Current practice in the care of children with functional constipation: What is the hold up?

OBJECTIVES: For children with intractable functional constipation (FC), there are no evidence-based guidelines for subsequent evaluation and treatment. Our objective was to assess the practice patterns of a large, international cohort of pediatric gastroenterologists. METHODS: We administered a survey to physicians who attended the 2nd World Congress of Pediatric Neurogastroenterology and Motility held in Columbus, Ohio (USA) in September 2023. The survey included 29 questions on diagnostic testing, nonpharmacological and pharmacological treatment, and surgical options for children with intractable FC. RESULTS: Ninety physicians from 18 countries completed the survey. For children with intractable FC, anorectal manometry was the most commonly used diagnostic test. North American responders were more likely than Europeans to use stimulant laxatives (97% vs. 77%, p = 0.032), prosecretory medications (69% vs. 8%, p < 0.001), and antegrade continence enemas (ACE; 83% vs. 46%, p = 0.009) for management. Europeans were more likely than North Americans to require colonic transit testing before surgery (85% vs. 30%, p < 0.001). We found major differences in management practices between Americans and the rest of the world, including use of prosecretory drugs (73% vs. 7%, p < 0.001), anal botulinum toxin injections (81% vs. 58%, p = 0.018), ACE (81% vs. 58% p = 0.018), diverting ileostomies (56% vs. 26%, p = 0.006), and colonic resections (42% vs. 16%, p = 0.012). No differences were found when respondents were compared by years of experience. CONCLUSIONS: Practice patterns in the evaluation and treatment of children with intractable FC differ widely among pediatric gastroenterologists from around the world. A clinical guideline regarding diagnostic testing and surgical decision-making is needed.

Practice variation in surgical treatment for lumbar degenerative disc disease: exploring regional and hospital factors influencing surgical rates.

The presence of significant, unwarranted variation in treatment suggests that clinical decision making also depends on where patients live instead of what they need and prefer. Historically, high practice variation in surgical treatment for lumbar degenerative disc disease (LDDD) has been documented. This study aimed to investigate current regional variation in surgical treatment for sciatica resulting from LDDD. We conducted a retrospective, cross-sectional analysis of all Dutch adults (>18 years) between 2016 and 2019. Demographic data from Statistics Netherlands were merged with a nationwide claims database, covering over 99% of the population. Inclusion criteria comprised LDDD diagnosis codes and relevant surgical codes. Practice variation was assessed at the level of postal code areas and hospital service areas (HSAs). Multivariable logistic regression analysis was employed to identify variables associated with surgical treatment. Among the 119,148 hospital visitors with LDDD, 14,840 underwent surgical treatment. Practice variation for laminectomies and discectomies showed less than two-fold variation in both postal code and HSAs. However, instrumented fusion surgery demonstrated a five-fold variation in postal code areas and three-fold variation in HSAs. Predictors of receiving surgical treatment included opioid prescription and patient referral status. Gender differences were observed, with males more likely to undergo laminectomy or discectomy, and females more likely to receive instrumented fusion surgery. Our study revealed low variation rates for discectomies and laminectomies, while indicating a high variation rate for instrumented fusion surgery in LDDD patients. High-quality research is needed on the extent of guideline implementation and its influence on practice variation.

The diagnostic accuracy of spirometry as screening tool for adult patients with a benign subglottic stenosis.

BACKGROUND: There is a considerable diagnostic delay in the diagnosis 'benign acquired subglottic stenosis in adults' (SGS, diagnosed by the reference standard, i.e. laryngo- or bronchoscopy). Patients are frequently misdiagnosed since symptoms of this rare disease may mimic symptoms of 'asthma.' The 'Expiratory Disproportion Index' (EDI) obtained by spirometry, may be a simple instrument to detect an SGS-patient. The aim of this study was to evaluate the diagnostic accuracy of the EDI in differentiating SGS patients from asthma patients. METHODS: We calculated the EDI from spirometry results of all SGS-patients in the Leiden University Medical Center (LUMC), who had not received treatment 2 years before their spirometry examination. We compared these EDI results with the EDI results of all true asthma patients between 2011 and 2019, who underwent a bronchoscopy (exclusion of SGS by laryngo- or bronchoscopy). RESULTS: Fifty patients with SGS and 32 true asthma patients were included. Median and IQR ranges of the EDI for SGS and asthma patients were 67.10 (54.33-79.18) and 37.94 (32.41-44.63), respectively. Area under the curve (ROC) of the accuracy of the EDI at discriminating SGS and asthma patients was 0.92 (95% CI = 0.86-0.98). The best cut-off point for the EDI was > 48 (i.e. possible upper airway obstruction), with a sensitivity of 88.0%% (95%CI = 77.2-95.0%%) and specificity of 84.4% (95%CI = 69.4-94.1%). CONCLUSIONS: The EDI has a good diagnostic accuracy discriminating subglottic stenosis patients from asthma patients, when compared to the reference standard. This measurement from spirometry may potentially shorten the diagnostic delay of SGS patients. Further studies are needed to evaluate clinical reproducibility.

Crohn's Disease in a Patient With Bardet-Biedl Syndrome: Random Anomaly or Rare Phenotypic Trait?

Bardet-Biedl syndrome (BBS) is an autosomal recessive multisystem nonmotile ciliopathy. There are anecdotal reports of the co-occurrence of BBS and autoimmune diseases, including inflammatory bowel disease (IBD). We present the first case report of a child with BBS7 who developed Crohn disease, adding to the evidence on the association between BBS and IBD. A 13-year-old girl with BBS7 presented with abdominal pain and significant weight loss (-13%), but without other classical symptoms of IBD, such as diarrhea and blood loss. Fecal calprotectin was elevated, but on gastroscopy and colonoscopy, no macroscopic abnormalities were found. Ultrasound and MRI revealed an intestinal stenosis which was treated surgically. Histopathological examination confirmed the diagnosis Crohn disease. In conclusion, the reported co-occurrence of BSS and autoimmune diseases and the atypical presentation of IBD in this patient warrant a low threshold to perform diagnostic tests for IBD in patients with BBS and gastrointestinal symptoms.

What are Normal Defecation Patterns in Healthy Children up to Four Years of Age? A Systematic Review and Meta-Analysis.

OBJECTIVE: To summarize available data on defecation frequency and stool consistency of healthy children up to age 4 in order to estimate normal references values. STUDY DESIGN: Systematic review including cross-sectional, observational, and interventional studies published in English, that reported on defecation frequency and/or stool consistency in healthy children 0-4 years old. RESULTS: Seventy-five studies were included with 16 393 children and 40 033 measurements of defecation frequency and/or stool consistency. Based on visual inspection of defecation frequency data, a differentiation was made between two age categories: young infants (0-14 weeks old) and young children (15 weeks-4 years old). Young infants had a mean defecation frequency of 21.8 per week (95 % CI, 3.9-35.2) compared with 10.9 (CI, 5.7-16.7) in young children (P < .001). Among young infants, human milk-fed (HMF) infants had the highest mean defecation frequency per week (23.2 [CI, 8.8-38.1]), followed by formula-fed (FF) infants (13.7 [CI 5.4-23.9]), and mixed-fed (MF) infants (20.7 [CI, 7.0-30.2]). Hard stools were infrequently reported in young infants (1.5%) compared with young children (10.5%), and a reduction in the frequency of soft/watery stools was observed with higher age (27.0% in young infants compared with 6.2% in young children). HMF young infants had softer stools compared with FF young infants. CONCLUSIONS: Young infants (0-14 weeks old) have softer and more frequent stools compared with young children (15 weeks-4 years old).

Time to first passage of meconium and defecation frequency preceding necrotizing enterocolitis in preterm infants: a case-control study.

Necrotizing enterocolitis (NEC) is associated with significant morbidity and mortality in preterm infants. Early recognition and treatment of NEC are critical to improving outcomes. Enteric nervous system (ENS) immaturity has been proposed as a key factor in NEC pathophysiology. Gastrointestinal dysmotility is associated with ENS immaturity and may serve as a predictive factor for the development of NEC. In this case-control study, preterm infants (gestational age (GA) < 30 weeks) were included in two level-IV neonatal intensive care units. Infants with NEC in the first month of life were 1:3 matched to controls based on GA (± 3 days). Odds ratios for NEC development were analyzed by logistic regression for time to first passage of meconium (TFPM), duration of meconial stool, and mean daily defecation frequency over the 72 h preceding clinical NEC onset (DF < T0). A total of 39 NEC cases and 117 matched controls (median GA 27 + 4 weeks) were included. Median TFPM was comparable in cases and controls (36 h [IQR 13-65] vs. 30 h [IQR 9-66], p = 0.83). In 21% of both cases and controls, TFPM was ≥ 72 h (p = 0.87). Duration of meconial stool and DF < T0 were comparable in the NEC and control group (median 4 and 3, resp. in both groups). Odds of NEC were not significantly associated with TFPM, duration of meconial stools, and DF < T0 (adjusted odds ratio [95% confidence interval]: 1.00 [0.99-1.03], 1.16 [0.86-1.55] and 0.97 [0.72-1.31], resp.). CONCLUSION: In this cohort, no association was found between TFPM, duration of meconium stool, and DF < T0 and the development of NEC. WHAT IS KNOWN: • Necrotizing enterocolitis (NEC) is a life-threatening acute intestinal inflammatory disease of the young preterm infant. Early clinical risk factors for NEC have been investigated in order to facilitate early diagnosis and treatment. • Signs of disrupted gastrointestinal mobility, such as gastric retention and paralytic ileus, have been established to support the diagnosis of NEC. Nevertheless, defecation patterns have insufficiently been studied in relation to the disease. WHAT IS NEW: • Defecation patterns in the three days preceding NEC did not differ from gestational age-matched controls of corresponding postnatal age. Additionally, the first passage of meconium and the duration of meconium passage were comparable between cases and controls. Currently, defecation patterns are not useful as early warning signs for NEC. It remains to be elucidated whether these parameters are different based on the location of intestinal necrosis.

Long-Term Outcomes of Antegrade Continence Enemas to Treat Constipation and Fecal Incontinence in Children.

OBJECTIVES: The objective of this study is to investigate long-term outcomes of antegrade continence enema (ACE) treatment in children with constipation or fecal incontinence. METHODS: Prospective cohort study including pediatric patients with organic or functional defecation disorders who started ACE treatment. Data were collected at baseline and at follow-up (FU) from 6 weeks until 60 months. We assessed parent and patient-reported gastrointestinal health-related quality of life (HRQoL) using the Pediatric Quality of Life Inventory Gastrointestinal Symptoms Module (PedsQL-GI), gastrointestinal symptoms, adverse events, and patient satisfaction. RESULTS: Thirty-eight children were included (61% male, median age 7.7 years, interquartile range 5.5-12.2). Twenty-two children (58%) were diagnosed with functional constipation (FC), 10 (26%) with an anorectal malformation, and 6 (16%) with Hirschsprung disease. FU questionnaires were completed by 22 children (58%) at 6 months, 16 children (42%) at 12 months, 20 children (53%) at 24 months, and 10 children (26%) at 36 months. PedsQL-GI scores improved overall with a significant increase at 12- and 24-month FU for children with FC and a significant increase in parent reported PedsQL-GI score at 36-month FU for children with organic causes. Minor adverse events, such as granulation tissue, were reported in one-third of children, and 10% of children needed a surgical revision of their ACE. The majority of all parents and children reported that they would "probably" or "definitely" choose ACE again. CONCLUSION: ACE treatment is perceived positively by patients and parents and can lead to long-term improvement in gastrointestinal HRQoL in children with organic or functional defecation disorders.

Accuracy of Anorectal Manometry to Detect the Rectoanal Inhibitory Reflex in Children: Awake Versus Under General Anesthesia.

OBJECTIVES: Our objective was to investigate if there is a difference in the detection of the rectoanal inhibitory reflex (RAIR) when an anorectal manometry (ARM) is performed awake or under general anesthesia. METHODS: A retrospective review of ARM studies was performed to identify children who had undergone ARMs both while awake and under general anesthesia. We compared ARM outcomes including the detection of the RAIR and anal canal resting pressure. RESULTS: Thirty-four children had received ARMs both while awake and under general anesthesia (53% female, median age at first ARM 7.5 years [range 3-18 years]). In 9 of 34 (26%) children the RAIR was solely identified during ARM under general anesthesia and not during ARM while awake. In 6 of 9 (66%) this was unrelated to the balloon volumes used during balloon inflations. In 4 of 34 (12%) children, assessment of the RAIR was inconclusive during ARM under general anesthesia due to too low, or loss of anal canal pressure. In 2 of those children, ARMs while awake showed presence of a RAIR. Anal canal resting pressures were higher during ARM while awake versus ARM under general anesthesia (median 70 [interquartile range, IQR 59-85] vs 46 mmHg [IQR 36-65] respectively, P < 0.001). CONCLUSIONS: General anesthesia may affect the detection of a RAIR in 2 ways. On the one hand, it may facilitate better visualization in children in whom a RAIR could not be visualized while awake. On the other hand, it may cause a loss of anal canal pressure resulting in an inconclusive test result.

An Update of Pharmacological Management in Children with Functional Constipation.

Functional constipation is a common problem in childhood worldwide and has a great impact on social, physical, and emotional functioning of affected children and their caregivers. It is a clinical diagnosis based on the Rome IV criteria. Non-pharmacological treatment involves education, demystification, lifestyle advice, and toilet training. Pharmacological treatment consists of disimpaction, maintenance treatment, and eventually weaning if possible. Polyethylene glycol is considered as the first choice of laxative for both disimpaction and maintenance treatment. Different osmotic laxatives, stimulant laxatives, lubricants, and enemas are available as alternative pharmacological treatment options. Novel drugs are emerging but evidence to support the widespread application of these drugs in the pediatric population is often lacking and more high-quality research is needed in this field. If children remain symptomatic despite optimal pharmacological treatment, botulinum toxin injections in the anal sphincter can be considered as an alternative, more invasive treatment option. This review provides an update on currently available literature concerning the pharmacologic treatment of functional constipation in children.

Fatal gastrointestinal complications in Pitt-Hopkins syndrome.

Pitt-Hopkins syndrome (PTHS) is a rare neurodevelopmental disorder caused by mutations of the transcription factor 4 (Tcf4) gene. Individuals with PTHS often suffer from severe abdominal bloating and constipation. In this short communication, we discuss two individuals with PTHS who died unexpectedly due to gastrointestinal complications. We aim to increase awareness among healthcare professionals who care for individuals with PTHS, to ensure adequate screening and management of gastrointestinal symptoms in this population. Moreover, we discuss how fatal gastrointestinal complications may be related to PTHS and provide an overview of the literature.

Transanal Irrigation in Children: Treatment Success, Quality of Life, Adherence, Patient Experience, and Independence.

OBJECTIVES: To investigate the clinical effectiveness and patient experience of transanal irrigation (TAI) in children with constipation or fecal incontinence. METHODS: Combined retrospective and cross-sectional study including pediatric patients who used a Navina TAI system. We retrospectively collected baseline characteristics and data on treatment success at 1- and 6-month follow-up (FU). Treatment success was defined as defecating at least 3 times per week and having less than 1 episode of fecal incontinence per week. We cross-sectionally assessed health-related quality of life (HRQoL), treatment adherence, treatment satisfaction (Treatment Satisfaction Questionnaire for Medication [TSQM]), illness perceptions, medication beliefs, and patient empowerment with validated questionnaires. RESULTS: Thirty-four patients were included (median age at start TAI: 11 years old [range, 6-18]), 32 in the retrospective review, and 26 in the cross-sectional survey (median of 3 years after initiation). Most patients were diagnosed with functional constipation (n = 26; 76%) or a neurogenic bowel disorder (n = 6; 18%). Treatment success rates significantly improved at each FU compared with baseline (baseline: 4/25 [16%]; 1-month FU: 12/16 [75%], P = 0.008; 6-month FU: 11/18 [61%], P = 0.016; cross-sectional FU: 13/26 [50%], P = 0.008). HRQoL scores were high (PedsQL median, 73 [IQR, 54-85]). Adherence (defined as Medication Adherence Report Scale [MARS] ≥ 23) was low (36%), whereas TSQM effectiveness scores were high (median, 69 [IQR, 47-86]). The majority of children (61%) reported an increase in independence since TAI treatment. Patient empowerment (GYPES) levels were similar to those reported in children with other chronic conditions. CONCLUSIONS: TAI with a Navina system is an effective bowel management system for children with intractable constipation or fecal incontinence.

Hypnosis to Reduce Distress in Children Undergoing Anorectal Manometry: A Randomized Controlled Pilot Trial.

Background/Aims: To assess the effectiveness and feasibility of a brief session of hypnosis to reduce distress in children with functional constipation undergoing anorectal manometry (ARM). Methods: A partially-blinded randomized controlled pilot trial was conducted in children 4-18 years old scheduled for ARM. Children were randomized to receive a brief session of hypnosis prior to ARM or standard care. Non-blinded and blinded observers rated the child's level of distress using the Observation Scale of Behavioral Distress and a 4-point-Likert scale, respectively. Differences between groups were analyzed using Fisher's exact test or Mann-Whitney U test as appropriate. Results: Data from 32 children (15 hypnosis and 17 standard care) were analyzed. Prior to insertion of the catheter, the observed mean levels of distress were lower in the hypnosis group according to both the non-blinded observer (median 0.0 [interquartile range {IQR} 0.0-0.3] vs 1.4 [IQR 0.3-2.4]; P = 0.009) and the blinded observer (median 0.0 [IQR 0.0-0.0] vs 0.5 [IQR 0.0-1.0]; P = 0.044). During ARM, observed and reported levels of distress did not differ significantly. In the hypnosis group, 92.9% of parents and children reported that hypnosis helped the child to relax. There were no significant differences in resting pressure, squeeze pressure, or duration of the procedure between both groups. Conclusion: A brief session of hypnosis for children before ARM is an easily incorporable intervention that lowers distress levels prior to the procedure and is positively perceived by children and parents.

Do we need an extra dimension? A pilot study on the use of three-dimensional anorectal manometry in children with functional constipation.

BACKGROUND: Recently, a new high-definition (or three-dimensional "3D") high-resolution anorectal manometry (3D-ARM) catheter has been introduced. This catheter allows for a more detailed visualization of the anal canal. However, its clinical utility and tolerability in children with constipation are unknown. Our primary objective was to evaluate the agreement between findings from solid-state high-resolution anorectal manometry (HR-ARM) and 3D-ARM. Secondary objectives were to investigate if 3D-ARM has additional value over HR-ARM and to evaluate patient and provider experience. METHODS: Prospective pilot study including children (8-18 years of age) with functional constipation scheduled for anorectal manometry. Children underwent HR-ARM and 3D-ARM consecutively. We compared manometry results of both procedures and collected data on patient and provider experience via self-developed questionnaires. KEY RESULTS: Data of ten patients were analyzed (60% female, median age 14.9 years). In the majority of patients, ARMs were performed awake (n = 8, 80%). In two patients, the recto-anal inhibitory reflex (RAIR) was visualized during HR-ARM but not during 3D-ARM. Anal canal resting pressures were significantly higher during 3D-ARM compared to HR-ARM (median 77 mmHg [IQR 59-94] vs. 69 mmHg [IQR 51-91], respectively, p = 0.037). No significant anatomical or muscular abnormalities were visualized during the 3D-ARM. The majority of children identified the 3D-ARM as the more unpleasant (5/7 [71%]) and more painful procedure (6/7 [86%]) and therefore preferred the HR-ARM (4/7 [57%]). CONCLUSIONS & INFERENCES: In our patient sample, 3D-ARM was associated with more discomfort without providing more useful information and even resulted in an inconsistent visualization of the RAIR.

Functional Constipation and Dyssynergic Defecation in Children.

Defecation is a complex physiological process, which relies on intricate mechanisms involving the autonomic and somatic nervous system, the pelvic floor muscles, and the anal sphincter complex. Anorectal dysfunction may result in constipation, a bothersome defecation disorder that can severely affect daily lives of children and their families. In this review, we focus on different mechanisms underlying anorectal dysfunction and specific treatment options aimed at improving defecation dynamics in children with functional constipation.

Practice Variation Research in Degenerative Lumbar Disc Surgery: A Literature Review on Design Characteristics and Outcomes.

STUDY DESIGN: Literature review. OBJECTIVE: To describe whether practice variation studies on surgery in patients with lumbar degenerative disc disease used adequate study methodology to identify unwarranted variation, and to inform quality improvement in clinical practice. Secondary aim was to describe whether variation changed over time. METHODS: Literature databases were searched up to May 4th, 2021. To define whether study design was appropriate to identify unwarranted variation, we extracted data on level of aggregation, study population, and case-mix correction. To define whether studies were appropriate to achieve quality improvement, data were extracted on outcomes, explanatory variables, description of scientific basis, and given recommendations. Spearman's rho was used to determine the association between the Extreme Quotient (EQ) and year of publication. RESULTS: We identified 34 articles published between 1990 and 2020. Twenty-six articles (76%) defined the diagnosis. Prior surgery cases were excluded or adjusted for in 5 articles (15%). Twenty-three articles (68%) adjusted for case-mix. Variation in outcomes was analyzed in 7 articles (21%). Fourteen articles (41%) identified explanatory variables. Twenty-six articles (76%) described the evidence on effectiveness. Recommendations for clinical practice were given in 9 articles (26%). Extreme Quotients ranged between 1-fold and 15-fold variation and did not show a significant change over time (rho= -.33, P= .09). CONCLUSIONS: Practice variation research on surgery in patients with degenerative disc disease showed important limitations to identify unwarranted variation and to achieve quality improvement by public reporting. Despite the availability of new evidence, we could not observe a significant decrease in variation over time.

Hypnosis to Reduce Distress in Children Undergoing Anorectal Manometry: A Randomized Controlled Pilot Trial

Background/Aims@#To assess the effectiveness and feasibility of a brief session of hypnosis to reduce distress in children with functional constipationundergoing anorectal manometry (ARM). @*Methods@#A partially-blinded randomized controlled pilot trial was conducted in children 4-18 years old scheduled for ARM. Children were randomized to receive a brief session of hypnosis prior to ARM or standard care. Non-blinded and blinded observers rated the child’s level of distress using the Observation Scale of Behavioral Distress and a 4-point-Likert scale, respectively. Differences between groupswere analyzed using Fisher’s exact test or Mann-Whitney U test as appropriate. @*Results@#Data from 32 children (15 hypnosis and 17 standard care) were analyzed. Prior to insertion of the catheter, the observed mean levels of distress were lower in the hypnosis group according to both the non-blinded observer (median 0.0 [interquartile range {IQR} 0.0-0.3] vs 1.4 [IQR 0.3-2.4]; P = 0.009) and the blinded observer (median 0.0 [IQR 0.0-0.0] vs 0.5 [IQR 0.0-1.0]; P = 0.044). During ARM, observed and reported levels of distress did not differ significantly. In the hypnosis group, 92.9% of parents and childrenreported that hypnosis helped the child to relax. There were no significant differences in resting pressure, squeeze pressure, or duration of the procedure between both groups. @*Conclusion@#A brief session of hypnosis for children before ARM is an easily incorporable intervention that lowers distress levels prior to theprocedure and is positively perceived by children and parents.

Outcomes after enterostomies in children with and without motility disorders: A description and comparison of postoperative complications.

PURPOSE: To provide an overview of complications after ileostomy or colostomy procedures in children, and to compare outcomes between patients with gastrointestinal motility disorders (i.e. functional constipation, Hirschsprung's disease, pediatric intestinal pseudo-obstruction (PIPO)) and children without motility disorders (including necrotizing enterocolitis, anorectal malformation and inflammatory bowel disease). METHODS: We performed a retrospective study of children who underwent an enterostomy procedure at our institution. The number and type of complications and subsequent reoperations after ostomy formation were determined. Complications were scored using the Clavien-Dindo classification. A complication of ≥ grade III-b was considered a high-grade complication. RESULTS: 129 children with an ileostomy and 61 children with a colostomy were included. Of these, 62 children (32.6%) had motility disorders; functional constipation (n=40), Hirschsprung's disease (n=18) and PIPO (n=4). The total prevalence of complications was 73.2%. Comparing the perioperative data, children with motility disorders significantly more often underwent a laparoscopic procedure (59.7% vs. 10.9%, p=0.000) and had an end stoma-configuration (37.1% vs. 14.1%, p=0.000) as compared to children without motility disorders. Children with motility problems had a higher complication rate (88.7% vs. 65.5%, OR 4.1, 95% CI 1.7-9.8, p=0.001) compared to children without motility problems, and a larger proportion of complications was classified as high-grade complications (61.8% vs. 31.0% p =0.002). CONCLUSION: A high complication rate after enterostomy formation was detected. Children with gastrointestinal motility disorders had more and more severe complications as compared to children without motility disorders. LEVEL OF EVIDENCE: Level III TYPE OF STUDY: Retrospective comparative study.