Clinical Outcomes In Children Research Articles

The impact of the distal ureteral diameter ratio, bladder volume at onset of vesicoureteral reflux, and/or grade in predictive models of clinical outcomes in children with vesicoureteral reflux

Vesicoureteral reflux (VUR) grade has been used as a primary factor in assessing a child's risk of clinical outcomes. Unfortunately, grade has poor inter-observer reliability. We hypothesized that more objective and reliable VCUG parameters including the distal ureteral diameter ratio (UDR) and volume at onset of VUR (Vol) may either augment or replace the current grading system to provide more reliable prediction of clinical outcomes. Multivariate clinical outcome models were analyzed to assess the impact on predictive accuracy by the addition of voiding cystourethrogram (VCUG) data including grade, UDR, and Vol, alone or in combinations. Clinical variables from retrospective review of 841 children's records included age, gender, presentation, VUR laterality, bowel and bladder dysfunction, history of febrile urinary tract infection (UTI), and number of UTIs. The primary outcomes assessed included VUR resolution or persistence and need for operative intervention. Grade, UDR, and Vol were independent predictors of resolution and operative intervention. Vol increased predictive accuracy in resolution models with grade or UDR alone; however, no significant difference occurred in models with the substitution of grade with UDR. A more reliable classification system for VUR, with improved predictive accuracy regarding clinical outcomes, may be developed incorporating UDR and Vol. Whether VUR grade can be completely replaced by Vol and UDR measurements requires further evaluation with larger number of patients.

Clinical validation and accuracy assessment of the Capsule Endoscopy-Crohn's Disease index (CE-CD).

To compare the recently proposed Capsule Endoscopy-Crohn's Disease index (CE-CD) to pre-existing capsule endoscopy (CE) scores, to measure its precision and accuracy to predict adverse clinical outcomes in children with Crohn's disease (CD). Children with CD who underwent CE at diagnosis and had, at least, 1-year follow-up postprocedure were selected. Capsule study was viewed and the different indices were independently scored by two trained paediatric gastroenterologists. The relationship between pre-existing scores and CE-CD was assessed by linear regression analysis. Clinical outcomes prediction assessment was based on receiver operating characteristics curves, survival analysis and Cox regression. Finally, interobserver agreement was measured. Fifty-nine patients were finally included. CE-CD showed a strong positive correlation with the Lewis score (ρ = 0.947) and the Capsule Endoscopy Crohn's Disease Activity Index (CECDAI) (ρ = 0.982). Both CE-CD and CECDAI were significant predictors of treatment escalation (hazard ratio 1.07 and 1.09, respectively, with both p-values < 0.01). However, no score predicted risk of hospital admission, surgeryor clinical/endoscopic relapse. The presence of moderate-to-severe small bowel (SB) inflammation, defined as a score of ≥9 on CE-CD, provided a hazard ratio of treatment escalation of 2.6 (95% confidence interval: 1.3-5.3). This cut-off provided the optimal sensitivity/specificity pair: 48.4%/89.3%. No interobserver misclassification among inflammation categories given by CE-CD were observed (kappa 100%). CE-CD is a useful tool to document SB inflammation in children with CD. It correlates strongly with classical scores, can better predict need for treatment escalation and shows good interobserver agreement.

Comparing long-term outcomes of children treated with new-onset type 2 diabetes in an outpatient versus inpatient setting: A retrospective chart review.

Early identification and management of pediatric type 2 diabetes mellitus (T2DM) is crucial for improving long-term outcomes. This study aimed to assess if the severity of T2DM at presentation, inferred by the location of treatment initiation (inpatient or outpatient), influences long-term clinical outcomes. A retrospective chart review was conducted on 116 pediatric T2DM patients. Data on treatment initiation location, initial and subsequent glycated hemoglobin (HbA1c) levels, prescribed insulin, and body mass index were collected from electronic medical records. Of the 116 patients, 69 were initially treated in an inpatient setting, and 47 received outpatient treatment. At treatment initiation, the inpatient group had significantly higher HbA1c levels compared to the outpatient group (p < .001), but 3 years after treatment initiation, no significant difference in HbA1c was observed between the two groups (p = .057). Prescribed insulin dosages were higher in the inpatient group at treatment initiation (p < .001) and remained higher after 3 years (p < 0.003) compared to the outpatient group. Pediatric patients initially treated in an inpatient setting had poorer glycemic control and higher prescribed insulin dosing at baseline. After 3 years, there was no significant difference in HbA1c levels, but patients treated as inpatients continued to have higher prescribed insulin. These findings suggest that the severity of diabetes at initial presentation may affect long-term clinical outcomes in children with T2DM.

Outcome of Pediatric Large Vessel Occlusion Stroke in Denmark

BACKGROUND We performed a nationwide study to examine clinical outcome in children with large‐vessel occlusion (LVO) stroke treated with mechanical thrombectomy (MT) or conservatively. METHODS Study participants were enrolled by 2 methods: (1) registration of children assessed through a pediatric stroke triage‐setup from January 2021 to June 2023 and (2) identification of children registered with a stroke or stroke‐related diagnosis in the Danish National Registry of Patients between January 2011 and December 2020. Medical records were reviewed to validate possible stroke events. Children aged 29 days to 17 years with arterial ischemic stroke were included. The children were followed up for cause of stroke, site of vessel occlusion, treatment characteristics, and clinical outcome according to the modified Rankin scale. RESULTS A total of 181 children with arterial ischemic stroke were identified. Angiography descriptions were available in 133 children and demonstrated LVOs in 28 (21.1%) of these. Fourteen children with LVOs underwent MT and 14 were treated conservatively. Thirteen of 14 (92.9%) children treated with MT achieved successful reperfusion. Periprocedural complications were observed in 2 children, including 1 child who developed symptomatic intracerebral hemorrhage &lt;24 hours from MT. Long‐term outcome was poor (modified Rankin scale score 3–6) in 7 out of 14 (50.0%) children with LVOs treated conservatively and 5 out of 14 (35.7%) children treated with MT. When limiting analysis to MT procedures performed within 24 hours from stroke onset, a poor outcome was observed in 3 out of 11 (27.3%) children treated with MT. Outcome did not differ significantly between treatment groups. CONCLUSION This nationwide study demonstrates that MT is feasible and apparently safe to use in children. Among children with LVOs, outcome tended to be better for those treated with MT than those treated conservatively, but outcome did not differ significantly between groups, likely due to small sample sizes.

Outcome of bleomycin electrosclerotherapy of slow-flow malformations in adults and children.

To evaluate the safety and clinical outcome of bleomycin electrosclerotherapy (BEST) for treating extracranial slow-flow malformations. In this retrospective investigation of a multicenter cohort presenting symptomatic slow-flow malformations, patient records were analyzed with respect to procedural details and complications. A treatment-specific, patient-reported questionnaire was additionally evaluated, obtained 3-12 months after the last treatment, to assess the subjective outcomes, including mobility, aesthetic aspects, and pain, as well as the occurrence of postprocedural skin hyperpigmentation. All outcome parameters were compared according to patients' age. Overall, 325 BEST treatments were performed in 233 patients after intralesional and/or intravenous bleomycin injection. The total complication rate was 10.2% (33/325), including 29/352 (8.9%) major complications. Patient-reported mobility decreased in 10/133 (8.8%), was stable in 30/113 (26.5%), improved in 48/113 (42.5%), and was rated symptom-free in 25/113 (22.1%) patients. Aesthetic aspects were rated impaired compared to baseline in 19/113 (16.8%), stable in 21/133 (18.6%), improved in 62/113 (54.9%), and perfect in 11/133 (9.7%) patients. Postprocedural skin hyperpigmentation occurred in 78/113 (69%) patients, remaining unchanged in 24/78 (30.8%), reduced in 51/78 (65.5%), and completely resolved in 3/78 (3.8%) patients. The median VAS pain scale was 4.0 (0-10) preprocedural and 2.0 (0-9) postprocedural. Children/adolescents performed significantly better in all parameters compared to adults (≥ 16 years) (mobility, p = 0.011; aesthetic aspects, p < 0.001; pain, p < 0.001). BEST is effective for treating slow-flow vascular malformations, with few but potentially significant major complications. Regarding patient-reported outcomes, children seem to benefit better compared to older patients, suggesting that BEST should not be restricted to adults. Bleomycin electrosclerotherapy is a safe and effective approach and therapy should not be restricted to adults due to good clinical outcomes in children.

The effect of respiratory muscle training on children and adolescents with cystic fibrosis: a systematic review and meta-analysis

BackgroundCystic fibrosis is a chronic genetic disease that can affect the function of the respiratory system. Previous reviews of the effects of respiratory muscle training in people with cystic fibrosis are uncertain and do not consider the effect of age on disease progression. This systematic review aims to determine the effectiveness of respiratory muscle training in the clinical outcomes of children and adolescents with cystic fibrosis.MethodsUp to July 2023, electronic databases and clinical trial registries were searched. Controlled clinical trials comparing respiratory muscle training with sham intervention or no intervention in children and adolescents with cystic fibrosis. The primary outcomes were respiratory muscle strength, respiratory muscle endurance, lung function, and cough. Secondary outcomes included exercise capacity, quality of life and adverse events. Two review authors independently extracted data and assessed study quality using the Cochrane Risk of Bias Tool 2. The certainty of the evidence was assessed according to the GRADE approach. Meta-analyses where possible; otherwise, take a qualitative approach.ResultsSix studies with a total of 151 participants met the inclusion criteria for this review. Two of the six included studies were published in abstract form only, limiting the available information. Four studies were parallel studies and two were cross-over designs. There were significant differences in the methods and quality of the methodology included in the studies. The pooled data showed no difference in respiratory muscle strength, lung function, and exercise capacity between the treatment and control groups. However, subgroup analyses suggest that inspiratory muscle training is beneficial in increasing maximal inspiratory pressure, and qualitative analyses suggest that respiratory muscle training may benefit respiratory muscle endurance without any adverse effects.ConclusionsThis systematic review and meta-analysis indicate that although the level of evidence indicating the benefits of respiratory muscle training is low, its clinical significance suggests that we further study the methodological quality to determine the effectiveness of training.Trial registrationThe protocol for this review was recorded in the International Prospective Register of Systematic Reviews (PROSPERO) under registration number CRD42023441829.

Comparison of Characteristics and Clinical Outcomes of Children with Confirmed Tuberculosis and Unconfirmed Rapid Molecular Test Examination

Background: Making a confirmation of TB diagnosis by bacteriological examination is difficult in children. Currently, the GeneXpert examination is better than AFB examination. However, obtaining a representative specimen is quite difficult in children cause some TB cases are established clinically. Objective: To analyze the comparison of characteristics and clinical outcomes of children with confirmed tuberculosis by GeneXpert examination with clinical TB. Method: A case-control study to evaluate the clinical characteristics and outcomes of TB patients aged 0-18 years who underwent GeneXpert examination at Dr. M Djamil Padang from July 2017 to June 2022. Results: A total of 153 subjects consisted of 24% confirmed TB through GeneXpert examination and 76% were clinical TB. It was found clinical presentations more frequent in confirmed TB than clinical TB in complaints; fever and cough more than 2 weeks, malaise, contact history, did not have BCG immunization, lymph nodes enlargement, radiological features, and prolonged ESR, except for findings rales. Most subjects have recovered of chest X-ray in both groups. Conclusion: Clinical presentations is more common in confirmed TB than clinical TB except for rales. Keywords: TB, confirmed TB, clinical TB, clinical characteristic, clinical outcome.

Clinical outcomes in children living with HIV treated for non-severe tuberculosis in the SHINE Trial.

Children living with HIV(CLWH) are at high risk of tuberculosis(TB) and face poor outcomes, despite antiretroviral treatment(ART). We evaluated outcomes in CLWH and HIV-uninfected children treated for non-severe TB in the SHINE trial. SHINE was a randomized trial that enrolled children aged <16 years with smear-negative, non-severe TB who were randomized to receive 4 vs 6 months of TB treatment and followed for 72 weeks. We assessed TB relapse/recurrence, mortality, hospitalizations, grade ≥3 adverse events by HIV status, and HIV virological suppression in CLWH. Of 1204 enrolled, 127(11%) were CLWH, of similar age (median(IQR) 3.6(1.2, 10.3) vs. 3.5(1.5, 6.9)years, p= 0.07), but more underweight (WAZ; -2.3(-3.3, -0.8) vs -1.0(-1.8, -0.2), p<0.01) and anemic (hemoglobin 9.5(8.7, 10.9) vs 11.5(10.4, 12.3)g/dl, p<0.01) compared to HIV-uninfected children. 68(54%) CLWH were ART-naïve; baseline median CD4 count 719(241-1134) cells/mm3, CD4% 16(10-26)%). CLWH were more likely to be hospitalized (aOR=2.4(1.3-4.6)) and die (aHR(95%CI) 2.6(1.2,5.8)). HIV status, age <3 years (aHR 6.3(1.5,27.3)), malnutrition (aHR 6.2(2.4,15.9)) and hemoglobin <7g/dl(aHR 3.8(1.3,11.5) independently predicted mortality. Among children with available VL, 45% and 61% CLWH had VL<1000copies/ml at weeks 24 and 48, respectively. There was no difference in the effect of randomized treatment duration (4 vs 6 months) on TB treatment outcomes by HIV status (p for interaction=0.42). We found no evidence of a difference in TB outcomes between 4 and 6 months of treatment for CLWH treated for non-severe TB. Irrespective of TB treatment duration, CLWH had higher rates of mortality and hospitalization than HIV-uninfected counterparts.

Variations in Management and Clinical Outcomes for Children With Diabetic Ketoacidosis in an Academic Pediatric Versus Community Emergency Department Setting.

Our objectives were to characterize variations from standardized, evidence-based guidelines in the management of pediatric patients with diabetic ketoacidosis (DKA) based on initial presentation to a tertiary pediatric emergency department (PED) versus a community emergency department (OSH) and compare clinical outcomes. We conducted a retrospective study on children 18 years and younger with DKA who presented to an OSH or PED over a 3-year period. Treatments monitored for variation included intravenous fluid management, insulin delivery, and sodium bicarbonate administrations. Clinical outcomes included time to anion gap correction and on insulin infusion, hypokalemia, hypoglycemia, rapid serum glucose decline, cerebral edema, mechanical ventilation, mortality, and time from initial presentation to hospital discharge. Children with DKA who presented to an OSH (n = 250) were more acidotic (pH 7.11 vs. 7.13, P = 0.001) and had larger anion gaps (28.8 vs. 25.5, P < 0.001) compared with children presenting to the PED (n = 237). The OSH patients were more likely to receive larger fluid boluses (>20 cc/kg or >1000 ml, 43% vs. 4%, P < 0.001), sodium bicarbonate (5% vs. 0%, P < 0.001), and intravenous bolus insulin (28% vs. 0%, P < 0.001). The OSH group were less likely to be started on maintenance intravenous fluids (70% vs. 99%, P < 0.001) or receive potassium in maintenance intravenous fluids (14% vs. 42%, P < 0.001). The OSH group had longer anion gap correction times (754 vs. 541 mins, P < 0.001), insulin infusion times (1018 vs. 854 min, P = 0.003), and times to hospital discharge (3358 vs. 3045 mins, P < 0.001). Incidence of hypokalemia, hypoglycemia, rapid glucose decline, cerebral edema, and deaths were similar between the 2 groups. Our study demonstrated significant variations in the initial management of pediatric DKA patients by OSH facilities that deviated from an evidence-based treatment pathway utilized by a PED. Statewide quality improvement initiatives could help improve the overall clinical care provided to pediatric DKA patients.

A Comprehensive Examination of Clinical Characteristics and Determinants of Long-Term Outcomes in Pediatric Cerebral Sinus Venous Thrombosis

BackgroundTo analyze the clinical and neuroimaging features, risk factors, treatment choices, and long-term clinical outcomes in children with cerebral sinus venous thrombosis (CSVT). MethodsThis is a retrospective cohort study of children diagnosed with CSVT between 2002 and 2018 at Texas Children's Hospital. ResultsA total of 183 children (male: 62.3%) with CSVT were included. The average presenting age was 7.7 years (S.D.: 5.6). The mean follow-up duration was 33.7 months (S.D.: 38.6). The most common presenting clinical feature was headache (36.6%). Head and neck infections other than meningitis (36.6%) were the most common risk factors. Prevalent neurological examination findings included motor deficit (21.3%) and altered mental status (AMS, 20.2%). Neuroimaging features included hemorrhagic infarction (19.6%), ischemic infarction (8.2%), and intracranial hemorrhage without infarction (5.5%). The most common site of thrombosis was the superior sagittal sinus (37.2%), with 78.2% of patients demonstrating involvement of multiple sinuses. Treatment of choice was low-molecular-weight heparin in 69.4% of patients. Factors associated with worse clinical outcomes included head and neck infections, malignancy (other than hematologic), cardiac disease, and recent surgery; seizure and dehydration on initial presentation; motor abnormalities and AMS on initial examination; ischemic infarct only; and involvement of vein of Trolard on neuroimaging. Thrombus condition on repeat imaging, receiving any anticoagulant/antithrombotic treatment, treatment duration, or follow-up duration was not associated with severity of long-term outcome. ConclusionsCSVT may lead to unfavorable long-term outcomes in a remarkable portion of pediatric patients. Thus, a high index of suspicion and early and appropriate management of pediatric CSVT is imperative.

Pan-enteric Capsule Endoscopy to Characterize Crohn's Disease Phenotypes and Predict Clinical Outcomes in Children and Adults: The Bomiro Study.

Pan-enteric capsule endoscopy (PCE) provides useful information for the management of Crohn's disease (CD), especially in children. No study has evaluated the ability of PCE to characterize CD phenotypes and outcomes in children and adults. In a prospective multicenter observational study, we recruited patients with CD >6 years from 4 centers in Italy. Patients underwent clinical, biomarker assessment and PCE. Lesions were graded using the PCE system. For each segment, the most common lesion (MCL), the most severe lesion (MSL), and the extent of involvement were defined. Disease severity, extent, and clinical outcomes were compared between children and adults. A logistic regression analysis was used to identify predictive factors for negative outcomes in both age groups. One hundred ninety-four consecutive patients (adults/children: 144/50) were evaluated for a total of 249 procedures. Children were more likely to have extensive disease, particularly in the colon. Higher MCL scores were independently associated with treatment escalation (odds ratio [OR], 4.09; 95% CI, 1.80-9.25; P = .001), while >30% disease extent was more indicative of clinical and endoscopic relapse (OR, 2.98; 1.26-7.08; P = .013). Disease extent was the only factor associated with endoscopic recurrence in children (OR, 4.50; 95% CI, 1.47-13.77; P = .008), while severe lesions in adults provided a better predictor of treatment escalation (OR, 4.31; 95% CI, 1.52-12.1; P = .006). Postexamination, PCE contributed to a change of therapy in 196/249 (79%) of the procedures. PCE allowed the characterization of CD phenotypes in children and adults by assessing disease severity and extent, which are of different importance in predicting clinical outcomes in these age groups.

Whole-lesion assessment of volume and signal changes after sclerotherapy of extremity venous malformations

PurposeTo investigate quantitative changes in MRI signal intensity (SI) and lesion volume that indicate treatment response and correlate these changes with clinical outcomes after percutaneous sclerotherapy (PS) of extremity venous malformations (VMs). MethodsVMs were segmented manually on pre- and post-treatment T2-weighted MRI using 3D Slicer to assess changes in lesion volume and SI. Clinical outcomes were scored on a 7-point Likert scale according to patient perception of symptom improvement; treatment response (success or failure) was determined accordingly. ResultsEighty-one patients with VMs underwent 125 PS sessions. Treatment success occurred in 77 patients (95 %). Mean (±SD) changes were –7.9 ± 24 cm3 in lesion volume and –123 ± 162 in SI (both, P <.001). Mean reduction in lesion volume was greater in the success group (–9.4 ± 24 cm3) than in the failure group (21 ± 20 cm3) (P =.006). Overall, lesion volume correlated with treatment response (ρ = –0.3, P =.004). On subgroup analysis, volume change correlated with clinical outcomes in children (ρ = –0.3, P =.03), in sodium tetradecyl sulfate–treated lesions (ρ = –0.5, P =.02), and in foot lesions (ρ = –0.6, P =.04). SI change correlated with clinical outcomes in VMs treated in 1 PS session (ρ = –0.3, P =.01) and in bleomycin-treated lesions (ρ = –0.4, P =.04). ConclusionsChange in lesion volume is a reliable indicator of treatment response. Lesion volume and SI correlate with clinical outcomes in specific subgroups.

Clinical outcomes before and after videofluoroscopic swallow study in children 24 months of age or younger.

To evaluate the combined impact of videofluoroscopic swallow study (VFSS) and therapeutic feeding and swallowing interventions on clinical outcomes in children with oropharyngeal dysphagia (OPD). This was an uncontrolled longitudinal analytical study in which OPD patients were evaluated before and after VFSS. Children ≤ 24 months of age diagnosed with OPD in a clinical setting and undergoing VFSS for investigation and management of OPD were included in the study. The study participants received therapeutic feeding and swallowing interventions after having undergone VFSS, being followed at an outpatient clinic for pediatric dysphagia in order to monitor feeding and swallowing difficulties. Respiratory and feeding outcomes were compared before and after VFSS. Penetration/aspiration events were observed in 61% of the VFSSs (n = 72), and therapeutic feeding and swallowing interventions were recommended for 97% of the study participants. After the VFSS, there was a reduction in the odds of receiving antibiotic therapy (OR = 0.007) and in the duration of antibiotic therapy (p = 0.014), as well as in the odds of being admitted to hospital (p = 0.024) and in the length of hospital stay (p = 0.025). A combination of oral and enteral feeding became more common than oral or enteral feeding alone (p = 0.002). A high proportion of participants exhibited penetration/aspiration on VFSS. Therapeutic feeding and swallowing interventions following a VFSS appear to be associated with reduced respiratory morbidity in this population.

The utility of elective flexible bronchoscopy to improve quality of life and clinical outcomes for children: A systematic review.

Elective flexible bronchoscopy (FB) is now widely available and standard practice for a variety of indications in children with respiratory conditions. However, there is limited evidence regarding the utility of elective FB in children. This systematic review (SRs) aimed to determine the utility of FB on its impact in clinical decision making and quality of life (QoL). We searched Pubmed, Cochrane central register of controlled trials, Embase, World Health Organization Clinical Trials Registry Platform and Cochrane database of SRs from inception to April 20, 2023. We included SRs and randomized controlled trials (RCTs) that used parallel group design (comparing use of elective FB vs. no FB, or a wait-list approach [early FB vs. usual wait FB]) in children aged ≤ 18 years. Our protocol was prospectively registered and used Cochrane methodology for systemic reviews of interventions. Our search identified 859 articles; 102 duplicates were removed, and 753 articles were excluded by title and abstract. Four full text articles were reviewed and subsequently excluded, as none met the inclusion criteria outlined in our patient, intervention, comparator, outcome measures framework. There is a paucity of high-quality RCT evidence to support the routine use of elective FB in children with respiratory conditions. However, available retrospective and a single prospective study demonstrate the high utility of FB in the elective pediatric setting. PROSPERO CRD42021291305.

Impact of initial high flow nasal cannula flow rates on clinical outcomes in children with bronchiolitis.

Our aim was to evaluate the impact of the initial high flow nasal cannula (HFNC) flow rate on clinical outcomes in children with bronchiolitis. This secondary analysis of retrospective data included children <2 years who required HFNC for bronchiolitis between 10/01/2018-04/20/2019, and following implementation of a revised institutional bronchiolitis pathway between 10/01/2021-04/30/2022. The new pathway recommended weight-based initiation of HFNC at 1.5-2 L/kg/min. We evaluated the effect of low (<1.0 L/kg/min), medium (1-1.5 L/kg/min) and high (>1.5 L/kg/min) HFNC flow rates on need for positive pressure ventilation (PPV), intensive care unit (ICU) transfer, HFNC treatment time, and hospital length of stay (LOS). The majority of the 885 included children had low initial flow rates (low [n = 450, 50.8%], medium [n = 332, 37.5%] and high [n = 103, 11.7%]). There were no significant differences in PPV (high: 7.8% vs. medium: 9.3% vs. low: 8.2%, p = 0.8) or ICU transfers (high: 4.9% vs. medium: 6.0% vs. low: 3.8%, p = 0.3). The low flow group had a significantly longer median HFNC treatment time (High: 29 [18, 45] vs. medium: 29 [16, 50] vs. low: 39 [25, 63], p < .001) and hospital LOS (High: 41 [27, 59] vs. medium: 42 [29, 66] vs. low: 50 (39, 75), p < .001). Logistic and linear regression models did not demonstrate any associations between HFNC flow rates and PPV or hospital LOS. Initial HFNC flow rates were not associated with significant changes in clinical outcomes in children in children with bronchiolitis.

ASSESSING THE CLINICAL IMPACTS OF IMMUNOMODULATORY WITHDRAWAL FROM ANTI-TNF COMBINATION THERAPY IN PEDIATRIC INFLAMMTORY BOWEL DISEASE

Abstract INTRODUCTION Combination therapy consists of both a monoclonal antibody against tumor necrosis factor (anti-TNF) (infliximab (IFX) or adalimumab (ADA)) and an immunomodulator (IMM) (thiopurines (TP) or methotrexate (MTX)). Although combination therapy improves clinical outcomes, the IMM may be discontinued to mitigate the risk of IMM-related adverse events. However, it is unknown how de-escalation impacts clinical outcomes in children with IBD. METHODS This is a retrospective review of pediatric patients with IBD (&amp;lt;18 years of age) initiated on combination therapy between January 2014 and December 2019. Demographic and laboratory data were recorded at initiation of combination therapy, prior to IMM discontinuation, and between 6-12 months after de-escalation. The primary objectives were to assess the impacts of de-escalation on clinical remission rates, laboratory markers, and anti-TNF trough levels, and to evaluate factors that predict a poor response to de-escalation. Linear mixed effects models with random intercepts accounting for correlated measures with a patient across time were used to compare differences between study groups (and subgroups). Chi-square and Kruskal-Wallis tests were used for comparisons between patients who did and did not require subsequent escalation. Hypothesis testing was conducted at an alpha of 0.05. RESULTS We included 152 pediatric patients, of whom 126 patients had CD and 26 patients had UC/IC. The mean age of initiating combination therapy was 13.76 (± 3.1) years, and the mean duration of combination therapy was 106 (± 56) weeks. De-escalation did not increase the risk of worsening disease activity or affect laboratory values, including albumin, hemoglobin, sedimentation rate, and c-reactive protein. In patients with CD on IFX and TP, calprotectin significantly increased from 107 ug/g to 383 ug/g (p&amp;lt;0.05) and anti-TNF trough levels significantly decreased from 19 ug/ml to 14 ug/ml (p&amp;lt;0.05) after de-escalation. Eighteen percent (27 patients) of patients required subsequent escalation in therapy. Amongst these patients, anti-TNF levels were lower and CRP and ESR were higher prior to de-escalation compared to patients who did not require adjustments (p&amp;lt;0.05). DISCUSSION Only patients with CD on IFX who discontinued the TP had a significant increase in fecal calprotectin and decrease in IFX levels, though the drug levels remained within therapeutic range &amp;gt;10 ug/ml, and there was no increased risk of worsening disease. Lower anti-TNF levels and higher inflammatory markers prior to de-escalation may be predictive of patients requiring escalation in therapy after stopping the IMM. De-escalation in children on combination therapy may be safely considered with close attention to clinical symptoms, inflammatory markers, and anti-TNF drug levels, especially in children with CD on IFX and TP combination therapy.

Health-related quality of life and clinical outcomes for magnetically controlled growing rod patients after treatment termination.

To determine the health-related quality of life (HRQoL) and clinical outcomes of children with early onset scoliosis (EOS) treated with magnetically controlled growing rods (MCGR) followed to definitive fusion (DF). A retrospective review of EOS patients treated with MCGR and followed to DF was performed. Outcomes included HRQoL scores, radiographic, clinical, and unplanned returns to the operating room (UPROR) data collected at pre-MCGR implantation, immediately post-MCGR implantation, pre-DF, and post-DF. HRQoL scores were collected at least 6months post-DF. Twenty-eight patients (57.1% females, mean age at MCGR insertion 7.19 ± 1.5years, mean pre-MCGR Cobb 64.7° ± 17.6) met inclusion criteria. MCGR treatment resulted in an overall 30.2% improvement in coronal plane deformity following DF. The mean growth rates between MCGR implantation and pre-DF for T1-T12 height and T1-S1 length were 0.33 ± 0.23mm/month and 0.49 ± 0.28mm/month, respectively. Of the 28 included patients, 26 (92.9%) experienced at least one UPROR, with a total of 52 surgical complications occurring in the total cohort, representing 1.9 UPROR/patient. Interestingly, there was a decline in scores reported between post-MCGR implantation and the pre-DF time-point (N = 16, 78.2 ± 14.9 vs 69.7 ± 17.8, p = 0.02). These scores recovered post-DF, resulting in an overall unchanged HRQoL when comparing pre-MCGR to post-DF (N = 11, 79.9 ± 15.1 vs 76.7 ± 17.9, p = 0.44). While MCGR treatment achieves coronal plane deformity control and facilitates spinal growth, only 7.1% of children experienced a complication-free treatment course when followed to definitive fusion. Patients achieved modest curve correction and spinal growth, while maintaining stable HRQoL outcomes between pre-MCGR and post-DF.

Effect of fatty acid profiles in varying recipes of ready-to-use therapeutic foods on neurodevelopmental and clinical outcomes of children (6-59 months) with severe wasting: a systematic review.

In 2020, 13.6 million children under 5 years suffered from severe acute malnutrition (SAM)/wasting. Standard ready-to-use therapeutic foods (RUTFs) improve polyunsaturated fatty acid (PUFA) status but contain suboptimal amounts of omega-3 (n-3) PUFAs with unbalanced n-6-to-n-3 PUFA ratios. The aim was to compare the effects of RUTFs with different essential fatty acid contents on PUFA status, neurodevelopmental, and clinical outcomes (mortality, comorbidities, and recovery) of children with severe wasting. Twelve databases, trial repositories, and article references with no publication limitations. Ten studies from randomized, quasi, and cluster-randomized controlled trials providing RUTFs as home treatment to children 6-59 months with SAM/wasting were included. Plasma phospholipid eicosapentaenoic acid content was higher in children receiving RUTF with altered essential fatty acid contents compared with standard RUTF (0.20 [0.15-0.25], P < 0.00001). Docosahexaenoic acid (DHA) status only improved in children receiving RUTF with added fish oil (0.33 [0.15-0.50], P = 0.0003). The Malawi Developmental Assessment tool (MDAT) global development and problem-solving assessment scores were higher in global assessment and gross motor domains in children receiving added fish oil compared with standard formulation (0.19 [0.0-0.38] and 0.29 [0.03-0.55], respectively). Children receiving high-oleic-acid RUTF (lowering the n-6:n-3 PUFA ratio of the RUTF) with or without fish oil had significantly higher scores in social domains compared with those receiving the standard formulation (0.16 [0.00-0.31] and 0.24 [0.09-0.40]). Significantly higher mortality risk was found in children receiving a standard formulation compared with RUTF with a lower n-6:n-3 PUFA ratio (0.79 [0.67-0.94], P = 0.008). Although lowering n-6:n-3 PUFA ratios did not increase plasma DHA, it improved specific neurodevelopmental scores and mortality due to lower linoleic acid (high-oleic-acid peanuts), higher alpha-linolenic acid (altered oil), or both. Additional preformed n-3 long-chain PUFAs (fish oil) with RUTF improved the children's DHA status, neurodevelopmental outcomes, and weight-for-height z score. More research is needed regarding cost, availability, stability, acceptability, and the appropriate amount of n-3 long-chain PUFAs required in RUTFs for the best clinical outcomes. PROSPERO registration no. CRD42022303694.

Nutritional status associated with clinical outcomes in children with solid tumors: A retrospective cohort study from China.

To investigate the long-term changes in nutritional status in children with solid tumors during treatment and the relationship between nutritional status and clinical outcomes. This study was a retrospective medical records review of data from children who were diagnosed with solid tumors and followed up for more than 3 months from January 2016 to December 2021 in China. Patient demographics and clinical information, including nutritional status, parenteral nutrition use, intensive care unit (ICU) transfers, infection during hospitalization, hospitalization frequency, length of stay, hospitalization costs and antibiotic costs, were collected to analyze the nutritional status of children with different types of solid tumors, the dynamic changes in nutritional status during treatment, and the relationship between nutritional status and clinical outcomes. Among the 764 patients (383 males (50.1%); 381 females (49.9%); mean age: 2.58 years), 41.6% of the solid tumors were neuroblastomas, 17.1% were hepatoblastomas, and Wilms tumors as the third most common solid tumors (8.9%). The median follow-up duration was 6 months (range: 3-40 months). At diagnosis, the proportion of children who were undernourished (underweight and wasting) versus overweight or obese were 26.71% versus 5.21% (25.86% vs. 2.89% in the third month; 29.77% vs. 2.28% in the sixth month; 24.77% vs. 3.27% in the 12th month). The body mass index Z scores decreased from the initial values after the first month (-0.56 (-1.47, 0.23) vs. -0.44 (-1.29, 0.41)) but improved later and decreased again at 6 months. The children in the undernutrition group had longer hospital stays (p < 0.001), higher hospitalization costs (p < 0.001), higher antibiotic costs (p < 0.001), a higher risk of neutropenia (OR = 4.781 (95% CI: 1.571-14.553), p = 0.006), and a higher risk of ICU transfers (OR = 1.498 (95% CI: 1.010-2.224), p = 0.044). No significant differences in those associations by malnutrition and infection, ICU duration, or length of parenteral nutrition were observed. There is a considerable prevalence of malnutrition in children with solid tumors. Malnutrition is related to adverse clinical outcomes and increases in total hospital expenses and antibiotic costs.

Dysphagia in pediatric intensive care unit patients (review)

The known negative consequences of intensive care unit stays, summarized as the post-intensive care syndrome (PICS) and including swallowing disorders (dysphagia) are also encountered in pediatric practice.Materials and methods. The non-systematic review of literature sources was carried out. Domestic publications were searched in the database on the elibrary website, foreign publications – in PubMed, Google Scholar, Cichrane Library, Cyberleninka, ResearchGate databases in the period of 1990–2023. When analyzed for the query «Dysphagia in Children», 1,496 results were found, «Post-intensive care syndrome in children» – 82 results. We analyzed 142 full-text publications describing the causes, mechanisms, and clinical presentation of dysphagia in children whose swallowing disorders occurred after hospitalization in intensive care units or were associated with severe somatic diseases.Results. The review analyzes the causes, features of diagnosis and treatment of dysphagia in pediatric patients with PIСS. 5 groups of causes in the structure of PIСS that can lead to the development of dysphagia were considered: infectious-trophic, vegetative-metabolic, neuromuscular, emotional-cognitivecomplications and decreased quality of life compared to the premorbid level. Complications associated with the development of dysphagia lead to increased length of stay in intensive care and hospitalization, lead to the development of malnutrition, aspiration pneumonia and other complications. The mechanisms of dysphagia development in children in intensive care units were analyzed. The main ways of dysphagia progression in pediatric practice are determined.Conclusion. Clarification of the causes and understanding of the mechanisms of dysphagia development in conjunction with the implementation of rehabilitation programs can contribute to the improvement of clinical outcomes in children who have undergone a critical condition in the immediate post-discharge period and in the future.