of fidaxomicin and its active metabolite OP-1118 were measured. Results Of 148 patients randomized, 142 were treated (30 <2 years old). The proportion of participants with treatment-emergent adverse events was similar with fidaxomicin (73.5%) and vancomycin (75.0%). Of 3 deaths in the fidaxomicin arm during the study, none were CDI or treatment related. The rate of CCR at 2 days after EOT was 77.6% (76 of 98 patients) with fidaxomicin and 70.5% (31 of 44) with vancomycin, whereas the rate of GC at EOS was significantly higher in participants receiving fidaxomicin (68.4% vs 50.0%; adjusted treatment difference, 18.8%; 95% confidence interval, 1.5%–35.3%). Systemic absorption of fidaxomicin and OP-1118 was minimal, and stool concentrations were high. Conclusions Compared with vancomycin, fidaxomicin was well tolerated and demonstrated significantly higher rates of GC in children and adolescents with CDI. ClinicalTrials.gov identifier NCT0221837

Demographic characteristics of children with early clinical manifestation of inflammatory bowel disease

Abstract Introduction: Inflammatory bowel disease (IBD), which includes Crohn's disease (CD) and ulcerative colitis (UC), is a chronic condition of the colon and small intestine. The disease is common in young people (children and young adults), but it is rare in children younger than five years of age. Therefore, IBD developing during the first years of life (under the age of 5) is known as an early-onset IBD (EO-IBD), and it is considered to be a specific entity with a distinct phenotype. However, the available data on that issue are still insufficient. Aim: To determine the characteristics and clinical course of children with early-onset IBD. Material and methods: We performed a retrospective database analysis of 47 infants younger than 5 years old diagnosed with IBD. Patient's demographic data, including age, sex, and age at disease onset, were collected in 6 paediatric hospitals in Poland. Disease location was established on the basis of the review of all endoscopic, colonoscopic, histopathological, and radiological records. All possible complications were reported, as well as any treatment and its efficacy. Since the diagnosis was established all patients have been on follow up. Results: Among 47 children registered in the database, 23 (49%) had a diagnosis of CD, 16 (34%) had UC, and 8 (17%) had IC (indeterminate colitis). The mean age at diagnosis was 28.5 ±27.5 months; 57.4% were male. The most common location/type of disease was ileocolonic disease (L3). The most common complication of IBD was anaemia, found in 30 (63.8%) children. The observed course of the disease was either severe or moderate. In 4 children younger than 2 years old, surgery was performed. Conclusions: Inflammatory bowel disease in children younger than 5 years old includes UC, CD, and a relatively high proportion of IC. In early-onset IBD severe and moderate course of the disease is usually observed. Disease manifestation in these patients is predominantly ileocolonic

Body composition as an indicator of the nutritional status in children with newly diagnosed ulcerative colitis and Crohn’s disease – a prospective study

Introduction : The prevalence of nutritional status disorders in children with ulcerative colitis (UC) is much lower than in the case of Crohn’s disease (CD). The largest variability in the components of body composition occurs at the time of a new diagnosis and in periods of disease exacerbation. Aim: Assessment of body composition in children with UC and CD. Material and methods: The preliminary study included 59 children with inflammatory bowel disease (IBD) (34 children with UC vs. 25 children with CD) aged 4–18 years. The final analysis included 26 newly diagnosed children (16 children with UC vs. 10 children with CD). The evaluation of body composition was conducted by means of BIA-101 bioimpedance analyser. Results : Decreased values of lean mass were found in children with newly diagnosed IBD (UC: 41.13 kg vs. control group: 42.06 kg; CD: 35.50 kg vs. control group: 45.50 kg). After a year interval, an increase in fat (UC 1: 7.67 kg vs. UC 2: 10.33 kg; CD 1: 7.36 kg vs. CD 2: 9.47 kg) as well as lean body mass (UC 1: 35.22 kg vs. UC 2: 39.00 kg; CD 1: 35.99 kg vs. CD 2: 42.41 kg) was found in children. Conclusions : Children with newly diagnosed IBD were highly vulnerable to nutritional status disturbances. The increase in fat and lean body mass in an annual interval may be due to the treatment regime and control of the children

Bioelectrical Impedance Phase Angle as an Indicator of Malnutrition in Hospitalized Children with Diagnosed Inflammatory Bowel Diseases—A Case Control Study

The phase angle (PhA) seems to be a reliable screening tool for the identification of malnutrition risk in hospitalized children with inflammatory bowel disease (IBD). The aim of the present study was to assess the body composition and nutritional status of hospitalized children and adolescents with IBD by using bioelectrical impedance analysis (BIA) with phase angle (PhA) calculation, which has not been evaluated in hospitalized children with IBD yet. A total of 59 children and adolescents aged 4–18 years, with IBD: 34 ulcerative colitis (UC) and 25 Crohn’s disease (CD) were included in the study. The control group consisted of healthy children and adolescents, strictly matched for gender and age in a 1:1 case-control manner. In both groups, BIA was performed and PhA was calculated. IBD patients had significantly lower PhA (UC: 5.34 ± 1.34 vs. 5.96 ± 0.76, p = 0.040; CD: 5.16 ± 1.18 vs. 5.90 ± 0.62, p = 0.009) compared to the control subjects. Significant changes in selected body composition parameters were observed particularly in CD, especially in fat free mass components. Lower phase angle score together with lower body composition parameters and selected nutrition indicators in children and adolescents with IBD demonstrate their worse nutritional and functional status compared to healthy subjects

Endoscopic therapy of oesophageal strictures in children : a multicentre study

Introduction: Oesophageal strictures are rare in children but may require endoscopic dilation. Aim: To gather information on centres performing endoscopic oesophageal dilation in Poland. Material and methods: The data were obtained from questionnaires concerning the relevant data mailed to 22 paediatric endoscopy centres. Completed questionnaires were received from 11 centres. Results: In 2010 the 11 Polish paediatric endoscopy centres performed a total of 10,650 endoscopic procedures. This included 347 oesophageal dilations in 106 paediatric patients aged from 1 month to 18 years. The numbers of patients treated at individual centres ranged from 2 to 40. The indications for oesophageal dilation were as follows: postoperative strictures in 68 children, oesophageal burns in 17 children, postinflammatory strictures in 14 children, achalasia in 4 children, and strictures caused by a foreign body in 3 children. Rigid guidewire dilators were used in the majority of procedures (271), rigid dilators without a guidewire in 32 procedures, and balloon dilators in 45 procedures. A total of 203 procedures were conducted under fluoroscopic guidance, and 144 without the use of fluoroscopy. The number of dilating sessions performed in individual children varied from 1 to 6 and more. Conclusions: Oesophageal dilation constituted a minor proportion of all paediatric endoscopic procedures. The majority of children requiring dilation were patients up to 3 years of age with postoperative oesophageal strictures. In the majority of the centres rigid guidewire dilators were used, and in one third of the procedures these dilators were introduced without fluoroscopic guidance

Decreased Bioelectrical Impedance Phase Angle in Hospitalized Children and Adolescents with Newly Diagnosed Type 1 Diabetes: A Case-Control Study

The aim of this study was to assess the body composition and nutritional status of hospitalized pediatric patients with newly diagnosed type 1 diabetes by using bioelectrical impedance analysis (BIA) with phase angle (PA) calculation. PA is considered to be a useful and very sensitive indicator of the nutritional and functional status, and it has not yet been evaluated in such a population. Sixty-three pediatric patients aged 4 to 18 years, with newly diagnosed type 1 diabetes, were included in the study. The control group consisted of 63 healthy children and adolescents strictly matched by gender and age in a 1:1 case: control manner. In both groups, BIA with PA calculation was performed. Diabetic patients, in comparison to control subjects, had a highly significantly lower PA of 4.85 ± 0.86 vs. 5.62 ± 0.81, p < 0.001. They also demonstrated a lower percentage of body cell mass (BCM%), 46.89 ± 5.67% vs. 51.40 ± 4.19%, p < 0.001; a lower body cell mass index (BCMI), 6.57 ± 1.80% vs. 7.37 ± 1.72%, p = 0.004; and a lower percentage of muscle mass (MM%), 44.61 ± 6.58% vs. 49.40 ± 7.59%, p < 0.001, compared to non-diabetic controls. The significantly lower PA value in diabetic patients indicate their worse nutritional and functional status compared to healthy subjects. To assess the predictive and prognostic value of this finding in this population, further prospective studies involving larger sample of patients are required

Subcutaneous engineered factor VIIa marzeptacog alfa (activated) in hemophilia with inhibitors: Phase 2 trial of pharmacokinetics, pharmacodynamics, efficacy, and safety.

BackgroundMarzeptacog alfa (activated) (MarzAA), a novel recombinant activated human factor VII (FVIIa) variant, was developed to provide increased procoagulant activity, subcutaneous (SC) administration, and longer duration of action in people with hemophilia.ObjectivesTo investigate if daily SC administration of MarzAA in subjects with inhibitors can provide effective prophylaxis.MethodsThis multicenter, open-label phase 2 trial (NCT03407651) enrolled men with severe congenital hemophilia with an inhibitor. All subjects had a baseline annualized bleeding rate (ABR) of ≥12 events/year. Subjects received a single 18 μg/kg intravenous dose of MarzAA to measure 24-hour pharmacokinetics (PK) and pharmacodynamics (PD), single 30 μg/kg SC dose to measure 48-hour PK/PD, then daily SC 30 μg/kg MarzAA for 50 days. If spontaneous bleeding occurred, the dose was sequentially escalated to 60, 90, or 120 μg/kg, with 50 days at the final effective dose without spontaneous bleeding to proceed to a 30-day follow-up. The primary end point was reduction in ABR. Secondary end points were safety, tolerability, and antidrug antibody (ADA) formation.ResultsIn the 11 subjects, the mean ABR significantly reduced from 19.8 to 1.6, and the mean proportion of days with bleeding significantly reduced from 12.3% to 0.8%. Of a total of 517 SC doses, six injection site reactions in two subjects were reported. No ADAs were detected. One fatal unrelated serious adverse event occurred: intracerebral hemorrhage due to untreated hypertension.ConclusionsThe data demonstrated that MarzAA was highly efficacious for prophylactic treatment in patients with inhibitors by significantly decreasing bleed frequency and duration of bleeding episodes