Efficacy of atypical antipsychotics in the treatment of fecal incontinence in children and adolescents: a randomized clinical trial.

OBJECTIVES: Functional retentive overflow incontinence (retentive FI) is the most common cause of fecal soiling in children. Based on the clinical experiences, the treatment of retentive FI in patients with comorbid psychiatric disorders was accelerated when Risperidone was used as treatment for their psychiatric comorbidities; therefore, this study was conducted to evaluate the effect of risperidone in the treatment of retentive FI in children and adolescents. METHODS: In this double-blind, randomized, placebo-controlled trial, 140 patients aged 4-16 years eligible for the study were randomized into two groups, receiving either 0.25-0.5 mg of Risperidone syrup (n = 70) or maltodextrin syrup (placebo group, n = 70) every 12 h daily for 12 weeks. Sociodemographic data, including age, sex, weight, height, BMI, BMI z-score, and socioeconomic status, was recorded, and the number of nocturnal FI, diurnal FI, and painful defecations was measured. RESULTS: 136 participants (69 on Risperidone and 67 on placebo) were included in the study. Mean age of participants in the intervention and placebo groups were 7.2 ± 2.4 years and 8.0 ± 3.1 years, respectively. The mean number of nocturnal FI (Ptrend=0.39) and diurnal FI (Ptrend=0.48) in patients without psychiatric comorbidities, and the number of painful defecations for participants with and without psychiatric comorbidities (P = 0.49, P = 0.47, respectively) were not significantly different between the groups, but a significant effect was observed in diurnal FI after Risperidone treatment in patients with psychiatric comorbidities (P < 0.001). CONCLUSION: Risperidone, when used along with other non-pharmacological interventions, may be helpful in treating FI in pediatric patients with psychiatric comorbidities.

Efficacy and safety of probiotics and synbiotics for functional constipation in children: A systematic review and meta-analysis of randomized clinical trials.

BACKGROUND & AIM: We aimed to evaluate the efficacy and safety of probiotics and synbiotics in childhood functional constipation. METHODS: PubMed, Embase, Cochrane Library, ClinicalTrials.gov, and the International Clinical Trials Registry Platform (ICTRP) were searched up to June 2023. Randomized controlled trials involving children diagnosed with FC with Rome III/IV criteria were included. Treatment success, defecation frequency, stool consistency, painful defecation, fecal incontinence, and adverse events were assessed as outcomes. Odds ratios (ORs) and standard mean difference (SMD) with 95% confidence intervals (CIs) were calculated for dichotomous and continuous variables as appropriate. Cochrane risk-of-bias tool version 2 assessed the risk of bias. RESULTS: Seventeen RCTs with 1504 patients were included. Compared to placebo, probiotics significantly improved defecation frequency (SMD 0.40, 95% CI 0.10 to 0.70, I2 = 0%) and fecal incontinence (OR 0.53, 95% CI 0.29 to 0.96, I2 = 0%). However, it did not significantly improve treatment success, painful defecation, and abdominal pain. Probiotics, as add-on therapy, failed to yield a significant difference in treatment success (OR 0.82, 95% CI 0.15 to 4.48, I2 = 52%), defecation frequency (SMD 0.13, 95% CI -0.13 to 0.39, I2 = 0%), defecation consistency (SMD -0.01, 95% CI -0.40 to 0.38, I2 = 1%), fecal incontinence (OR 0.95, 95% CI 0.48 to 1.90, I2 = 0%), and abdominal pain (OR, 0.60, 95% CI 0.24 to 1.53, I2 = 0%) versus laxatives monotherapy. Synbiotics plus laxatives showed no significant effect on defecation frequency (SMD -0.57; 95% CI -1.29 to 0.14, I2 = 74%) and painful defecation (OR, 3.39; 95% CI 0.74 to 15.55, I2 = 0%) versus laxatives alone. CONCLUSIONS: Current evidence did not advocate using probiotics and synbiotics in treating functional constipation in children. At this time, the effects of strain-specific probiotics, probiotics mixtures, and the optimal doses and treatment durations of the probiotics and synbiotics were unclear. Additional rigorous evidence is required to evaluate and establish the effectiveness and safety of probiotics and synbiotics for childhood functional constipation. PROSPERO ID: CRD42020195869.

An association between incontinence and antipsychotic drugs: A systematic review.

To date, due to the increasing prevalence of psychiatric diseases, the use of antipsychotic drugs has expanded. One of the proven side effects of these drugs is incontinence. Treatment of this complication improves the quality of life in these patients, increases self-confidence, and betters cope with their psychiatric illness. The exact mechanism of this side effect is not fully understood, but various methods have been used experimentally to deal with it. Strategies such as behavior therapy, discontinuation or change of drugs, reducing the dose of drugs, and adding drugs with less incontinence have been used. Each of these methods and studies has different results that need to be summarized to make optimal use of them. Since most of these reports are case reports with a low statistical population, our study has systematically reviewed these studies to find a comprehensive model to deal with this complication.

Impact of bowel movement condition on immune checkpoint inhibitor efficacy in patients with advanced non-small cell lung cancer.

BACKGROUND: Cancer immunotherapy is under development as a promising alternative strategy for treating advanced non-small cell lung cancer (NSCLC). However, the development of novel biomarkers to optimize the use of immune checkpoint inhibitors (ICIs) is still ongoing. Gut microbiota are known to regulate a host's immunity and are associated with the response to ICIs in melanoma. Therefore, we analyzed the association between ICI treatment efficacy and bowel movement condition in patients with NSCLC. METHODS: This retrospective study analyzed patients with advanced NSCLC who were treated with ICIs between December 2015 and March 2018 at University Hospital Kyoto Prefectural University of Medicine in Kyoto, Japan. The association between stool abnormalities and ICI efficacy was investigated. We defined patients with constipation or those who used a laxative as the stool abnormality group. RESULTS: We retrospectively enrolled 40 patients with advanced NSCLC who were treated with ICIs. The median age was 69.5 years; 20 patients had a stool abnormality and 20 patients did not. The disease control rates were lower in NSCLC patients with stool abnormalities than in those without stool abnormalities (20% vs. 77.8%, respectively; P = 0.0016). The time to treatment failure with ICI treatment was shorter in NSCLC patients with stool abnormalities compared with those without stool abnormalities (P = 0.003; odds ratio, 3.09; 95% confidence interval 1.41-6.78). CONCLUSION: Stool abnormality might be a predictive biomarker for the clinical benefit of ICI treatment in patients with NSCLC. Further investigations are warranted to validate our findings.

REGOSARC: Regorafenib versus placebo in doxorubicin-refractory soft-tissue sarcoma-A quality-adjusted time without symptoms of progression or toxicity analysis.

BACKGROUND: In a placebo-controlled, randomized phase 2 trial (ClinicalTrials.gov identifier NCT01900743), regorafenib improved progression-free survival (PFS) for patients with doxorubicin-pretreated advanced nonadipocytic sarcoma. A quality-adjusted time without symptoms of progression or toxicity (Q-TWiST) post hoc exploratory analysis was applied to provide an integrated measure of its clinical benefit. METHODS: In the base-case analysis, each patient's overall survival (OS) was partitioned into 3 mutually exclusive health states: the time with a grade 3 or 4 adverse event (TOX), the time without symptoms of disease or grade 3 or 4 toxicity from treatment, and the time after tumor progression or relapse. The time spent in each state was weighted with a health-state utility associated with that state and was summed to calculate the Q-TWiST. The stability of the base-case analysis was explored with several sensitivity analyses. RESULTS: In nonadipocytic sarcoma, the PFS was (4.0 months [2.6-5.5 months] with regorafenib vs 1.0 month [0.9-1.8 months] with a placebo; hazard ratio, 0.36 [0.25-0.53]; P < .0001); the OS was 13.4 months (8.6-17.3 months) with regorafenib and 9.0 months (6.8-12.5 months) with a placebo (hazard ratio, 0.67 [0.44-1.02]). With the classic definition of TOX (including all grade 3 and 4 clinical adverse events), the Q-TWiSTs were 8.0 months (7.0-9.0 months) with regorafenib and 5.7 months (4.9-6.4 months) with a placebo (P < .001). CONCLUSIONS: For patients with doxorubicin-pretreated soft-tissue sarcoma, regorafenib significantly improved quality-adjusted survival in comparison with a placebo. Cancer 2017;123:2294-2302. © 2017 The Authors. Cancer published by Wiley Periodicals, Inc. on behalf of American Cancer Society. This is an open access article under the terms of the Creative Commons Attribution NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.

Menopausal Hormone Therapy Is Associated With Increased Risk of Fecal Incontinence in Women After Menopause.

BACKGROUND & AIMS: Low estrogen levels can contribute to development of fecal incontinence (FI) in women after menopause by altering neuromuscular continence mechanisms. However, studies have produced conflicting results on the association between menopausal hormone therapy (MHT) and risk of FI. METHODS: We studied the association between MHT and risk of FI among 55,828 postmenopausal women (mean age, 73 years) who participated in the Nurses' Health Study, were enrolled since 2008, and with no report of FI. We defined incident FI as a report of at least 1 liquid or solid FI episode per month during 4 years of follow-up from self-administered, biennial questionnaires administered in 2010 and 2012. We used Cox proportional hazard models to calculate multivariate-adjusted hazard ratios and 95% confidence intervals (CIs) for FI risk in women receiving MHT, adjusting for potential confounding factors. RESULTS: During more than 185,000 person-years of follow-up, there were 6834 cases of incident FI. Compared with women who never used MHT, the multivariate hazard ratio for FI was 1.26 (95% CI, 1.18-1.34) for past users of MHT and 1.32 (95% CI, 1.20-1.45) for current users. The risk of FI increased with longer duration of MHT use (P trend ≤ .0001) and decreased with time since discontinuation. There was an increased risk of FI among women receiving MHT that contained a combination of estrogen and progestin (hazard ratio, 1.37; 95% CI, 1.10-1.70) compared with estrogen monotherapy. CONCLUSIONS: Current or past use of MHT was associated with a modestly increased risk of FI among postmenopausal women in the Nurses' Health Study. These results support a potential role for exogenous estrogens in the impairment of the fecal continence mechanism.

Botulinum Toxin Injection for Treatment of Chronic Anal Fissure: Is There Any Dose-Dependent Efficiency? A Meta-Analysis.

BACKGROUND: Chronic anal fissure (CAF) is a linear split of the anoderm. The minimally invasive management of CAF such as botulinum toxin (BT) injection is recommended. However, the exact efficient dose of BT, number of injections per session and the injection sites are still debatable. The aim of this analysis was to assess the dose-dependent efficiency of botulinum toxin injection for CAF. METHODS: PubMed and Web of Science databases were searched for terms: "anal fissure" AND "botulinum toxin." Studies published between October 1993 and May 2015 were included and had to meet the following criteria: (1) chronic anal fissure, (2) prospective character of the study, (3) used simple BT injection without any other interventions and (4) no previous treatment with BT. RESULTS: A total of 1577 patients from 34 prospective studies used either Botox or Dysport formulations were qualified for this meta-analysis. A total number of BT units per session ranged from 5 to 150 IU, whereas the efficiency across analyzed studies ranged from 33 to 96 %. Surprisingly, we did not observe a dose-dependent efficiency (Spearman's rank correlation coefficient, ρ = 0.060; p = 0.0708). Moreover, there were no BT dose-dependent postoperative complications or fecal incontinence and significant difference in healing rates compared BT injection into the anal sphincter muscles. CONCLUSIONS: BT injection has been an accepted method for the management of CAF. Surprisingly, there is no dose-dependent efficiency, and the postoperative incontinence rate is not related to the BT dosage regardless the type of formulation of botulinum neurotoxin used. Moreover, no difference in healing rate has been observed in regard to the site and number of injections per session.

Polyethylene Glycol 3350 and Docusate Sodium Compared With Docusate Sodium Alone After Urogynecologic Surgery: A Randomized Controlled Trial.

OBJECTIVE: To compare time to first bowel movement and additional gastrointestinal outcomes between women receiving polyethylene glycol 3350 (PEG3350) and docusate sodium and docusate sodium alone after urogynecologic surgery. METHODS: Participants received twice-daily 100 mg docusate sodium and were randomized to daily 1) PEG3350 or 2) inert placebo for 5 days after urogynecologic surgery. They completed bowel diaries, Bristol stool scale, validated Patient Assessment of Constipation Symptom Questionnaire, and Patient Assessment of Constipation Quality-of-Life Questionnaire preoperatively and 1 week after surgery. Our primary outcome was time to first bowel movement after surgery. To detect a 1-day difference in time to first bowel movement (4 compared with 3 days), 63 participants were needed in each group. RESULTS: From September 2012 through March 2015, 145 women were randomized and 131 (90%) analyzed: 66 received PEG3350, and 65 received placebo. Polyethylene glycol 3350 did not significantly reduce time to first bowel movement after surgery compared with placebo (2.77 days [interquartile range 1.86-3.40] compared with 2.92 days [interquartile range 1.85-4.02] P=.25). Women in the PEG3350 group were less likely to take additional laxatives postoperatively, and the PEG3350 group was more adherent to the study drug regimen. Questionnaire scores, fecal incontinence, and urgency were similar between groups. CONCLUSION: In women taking routine docusate sodium after urogynecologic surgery, adding PEG3350 postoperatively did not reduce time to first bowel movement. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, https://clinicaltrials.gov, NCT01691742.

Utilizing Cerebral Perfusion Scan and Diffusion-tensor MR Imaging to Evaluate the Effect of Hyperbaric Oxygen Therapy in Carbon Monoxide-induced Delayed Neuropsychiatric Seqeulae- A Case Report and Literature Review.

PURPOSE: Detection of regional cerebral blood flow (rCBF) and/or brain magnetic resonance imaging (MRI) has been used to investigate functional defect of brain caused by carbon monoxide (CO) poisoning. In this report, we attempted to demonstrate the correlation of changes in brain singlephoton emission computed tomography (SPECT) and diffusion-tensor MR image (DTI) with functional improvement of severe delayed neuropsychiatric sequelae (DNS) after CO intoxication during the treatment of hyperbaric oxygen therapy (HBOT). CASE REPORT: The patient had normal activities of daily life after he recovered from acute CO poisoning. One month later, he presented symptoms of declined cognitive functioning, aphasia, apraxia, dysphagia, muscle rigidity, urine and fecal incontinence. After one course of HBOT, these symptoms improved significantly and the patient could regain most of his previous functioning. The patient's improvement was evidenced by increased rCBF in Brodmann areas 7, 8, 11 and 40, as well as higher mean fractional anisotropy (FA) value of DTI. CONCLUSION: Although the efficacy of HBOT in DNS patients is still needed to be evaluated in large clinical study, these data suggest that HBOT may be the choice to improve DNS efficiently and shorten the duration of suffering with favorable outcome.

Risperidone-associated urinary incontinence in patients with autistic disorder with mental retardation.

We report several cases in which patients with autistic disorder with mental retardation who received risperidone experienced urinary incontinence. We retrospectively investigated the medical records of patients housed in facilities for patients with autistic disorder with mental retardation. Those who had undergone a medical examination at a hospital in Tokyo from April 1999 to March 2009 were included in the study.Retrospective data were gathered including age, sex, IQ, birth weight, dosage of risperidone, urinary density, as well as existence of urinary and fecal incontinence. We divided the participants into those who did and did not experience urinary incontinence after taking risperidone and compared the 2 groups. Risperidone had been prescribed to 35 patients. In spite of the fact that no patient had a history of urinary incontinence, 14 patients experienced urinary incontinence after receiving risperidone. Moreover, 4 of these 14 patients also had fecal incontinence. Among the variables we examined, the only significant difference between groups was in sex, with significantly more women experiencing incontinence compared with men. When the dose of risperidone was reduced or the patients switched to other drugs, urinary incontinence of the patients improved.Hence, risperidone may have a casual relationship with urinary incontinence. Further research is needed to understand the pathophysiology of possible effect.

Botulinum toxin type A (BOTOX) for refractory myofascial pelvic pain.

OBJECTIVE: To assess intralevator botulinum toxin type A (Botox) injections for refractory myofascial pelvic pain with short tight pelvic floor. METHODS: Retrospective cohort study of all women with intralevator Botox injection (100-300 Units) from 2005 through 2010 for refractory myofascial pelvic pain. Primary outcomes were self-reported pain on palpation and symptom improvement. Secondary outcomes included postinjection complications and a second injection. Pain was assessed during digital palpation of the pelvic floor muscles using a scale of 0 to 10, with 10 being the worst possible pain. Follow-up occurred at less than 6 weeks after injection and again at 6 weeks or more. Data are presented as median (interquartile range) or proportion. RESULTS: Thirty-one patients met eligibility criteria; 2 patients were lostto follow-up and excluded. The median age was 55.0 years (38.0-62.0 years). Before Botox injection, the median pain score was 9.5 (8.0-10.0). Twenty-nine patients (93.5%) returned for the first follow-up visit; 79.3% reported improvement in pain, whereas 20.7% reported no improvement. The median pain with levator palpation was significantly lower than before injection (P<0.0001). Eighteen women (58.0%) had a second follow-up visit with a median pain score that remained lower than before injection (P<0.0001). Fifteen (51.7%) women elected to have a second Botox injection; the median time to the second injection was 4.0 months (3.0-7.0 months). Three (10.3%) women developed de novo urinary retention, 2 patients (6.9%) reported fecal incontinence, and 3 patients (10.3%) reported constipation and/or rectal pain; all adverse effects resolved spontaneously. CONCLUSIONS: Intralevator injection of Botox demonstrates effectiveness in women with refractory myofascial pelvic pain with few self-limiting adverse effects.

Evaluation of treatment continuation with alosetron by IBS-D severity criteria.

OBJECTIVES: This article evaluates the characteristics and treatment patterns of female patients with severe diarrhea-predominant irritable bowel syndrome (IBS-D) who were treated with alosetron under a risk management program. METHODS: Patients prescribed alosetron (2002-2009) and who voluntarily enrolled in the follow-up study were evaluated. Questionnaires were administered at baseline, Wk 5, Wk 10, and quarterly thereafter for ≤1 year. Subgroup analyses were conducted in female patients with IBS-D ≥6 months, stratified by IBS-D severity criteria met (1-3) from the alosetron prescribing information (treatment recommended in female patients meeting ≥1 severity criterion). The voluntary and observational nature of the study are potential limitations, such that eligible patients in the clinical practice setting may have had more severe IBS-D, possibly representing a more motivated and homogeneous subpopulation of patients than the broader IBS-D population. RESULTS: A total of 7841 patients enrolled in the study; 92.4% were adult females; 79.4% (n = 6229) met label criteria. Mean follow-up time was ∼10.3 months; 50.3% completed 1 year. Of the 6229 female patients, 76.9% met 3/3 severity criteria; 21.5% met 2/3 severity criteria; 1.4% met 1/3 severity criteria. The most common complaint was restriction of daily activities, followed by accidents/fecal incontinence, and stomach cramps/bloating. One-year treatment continuation was ≥64% across IBS-D severity groups. CONCLUSIONS: One-year treatment continuation with alosetron was high, irrespective of the number of IBS-D severity criteria met. Restriction of daily activities was the primary indicator of disease severity. These findings demonstrate that alosetron continues to be safely and effectively used under the risk management program, and appears to provide long-term benefit in appropriate patients with IBS-D.

Adverse events and health status following botulinum toxin type A injections in children with cerebral palsy.

AIM: The aim of this study was to assess changes in health status before and after, as well as adverse events after, botulinum toxin type A (BoNT-A) injections in children with cerebral palsy (CP). METHOD: A total of 334 children (190 male; 144 female) aged 1y 6mo to 19y 4mo (mean 9y 2mo, SD 4y) with CP who were undergoing BoNT-A injections (596 injection courses in total) were clinically audited over a 16-month period. Of the 334 children, 62 were classified at Gross Motor Function Classification System (GMFCS) level I, 52 of whom had unilateral CP and 10 of whom had bilateral CP. Eighty-six children were classified at GMFCS level II, 39 of whom had unilateral CP and 47 of whom had bilateral CP. Forty-four children were classified at GMFCS level III, two of whom had unilateral CP and 42 of whom had bilateral CP. Sixty-six of the 334 children were classified at GMFCS level IV and 76 as level V. All the children classified as level IV or V had bilateral involvement. The health status of the children in the month before and a prospective audit of health status and adverse events in the month after BoNT-A injections were examined in order to assess the effects of the toxin. RESULTS: The data gathered for the month before administration of BoNT-A indicated that children with CP had significant background morbidities. After injection of BoNT-A, adverse events occurred in 23.2% of children. All adverse events were temporary and there were no deaths. INTERPRETATION: The results of this audit indicate that there is insufficient evidence to warrant restriction of the administration of BoNT-A in children with CP at any GMFCS level in our service.

Sacral neuromodulation for the treatment of faecal incontinence in a patient with organophosphate poisoning.

Faecal incontinence is a debilitating condition. Sacral neuromodulation may have a role in the treatment of faecal incontinence. We report a case of faecal incontinence secondary to chronic organophosphate poisoning, which was successfully treated with sacral neuromodulation. The patient's faecal incontinence and quality of life improved significantly.

Systemic adverse events following botulinum toxin A therapy in children with cerebral palsy.

AIM: We studied the incidence of incontinence and respiratory events in children with cerebral palsy who received injections of botulinum toxin A (BoNT-A). METHOD: We used multivariable logistic regression to investigate relationships between (BoNT-A) dose, Gross Motor Function Classification System (GMFCS) level, and the incidence of bladder or bowel incontinence, unplanned hospital admission, emergency department consultation or prescription of antibiotics for respiratory symptoms, and diagnosis of upper respiratory tract infection. RESULTS: Of 1980 injection episodes in 1147 children (mean age 4y 7mo, SD 1y 10mo, range 9mo-23y), 488 (25%) were in children with unilateral involvement and 1492 (75%) in children with bilateral involvement. At the time of injection 440 (22.2%) of children were at GMFCS level I, 611 (30.9%) were at level II, 330 (16.7%) were at level III, 349 (17.6%) were at level IV, and 250 (12.6%) were at level V. The incidence of serious adverse events was low, with 19 episodes of incontinence (1% of injection episodes) and 25 unplanned hospital admissions due to respiratory symptoms (1.3%). Incontinence typically resolved spontaneously 1 to 6 weeks after injection. The incidence of adverse events was associated with GMFCS level and dose of BoNT-A. INTERPRETATION: The incidence of serious adverse events was low but suggests systemic spread as well as a procedural effect. We recommend reviewing upper dose limits for children at all GMFCS levels, particularly those at levels IV and V with a history of aspiration and respiratory disease. In these children, alternatives to mask anaesthesia may be particularly important.