Medicine

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This repository contains the published and unpublished research of the Faculty of Medicine by the staff members of the faculty

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    Navigating through 65 years of insights: lessons learned on functional abdominal pain in children
    (Springer Verlag, 2024) Rajindrajith, S.; Boey, C.C.M.; Devanarayana, N.M.; Niriella, M.A.; Thapar, N.; Benninga, M.A.
    In 1958, Apley and Naish authored a groundbreaking paper in Archives of Disease in Childhood, elucidating the epidemiology and risk factors of recurrent abdominal pain in children-a subject that had confounded clinicians of their time. Surprisingly, even after 65 years, there are several unanswered questions regarding the etiology, pathophysiology, and management of pediatric abdominal pain. Contrary to the prevailing notion that children naturally outgrow functional abdominal pain, compelling evidence suggests it's possible these children develop a number of clinically significant psychological issues that could profoundly impact their quality of life and, consequently, future health and educational outcomes. In this light, we aimed to comprehensively review the current literature to update the knowledge of practicing clinicians on functional abdominal pain, summarizing the evidence from the last 65 years.Conclusion: The enduring unanswered questions surrounding childhood abdominal pain continue to challenge clinicians, resulting in unnecessary investigations, thereby contributing to substantial healthcare expenditures. It is also evident that children with long-standing symptoms would progress to adulthood with the potential to develop irritable bowel syndrome and many psychological disturbances. Several key interventions using pharmacological agents, such as amitriptyline, showed that some of these drugs are no more effective than the placebo in clinical trials. Several research during the recent past suggest that psychological interventions such as gut-directed hypnotherapy alleviate symptoms and ensure better prognosis in the long run. Therefore, clinicians and researchers must join hands to explore the pathophysiological mechanisms underpinning functional abdominal pain and novel therapeutic strategies to ensure the well-being of these children. What is Known: • Functional abdominal pain disorders are common among children, with a worldwide prevalence of 13.5% of children suffering from at least one of these disorders • These disorders contribute to a significant reduction in the quality of life of affected children and their families and lead to an array of psychological problems What is New: • The biological basis of functional abdominal pain is becoming more explicit, including complex interactions between altered microbiome, deranged motility, and psychological dysfunction with gut-brain interactions • Novel approaches giving minimal emphasis on pharmacological interventions and exploring psychological interventions are showing promising results.
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    Defecation disorders in children: Constipation and fecal incontinence
    (Springer International, 2021) Baaleman, D.F.; Rajindrajith, S.; Devanarayana, N.M.; Lorenzo, C.D.; Benninga, M.A.
    Defecation disorders denote a state of altered defecation dynamics leading to an array of clinical presentations. With the currently available epidemiological studies, it is evident that these disorders have become widely spread global health problems. Due to the broadening of the understanding of escalating healthcare costs and poor quality of life, these disorders demand attention of clinicians and researchers, more than at any other time in history. However, it is regrettable that only little guidance is available for healthcare professionals to manage these disorders. Most of the therapeutic trials and investigation plans are archaic from the viewpoint of a twenty-first-century clinician and are not evidence based. However, new research ventures are being carried out, and the horizon of the knowledge base is expanding, perhaps indicating a brighter future. In this chapter, we discuss emerging concepts of definitions, epidemiology, pathophysiology, clinical evaluation, and management of defecation disorders in children and adolescents.
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    Myths and misconceptions about childhood constipation
    (Springer-Verlag., 2023) Rajindrajith, S.; Devanarayana, N.M.; Thapar, N.; Benninga, M.A.
    Many widely held beliefs and assumptions concerning childhood constipation continue to interfere with rational management of childhood constipation. Although many still believe that constipation is not a common disease, about 9.5% of the world's children suffer from chronic constipation. Most of these children live in non-Western countries. There are major misconceptions about the etiology of constipation as a significant proportion of clinicians still believe that constipation is caused by some form an organic pathology, whereas in reality, the majority have functional constipation. Contrary to a commonly held belief that children outgrow constipation without long-term problems, there is evidence that constipation leads to significant bowel and psychological consequences and has a major impact on the quality of life which detrimentally affects future health and education. Finally, ineffective management strategies such as increasing fiber and water in the diet, and short duration of treatment owing to the fear that long-term laxative treatment leads to colonic dysfunction, interfere with effective therapeutic strategies. Conclusions: It is apparent that myths and misconception often lead to wrong assumptions regarding the distribution of the disease, its etiology, pathophysiology, and management leading to ordering incorrect investigations and ineffective therapeutic strategies while spending large sums of public funds unnecessarily. Poorly treated constipation leads to deleterious psychological consequences predisposing children to develop significant psychological damage and bowel dysfunctions. This review aims to challenge these myths about various elements of constipation by exploring the existing literature and encouraging clinicians to have a fresh look at old concepts that could interfere with the well-being of children with constipation. What is Known: • Childhood constipation is a growing problem in the world leading to significant suffering and high healthcare expenditure • Myths and misconceptions lead to poor management strategies causing psychological and bowel damage What is New: • Organic, systemic, and bowel disorders leading to constipation are uncommon, and in the majority, it arises due to deliberate fecal withholding and most investigations ordered by clinicians are not very helpful in the management • Most non-pharmacological interventions are not effective in the day-to-day management of childhood constipation. The use of laxatives is considered to be the first-line management strategy.
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    Childhood constipation: Current status, challenges, and future perspectives
    (Baishideng Publishing Group, 2022) Rajindrajith, S.; Devanarayana, N.M.; Benninga, M.A.
    Constipation in children is a major health issue around the world, with a global prevalence of 9.5%. They present to clinicians with a myriad of clinical signs. The Rome IV symptom-based criteria are used to diagnose functional constipation. Functional constipation is also a huge financial burden for healthcare system and has a detrimental impact on health-related quality of life of children. There are various risk factors identified globally, including centrally connected factors such as child abuse, emotional and behavioral issues, and psychological stress. Constipation is also precipitated by a low-fiber diet, physical inactivity, and an altered intestinal microbiome. The main pathophysiological mechanism is stool withholding, while altered rectal function, anal sphincter, pelvic floor, and colonic dysfunction also play important roles. Clinical evaluation is critical in making a diagnosis, and most investigations are only required in refractory patients. In the treatment of childhood constipation, both nonpharmacological (education and de-mystification, dietary changes, toilet training, behavioral interventions, biofeedback, and pelvic floor physiotherapy), and pharmacological (osmotic and stimulant laxatives and novel drugs like prucalopride and lubiprostone) interventions are used. For children with refractory constipation, transanal irrigation, botulinum toxin, neuromodulation, and surgical treatments are reserved. While frequent use of probiotics is still in the experimental stage, healthy dietary habits, living a healthy lifestyle and limiting exposure to stressful events, are all beneficial preventive measures.
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    Association between childhood constipation and exposure to stressful life events: a systematic review
    (Blackwell Scientific Publications, 2022) Liyanarachchi, H.; Rajindrajith, S.; Kuruppu, C.; Chathurangana, P.; Ranawaka, R.; Devanarayana, N.M.; Benninga, M.A.
    BACKGROUND: Several cross-sectional studies have reported an association between childhood constipation and exposure to stressful events. We planned to systematically review the literature on constipation and its associated stressful events. METHODS: PubMed, Embase, and PsycINFO databases were searched (until February 2021) using standard search terms related to "constipation" and "stress" from 0 to 18 years that describe the association between psychological stressors and constipation. Studies were screened using pre-designed eligibility criteria. Studies that fulfilled the criteria were reviewed in a full-text format. The quality assessment of selected articles was conducted using standard methods. KEY RESULTS: Of 2296 titles and abstracts screened, 38 were included in the full-text review. Out of that, 15 articles were included in this systematic review. There were 2954 children with constipation, and the age range was from 6 months to 16 years. Exposure to home-related stressors (divorce or separation of parents, severe illness in family, and parental job loss) school-related stressors (including being bullied at school, change in school, separation from the best friend at school, and failure in an examination), exposure to child maltreatments and exposure to war/civil unrest were associated with childhood constipation. CONCLUSIONS AND INFERENCES: Exposure to day-to-day home- and school-related stressors, to child maltreatment, and to civil unrest is associated with constipation in children and adolescents. These factors need to be explored during clinical evaluation of children with constipation. KEYWORDS: adolescents; child maltreatment; children; civil unrest; constipation; stress.
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    Functional fecal incontinence in children: epidemiology, pathophysiology, evaluation, and management
    (Lippincott Williams & Wilkins, 2021) Rajindrajith, S.; Devanarayana, N.M.; Thapar, N.; Benninga, M.A.
    ABSTRACT: Functional fecal incontinence (FI) is a worldwide problem in children and comprises constipation-associated fecal incontinence and nonretentive fecal incontinence. Irrespective of pathophysiology, both disorders impact negatively on the psychological well-being and quality of life of affected children. A thorough clinical history and physical examination using the Rome IV criteria is usually sufficient to diagnose these conditions in most children. Evolving investigations such as high resolution anorectal and colonic manometry have shed new light on the pathophysiology of functional FI. Although conventional interventions such as toilet training and laxatives successfully treat most children with constipation associated FI, children with nonretentive fecal incontinence need more psychologically based therapeutic options. Intrasphincteric injection of botulinum toxin, transanal irrigation and, in select cases, surgical interventions have been used in more resistant children with constipation associated FI.
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    Behavioral and emotional problems in adolescents with constipation and their association with quality of life
    (Public Library of Science, 2020) Rajindrajith, S.; Ranathunga, N.; Jayawickrama, N.; van Dijk, M.; Benninga, M.A.; Devanarayana, N.M.
    Objectives: To assess behavioral and emotional problems in children and adolescents with functional constipation and their relationship with psychological maladjustment and health-related quality of life (HRQoL). Design: A school-based cross-sectional survey conducted in 8 randomly selected schools from 4 randomly selected districts in Sri Lanka. A previously validated questionnaire was used for data collection. Behavioral and emotional problems were assessed using the Sinhala version of the Child Behavior Check List (CBCL-S/4-18). Constipation was diagnosed by applying the Rome III criteria. Results: A total of 1000 questionnaires were distributed, and 913 completed questionnaires were included in the analysis. Sixty adolescents (6.5%) had functional constipation. Scores obtained for isolated psychological problems such as withdrawal (3.1 [3.1] vs. 1.9 [2.4], p<0.001), somatic complaints (3.2 [2.8] vs. 2.3 [2.5], p<0.05) anxiety/depression (5.8 [2.5] vs. 3.9 [3.6], p<0.001), social problems (3.0 [2.7] vs. 2.2 [1.9] p<0.001) and attention problems (5.4 [4.1] vs. 3.9 [3.4], p<0.001), and broadband scale of internalization (12.1 [8.4] vs. 8.3 [7.2], p<0.05) and mean total CBCL-S/4-18 score (29.4 [19.5] vs. 23.2 [17.0], p<0.001) were higher in adolescents with functional constipation. Clinical characteristics, socio-demographic and family factors and psychological maladjustment had no relationship with externalization, internalization and total CBCL-S/4-18 score. Internalization (-0.49, p<0.0001), externalization (-0.30, p<0.05), and total CBCL-S/4-18 (-0.44, p<0.001) scores had a negative impact on HRQoL of adolescents with functional constipation. Conclusions: Adolescents with functional constipation are suffering from significant behavioral and emotional problems. These problems negatively affect their HRQoL.
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    Epidemiology of functional abdominal pain disorders and functional defecation disorders in adolescents in Curacao. [Letter to the editor]
    (Raven Press., 2020) Zeevenhooven, J.; van der Heijden, S.; Devanarayana, N.M.; Rajindrajith, S.; Benninga, M.A.
    This is response to the article (J. Pediatr. Gastroenterol. Nutr. . 2020;70(4):e71-e76.) by same authors.
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    Epidemiology of functional abdominal pain disorders and functional defecation disorders in adolescents in Curacao.
    (Raven Press., 2020) Zeevenhooven, J.; van der Heijden, S.; Devanarayana, N.M.; Rajindrajith, S.; Benninga, M.A.
    OBJECTIVES: Functional abdominal pain disorders (FAPDs) and functional defecation disorders (FDDs) are common in children and adolescents, but prevalence rates from the Caribbean are lacking. Therefore, our aim was to determine the prevalence of FAPDs and FDDs in adolescents in Curacao and to assess the influence of psychosocial factors on the prevalence of FAPDs and FDDs. METHODS: The prevalence of FAPDs and FDDs in children and adolescents living in Curacao, ages 11 to 18 years, was assessed using the Rome IV Questionnaire on Pediatric Gastrointestinal Disorders (RIV-QPGD). FAPDs and FDDs were diagnosed according to the Rome IV criteria. Sociodemographic characteristics, somatic symptoms, early adverse life events, stressful life events, and physical and emotional abuse were evaluated as associated factors. RESULTS: Out of 946 questionnaires distributed, 783 were included for further analysis. The mean age of adolescents was 14.7 years (±1.6) with 61.7% being girls. A total of 266 adolescents (34%, 95% confidence interval [CI] 30.7-37.5) met Rome IV criteria for at least 1 FAPD or FDD. Twenty-nine adolescents (3.7%) qualified for 2 functional gastrointestinal disorders. Functional constipation (18.6%) and irritable bowel syndrome (12.3%) were the most prevalent disorders. After multivariate logistic regression analyses, dizziness (odds ratio [OR] 1.84, 95% CI 1.28-2.64) was significantly associated with having a FAPD or FDD. CONCLUSIONS: FAPDs and FDDs are common in adolescents in Curacao. Dizziness is associated with the presence of a FAPD or FDD.
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    A Core outcome set for clinical trials in pediatric functional abdominal pain disorders.
    (Mosby, 2020) Zeevenhooven, J.; Rexwinkel, R.; Van Berge Henegouwen, V.W.A.; Krishnan, U.; Vandenplas, Y.; Strisciuglio, C.; Staiano, A.; Devanarayana, N.M.; Rajindrajith, S.; Benninga, M.A.; Tabbers, M.M.; Consensus Group on Outcome Measures Made in Pediatric Enteral Nutrition Clinical Trials Working Group
    OBJECTIVE: To ensure consistency and reduce outcome measure reporting heterogeneity in clinical trials on pediatric functional abdominal pain disorders (FAPDs), a core outcome set (COS) was developed for pediatric FAPD trials. STUDY DESIGN: A mixed-method 2-round Delphi technique was used and key stakeholders, including healthcare professionals (HCPs), patients with FAPD, and their parents were invited to participate. In the first round, key stakeholders identified outcomes of importance through an open-ended questionnaire. Outcomes mentioned by ≥10% of the participants were included in a shortlist. In the second round, this shortlist was rated and prioritized. During a consensus meeting with an expert panel, the final COS was defined. RESULTS: The first round was completed by 152 of 210 (72%) HCPs, 103 (100%) parents, and 50 of 54 (93%) patients. A total of 104 from 167 (62%) HCPs, 102 (100%) parents, and 53 (100%) patients completed round 2. Pain intensity, pain frequency, quality of life, school attendance, anxiety/depression, adequate relief, defecation pattern (disease specific, irritable bowel syndrome), and adverse events were included in the final COS for FAPDs. CONCLUSION: A set of 8 core outcomes has been identified that should minimally be measured in pediatric FAPD trials. Implementation of the use of this COS will increase comparison between studies and, therefore, improve management of children with FAPDs.
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