Diagnosis and management of eosinophilic esophagitis in children: An update from the European Society for Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN).

INTRODUCTION: Eosinophilic esophagitis (EoE) is a chronic inflammatory disease of the esophagus characterized by symptoms of esophageal dysfunction and histologically by predominantly eosinophilic infiltration of the squamous epithelium. European Society for Pediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) published a guideline in 2014; however, the rapid evolution of knowledge about pathophysiology, diagnostic criteria, and therapeutic options have made an update necessary. METHODS: A consensus group of pediatric gastroenterologists from the ESPGHAN Working Group on Eosinophilic Gastrointestinal Diseases (ESPGHAN EGID WG) reviewed the recent literature and proposed statements and recommendations on 28 relevant questions about EoE. A comprehensive electronic literature search was performed in MEDLINE, EMBASE, and Cochrane databases from 2014 to 2022. The Grading of Recommendations Assessment, Development and Evaluation system was used to assess the quality of evidence and formulate recommendations. RESULTS: A total of 52 statements based on the available evidence and 44 consensus-based recommendations are available. A revision of the diagnostic protocol, options for initial drug treatment, and the new concept of simplified empiric elimination diets are now available. Biologics are becoming a part of the potential armamentarium for refractory EoE, and systemic steroids may be considered as the initial treatment for esophageal strictures before esophageal dilation. The importance and assessment of quality of life and a planned transition to adult medical care are new areas addressed in this guideline. CONCLUSION: Research in recent years has led to a better understanding of childhood EoE. This guideline incorporates the new findings and provides a practical guide for clinicians treating children diagnosed with EoE.

Joint ESPGHAN/NASPGHAN Guidelines on Childhood Eosinophilic Gastrointestinal Disorders Beyond Eosinophilic Esophagitis.

INTRODUCTION: Eosinophilic gastrointestinal disorders beyond eosinophilic esophagitis (non-EoE EGIDs) are rare chronic inflammatory disorders of the gastrointestinal (GI) tract. Diagnosis is based on clinical symptoms and histologic findings of eosinophilic inflammation after exclusion of a secondary cause or systemic disease. Currently, no guidelines exist for the evaluation of non-EoE EGIDs. Therefore, the European Society for Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) and the North American Society for Pediatric Gastroenterology, Hepatology and Nutrition (NASPGHAN) formed a task force group to provide consensus guidelines for childhood non-EoE EGIDs. METHODS: The working group was composed of pediatric gastroenterologists, adult gastroenterologists, allergists/immunologists, and pathologists. An extensive electronic literature search of the MEDLINE, EMBASE, and Cochrane databases was conducted up to February 2022. General methodology was used in the formulation of recommendations according to the Appraisal of Guidelines for Research and Evaluation (AGREE) II and the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system to meet current standards of evidence assessment. RESULTS: The guidelines provide information on the current concept of non-EoE EGIDs, disease pathogenesis, epidemiology, clinical manifestations, diagnostic and disease surveillance procedures, and current treatment options. Thirty-four statements based on available evidence and 41 recommendations based on expert opinion and best clinical practices were developed. CONCLUSION: Non-EoE EGIDs literature is limited in scope and depth, making clear recommendations difficult. These consensus-based clinical practice guidelines are intended to assist clinicians caring for children affected by non-EoE EGIDs and to facilitate high-quality randomized controlled trials of various treatment modalities using standardized, uniform disease definitions.

Do patients with different craniofacial patterns have differences in upper airway volume? A systematic review with network meta-analysis.

BACKGROUND: Craniofacial skeletal discrepancies have been associated with upper airway dimensions. OBJECTIVE: To identify differences in upper airway volume across different sagittal and vertical skeletal patterns. SEARCH METHODS: Unrestricted literature searches in eight databases/registers for human studies until May 2023. SELECTION CRITERIA: Cross-sectional studies measuring upper airway volumes using three-dimensional imaging in healthy patients of different sagittal (Class I, Class II, and Class III) or vertical (normodivergent, hypodivergent, and hyperdivergent) craniofacial morphology. DATA COLLECTION AND ANALYSIS: Duplicate independent study selection, data extraction, and risk of bias assessment. Random-effects frequentist network meta-analysis was performed followed by subgroup-analyses and assessment of the quality of clinical recommendations (confidence in effect estimates) with the CINeMA (Confidence in Network Meta-Analysis) approach. RESULTS: Seventy publications pertaining to 66 unique studies were included with 56 studies (5734 patients) contributing to meta-analyses. Statistically significant differences were found for total  pharyngeal airway volume, with Class II having decreased airway volume (-2256.06 mm3; 95% Confidence Interval [CI] -3201.61 to -1310.51 mm3) and Class III increased airway volume (1098.93 mm3; 95% CI 25.41 to 2172.45 mm3) compared to Class I. Significant airway volume reductions for Class II were localized mostly at the oropharynx, followed by the palatopharynx, and the glossopharynx. Significant airway volume increases for Class III were localized mostly at the oropharynx, followed by the intraoral cavity, and hypopharynx. Statistically significant differences according to vertical skeletal configuration were seen only for the oropharynx, where hyperdivergent patients had reduced volumes compared to normodivergent patients (-1716.77 mm3; 95% CI -3296.42 to -137.12 mm3). Airway differences for Class II and Class III configurations (compared to Class I) were more pronounced in adults than in children and the confidence for all estimates was very low according to CINeMA. CONCLUSIONS: Considerable differences in upper airway volume were found between sagittal and vertical skeletal configurations. However, results should be interpreted with caution due to the high risk of bias, owing to the retrospective study design, inconsistencies in anatomic compartment boundaries used, samples of mixed children-adult patients, and incomplete reporting. CLINICAL TRIAL REGISTRATION: PROSPERO (CRD42022366928).

Approach to Endoscopic Balloon Dilatation in Pediatric Stricturing Crohn Disease: A Position Paper of the Endoscopy Special Interest Group of ESPGHAN.

Crohn disease (CD) is often complicated by bowel strictures that can lead to obstructive symptoms, resistant inflammation, and penetrating complications. Endoscopic balloon dilatation of CD strictures has emerged as a safe and effective technique for relieving these strictures, which may obviate the need for surgical intervention in the short and medium term. This technique appears to be underutilized in pediatric CD. This position paper of the Endoscopy Special Interest Group of European Society for Pediatric Gastroenterology, Hepatology and Nutrition describes the potential applications, appropriate evaluation, practical technique, and management of complications of this important procedure. The aim being to better integrate this therapeutic strategy in pediatric CD management.

Joint ESPGHAN/NASPGHAN Guidelines on Childhood Eosinophilic Gastrointestinal Disorders beyond Eosinophilic Esophagitis.

INTRODUCTION: Eosinophilic Gastrointestinal Disorders beyond Eosinophilic Esophagitis (non-EoE EGIDs) are rare chronic inflammatory disorders of the gastrointestinal (GI) tract. Diagnosis is based on clinical symptoms and histologic findings of eosinophilic inflammation after exclusion of a secondary cause or systemic disease. Currently, no guidelines exist for the evaluation of non-EoE EGIDs. Therefore, the European Society for Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) and the North American Society for Pediatric Gastroenterology, Hepatology and Nutrition (NASPGHAN) formed a task force group to provide consensus guidelines for childhood non-EoE EGIDs. METHODS: The working group was composed of pediatric gastroenterologists, adult gastroenterologists, allergists/immunologists, and pathologists. An extensive electronic literature search of the MEDLINE, EMBASE, and Cochrane databases was conducted up to February 2022. General methodology was used in the formulation of recommendations according to the Appraisal of Guidelines for Research and Evaluation (AGREE) II and the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system to meet current standards of evidence assessment. RESULTS: The guidelines provide information on the current concept of non-EoE EGIDs, disease pathogenesis, epidemiology, clinical manifestations, diagnostic and disease surveillance procedures, and current treatment options. Thirty-four statements based on available evidence and 41 recommendations based on expert opinion and best clinical practices were developed. CONCLUSION: Non-EoE EGIDs literature is limited in scope and depth, making clear recommendations difficult. These consensus-based clinical practice guidelines are intended to assist clinicians caring for children affected by non-EoE EGIDs and to facilitate high-quality randomized controlled trials of various treatment modalities using standardized, uniform disease definitions.

Pain profile during orthodontic levelling and alignment with fixed appliances reported in randomized trials: a systematic review with meta-analyses.

OBJECTIVE: To assess the pain profile of patients in the levelling/alignment phase of orthodontic treatment, as reported from randomized clinical trials. MATERIALS AND METHODS: Five databases were searched in September 2022 for randomized clinical trials assessing pain during levelling/alignment with a visual analogue scale (VAS). After duplicate study selection, data extraction, and risk-of-bias assessment, random effects meta-analyses of mean differences (MDs) and their 95% confidence intervals (CIs) were performed, followed by subgroup/meta-regression, and certainty analyses. RESULTS: A total of 37 randomized trials including 2277 patients (40.3% male; mean age 17.5 years) were identified. Data indicated quick pain initiation after insertion of orthodontic appliances (n = 6; average = 12.4 mm VAS), a quick increase to a peak at day 1 (n = 29; average = 42.4 mm), and gradually daily decrease the first week until its end (n = 23; average = 9.0 mm). Every second patient reported analgesic use at least once this week (n = 8; 54.5%), with peak analgesic use at 6 h post-insertion (n = 2; 62.3%). Patients reported reduced pain in the evening compared to morning (n = 3; MD = - 3.0 mm; 95%CI = - 5.3, - 0.6; P = 0.01) and increased pain during chewing (n = 2; MD = 19.2 mm; 95% CI = 7.9, 30.4; P < 0.001) or occlusion of the back teeth (n = 2; MD = 12.4 mm; 95% CI = 1.4, 23.4; P = 0.3), while non-consistent effects were seen for patient age, sex, irregularity, or analgesic use. Subgroup analyses indicated increased pain among extraction cases and during treatment of the lower (rather than the upper) arch, while certainty around estimates was moderate to high. CONCLUSIONS: Evidence indicated a specific pain profile during orthodontic levelling/alignment, without signs of consistent patient-related influencing factors.

The Sclerosing Cholangitis Outcomes in Pediatrics (SCOPE) Index: A Prognostic Tool for Children.

BACKGROUND AND AIMS: Disease progression in children with primary sclerosing cholangitis (PSC) is variable. Prognostic and risk-stratification tools exist for adult-onset PSC, but not for children. We aimed to create a tool that accounts for the biochemical and phenotypic features and early disease stage of pediatric PSC. APPROACH AND RESULTS: We used retrospective data from the Pediatric PSC Consortium. The training cohort contained 1,012 patients from 40 centers. We generated a multivariate risk index (Sclerosing Cholangitis Outcomes in Pediatrics [SCOPE] index) that contained total bilirubin, albumin, platelet count, gamma glutamyltransferase, and cholangiography to predict a primary outcome of liver transplantation or death (TD) and a broader secondary outcome that included portal hypertensive, biliary, and cancer complications termed hepatobiliary complications (HBCs). The model stratified patients as low, medium, or high risk based on progression to TD at rates of <1%, 3%, and 9% annually and to HBCs at rates of 2%, 6%, and 13% annually, respectively (P < 0.001). C-statistics to discriminate outcomes at 1 and 5 years were 0.95 and 0.82 for TD and 0.80 and 0.76 for HBCs, respectively. Baseline hepatic fibrosis stage was worse with increasing risk score, with extensive fibrosis in 8% of the lowest versus 100% with the highest risk index (P < 0.001). The model was validated in 240 children from 11 additional centers and performed well. CONCLUSIONS: The SCOPE index is a pediatric-specific prognostic tool for PSC. It uses routinely obtained, objective data to predict a complicated clinical course. It correlates strongly with biopsy-proven liver fibrosis. SCOPE can be used with families for shared decision making on clinical care based on a patient's individual risk, and to account for variable disease progression when designing future clinical trials.

Functional Gastrointestinal Disorders in Mediterranean Countries According to Rome IV Criteria.

OBJECTIVES: The aim of this study was to assess the prevalence of functional gastrointestinal disorders (FGIDs) in children of Mediterranean area using Rome IV criteria and to compare the prevalence of FGIDs using Rome IV and Rome III criteria. METHODS: This was a cross-sectional study enrolling children and adolescents living in Croatia, Greece, Israel, Italy, Macedonia, and Serbia. Subjects were examined in relation to the presence of FGIDs, using the Rome IV criteria. Data were compared with the results of a previous study using Rome III data. RESULTS: We analyzed 1972 children ages 4 to 9 years (group A), and 2450 adolescents 10 to 18 years old (group B). The overall prevalence of FGIDs was 16% in group A and 26% in group B, with statistical differences among countries in both groups (P < 0.001). In group A, the prevalence of FGIDs and of functional constipation (FC) was significantly lower than in the previous study (P < 0.001), whereas in group B no significant difference was found. In both groups of age, the prevalence of abdominal migraine and irritable bowel syndrome decreased significantly (P < 0.001 and P < 0.001, respectively) using Rome IV versus Rome III criteria, conversely functional dyspepsia increased (P < 0.001). CONCLUSIONS: FGIDs are common in children and adolescents, their frequency increases with age, and there is a significant variation in the prevalence of some FGIDs among different European countries. The application of the Rome IV criteria resulted in a significantly lower prevalence of FGIDs in children compared with Rome III criteria.

Systematic Review and Meta-analysis of Histological Gastric Biopsy Aspects According to the Updated Sydney System in Children.

OBJECTIVES: A descriptive and comparative study of gastric histological aspects according to the updated Sydney classification (USC), obtained from Helicobacter pylori-positive versus H pylori-negative children referred for upper gastrointestinal endoscopy. METHODS: The Prisma method was used to perform a systematic review and meta-analysis. Selection criteria were based on following key words USC, H pylori, children, endoscopy, or biopsy. Publication biases were assessed according to the Newcastle-Ottawa Scale, and a meta-regression analysis was done. The study was registered on the PROSPERO platform. RESULTS: Between 1994 and 2017, 1238 references were found; 97 studies were retained for the systematic review with a total number of 25,867 children; 75 studies were selected for the meta-analysis concerning 5990 H pylori-infected and 17,782 uninfected children.H pylori-positive versus H pylori-negative children, according to the USC, showed significantly higher relative risk for gastric antral and corpus chronic inflammation, presence of neutrophils, and of lymphoid follicles, and gastric mucosa atrophy, whereas, intestinal metaplasia showed a significantly higher RR only in antral biopsies. The meta-regression analysis showed that H pylori-positive versus H pylori-negative children had significantly higher risk only for corpus activity according to age, recurrent abdominal pain, and geographical area of low H pylori prevalence. CONCLUSIONS: H pylori infection in children was associated with higher relative risk for gastric antral and corpus chronic inflammation, presence of neutrophils, lymphoid follicles, and rare gastric mucosa atrophy, whereas, rare intestinal metaplasia was only significantly higher in the antral area.

Characterization of Eosinophilic Esophagitis From the European Pediatric Eosinophilic Esophagitis Registry (pEEr) of ESPGHAN.

OBJECTIVES: Few pediatric data on phenotypic aspects of eosinophilic esophagitis (EoE) are available. The pEEr registry was developed to prospectively characterize children with EoE from Europe and Israel. METHODS: pEEr is an ongoing prospective registry enrolling children with esophageal eosinophilia (≥15 eos/HPF). Anonymized data were collected from 19 pediatric centers. Data regarding demographics, clinical manifestations, endoscopy, histology, and therapies were collected. RESULTS: A total of 582 subjects (61% male) were analyzed. The median age at diagnosis was 10.5 years [interquartile range (IQR): 5.7-17.7], whereas the age at symptom onset was 9.2 years (IQR: 4.3-16.4), resulting in a median diagnostic delay of 1.2 years (IQR: 0.7-2.3). The diagnostic delay was longer below age <6 years. Shorter diagnostic delays were associated with the presence of food allergy or a family history for EoE. Symptoms varied by age with dysphagia and food impaction more common in adolescents, while vomiting and failure to thrive more common in younger children ( P < 0.001). Among endoscopic findings, esophageal rings were more common in adolescents, whereas exudates were more frequent in younger children( P < 0.001). Patients who responded to proton pump inhibitors (PPIs) were more likely to be older, males, and less often presented severe endoscopic findings. Patients unresponsive to PPIs received topical steroids (40%), elimination diet (41%), or a combined therapy (19%). CONCLUSIONS: EoE findings vary according to age in pediatric EoE. Young children are commonly characterized by non-specific symptoms, atopic dermatitis, food allergy, and inflammatory endoscopic lesions. Adolescents usually have dysphagia or food impaction, fibrostenotic lesions, and a better PPI response.

Training in Paediatric Clinical Nutrition Across Europe: A Survey of the National Societies Network (2016-2019) of the European Society for Paediatric Gastroenterology, Hepatology and Nutrition.

OBJECTIVES/BACKGROUND: Disease-related malnutrition is common in patients with chronic diseases and has detrimental effects, therefore, skills in nutrition care are essential core competencies for paediatric digestive medicine. The aim of this survey, conducted as part of a global survey of paediatric gastroenterology, hepatology and nutrition (PGHN) training in Europe, was to assess nutrition care-related infrastructure, staff, and patient volumes in European PGHN training centres. METHODS: Standardized questionnaires related to clinical nutrition (CN) care were completed by representatives of European PGHN training centres between June 2016 and December 2019. RESULTS: One hundred training centres from 17 European countries, Turkey, and Israel participated in the survey. Dedicated CN clinics exist in 66% of the centres, with fulltime and part-time CN specialists in 66% and 42%, respectively. Home tube feeding (HTF) andhome parenteral nutrition (HPN) programmes are in place in 95% and 77% of centres, respectively. Twenty-four percent of centres do not have a dedicated dietitian and 55% do not have a dedicated pharmacist attached to the training centre. Even the largest centres with >5000 outpatients reported that 25% and 50%, respectively do not have a dedicated dietitian or pharmacist. Low patient numbers on HTF and HPN of <5 annually are reported by 13% and 43% of centres, respectively. CONCLUSIONS: The survey shows clear differences and deficits in Clinical Nutrition training infrastructure, including staff and patient volumes, in European PGHN training centres, leading to large differences and limitations in training opportunities in Clinical Nutrition.

A comparative assessment of the dentoskeletal effects of clear aligners vs miniplate-supported posterior intrusion with fixed appliances in adult patients with anterior open bite. A multicenter, retrospective cohort study.

INTRODUCTION: This study aimed to retrospectively evaluate the dentoskeletal effects of clear aligners (Invisalign) vs miniplate-supported posterior intrusion (MSPI) and identify factors associated with posttreatment overbite in adults with anterior open bite. METHODS: Twenty-nine patients treated with Invisalign and 24 with MSPI combined with full-fixed orthodontic appliances were included from 5 orthodontic practices. Pretreatment and posttreatment lateral cephalometric measurements were included as outcomes. Comparisons across groups and identification of final overbite predictors were assessed with regression modeling and machine learning techniques. RESULTS: MSPI induced significantly greater maxillary molar intrusion (1.5 mm; 95% confidence interval [CI], 0.83-2.17; P <0.001), with subsequent reduction of anterior face height (ANS-Me) (-2.77 mm; 95% CI, -3.64 to -1.91; P <0.001), Mp-SN° (-1.95°; 95% CI, -2.77 to -1.12; P <0.001), and ANB° (-1.69°; 95% CI, -2.44 to -0.94; P <0.001) compared with Invisalign. MSPI resulted in a significantly larger increase in SNB° (0.94°; 95% CI, 0.23-1.65; P = 0.01) and point-Pog projection (2.45 mm; 95% CI, 1.12-3.77; P = 0.001). Compared with MSPI, Invisalign had a significantly greater increase in the distance of maxillary (1.05 mm; 95% CI, 0.38-1.72; P = 0.003) and mandibular (0.9 mm; 95% CI, 0.19-1.60; P = 0.01) incisal edges relative to their apical bases, with borderline greater lingual tipping of only the maxillary incisors (2.82°; 95% CI, -0.44 to 6.09; P = 0.09). Appliance type and initial overbite were significant final overbite predictors across all models. However, this difference was only evident in male patients (males [1.65; 95% CI, 0.99-2.32; P <0.001]; female [-0.04; 95% CI, -0.52 to 0.44; P = 0.87]). CONCLUSIONS: Both appliances effectively improve overbite. MSPI applied the correction via molar intrusion and counterclockwise mandibular autorotation, whereas Invisalign via maxillary and mandibular incisor extrusion.

The effect of piezocision vs no piezocision on maxillary extraction space closure: A split-mouth, randomized controlled clinical trial.

INTRODUCTION: The aim of this 2-arm-parallel, split-mouth trial was to investigate the effects of piezocision compared with no piezocision on maxillary canine distalization and to evaluate patient perceptions on the surgical procedure. METHODS: Twenty-two participants requiring extractions of maxillary first premolars were recruited from the Department of Orthodontics (Sydney Dental Hospital) waiting list. After leveling and alignment, a minimum of 3 mm space was required for canine retraction. Piezocision cuts distal to the canines were 4 mm long and 3 mm deep into the buccal cortical plate. The canine retraction was initiated on both sides immediately after surgery, with coil springs delivering 150 g of force per side. Random assignment of piezocision or control intervention on the patient's right side was performed (www.randomisation.com) for the random number generation, and allocation concealment was accomplished with opaque, sealed envelopes. Patients were assessed every 6 weeks for coil activation and alginate impressions over 18 weeks. The primary outcome was the amount of tooth movement in mm. Secondary outcomes were canine rotation, anchorage loss measured on scanned dental models, and patient pain levels and perception on piezocision using visual analog scale questionnaires. Blinding was feasible for the dental model measurements. RESULTS: Twenty patients completed the trial. The treatment × time interaction showed no statistically or clinically significant differences in maxillary extraction space closure (b = -0.02; 95% confidence interval [CI], -0.29 to 0.25; P = 0.89) canine rotation (b = -1.45; 95% CI, -4 to 1.09; P = 0.26) and anchorage loss (b = -0.02; 95% CI, -0.38 to 0.34; P = 0.92). All patients except for one had minimal pain associated with the piezocision surgery but found the procedure tolerable and would recommend it. No harm occurred during the trial. CONCLUSIONS: Piezocision-assisted maxillary canine distalization was similar to distalization with conventional orthodontics with patients tolerating the procedure.

Gender disparity in speakers of the European Orthodontic Society conferences held between 2015 and 2020: a cross-sectional report.

OBJECTIVES: To assess the representation of female scientists as speakers of blindly selected oral presentations or invited speakers in the latest European Orthodontic Society (EOS) conferences between 2015 and 2020. To examine the association with a number of study- and author-related characteristics. MATERIALS AND METHODS: Abstract books and programmes of the EOS conferences held between 2015 and 2020, were electronically searched to identify the gender of all speakers. The following predictor variables were assessed: year, continent of authorship, number of centres, number of authors involved, study design, study topic, and presentation as a WJB Houston Award nominee. RESULTS: A total of 312 oral presentations were recorded with almost even distribution of female/male gender. In the majority of oral presentations, a European-origin speaker affiliation was confirmed (208/312; 66.7%), with a relatively equal representation of women (P = 0.05). Seniority in authorship of oral presentations belonged to male scientists (209/312; 67%). Furthermore, a total of 84 invited speakers were identified, of which only 15 (17.9%) were female, indicating a substantial gender gap. No more than four women were invited to lecture annually, compared to a minimum of 10 male scientists. Overall, a significant difference was recorded for the odds of a female scientist to be invited as a speaker in the EOS conference (range of odds across years: 0.20-0.36), compared to the odds for conducting an oral presentation in the same context and timescale (range of odds across years: 0.75-1.45) (Mantel-Haenszel test for homogeneity, P-value < 0.001). LIMITATIONS: Findings were based solely on the annual orthodontic conference of the EOS, without further insights on national conferences, or identification of wide-range timescale effects. CONCLUSIONS AND IMPLICATIONS: Gender disparity related to invited speakers at the EOS 2015-20 annual conferences was unequivocally confirmed. Nevertheless, gender differences were not identified in oral presentations. Firm efforts to ensure female scientist's voice is equally represented are needed including a move from theory to practice.

Physical properties of root cementum: Part 29. The effects of LED-mediated photobiomodulation on orthodontically induced root resorption and pain: a pilot split-mouth randomized controlled trial.

OBJECTIVES: To examine the effects of light-emitting diode (LED)-mediated photobiomodulation (PBM) on orthodontic root resorption and pain. METHODS: Twenty patients (3 males, 17 females, mean age 15 years 6 months) needing bilateral maxillary first premolar extractions for orthodontic treatment were included in this single-centre, split-mouth randomized controlled trial. Both premolars received 150 g of buccal tipping force for 28 days. One side was randomly assigned to receive intraoral 850 nm wavelength, 60 mW/cm2 power, continuous LED illumination via OrthoPulse device (Biolux Research Ltd, Vancouver, British Columbia, Canada) for 5 minutes/day. The other side served as control. After 28 days, both premolars were extracted and scanned with micro-computed tomography for primary outcome assessment of root resorption crater volume measurements. For secondary outcome assessment, visual analogue scale pain questionnaires were used for both sides at 24 hours, 48 hours, 72 hours, and 7 days. Randomization was generated using www.randomization.com and allocation was concealed in sequentially numbered, opaque, sealed envelopes. Blinding was not possible during the experiment due to the use of tape to block light on control side of the devices. Assessors were blinded during outcome assessments. RESULTS: All 40 premolars from 20 patients were included. There was no significant difference in the mean total root resorption between the LED PBM and control sides (mean 0.216 versus 0.284 mm3, respectively, P = 0.306). The LED side was associated with less pain at 24 hours (P = 0.023) and marginally more pain at subsequent time points, which was not statistically significant. No harms were observed. LIMITATIONS: Short study duration and the inability to blind patients and clinician during clinical part of study. CONCLUSION: This 28-day randomized split-mouth controlled trial showed that daily, LED-mediated PBM application, when applied for 5 minute/day, does not influence orthodontic root resorption. It is associated with significantly less pain 24 hours after the application of orthodontic force, but no difference thereafter. These results should be tested on patients undergoing a full course of orthodontic treatment. TRIAL REGISTRATION: Clinical Trials Registry ACTRN12616000652471.

The effect of micro-osteoperforations on orthodontic space closure investigated over 12 weeks: a split-mouth, randomized controlled clinical trial.

OBJECTIVES: To evaluate the effects of minimally invasive micro-osteoperforations (MOPs) on orthodontic tooth movement and pain. DESIGN: Prospective, split-mouth, randomized controlled trial. SETTING: Single-centre, university hospital. METHODS: Twenty subjects requiring maxillary first premolar extractions were included. Right and left sides of the maxilla were randomly allocated into experimental and controls. Space closure was initiated following alignment on 0.20″ stainless steel archwires, using 150 g force, applied by coil springs on power arms. Nance-TPA was used for anchorage. On the experimental side, two 5 mm deep MOPs in vertical alignment on distal aspect of the maxillary canine mid-root region were performed prior to space closure. OUTCOMES: The primary outcome was the amount of tooth movement during space closure, measured every 4 weeks for 12 weeks (T1, T2, and T3). Secondary outcome was the pain levels related to MOP, measured using Visual Analogue Scale (VAS) questionnaires. Significance was set at P < 0.01. RANDOMIZATION: Randomization was generated using a randomization table, and allocation was concealed in sequentially numbered, opaque, sealed envelopes. BLINDING: Blinding was not possible during the experiment but assessor was blinded during outcome assessment. RESULTS: All subjects completed the study, with tooth movement measurements available for all 20 patients for T0-T2. In three patients, space was closed on one side at T2. The average tooth movement between sides at three intervals (T0-T1, T1-T2, and T2-T3) were not significantly different. Overall difference following 12 weeks (T0-T3) was 0.69 mm higher on the experimental side (P < 0.001). No harms were observed. LIMITATIONS: Short-term study, cast measurements done with digital callipers. CONCLUSION: This 12-week randomized split-mouth controlled clinical trial showed two MOPs that are 5 mm deep, applied once prior to space closure, did not create clinically significant increase in maxillary premolar space closure. PROTOCOL: The protocol was not published before trial commencement. REGISTRATION: Trial was not registered. FUNDING: The Australian Society of Orthodontists Foundation for Research and Education.

Clinical Outcome, Socioeconomic Status and Psychological Constrains of Patients Undergoing Preimplantation Genetic Testing (PGT) in Northern Greece.

Background and objectives: Preimplantation genetic testing (PGT) offers patients the possibility of having a healthy baby free of chromosomal or genetic disorders. The present study focuses on the application of PGT for patients located in Northern Greece, investigating their clinical outcomes, their motives, and their overall physical and emotional experience during the treatment, in association with their socioeconomic background. Materials and Methods: Couples who underwent PGT for a monogenic condition (PGT-M, n = 19 cycles) or aneuploidy (PGT-A, n = 22 cycles) participated in the study. Fertilization, implantation, and pregnancy rates were recorded for all cycles. The couples were asked to fill in a questionnaire about the consultation they had received prior to treatment, their sociodemographic information, and the psychological impact PGT had on both the female and male partner. Results: The fertilization, implantation, and ongoing pregnancy rates for the PGT-M and PGT-A cycles were 81.3%, 70.6%, and 52.9%, and 78.2%, 64.3%, and 57.1%, respectively. Females experienced more intense physical pain than their male partners while psychological pain was encountered by both partners and occasionally in higher instances in males. No typical socioeconomic background of the patients referred for PGT in Northern Greece was noticed. Conclusion: PGT is an attractive alternative to prenatal diagnosis (PND), aiming to establisha healthy pregnancy by identifying and avoiding the transfer of chromosomally or genetically abnormal embryos to the uterus. Although the benefits of PGT were well-received by all patients undergoing the procedure, psychological pain was evident and especially prominent in patients with a previous affected child or no normal embryos for transfer. Holistic counseling is of utmost importance in order to make patients' experience during their journey to have a healthy baby less emotionally demanding and help them make the right choices for the future.

Drugs in Focus: Proton Pump Inhibitors.

ABSTRACT: Proton pump inhibitors (PPIs) are amongst the most commonly prescribed drugs in infants and children with the last decades witnessing a dramatic rise in their utilization. Although PPIs are clearly effective when used appropriately and have been regarded as safe drugs, there is growing evidence regarding their potential adverse effects. Although, largely based on adult data it is clear that many of these are also relevant to pediatrics. PPI use potentially affects gastrointestinal microbiota composition and function, decreases defence against pathogens resulting in increased risk for infections, interferes with absorption of minerals and vitamins leading to specific deficiencies and increased risk for bone fractures as well as interferes with protein digestion resulting in increased risk of sensitization to allergens and development of allergic diseases and eosinophilic esophagitis. An association with gastric, liver and pancreatic cancer has also been inferred from adult data but is tenuous and causation is not proven. Overall, evidence for these adverse events is patchy and not always compelling. Overall, the use of PPIs, for selected indications with a good evidence base, has significant potential benefit but carries more caution in infants and children. Pediatricians should be aware of the concerns regarding the potential adverse events associated with their use.

Management of Gastrointestinal and Nutritional Problems in Children With Neurological Impairment: A Survey of Practice.

OBJECTIVES: The main aim of this study was to determine the impact on clinical practice of the first European Society of Gastroenterology, Hepatology, and Nutrition (ESPGHAN) position paper on the diagnosis and management of nutritional and gastrointestinal problems in children with neurological impairment (NI). METHODS: In this pilot-study, a web-based questionnaire was distributed between November, 2019 and June, 2020, amongst ESPGHAN members using the ESPGHAN newsletter. Fifteen questions covered the most relevant aspects on nutritional management and gastrointestinal issues of children with NI. A descriptive analysis of responses was performed. RESULTS: A total of 150 health professionals from 23 countries responded to the survey. A considerable variation in clinical practice concerning many aspects of nutritional and gastrointestinal management of children with NI was observed. The most frequently used method for diagnosing oropharyngeal dysfunction was the direct observation of meals with or without the use of standardised scores (n = 103). Anthropometric measurements were the most commonly used tools for assessing nutritional status (n = 111). The best treatment for gastroesophageal reflux disease (GERD) was considered to be proton pump inhibitor therapy by most (n = 116) participants. Regarding tube feeding, nearly all respondents (n = 114) agreed that gastrostomy is the best enteral access to be used for long-term enteral feeding. Fundoplication was indicated at the time of gastrostomy placement especially in case of uncontrolled GERD. CONCLUSIONS: More studies are required to address open questions on adequate management of children with NI. Identifying knowledge gaps paves the way for developing updated recommendations and improving patient care.

The Use of Fecal Calprotectin Testing in Paediatric Disorders: A Position Paper of the European Society for Paediatric Gastroenterology and Nutrition Gastroenterology Committee.

OBJECTIVES: The aim of the study was to review the evidence regarding the clinical use and value of fecal calprotectin (FC) measurements in different gastrointestinal disorders in children. METHODS: A literature search was conducted in the PubMed, MEDLINE, EMBASE, and Cochrane databases until October 31, 2019. Subtopics were identified and each assigned to individual authors. RESULTS: A total of 28 recommendations were voted on using the nominal voting technique. Recommendations are given related to sampling, measurement methods, and results interpretation. The 14 authors anonymously voted on each recommendation using a 9-point scale (1 strongly disagree to 9 fully agree). Consensus was considered achieved if at least 75% of the authors voted 6, 7, 8, or 9. CONCLUSIONS: Consensus was reached for all recommendations. Limitations for the use of FC in clinical practice include variability in extraction methodology, performance of test kits as well as the need to establish local reference ranges because of the influence of individual factors, such as age, diet, microbiota, and drugs. The main utility of FC measurement at present is in the diagnosis and monitoring of inflammatory bowel disease (IBD) as well as to differentiate it from functional gastrointestinal disorders (FAPDs). FC, however, has neither utility in the diagnosis of infantile colic nor to differentiate between functional and organic constipation. A rise in FC concentration, may alert to the risk of developing necrotizing enterocolitis and help identifying gastrointestinal involvement in children with Henoch-Schönlein purpura. FC measurement is of little value in Cow's Milk Protein Allergy, coeliac disease (CD), and cystic fibrosis. FC does neither help to distinguish bacterial from viral acute gastroenteritis (AGE), nor to diagnose Helicobacter Pylori infection, small intestinal bacterial overgrowth (SIBO), acute appendicitis (AA), or intestinal polyps.