Trastornos funcionales gastrointestinales. Cómo tratar sin medicar / Functional gastrointestinal disorders. How to manage them without medication

Los trastornos funcionales gastrointestinales (TFGI) se caracterizan por síntomas atribuibles al tracto gastrointestinal que no pueden ser explicados por anormalidades estructurales ni bioquímicas. Durante el primer año de vida, pueden generar mucho malestar en el lactante y preocupación en sus padres. Su diagnóstico se basa en criterios clínicos que expertos han determinado y en una historia clínica y un examen físico completo que descartan causas orgánicas. El objetivo de esta actualización es presentar estrategias para el manejo de los TFGI más frecuentes durante el primer año de vida: cólicos, regurgitaciones, disquecia y estreñimiento, bajo la visión de los nuevos conocimientos fisiopatológicos, que eviten los estudios y medicaciones innecesarias.

Functional gastrointestinal disorders (FGIDs) are characterized by symptoms attributable to the gastrointestinal tract that cannot be explained by the presence of structural or biochemical abnormalities. During the first year of life, FGIDs can cause great discomfort in infants and concern in their parents. The diagnosis of FGIDs is based on clinical criteria determined by experts and on a comprehensive case-taking process and physical exam to rule out organic causes. The objective of this update is to describe strategies for the management of the most frequent FGIDs during the first year of life: colics, regurgitations, dyschezia, and constipation, in light of new pathophysiological insights, to avoid unnecessary tests and medications.

Efficacy of the herbal formula of Foeniculum vulgare and Rosa damascena on elderly patients with functional constipation: A double-blind randomized controlled trial / 中西医结合学报

BACKGROUND@#Constipation is a common chronic bowel disorder with an incidence of more than 50% in the elderly population. Complementary and alternative medicine is a cost-effective and satisfactory treatment for constipation used widely by the elderly.@*OBJECTIVE@#This study evaluates the efficacy of an herbal formula made from Foeniculum vulgare Mill. and Rosa damascena for the treatment of constipation in an elderly population and consequent changes to their quality of life.@*DESIGN, SETTING, PARTICIPANTS AND INTERVENTION@#This double-blind randomized active controlled clinical trial, with parallel group allocation ratio of 1:1, was conducted in a referral clinic in Afzalipour Hospital, affiliated to Kerman University of Medical Sciences in Kerman, Southeastern Iran. Individuals over 60 years of age, diagnosed with functional constipation (based on the Rome IV criteria), were included in this study. Participants received a sachet of 10 g F. vulgare and R. damascena (herbal formula group) or polyethylene glycol 4000 (PEG 4000 group) with a glass of warm water two times a day for 4 weeks and were followed up for 4 additional weeks.@*MAIN OUTCOME MEASURES@#Constipation severity, stool consistency, and the quality of life were used as the primary outcomes. Drug side effects were used as a secondary outcome. The outcomes were assessed using the Constipation Assessment Scale, the Bristol Stool Form Scale, and the Patient Assessment of Constipation Quality of Life questionnaire.@*RESULTS@#A total of 25 participants in each group completed the four-week treatment cycle and the eight-week follow-up. At the end of the four-week treatment cycle, all clinical outcomes had significant improvements in both groups (P < 0.05). The analysis of constipation severity (P < 0.001), stool consistency (P < 0.001), and the quality of life (P < 0.001) showed significant improvements with fewer side effects (mild diarrhea) and a longer duration of symptom relief in the herbal formula group compared to the PEG 4000 group.@*CONCLUSION@#Although both interventions significantly improved the treatment outcomes, constipation severity, stool consistency and the quality of life were improved more effectively by the herbal formula than by PEG 4000; however, the mechanism of action is not yet understood.@*TRIAL REGISTRATION@#This trial was registered in the Iranian Registry of Clinical Trials (IRCTID: IRCT20200108046056N1).

Clinical efficacy of adaptive biofeedback training combined with oral administration of compound polyethylene glycol 4000-electrolyte powder in the treatment of children with outlet obstruction constipation: a prospective randomized controlled trial / 中国当代儿科杂志

OBJECTIVES@#To study the clinical efficacy, advantages, and disadvantages of adaptive biofeedback training combined with oral administration of compound polyethylene glycol 4000-electrolyte powder in the treatment of children with outlet obstruction constipation (OOC).@*METHODS@#A total of 168 children with OOC were enrolled in this prospective study. All the subjects were randomly divided into a test group and a control group based on the order of visiting time, 84 in each group. The test group was treated with adaptive biofeedback training combined with oral administration of compound polyethylene glycol 4000-electrolyte powder, and the control group was treated with oral administration of compound polyethylene glycol 4000-electrolyte powder alone. Eleven children in the test group and two children in the control group withdrew from the study since they could not finish the whole treatment course. Finally, 73 children in the test group and 82 children in the control group were included in this analysis. As clinical outcomes, the total score of clinical symptoms and overall response rate were compared between the two groups at weeks 4 and 8 of treatment.@*RESULTS@#There was no significant difference in the total score of clinical symptoms between the two groups at beginning of treatment and at week 4 (P>0.05), while the test group had a significantly lower total score of clinical symptoms than the control group at week 8 (P<0.05). At week 4, there was no significant difference in overall response rate between the two groups (P>0.05), while the test group had a significantly higher overall response rate than the control group at week 8 (P<0.05).@*CONCLUSIONS@#Adaptive biofeedback training combined with oral administration of compound polyethylene glycol 4000-electrolyte powder is significantly associated with improvement of clinical outcomes in the treatment of children with OOC.

Estreñimiento funcional en pediatría, diagnóstico y tratamiento / Functional constipation in pediatrics, diagnosis and treatment

El estreñimiento funcional es un motivo de consulta frecuente en pediatría, con una prevalencia del 3 %. El Grupo de Trabajo de Constipación del Comité de Gastroenterología de la Sociedad Argentina de Pediatría se reunió con el objetivo de actualizar el diagnóstico y tratamiento de la constipación funcional en pediatría.Se realizó una búsqueda de literatura para evaluar la calidad de la evidencia. Ante un paciente constipado, es fundamental una historia y examen clínico completos. Los Criterios de Roma IV establecen pautas que, habitualmente, permiten diagnosticar la constipación funcional y evitar estudios innecesarios. La realización de estudios diagnósticos solo se pondrá en consideración ante la presencia de respuesta refractaria al tratamiento médico o en los casos de signos de alarma (banderas rojas). El primer paso del tratamiento es la desimpactación (por vía oral o enemas), seguida del tratamiento dietético, de hábitos y laxantes (es de primera elección el polietilenglicol).

Functional constipation is a common disease and one of the most frequent reasons of visit in pediatric clinics with a 3 % of prevalence. The Constipation Working Group of the Gastroenterology Committee of the Sociedad Argentina de Pediatría met with the objective of updating the diagnosis and treatment of functional constipation in pediatrics.A literature search was performed to assess the quality of the evidence. In a constipated patient, a complete history and clinical examination is essential. The Rome IV Criteria establish guidelines that usually allow us to diagnose functional constipation, avoiding unnecessary studies. The performance of diagnostic studies will only be considered in the absence of response to medical treatment or in cases of alarm signs (red flags). The first step of treatment is disimpaction (orally or enemas), followed by dietary treatment, habits and laxatives, with polyethylene glycol being the first choice.

Effect of Dendrobium officinale on Yin deficiency constipation induced by warm-drying medicine in mice / 中国中药杂志

Dendrobium officinale is a sacred product for nourishing Yin and has a clear "thick gastrointestinal" effect. Modern pharmacological studies had found that it could improve gastrointestinal function. This study observed the improvement effect of D. officinale on constipation model mice with Yin deficiency caused by warm-drying medicine. It provided experimental basis for the treatment of Yin deficiency constipation. The male and female ICR mice were randomly divided into normal group, model group, D. officinale high, medium and low dose groups(0.6, 0.4, 0.2 g·kg~(-1)), and phenolphthalein tablets group. The model mice of Yin deficiency constipation were established by gavage with warm-drying medicine. The overall state and body temperature of the mice were observed and recorded. The number of feces, feces weight, fecal moisture content and intestinal propulsion were measured. The morphological damage of colon tissue was observed by hematoxylin-eosin(HE) staining. The expression of inducible nitric oxide synthase(iNOS) in the colon was detected by Western blot and immunohistochemical method. The expression of iNOS mRNA in the colon was detected by Real-time fluorescence quantitative PCR, and the serum cyclic guanosine phosphate(cGMP) level was detected the enzyme-linked immunosorbent assay(ELISA). The results showed that D. candidum could reduce the body temperature of mice with Yin deficiency constipation, increase the number of feces, wet feces, dry feces and intestinal propulsion ability, reduce the expression of iNOS protein and mRNA in the colon, and reduce the content of cGMP in the serum. It showed that D. candidum could improve the symptoms of Yin deficiency constipation mice caused by warm-drying medicine, and the mechanism may be related to reducing the expression of iNOS in the colon and increasing intestinal motility.

Metabonomics study of Shouhui Tongbian Capsules in slow transit constipation based on UPLC-ESI-QE-Orbitrap-MS / 中国中药杂志

The effect of Shouhui Tongbian Capsules(SHTB) on the endogenous metabolites of colon tissue in mice with slow transit constipation was analyzed by metabolomics methods to explore its mechanism in the treatment of constipation. ICR mice were randomly divided into normal group, model group and SHTB group according to the body weight. The mice were given diphenoxylate to establish the slow transit constipation model. Mouse carbon ink pushing rate, first defecation time and the number of defecation particles in 12 h were observed. The mouse colon tissue was separated and the mucous cells were detected by Periodic acid Schiff and Alcian blue(AB-PAS) staining. Ultra-high-performance liquid chromatography electrospray ionization orbitrap tandem mass spectrometry(UPLC-ESI-Orbitrap-MS/MS) technology was used to characterize the differences in tissue metabolism to screen out the potential different metabolites and possible metabolic pathways in colon tissue. The results indicated that SHTB could significantly shorten the first defecation time and the number of defecations, and increase the number of intestinal peristalsis and mucous cells in the colonic mucosa compared to the model mice. Metabolomics results showed that, compared with the normal group, a total of 17 potential biomarkers, including L-kynurenine, N6,N6,N6-trimethyl-L-lysine, L-formylkynurenine, N6-acetyl-L-lysine, L-phenylalanine, phenylacetaldehyde, xanthoxin, thymidine, glycyl-L-leucine, cystathionine,(R)-1-aminopropan-2-ol, deoxycytidine, gamma-glutamyl-gamma-aminobutyraldehyde, D-galactose, L-arginine, L-proline and pyruvate, were found and identified in colon tissue. Treated with SHTB, these metabolic differences tended to return to normal levels. Therefore, it could be made a conclusion that the therapeutic effect of SHTB on chronic transit constipation may be related to regulating phenylalanine metabolism, phenylalanine, tyrosine and tryptophan biosynthesis, arginine and proline metabolism, cysteine and methionine metabolism, tyrosine metabolism, arginine biosynthesis, pyruvate metabolism, glycolysis, pyrimidine metabolism, tricarboxylic acid cycle and galactose metabolism.

Therapeutic effect and mechanism of Shouhui Tongbian Capsules on slow transit constipation model mice / 中国中药杂志

Shouhui Tongbian Capsules was used to explore the therapeutic effect and potential mechanism on slow transit constipation model mice induced by loperamide hydrochloride. In the experiment, loperamide hydrochloride-induced ICR mice were used as the model of slow transit constipation. Fifty ICR mice were divided into the blank group, model group and high, medium and low dose groups of Shouhui Tongbian Capsules extract(100, 200 and 400 mg·kg~(-1)). The model group and the administration groups were then modeled using loperamide hydrochloride intragastrically to obtain slow transit constipation. After successful modeling, high, medium and low doses of drugs were given to each drug group by intragastric administration. After 14 days of administration, the first defecation time, 6 h defecation grain number, 6 h defecation wet weight and dry weight, black feces discharged within 6 h and the fecal water content were measured. Intestinal tissues were taken for c-Kit and SCF immunohistochemical sections to detect the expression of c-Kit and SCF in the blank group, model group and high, medium and low dose groups of the medicinal extract of Shouhui Tongbian Capsules. The tissue changes in the intestinal wall of mice were detected by HE staining. At the same time, partial intestinal tissues were taken to test the activity of ATP synthase and isocitrate dehydrogenase in intestinal tissues of mice. RESULTS:: showed that Shouhui Tongbian Capsules effectively improved the symptoms of slow transit constipation in ICR mice and promoted intestinal movement. Shouhui Tongbian Capsules obviously shortened the time of discharging black stool for the first time, improved the intestinal propulsion rate, increased the water content and amount of feces, and improved the constipation symptoms. Mechanism study revealed that Shouhui Tongbian Capsules increased ATP synthase activity and mitochondrial isocitrate dehydrogenase activity in intestinal tissue, and up-regulated c-Kit/SCF signaling pathway to promote interstitial Cajal cells proliferation, intestinal nerve transmission, intestinal motility and transport capacity.

Rule mining of acupoint and medication selection of acupoint application therapy for functional constipation / 中国针灸

OBJECTIVE@#To analyze the rules of acupoint and medication selection of acupoint application therapy for functional constipation (FC) by data mining technology.@*METHODS@#The clinical research literature regarding acupoint application therapy for FC from published to February 26, 2020 was searched in CNKI, VIP, Wanfang, SinoMed and PubMed. The prescriptions were extracted, and by using SPSS24.0 and SPSS Modeler14.0 software, the use of high-frequency acupoints and medication was summarized. The association rule analysis, cluster analysis and core prescription analysis of acupoints and medication were analyzed.@*RESULTS@#A total of 122 prescriptions of acupoint application therapy were included, involving 32 acupoints. The core prescription of acupoints was Tianshu (ST 25), Dachangshu (BL 25), Shenque (CV 8) and Guanyuan (CV 4). The high-frequency meridians mainly included conception vessel, @*CONCLUSION@#The use of local acupoint and regulating-

Systematic review with meta-analysis: lubiprostone efficacy on the treatment of patients with constipation / Revisão sistemática com metanálise: eficácia da lubiprostona no tratamento de pacientes com constipação

ABSTRACT BACKGROUND: Lubiprostone is a type 2 chloride channel activator that has been shown to be efficacious and safe in the treatment for chronic constipation. OBJECTIVE: To systematically review randomized clinical trials (RCTs) assessing efficacy of lubiprostone for patients with chronic idiopathic constipation (CIC), irritable bowel syndrome with predominant constipation (IBS-C) and opioid-induced constipation (OIC). METHODS: Searches were conducted in PubMed, LILACS, Cochrane Collaboration Database, and Centre for Reviews and Dissemination. Lubiprostone RCTs reporting outcomes of spontaneous bowel movements (SBM) and abdominal pain or discomfort were deemed eligible. Meta-analysis was performed calculating risk ratios and 95% confidence intervals, using the Mantel-Haenszel method and random effects model. RESULTS: Searches yielded 109 records representing 93 non-duplicate publications, and 11 RCTs (978 CIC, 1,366 IBS-C, 1,300 OIC, total = 3,644) met inclusion criteria. Qualitative synthesis showed that for CIC patients, lubiprostone is superior to placebo in terms of SBM outcomes. Meta-analysis for CIC was feasible for full responder and SBM within 24h rates, indicating superiority of lubiprostone over placebo. For IBS-C, lubiprostone was significantly superior for all SBM outcomes in follow-ups ranging from 1 week-3 months. In terms of abdominal pain, lubiprostone provided significantly better symptoms relief, particularly after 1 month of treatment. For OIC, lubiprostone was more effective than placebo for both SBM and discomfort measures. CONCLUSION: Our findings demonstrated that lubiprostone is superior to placebo in terms of SBM frequency for CIC, IBS-C and OIC. In terms of abdominal symptoms, the most pronounced effect was seen for abdominal pain in IBS-C patients.

RESUMO CONTEXTO: Lubiprostona é um ativador de canal de cloreto tipo 2 que tem se demonstrado eficaz e seguro no tratamento da constipação crônica. OBJETIVO: Revisar sistematicamente ensaios clínicos randomizados (ECRs) avaliando a eficácia da lubiprostona para pacientes com constipação idiopática crônica (CIC), síndrome do intestino irritável com constipação predominante (IBS-C) e constipação induzida por opioide (OIC). MÉTODOS: Buscas foram conduzidas no PubMed, LILACS, Cochrane Collaboration Database e Centre for Reviews and Dissemination. ECRs de lubiprostona relatando desfechos de movimentos intestinais espontâneos (SBM) e dor ou desconforto abdominal foram considerados elegíveis. Metanálise foi realizada calculando razão de riscos e intervalos de confiança de 95%, utilizando o método de Mantel-Haenszel e modelo de efeitos aleatórios. RESULTADOS: As buscas identificaram 109 registros representando 93 publicações não-duplicadas e 11 ECRs (978 pacientes de CIC, 1366 de IBS-C e 1300 OIC, total = 3644) preencheram os critérios de inclusão. Síntese qualitativa mostrou que, para pacientes com CIC, a lubiprostona foi superior ao placebo em termos de desfechos SBM. Metanálise para CIC foi possível para os desfechos de responder completo e taxa de SBM em 24 horas, indicando superioridade da lubiprostona sobre o placebo. Para IBS-C, lubiprostona foi significativamente superior para todos os desfechos de SBM em tempos de seguimento variando de 1 semana a 3 meses. Em termos de dor abdominal, lubiprostona proporciono alívio dos sintomas significativamente melhor, particularmente após 1 mês de tratamento. Para OIC, lubiprostona foi mais efetiva do que placebo tanto para medidas de SBM quando de desconforto abdominal. CONCLUSÃO: Nossos achados demonstraram que lubiprostona é superior ao placebo em termos de frequência de SBM para CIC, IBS-C e OIC. Em termos de sintomas abdominais, o efeito mais pronunciado foi visto para dor abdominal em pacientes com IBS-C.

The real impact of colonic transit time and anorectal manometry in the diagnosis of adult patients with chronic constipation / O real impacto do tempo de trânsito cólico e da manometria anorretal no diagnóstico de pacientes adultos com constipação crônica

Abstract Introduction: Anorectal physiology tests are indicated for patients who have refractory symptoms of constipation, but the best sequence of investigation remains controversial. Objective: To evaluate the influence of colonic transit time and anorectal manometry in the diagnosis of chronic constipation in adults. Method: This was a study of adult patients with constipation at a private clinic in a city in southern Brazil, from January 1, 2009 to December 31, 2018. Those who showed warning signs were referred for colonoscopy and those with any anatomical alterations were excluded. The patients received 10 g of psyllium and those who remained symptomatic after three weeks were referred for functional assessment with colonic transit time (CTT). Those who presented outlet obstruction in the colonic transit time were referred to anorectal manometry. Results: Of the 889 adult patients surveyed, 227 were included. Of the 216 who completed the study, 167 responded to primary treatment. Forty-nine underwent CTT. In these, 16 had normal colonic transit time and 33 were altered. In those with altered colonic transit time, eight had a pattern of colonic inertia and 25 had an obstruction pattern. The 25 patients with an outlet obstruction pattern underwent anorectal manometry. Eighteen had signs of paradoxical contracture of the puborectal muscle (PPRC) and seven did not. Conclusion: This study concluded that anorectal physiology exams contribute to the diagnosis of constipation, often changing the behavior. These exams should be performed whenever the patient does not respond to hygienic changes and fiber replacement.

Resumo Introdução: Os exames de fisiologia anorretal estão indicados nos pacientes que mantém sintomas refratários de constipação, porém uma sequência desejada de investigação permanece contraditória. Objetivo: Avaliar a influência do tempo de trânsito colônico e da manometria anorretal no diagnóstico da constipação crônica de adultos. Método: Estudamos os pacientes adultos de uma clínica privada em uma cidade do sul do Brasil, no período de 01 de Janeiro de 2009 a 31 de Dezembro de 2018 apresentando constipação. Aqueles que apresentassem sinais de alerta, eram encaminhados a colonoscopia e com qualquer alteração anatômica eram excluídos. Foram prescritos 10 g de Psyllium e aqueles que permaneceram sintomáticos após três semanas foram encaminhados à avaliação funcional com tempo de trânsito colônico (TTC). Os que apresentavam obstrução de saída ao tempo de trânsito colônico foram encaminhados a manometria anorretal. Resultados: Dos 889 pacientes adultos levantados, 227 foram incluídos. Dos 216 que concluíram o estudo, 167 responderam ao tratamento primário. Quarenta e nove realizaram TTC. Nestes, 16 tiveram tempo de trânsito colônico normal e 33 alterado. Naqueles com tempo de trânsito colônico alterado: oito tinham padrão de inércia colônica e 25, padrão de obstrução de saída. Os 25 pacientes com padrão de obstrução de saída foram submetidos à manometria anorretal. Dezoito tinham sinais de Contratura Paradoxal do músculo Puborretal (CPPR) e sete não. Conclusão: Concluímos que os exames de fisiologia anorretal contribuem para o diagnóstico da constipação, muitas vezes alterando a conduta. Estes exames devem ser realizados sempre que o paciente não responder as alterações higienodietéticas e a reposição de fibras.

Effect of polyethylene glycol versus lactulose on abdominal pain in children occult constipation: a randomized controlled study: un estudio controlado aleatorio / Efecto del polietilenglicol versus lactulosa sobre el dolor abdominal en el estreñimiento oculto en niños

Introduction and aim: Functional abdominal pain (FAP) is one of the major gastrointestinal complaints in childhood. Studies have reported occult constipation (OC) as one of the leading causes of abdominal pain. Recent researches have proposed laxatives as potent therapeutic targets for abdominal pain in patients with OC. However, no study has compared effect of poly ethylene glycol (PEG) and lactulose on occult constipation. Materials and methods: 51 patients aged 4 to 18 years with abdominal pain who had OC (defined as fecal impaction in abdominal X ray) were studied. Demographic and clinical data including age, sex, body weight, height, abdominal pain duration, abdominal pain rate and fecal odor were registered. They were randomly assigned to receive PEG (1gr/kg) or Lactulose (1cc/kg) for at least two weeks. All patients were reevaluated by pain measurement scale after at least two weeks of treatment. Results: It is indicated that the efficacy of PEG for reducing abdominal pain in OC was 48% while it was 37% for Lactulose. This study indicated that this efficacy is not affected significantly by sex and fecal odor, however this efficacy is influenced by age, body weight, abdominal pain duration and abdominal pain rate for both PEG and Lactulose. Conclusion: It could be concluded that PEG is a more efficient drug for treating abdominal pain in occult constipation than Lactulose and its optimum effect can be achieved in elder patients with more severe abdominal pain.

Introducción y objetivo: El dolor abdominal funcional (FAP) es una de las principales molestias gastrointestinales en la infancia. Los estudios han informado que el estreñimiento oculto (OC) es una de las principales causas de dolor abdominal. Investigaciones recientes han propuesto laxantes como objetivos terapéuticos potentes para el dolor abdominal en pacientes con OC. Sin embargo, ningún estudio ha comparado el efecto del polietilenglicol (PEG) y la lactulosa sobre el estreñimiento oculto. Materiales y métodos: Se estudiaron 51 pacientes de 4 a 18 años con dolor abdominal que tenían OC (definida como impactación fecal en rayos X abdominales). Se registraron datos demográficos y clínicos que incluyen edad, sexo, peso corporal, altura, duración del dolor abdominal, tasa de dolor abdominal y olor fecal. Fueron asignados aleatoriamente para recibir PEG (1 gr/kg) o lactulosa (1 cc/kg) durante al menos dos semanas. Todos los pacientes fueron reevaluados por la escala de medición del dolor después de al menos dos semanas de tratamiento. Resultados: Se indica que la eficacia de PEG para reducir el dolor abdominal en OC fue del 48% mientras que fue del 37% para la lactulosa. Este estudio indicó que esta eficacia no se ve afectada significativamente por el sexo y el olor fecal, sin embargo, esta eficacia está influenciada por la edad, el peso corporal, la duración del dolor abdominal y la tasa de dolor abdominal tanto para PEG como para lactulosa. Conclusión: Se podría concluir que el PEG es un fármaco más eficaz para tratar el dolor abdominal en el estreñimiento oculto que la lactulosa y que su efecto óptimo se puede lograr en pacientes mayores con dolor abdominal más severo.Palabras clave: dolor abdominal, estreñimiento oculto, polietilenglicol, lactulosa.

Combinations of laxatives and green banana biomass on the treatment of functional constipation in children and adolescents: a randomized study / Combinações de laxantes e biomassa de banana verde no tratamento de constipação funcional em crianças e adolescentes: estudo randomizado

Abstract Objectives: Evaluate the effect of combinations of green banana biomass and laxatives in children and adolescents with chronic constipation. Methods: This was a randomized study of 80 children and adolescents with functional constipation according to the Rome IV Criteria, who were divided into five groups: (1) green banana biomass alone; (2) green banana biomass plus PEG 3350 with electrolytes; (3) green banana biomass plus sodium picosulfate; (4) PEG 3350 with electrolytes alone; and (5) sodium picosulfate alone. Primary outcome measure was the reduction of the proportion of patients with Bristol Stool Form Scale ratings 1 or 2. Secondary outcome measures were: increase of the proportion of >3 bowel movements/week and reduction of the proportion of fecal incontinence, straining on defecation, painful defecation, blood in stool, abdominal pain, and decreased laxative doses. Results: On consumption of green banana biomass alone, a statistically significant reduction was observed in the proportion of children with Bristol Stool Form Scale rating 1 or 2, straining on defecation, painful defecation, and abdominal pain. Conversely, no reduction was observed in fecal incontinence episodes/week, blood in stool, and no increase was observed in the proportion of children with >3 bowel movements/week. The percentage of children who required decreased laxative dose was high when green banana biomass was associated with sodium picosulfate (87%), and PEG 3350 with electrolytes (63%). Green banana biomass alone and associated with laxatives was well tolerated, and no adverse effects were reported. Conclusion: Green banana biomass is advantageous as an adjunct therapy on functional constipation, mainly for reducing doses of laxatives.

Resumo Objetivos: Avaliar o efeito das combinações da biomassa de banana verde e laxantes em crianças e adolescentes com constipação crônica. Métodos: Estudo randomizado de 80 crianças e adolescentes com constipação funcional de acordo com os Critérios de Roma IV divididos em cinco grupos: 1) Somente biomassa de banana verde; 2) Biomassa de banana verde mais PEG 3350 com eletrólitos; 3) Biomassa de banana verde mais picossulfato de sódio; 4) PEG 3350 somente com eletrólitos e 5) somente picossulfato de sódio. O desfecho primário foi a redução da proporção de pacientes com as classificações 1 ou 2 da Escala de Bristol para Consistência de Fezes. Os desfechos secundários foram: aumento da produção de > 3 evacuações/semana e redução da proporção de incontinência fecal, esforço na defecação, defecação dolorosa, sangue nas fezes, dor abdominal e redução nas dose de laxantes. Resultados: No consumo somente de biomassa de banana verde há uma redução estatisticamente significativa na proporção de crianças com classificação 1 ou 2 da Escala de Bristol para Consistência de Fezes, esforço na defecação, defecação dolorosa e dor abdominal. Por outro lado, não houve redução nos episódios fecais/semana de incontinência, sangue nas fezes e nenhum aumento na proporção de crianças com > 3 evacuações/semana. O percentual de crianças que tiveram sua dose de laxante reduzida foi alto quando a biomassa de banana verde foi associada a picossulfato de sódio (87%) e PEG 3350 com eletrólitos (63%). A biomassa de banana verde sozinha e associada a laxantes foi bem tolerada e não houve efeitos adversos relatados. Conclusão: A biomassa de banana verde é vantajosa como uma terapia adjuvante na constipação funcional, principalmente na redução das doses de laxantes.

Eficiência e segurança de secretagogos intestinais para constipação crônica: uma revisão sistemática e meta-análise / Efficacy and safety of intestinal secretagogues for chronic constipation: a systematic review and meta-analysis

ABSTRACT BACKGROUND: Intestinal secretagogues have been tested for the treatment of chronic constipation and constipation-predominant irritable bowel syndrome. The class-effect of these type of drugs has not been studied. OBJECTIVE: To determine the efficacy and safety of intestinal secretagogues for the treatment of chronic constipation and constipation-predominant irritable bowel syndrome. METHODS: A computer-based search of papers from 1966 to September 2017 was performed. Search strategy consisted of the following MESH terms: intestinal secretagogues OR linaclotide OR lubiprostone OR plecanatide OR tenapanor OR chloride channel AND chronic constipation OR irritable bowel syndrome. Data were extracted as intention-to-treat analyses. A random-effects model was used to give a more conservative estimate of the effect of individual therapies, allowing for any heterogeneity among studies. Outcome measures were described as Relative Risk of achieving an improvement in the symptom under consideration. RESULTS: Database Search yielded 520 bibliographic citations: 16 trials were included for analysis, which enrolled 7658 patients. Twelve trials assessed the efficacy of intestinal secretagogues for chronic constipation. These were better than placebo at achieving an increase in the number of complete spontaneous bowel movements per week [RR 1.87 (1.24-2.83)], at achieving three or more spontaneous bowel movements per week [RR 1.56 (1.31-1.85)] and at inducing spontaneous bowel movement after medication intake [RR 1.49 (1.07-2.06)]. Similar results were observed when assessing the efficacy of intestinal secretagogues on constipation-predominant irritable bowel syndrome based on the results of six trials. CONCLUSION: Intestinal secretagogues are useful and safe therapeutic alternatives for the treatment of constipation-related syndromes.

RESUMO CONTEXTO: Os secretagogos intestinais têm sido testados para o tratamento da constipação crônica e síndrome do intestino irritável com constipação predominante. O efeito classe desses tipos de drogas ainda não foi estudado. OBJETIVO: Determinar a eficácia e a segurança de secretagogos intestinais para o tratamento da constipação crônica e síndrome do intestino irritável de constipação predominante. MÉTODOS: Realizada pesquisa baseada em banco de dados de trabalhos publicados entre 1966 e setembro de 2017. A estratégia de pesquisa consistia dos seguintes termos MeSH: secretagogos intestinais OU linaclotide OU lubiprostona OU plecanatide OU tenapanor OU canal de cloro E constipação crônica OU síndrome do intestino irritável. Os dados foram extraídos como análises de intenção de tratar. Um modelo de efeitos aleatórios foi usado para dar uma estimativa mais conservadora do efeito das terapias individuais, permitindo a qualquer heterogeneidade entre os estudos. Os desfechos foram descritos como risco relativo de alcançar uma melhoria no sintoma em consideração. RESULTADOS: A busca no banco de dados rendeu 520 citações bibliográficas: 16 ensaios foram incluídos para análise, que incluiu 7658 pacientes. Doze trabalhos avaliaram a eficácia de secretagogos intestinais para constipação crônica. Estes foram melhores do que placebo, alcançando um aumento no número de evacuações completas espontâneas por semana [RR 1,87 (1,24-2,83)], para a aquisição de três ou mais evacuações espontâneas por semana [RR 1,56 (1,31-1,85)] e na indução espontânea do movimento intestinal após a ingestão de medicação [RR 1,49 (1,07-2,06)]. Resultados semelhantes foram observados ao avaliar a eficácia de secretagogos intestinais na síndrome do intestino irritável de constipação predominante com base em resultados de seis ensaios. CONCLUSÃO: Os secretagogos intestinais são alternativas terapêuticas úteis e seguras para o tratamento de síndromes relacionadas à constipação.

Diagnosis and treatment of constipation: a clinical update based on the Rome IV criteria / Diagnóstico e tratamento da constipação crônica: atualização baseado nos critérios Roma IV

ABSTRACT The aim of this study was to evaluate the published professional association guidelines regarding the current diagnosis and treatment of functional intestinal constipation in adults and to compare those guidelines with the authors' experience to standardize actions that aid clinical reasoning and decision-making for medical professionals. A literature search was conducted in the Medline/PubMed, Scielo, EMBASE and Cochrane online databases using the following terms: chronic constipation, diagnosis, management of chronic constipation, Roma IV and surgical treatment. Conclusively, chronic intestinal constipation is a common condition in adults and occurs most frequently in the elderly and in women. Establishing a precise diagnosis of the physiopathology of functional chronic constipation is complex and requires many functional tests in refractory cases. An understanding of intestinal motility and the defecatory process is critical for the appropriate management of chronic functional intestinal constipation, with surgery reserved for cases in which pharmacologic intervention has failed. The information contained in this review article is subject to the critical evaluation of the medical specialist responsible for determining the action plan to be followed within the context of the conditions and clinical status of each individual patient.

RESUMO O objetivo deste trabalho foi avaliar os consensos de sociedade de especialistas e guidelines publicados sobre o diagnóstico e tratamento da constipação intestinal crônica em adultos, e confrontar com a experiência dos autores, a fim de padronizar condutas que auxiliem o raciocínio e a tomada de conduta do médico. Foi realizada busca na literatura científica, mais precisamente nas bases de dados eletrônicos Medline/Pubmed, Scielo, EMBASE and Cochrane, tendo sido utilizado os seguintes descritores: chronic constipation, diagnosis, management of chronic constipation, Roma IV and surgical treatment. Pode-se concluir que constipação crônica é condição comum em adultos, ocorrendo com maior frequência em idosos e mulheres. Identificar com precisão a fisiopatologia presente na constipação crônica funcional é complexo, requerendo a realização de testes funcionais nos casos refratários. O entendimento da motilidade intestinal e do mecanismo defecatório é importante para o manejo da constipação intestinal crônica funcional, sendo o tratamento cirúrgico indicado para casos selecionados, onde à abordagem medicamentosa não surtiu efeito. As informações contidas neste artigo de revisão devem ser submetidas à avaliação e à crítica do médico especialista responsável pela conduta a ser tomada, frente à sua realidade e ao estado clínico de cada paciente.

Effect of bisacodyl on rats with slow transit constipation

The effect of bisacodyl on the treatment of rats with slow transit constipation (STC) was studied. Forty-five female Wister rats were divided into control group, STC group, and STC bisacodyl group. The immunohistochemical method was used to determine interstitial cells of Cajal (ICC) and the expression of c-Kit protein. Body mass and the number of defecations were significantly decreased in the STC group compared with the control group on the 100th day after diphenoxylate administration, while dry weight of feces was significantly increased and the intestinal transit time was prolonged. There were significant differences in the number of defecations, dry weight of feces, and intestinal transit time among the three groups. The number of defecations was higher, dry weight of feces was lower, and intestinal transit time was shorter in the STC bisacodyl group compared to the STC group. In addition, ICC basement membrane dissolution occurred in the colon wall of the STC group. The connection between ICC and surrounding cells was destroyed, and the nucleus shrunken to different degrees. Moreover, c-Kit expression in the STC group was significantly lower than the control group. The connection between ICC and surrounding cells in the STC bisacodyl group was significantly stronger than the STC group, and the number of ICC and the expression of c-Kit were increased. Bisacodyl could reduce the severity of STC in rats by increasing the number of ICC and the expression of c-Kit.

Colonic Inertia: approach and treatment / Inércia Cólica: abordagem e tratamento

ABSTRACT Objective: Revision of the state of the art of the knowledge regarding pathophysiology, diagnosis and treatment of Colonic Inertia, which predominantly affects young women and has a significant socio-economic impact. Methods: A search was made in “colonic inertia”, “colon inertia” and “slow transit constipation” in PubMed database for articles of the last 5 years, in Portuguese or English with available abstract and full text. 59 articles and 2013 guidelines of the American Gastroenterological Association on constipation were included. Results: The pathophysiology is not completely elucidated and the reduction of the interstitial cells of Cajal is the most consistent histological finding. Diagnosis requires the exclusion of secondary causes of constipation and obstructed defecation syndrome, to which contribute several complementary diagnostic tests. Given the frequency of failure of the medical treatment, surgery is often the only possible option. Sacral nerve stimulation seems to be a promising therapeutical alternative. Conclusion: A deeper investigation of the pathophysiological mechanisms is fundamental to acquire a more global and integrated vision. Rigorous patient selection for each treatment and the discovery of new therapeutical targets may avoid the use of surgical therapies.

RESUMO Objetivo: Revisão do estado da arte do conhecimento da patofisiologia, diagnóstico e tratamento da Inércia Cólica, que afeta predominantemente mulheres jovens e tem um impacto socioeconómico significativo. Métodos: Pesquisou-se na base de dados PubMed por “colonic inertia”, “colon inertia” e “slow transit constipation” por artigos apenas dos últimos 5 anos, em português ou em inglês com resumo e texto completo disponíveis. Incluíram-se 59 artigos e as recomendações de 2013 da Associação Americana de Gastroenterologia para a obstipação. Resultados: A patofisiologia ainda não está completamente esclarecida, sendo que a redução das células intersticiais de Cajal constitui o achado histológico mais consistente. O diagnóstico requer a exclusão de causas secundárias de obstipação e de síndrome de obstrução defecatória, para o qual contribuem vários exames complementares de diagnóstico. Dada a frequência do insucesso do tratamento médico, a cirurgia é, muitas vezes, a única opção possível. A estimulação nervosa sagrada parece ser uma alternativa terapêutica promissora. Conclusão: É fundamental uma investigação mais profunda dos mecanismos patofisiológicos envolvidos para adquirir uma visão mais global e integrada. A seleção rigorosa de pacientes para cada tratamento e a descoberta de novos alvos terapêuticos poderão evitar a utilização de terapêuticas cirúrgicas.

Efeito do galactooligossacarídeo sobre os sintomas de constipação / Effect of 4′galactooligosaccharide on constipation symptoms

Resumo Objetivo A adição de frutooligossacarídeos e galactooligossacarídeos a fórmulas infantis pode diminuir a consistência fecal e aumentar a frequência das evacuações. O objetivo do presente estudo foi determinar o efeito do galactooligossacarídeo em crianças com constipação crônica. Métodos Entre 2010 e 2012, 20 pacientes constipados (4-16 anos), atendidos numa unidade básica de saúde, completaram ensaio clínico duplo cego, placebo-controlado e de delineamento crossover. Onze pacientes receberam galactooligossacarídeo (1,7 g) por 30 dias, seguidos por 15 dias de washout, e, após, placebo (maltodextrina) por 30 dias; nove pacientes receberam placebo 30 dias, seguidos de 15 dias de washout e 30 dias de galactooligossacarídeo (1,7 g). Os desfechos primários foram frequência semanal de evacuações, esforço evacuatório e consistência fecal, classificada por escala numérica elaborada para este estudo e compilada no primeiro, 15̊ e 30̊ dias de cada período de crossover. Análise estatística foi feita por método de análise de variância (Anova) para medidas repetidas. Resultados Intensidade dos sintomas nos grupos foi semelhante no início do estudo (p = 0,45). Durante a ingestão de galactooligossacarídeo constatou-se maior frequência de evacuações, p < 0,0001, menor dificuldade evacuatória, p < 0,0001 e diminuição da consistência fecal, p = 0,0014. Efeitos colaterais não foram referidos durante a ingestão do prebiótico. Conclusão Durante a ingestão de galactooligossacarídeo os sintomas clínicos da constipação em crianças e adolescentes foram significantemente aliviados.

Abstract Objective Fructooligosacharides and galactooligosacharides soften fecal bolus and increase frequency of depositions when added to infant formula. This study aimed to determine the effects of galactooligosaccharide in pediatric patients with chronic constipation. Methods From 2010 to 2012, 20 constipated patients (4-16 years of age) attended to at a primary healthcare unit were enrolled in a double-blinded, placebo-controlled crossover trial. Eleven children ingested galactooligosaccharide (1.7 g) for 30 days, followed by a 15-day washout period, and a 30-day period of placebo (maltodextrin). Nine patients ingested maltodextrin for 30 days, followed by 15-day washout period, and galactooligosaccharide (1.7 g) for 30 days. Constipation symptoms were considered as primary outcomes: bowel movements/week, straining during defecation, and stool consistency. Outcome symptoms were ranked according to a numerical scale elaborated for this study. Data were recorded at baseline, and on days 15 and 30 of each 30-day crossover period. Repeated-measures analysis of variance (ANOVA) was used to analyze symptoms along time. Results At baseline, there was no significant difference in symptoms severity between groups (p = 0.45). Galactooligosaccharide ingestion was related to increase of the bowel movement frequency, p < 0.0001; relief of defecation straining, p < 0.0001; and decrease in stool consistency, p = 0.0014, compared to placebo ingestion. Patients reported no side effects from galactooligosaccharide. Conclusion Galactooligosaccharide was effective at improving clinical symptoms in this group of constipated children.

Factors Predictive of Treatment-Emergent Adverse Events of Prucalopride: An Integrated Analysis of Four Randomized, Double-Blind, Placebo-Controlled Trials

BACKGROUND/AIMS: This integrated analysis aimed to identify the factors associated with the most frequently reported treatment-emergent adverse events (TEAEs) in Asian and non-Asian patients with chronic constipation (CC) who receive prucalopride or placebo over 12 weeks. METHODS: Pooled data from four randomized, double-blind, placebo-controlled, multicenter, phase III studies (NCT00488137, NCT00483886, NCT00485940, and NCT01116206) on patients treated with prucalopride 2 mg or placebo were analyzed. The associations between predictors and TEAEs were evaluated based on a logistic regression model. RESULTS: Overall, 1,821 patients (Asian, 26.1%; non-Asian, 73.9%) were analyzed. Prucalopride treatment was significantly associated with diarrhea, headache, and nausea (p<0.001), but not with abdominal pain, compared with placebo. Differences in the prevalence of TEAEs between prucalopride and placebo decreased greatly after the first day of treatment. Compared with non-Asians, Asians were more likely to experience diarrhea and less likely to develop abdominal pain, headache, and nausea. Prior laxative use, CC duration, and body weight were not predictive of any of these TEAEs. CONCLUSIONS: Prucalopride treatment was positively associated with diarrhea, headache, and nausea. Asian patients tended to have a higher frequency of diarrhea but lower frequencies of headache, abdominal pain, and nausea compared with non-Asians.

Factors Predictive of Treatment-Emergent Adverse Events of Prucalopride: An Integrated Analysis of Four Randomized, Double-Blind, Placebo-Controlled Trials

BACKGROUND/AIMS: This integrated analysis aimed to identify the factors associated with the most frequently reported treatment-emergent adverse events (TEAEs) in Asian and non-Asian patients with chronic constipation (CC) who receive prucalopride or placebo over 12 weeks. METHODS: Pooled data from four randomized, double-blind, placebo-controlled, multicenter, phase III studies (NCT00488137, NCT00483886, NCT00485940, and NCT01116206) on patients treated with prucalopride 2 mg or placebo were analyzed. The associations between predictors and TEAEs were evaluated based on a logistic regression model. RESULTS: Overall, 1,821 patients (Asian, 26.1%; non-Asian, 73.9%) were analyzed. Prucalopride treatment was significantly associated with diarrhea, headache, and nausea (p<0.001), but not with abdominal pain, compared with placebo. Differences in the prevalence of TEAEs between prucalopride and placebo decreased greatly after the first day of treatment. Compared with non-Asians, Asians were more likely to experience diarrhea and less likely to develop abdominal pain, headache, and nausea. Prior laxative use, CC duration, and body weight were not predictive of any of these TEAEs. CONCLUSIONS: Prucalopride treatment was positively associated with diarrhea, headache, and nausea. Asian patients tended to have a higher frequency of diarrhea but lower frequencies of headache, abdominal pain, and nausea compared with non-Asians.

Avaliação comparativa de eficácia clínica e tolerabilidade para a combinação de Cassia fistula e Senna alexandrina Miller em pacientes com constipação intestinal funcional crônica / Comparative evaluation of clinical efficacy and tolerability for the combination of Cassia fistula and Senna alexandrina Miller in patients with chronic functional constipation

JUSTIFICATIVA E OBJETIVO: A constipação intestinal é um problema crônico, frequente, que afeta a Qualidade de Vida dos indivíduos. O objetivo deste estudo foi avaliar a eficácia clínica e a tolerabilidade da composição Cassia fistula e Senna alexandrina Miller, na apresentação geleia sem açúcar, em pacientes diagnosticados com constipação intestinal funcional crônica. MÉTODOS: Estudo envolvendo 96 voluntários com diagnóstico de constipação intestinal funcional crônica, conforme Critérios de Roma III, randomizados em grupos ativo e placebo. A avaliação da eficácia primária foi realizada por meio da frequência média de evacuações, consistência média das fezes e melhora global da constipação. Foram realizadas ainda avaliações secundárias, como número de dias seguidos sem evacuação, proporção de evacuações com dor, esforço, sensação de evacuação incompleta ou bloqueio, uso de manobras manuais, sujeitos de pesquisa que aderiram às recomendações de hábitos de vida, uso de fármacos de resgate e melhora da constipação segundo avaliação do sujeito de pesquisa. RESULTADOS: A proporção de sujeitos da pesquisa que apresentou melhora global da constipação foi de 65,1% no grupo ativo e de 22,0% grupo placebo (p<0,0001). Para a maioria das avaliações secundárias de eficácia, o grupo ativo apresentou melhor desempenho quando comparado ao grupo pesquisa. De acordo com a avaliação dos sujeitos de pesquisa sobre a melhora da constipação, o grupo ativo apresentou melhor desempenho do que o grupo pesquisa. Quanto à segurança, os dois grupos apresentaram resultados similares. CONCLUSÃO: A geleia sem açúcar composta de Cassia fistula e Senna alexandrina Miller apresentou um comportamento seguro e eficaz, sendo uma alternativa para tratamento da constipação intestinal funcional crônica.

BACKGROUND AND OBJECTIVE: Intestinal constipation is a chronic and frequent problem that affects Quality of Life. The aim of this study was to evaluate the efficacy and tolerability of the composition Cassia fistula and Senna alexandrina Miller, as sugar free jelly, in patients diagnosed with chronic functional constipation. METHODS: We evaluated 96 volunteers diagnosed with functional constipation according to Rome III criteria. Volunteers were randomized into active and placebo groups. Primary efficacy endpoint was evaluated by mean frequency of bowel movements, consistency of stools and global improvement of constipation. Secondary endpoints were evaluated, such as number of days without bowel movements, proportion of bowel movements with pain, with strain, sensation of incomplete or blocked bowel movement, use of, manual maneuvers to facilitate defecation, subjects who adhered to the diet recommendation, use of rescue medication, and level of constipation improvement, according to subject evaluation. RESULTS: Global improvement of constipationwas observed in 65.1% of subjects enrolled in active group versus 22% in placebo group (p<0.0001). For most secondary efficacy evaluations, the active group performed better when compared to placebo group. According to the evaluation of the subjects on the improvement of constipation, the active group performed better than the placebo group. As for security, the two groups showed similar results. CONCLUSION: Cassia fistula and Senna alexandrina Miller sugar free jelly demonstrated to be safe and effective and it can be used as an alternative for the treatment of functional constipation.