Randomized Placebo-Controlled Phase 3 Trial of Vibrating Capsule for Chronic Constipation.

BACKGROUND & AIMS: Despite therapeutic advances, effective treatments for chronic constipation remain an unmet need. The vibrating capsule is a nonpharmacologic, orally ingested, programmable capsule that vibrates intraluminally to induce bowel movements. We aimed to determine the efficacy and safety of the vibrating capsule in patients with chronic constipation. METHODS: We conducted a phase 3, double-blind, placebo-controlled trial of patients with chronic constipation, who were randomized to receive either a vibrating or placebo capsule, once daily, 5 days a week for 8 weeks. The primary efficacy end points were an increase of 1 or more complete spontaneous bowel movements per week (CSBM1 responder) or 2 or more CSBMs per week (CSBM2) from baseline during at least 6 of the 8 weeks. Safety analyses were performed. RESULTS: Among 904 patients screened, 312 were enrolled. A greater percentage of patients receiving the vibrating capsule achieved both primary efficacy end points compared with placebo (39.3% vs 22.1%, P = .001 for CSBM1; 22.7% vs 11.4% P = .008 for CSBM2). Significantly greater improvements were seen with the vibrating capsule for the secondary end points of straining, stool consistency, and quality-of-life measures compared with placebo. Adverse events were mild, gastrointestinal in nature, and similar between groups, except that a mild vibrating sensation was reported by 11% of patients in the vibrating capsule group, but none withdrew from the trial. CONCLUSIONS: In patients with chronic constipation, the vibrating capsule was superior to placebo in improving bowel symptoms and quality of life. The vibrating capsule was safe and well tolerated. (Clinical trials.gov, Number: NCT03879239).

Comparative profiles of lubiprostone, linaclotide, and elobixibat for chronic constipation: a systematic literature review with meta-analysis and number needed to treat/harm.

OBJECTIVE: To comprehensively evaluate the efficacy, safety, patient symptoms, and quality-of-life (QoL) of lubiprostone, linaclotide, and elobixibat as treatment for chronic constipation (CC). DESIGN: Systematic literature review (SLR) and meta-analysis (MA). Literature searches were conducted on PubMed and Embase using the Ovid platform. METHODS: SLR including randomized controlled trials (RCTs) and observational studies was conducted to identify the overall efficacy and safety of lubiprostone, linaclotide, and elobixibat. Thereafter, MA was performed using only RCTs. The number needed to treat (NNT) and number needed to harm (NNH) analyses were additionally conducted. PRIMARY AND SECONDARY OUTCOME MEASURES: The primary outcome was efficacy regarding change in spontaneous bowel movements. Secondary outcomes included safety, constipation-related symptoms, and QoL. RESULTS: Twenty-four studies met the inclusion criteria for the SLR: 17 RCTs, 4 observational studies, and 3 single-arm trials. Feasibility assessment for the MA resulted in 14 studies available for safety data analysis, and 8 available for efficacy analysis, respectively. Three drugs showed similar efficacy in the MA and NNT analysis. However, the NNH analysis revealed distinct safety profiles: lubiprostone, linaclotide, and elobixibat were linked to the highest risk of nausea, diarrhea, and abdominal pain, respectively. CONCLUSION: The current study provides an updated overview of the efficacy, safety, patient symptoms, and QoL of the three drugs with different mechanisms of action for CC treatment.The findings could help physicians adopt an individualized approach for treating patients with CC in clinical practice.

Capsules for the Diagnosis and Treatment of Gastrointestinal Motility Disorders- A Game Changer.

PURPOSE OF REVIEW: Over the last few decades, there have been remarkable strides in endoscopy and radiological imaging that have advanced gastroenterology. However, the management of neurogastroenterological disorders has lagged behind, in part handicapped by the use of catheter-based manometry that is both non-physiological and uncomfortable. The advent of capsule technology has been a game changer for both diagnostic and therapeutic applications. RECENT FINDINGS: Here, we discuss several capsule devices that are available or under investigation. There are three technologies that are FDA approved. Wireless motility capsule measures pH and pressure and provides clinically impactful information regarding gastric, small intestine and colonic transit, without radiation that has been demonstrated to guide management of gastroparesis, dyspepsia and constipation. Wireless ambulatory pH monitoring capsule is currently the gold standard for assessing gastroesophageal acid reflux. In the therapeutics arena, an orally ingested vibrating capsule has been recently FDA approved for the treatment of chronic constipation, supported by a robust phase 3 clinical trial which showed significant improvement in constipation symptoms and quality of life. There are several capsules currently under investigation. Smart capsule bacterial detection system and Capscan® are capsules that can sample fluid in the small or large bowel and provide microbiome analysis for detection of small intestinal bacterial (SIBO) or fungal overgrowth (SIFO). Another investigational gas sensing capsule analyzing hydrogen, CO2, volatile fatty acids and capsule orientation, can measure regional gut transit time and luminal gas concentrations and assess gastroparesis, constipation or SIBO. Therapeutically, other vibrating capsules are in development. Innovations in capsule technology are poised to transform our ability to investigate gut function physiologically, and non-invasively deliver targeted treatment(s), thereby providing both accurate diagnostic information and luminally-directed, safe therapy.

Plecanatide Improves Abdominal Bloating and Bowel Symptoms of Irritable Bowel Syndrome with Constipation.

BACKGROUND: Bloating is a bothersome symptom in irritable bowel syndrome with constipation (IBS-C). AIM: To evaluate plecanatide efficacy in patients with IBS-C stratified by bloating intensity. METHODS: Pooled phase 3 data (2 randomized, controlled IBS-C trials) from adults treated with plecanatide 3 mg or placebo for 12 weeks were analyzed. Patients were stratified post-hoc by baseline bloating severity (11-point scale: mild [≤ 5] and moderate-to-severe [> 5]). Assessments included change from baseline in bloating, abdominal pain, and complete spontaneous bowel movement (CSBM) frequency. Abdominal pain and bloating composite responders were defined as patients with ≥ 30% improvement from baseline in both bloating and abdominal pain at Week 12. RESULTS: At baseline, 1104/1436 patients with IBS-C (76.9%) reported moderate-to-severe bloating. In the moderate-to-severe bloating subgroup, plecanatide significantly reduced bloating severity versus placebo (least-squares mean change [LSMC]: - 1.7 vs - 1.3; P = 0.002), reduced abdominal pain (- 1.7 vs - 1.3; P = 0.006), and increased CSBM frequency (1.4 vs 0.8; P < 0.0001). In the mild bloating subgroup, significant improvements were observed with plecanatide versus placebo for abdominal pain (LSMC: - 1.3 vs - 1.0; P = 0.046) and CSBM frequency (2.0 vs 1.2; P = 0.003) but not bloating (- 0.9 vs - 0.8; P = 0.28). A significantly greater percentage of patients were abdominal pain and bloating composite responders with plecanatide versus placebo (moderate-to-severe bloating: 33.6% vs 26.8% [P = 0.02]; mild bloating: 38.4% vs 27.2% [P = 0.03]). CONCLUSION: Plecanatide treatment improved IBS-C abdominal and bowel symptoms, including in those who present with moderate-to-severe bloating.

Optimizing the Utility of Anorectal Manometry for Diagnosis and Therapy: A Roundtable Review and Recommendations.

BACKGROUND & AIMS: Anorectal manometry (ARM) is a comprehensive diagnostic tool for evaluating patients with constipation, fecal incontinence, or anorectal pain; however, it is not widely utilized for reasons that remain unclear. The aim of this roundtable discussion was to critically examine the current clinical practices of ARM and biofeedback therapy by physicians and surgeons in both academic and community settings. METHODS: Leaders in medical and surgical gastroenterology and physical therapy with interest in anorectal disorders were surveyed regarding practice patterns and utilization of these technologies. Subsequently, a roundtable was held to discuss survey results, explore current diagnostic and therapeutic challenges with these technologies, review the literature, and generate consensus-based recommendations. RESULTS: ARM identifies key pathophysiological abnormalities such as dyssynergic defecation, anal sphincter weakness, or rectal sensory dysfunction, and is a critical component of biofeedback therapy, an evidence-based treatment for patients with dyssynergic defecation and fecal incontinence. Additionally, ARM has the potential to enhance health-related quality of life and reduce healthcare costs. However, it has significant barriers that include a lack of education and training of healthcare providers regarding the utility and availability of ARM and biofeedback procedures, as well as challenges with condition-specific testing protocols and interpretation. Additional barriers include understanding when to perform, where to refer, and how to use these technologies, and confusion over billing practices. CONCLUSIONS: Overcoming these challenges with appropriate education, training, collaborative research, and evidence-based guidelines for ARM testing and biofeedback therapy could significantly enhance patient care of anorectal disorders.

Pathoetiology of Levator Ani Syndrome and Its Treatment With Translumbosacral Neuromodulation Therapy.

INTRODUCTION: The pathoetiology and treatment of levator ani syndrome (LAS) remain unclear. METHODS: We evaluated pathophysiology using translumbosacral motor-evoked potentials and anorectal manometry in patients with LAS and compared with healthy controls. A cohort underwent translumbosacral neuromodulation therapy (TNT). RESULTS: Lumbar and sacral motor-evoked potential latencies were prolonged in 32 patients with LAS compared with 31 controls ( P < 0.013), with higher prevalence of anal neuropathy ( P = 0.026). TNT improved anorectal pain ( P = 0.003) and neuropathy ( P < 0.02) in 13 patients with LAS. DISCUSSION: Patients with LAS demonstrate significant lumbosacral neuropathy that may cause anorectal pain. TNT improved anorectal pain and neuropathy, providing a novel therapeutic option.

Luminescent Pyrene-based Schiff base Receptor for Hazardous Mercury(II) Detection Demonstrated by Cell Imaging and Test Strip.

Qualitative and quantitative analysis of mercury at concentration levels as low as parts per billion (ppb) is a basic and practical concern. The vast majority of research in this field has centered on the development of potent chemosensor to monitor mercuric (Hg2+) ions. Mercury exists in three oxidation states, + 2, + 1 and 0, all of which are highly poisonous. In this study, (N1E,N2E)-N1,N2-bis(pyrene-1-ylmethylene)benzene-1,2-diamine (PAPM), a novel photoluminescent sensor based on pyrene platform was synthesized. Over the tested metal ions (Cd2+, Co2+, Cu2+, Mg2+, Mn2+, Ni2+, K+, Na+, Zn2+, Sr2+, Pb2+, Al3+, Cr3+ and Fe3+) the sensor responds only to Hg2+ by showing high selectivity and sensitivity. After treatment with mercuric ions at room temperature, the luminescence intensity of probe was quenched at 456 nm. The quenching of fluorescence intensity of probe upon addition of mercury is due to the effect of "turn-off" chelation enhanced quenching (CHEQ) by the formation of 1:1 complex. The ESI-MS spectrum and the Job's experimental results confirm the formation of 1:1 complex between PAPM and Hg2+. The detection limit and association constant of sensor for mercury is computed using fluorescence titration data and were found to be 9.0 × 10-8 M and 1.29 × 105 M-1 respectively. The practical application of sensor towards recognition of mercury(II) ions was explored through economically viable test strips and also using cell imaging studies.

Effect of Preoperative Carbohydrate Drink and Postoperative Chewing Gum on Postoperative Nausea and Vomiting in Patients Undergoing Day Care Laparoscopic Cholecystectomy: A Randomized Controlled Trial.

BACKGROUND: Postoperative nausea and vomiting (PONV) causes an unexpected prolonged hospital stay after ambulatory surgery. Novel measures such as preoperative loading of oral carbohydrates and postoperative chewing gum have recently gained momentum for postoperative recovery. This study evaluated the effects of preoperative carbohydrate loading and postoperative chewing gum (CG) on PONV after daycare laparoscopic cholecystectomy (LC). METHODS: A total of 100 patients were randomized to group A (preoperative carbohydrate loading with 200 ml of water with 25 g of carbohydrate and postoperative chewing gum (CG) when the patient responded to his/her name) and group B (standard care). The incidence of PONV and pain was assessed by using visual analogue scale. Quality of recovery (QoR-15) was assessed by using QoR15 questionnaire at 6 h, 24 h and 48 h after surgery. RESULTS: The incidence of PONV and pain was lower in group A; however, it was not significant (p > 0.05). The severity of PONV, pain and the need for rescue antiemetic was significantly lower in group A (p < 0.05). The episodes of PONV and required dose of antiemetic were less in group A. Group A also had a significantly higher QoR-15 score at all time points (p < 0.001). Preoperative dyspepsia was also noticed as a significant confounding predictor for postoperative vomiting. CONCLUSION: Preoperative carbohydrate drinks and early postoperative CG reduces the severity of PONV and requirement of antiemetics in patients undergoing LC. Hence, these simple measures can be used as a standard of care to optimize perioperative care in patients undergoing daycare surgery.

Saksenaea vasiformis infection: Extensive abdominal wall necrotizing fasciitis with systematic review and analysis of 65 cases.

INTRODUCTION: Saksenaea vasiformis is a rarely reported Mucorales causing mucormycosis in both immunocompromised and immunocompetent individuals. Due to few reported cases, the clinical characteristics and optimal management strategy for this rare agent are not clearly described. METHODS: We systematically reviewed Medline, EmBase and CINHAL for studies on S. vasiformis infections reported until 1 January 2022 and 57 studies (63 patients) were retrieved. Additionally, one more case of extensive abdominal wall necrotizing fasciitis managed by our team was also included. The clinical and demographic characteristics and outcomes were extracted and analysed. RESULTS: Out of the 65 included cases, the majority were reported from India (26.6%). The most common risk factors for infection were accidental trauma wounds (31.3%), health-care-related wounds (14.1%) and animal/insect bites (12.5%). Most common clinical presentation was subcutaneous mucormycosis (60.9%) followed by rhino-orbito cerebral mucormycosis (14%), necrotizing fasciitis (10%), disseminated infection (9.3%), pulmonary mucormycosis (3.2%) and osteomyelitis (1.6%). Mortality was observed in 24 (37.5%) patients and health care related injuries were significantly associated with higher mortality (p = .001). The use of posaconazole (p = .019) and the use of surgical management (p = .032) was associated with significantly better survival. DISCUSSION: In this study, we describe the largest compendium of mucormycosis due to S. vasiformis, which can be useful in increasing awareness regarding this rare Mucorales and guiding patient management.

Recognizing and Defining Occasional Constipation: Expert Consensus Recommendations.

Constipation is a common problem, affects 15% of the population, and is often self-diagnosed and self-managed. Over the past 3 decades, there have been significant advances in our understanding and management of chronic constipation, with the emerging recognition that occasional constipation (OC) is another subtype that falls outside current classifications. The purpose of this review was to describe the process of developing and proposing a new definition for OC based on expert consensus and taking into consideration the multifactorial nature of the problem such as alterations in bowel habit that include stool frequency and difficulty with stool passage, perception of the sufferer, duration of symptoms, and potential responsiveness to treatment. Leading gastroenterologists from 5 countries met virtually on multiple occasions through an online digital platform to discuss the problem of OC and recommended a practical, user-friendly definition: "OC can be defined as intermittent or occasional symptomatic alteration(s) in bowel habit. This includes a bothersome reduction in the frequency of bowel movements and/or difficulty with passage of stools but without alarming features. Bowel symptoms may last for a few days or a few weeks, and episodes may require modification of lifestyle, dietary habits and/or use of over-the-counter laxatives or bulking agents to restore a satisfactory bowel habit." Prospective studies are required to validate this definition and determine OC prevalence in the community. This review highlights current knowledge gaps and could provide impetus for future research to facilitate an improved understanding of OC and development of evidence-based management guidelines.

Bacterial overgrowth and lactose intolerance: how to best assess.

PURPOSE OF REVIEW: To provide an up-to-date review on the clinical assessment of two important gastrointestinal problems with overlapping symptomatology but diverse cause and testing methods. Small intestinal bacterial overgrowth (SIBO) is characterized by the presence of excess bacteria in the small intestine associated with bloating, distention, gas, and diarrhea. Lactose intolerance is caused by lactase enzyme deficiency in the small bowel mucosa leading to lactose malabsorption and symptoms of bloating, gas, and diarrhea. RECENT FINDINGS: SIBO is assessed by hydrogen/methane breath test using glucose as a substrate and/or small bowel aspirate and culture but these tests have shortcomings. Consequently, several new diagnostic techniques, including novel capsule technologies and other approaches are being evaluated. Lactose intolerance can be assessed by hydrogen/methane breath test using lactose as a substrate, or small bowel mucosal lactase assay, genetic testing and lactose tolerance test, although the efficacy and practicality of these diagnostic modalities are not equal. SUMMARY: In clinical practice, gas, bloating, distention, pain, and diarrhea are common gastrointestinal symptoms that often remain unexplained when routine gastrointestinal endoscopy, imaging, and stool tests are negative. These patients should be evaluated for SIBO and/or food intolerances including lactose intolerance.

Translumbosacral Anorectal Magnetic Stimulation Test for Fecal Incontinence.

BACKGROUND: Neuropathy may cause fecal incontinence and mixed fecal incontinence/constipation, but its prevalence is unclear, partly due to the lack of comprehensive testing of spino-anorectal innervation. OBJECTIVE: This study aimed to develop and determine the clinical usefulness of a novel test, translumbosacral anorectal magnetic stimulation for fecal incontinence. DESIGN: This observational cohort study was conducted from 2012 to 2018. SETTINGS: This study was performed at a tertiary referral center. PATIENTS: Patients with fecal incontinence, patients with mixed fecal incontinence/constipation, and healthy controls were included. INTERVENTIONS: A translumbosacral anorectal magnetic stimulation test was performed by using an anorectal probe with 4 ring electrodes and magnetic coil, and by stimulating bilateral lumbar and sacral plexuses, uses and recording 8 motor-evoked potentials at anal and rectal sites. MAIN OUTCOME MEASURES: The prevalence of lumbar and/or sacral neuropathy was examined. Secondary outcomes were correlation of neuropathy with anorectal sensorimotor function(s) and morphological changes. RESULTS: We evaluated 220 patients: 144 with fecal incontinence, 76 with mixed fecal incontinence/constipation, and 31 healthy controls. All 8 lumbar and sacral motor-evoked potential latencies were significantly prolonged (p < 0.01) in fecal incontinence and mixed fecal incontinence/constipation groups compared with controls. Neuropathy was patchy and involved 4.0 (3.0) (median (interquartile range)) sites. Lumbar neuropathy was seen in 29% to 65% of the patients in the fecal incontinence group and 22% to 61% of the patients in the mixed fecal incontinence/constipation group, and sacral neuropathy was seen in 24% to 64% and 29% to 61% of these patients. Anal neuropathy was significantly more (p < 0.001) prevalent than rectal neuropathy in both groups. There was no correlation between motor-evoked potential latencies and anal sphincter pressures, rectal sensation, or anal sphincter defects. LIMITATIONS: No comparative analysis with electromyography was performed. CONCLUSION: Lumbar or sacral plexus neuropathy was detected in 40% to 75% of patients with fecal incontinence with a 2-fold greater prevalence at the anal region than the rectum. Lumbosacral neuropathy appears to be an independent mechanism in the pathogenesis of fecal incontinence, unassociated with other sensorimotor dysfunctions. Translumbosacral anorectal magnetic stimulation has a high yield and is a safe and clinically useful neurophysiological test. See Video Abstract at http://links.lww.com/DCR/B728. PRUEBA DE ESTIMULACIN MAGNTICA TRANSLUMBOSACRAL ANORECTAL PARA LA INCONTINENCIA FECAL: ANTECEDENTES:La neuropatía puede causar incontinencia fecal y una combinación de incontinencia fe-cal/estreñimiento, pero su prevalencia no está clara, en parte debido a la falta de pruebas comple-tas de inervación espino-anorrectal.OBJETIVO:Desarrollar y determinar la utilidad clínica de una nueva prueba, estimulación magnética trans-lumbosacral anorrectal para la incontinencia fecal.DISEÑO:Estudio de cohorte observacional del 2012 al 2018.ENTORNO CLINICO:Centro de referencia terciario.PACIENTES:Pacientes con incontinencia fecal, combinación de incontinencia fecal/estreñimiento y controles sanos.INTERVENCIONES:Se realizó una prueba de estimulación magnética translumbosacral anorrectal utilizando una sonda anorrectal con 4 electrodos anulares y bobina magnética, y estimulando los plexos lumbares y sacros bilaterales y registrando ocho potenciales evocados motores las regiones anal y rectal.PRINCIPALES MEDIDAS DE RESULTADO:Se examinó la prevalencia de neuropatía lumbar y/o sacra. Los resultados secundarios fueron la correlación de la neuropatía con las funciones sensitivomotoras anorrectales y cambios morfológi-cos.RESULTADOS:Evaluamos 220 pacientes, 144 con incontinencia fecal, 76 con combinación de incontinencia fe-cal/estreñimiento y 31 sujetos sanos. Las ocho latencias de los potenciales evocadas motoras lum-bares y sacras se prolongaron significativamente (p <0,01) en la incontinencia fecal y el grupo mixto en comparación con los controles. La neuropatía fue irregular y afectaba 4,0 (3,0) (mediana (rango intercuartílico) sitios. Se observó neuropatía lumbar en 29-65% en la incontinencia fecal y 22-61% en el grupo mixto, y neuropatía sacra en 24-64% y 29-61 % de pacientes respectivamen-te. La neuropatía anal fue significativamente más prevalente (p <0,001) que la rectal en ambos grupos. No hubo correlación entre las latencias de los potenciales evocadas motoras y las presio-nes del esfínter anal, la sensación rectal o los defectos del esfínter anal.LIMITACIONES:Sin análisis comparativo con electromiografía.CONCLUSIÓNES:Se detectó neuropatía del plexo lumbar o sacro en el 40-75% de los pacientes con incontinencia fecal con una prevalencia dos veces mayor en la región anal que en el recto. La neuropatía lumbo-sacra parece ser un mecanismo independiente en la patogenia de la incontinencia fecal, no asocia-do con otras disfunciones sensitivomotoras. La estimulación magnética translumbosacral anorrec-tal tiene un alto rendimiento, es una prueba neurofisiológica segura y clínicamente útil. Consulte Video Resumen en http://links.lww.com/DCR/B728.

Organizing and Developing a GI Motility Lab in Community Practice: Challenges and Rewards.

PURPOSE OF REVIEW: Neurogastroenterology and motility is a rapidly evolving subspecialty that encompasses over 33% of gastroenterological disorders, and up to 50% of referrals to gastroenterology practice. It includes common problems such as dysphagia, gastroesophageal reflux disease, irritable bowel syndrome, chronic constipation, gastroparesis, functional dyspepsia, gas/bloating, small intestinal bacterial overgrowth, food intolerance and fecal incontinence Standard diagnostic tests such as endoscopy or imaging are normal in these conditions. To define the underlying mechanism(s)/etiology of these disorders, diagnostic motility tests are often required. These are best performed by well-trained personnel in a dedicated motility laboratory. Our purpose is to provide an up-to-date overview on how to organize and develop a motility laboratory based on our collective experiences in setting up such facilities in academia and community practice. RECENT FINDINGS: A lack of knowledge, training and facilities for providing diagnostic motility tests has led to suboptimal patient care. A motility laboratory is the hub for diagnostic and therapeutic motility procedures. Common procedures include esophageal function tests such as esophageal manometry and pH monitoring, anorectal function tests suchlike anorectal manometry, neurophysiology and balloon expulsion, dysbiosis and food intolerance tests such as hydrogen/methane breath tests, and gastrointestinal transit assessment. These tests provide an accurate diagnosis and guide clinical management including use of medications, biofeedback therapy, neuromodulation, behavioral therapies, evidence-based dietary interventions and endoscopic or surgical procedures. Further, there have been recent developments in billing and coding of motility procedures and training requirements that are not well known. This review provides a stepwise approach on how to set-up a motility laboratory in the community or academic practice and includes the rationale, infrastructure, staffing needs, commonly performed motility tests and their clinical utility, billing and coding strategies, training needs and economic considerations for setting up this service.

Gefitinib induced Pemphigus Vulgaris with PRIDE complex.

Introduction: Pemphigus Vulgaris is a rare, noncommunicable, non-hereditary fatal autoimmune dermatological manifestation in which a painful blister initiates from the oral cavity. PRIDE complex stands for Papulopustules or paronychia, regulatory abnormality of hair and nails, itching, and dryness due to inhibition of EGFR. Both of these mucocutaneous manifestations are rare and are often caused by drugs. Case report: Our case reports 53-year-old patient presented with multiple crusted plaques, multiple hyperpigmented macules to patches, Solitary fluid-filled lesions on several parts of the body, and numerous erosions positive over buccal mucosa on initial follow up which was diagnosed as Pemphigus Vulgaris with PRIDE complex induced by Gefitinib. Management and outcome: The patient was treated with almost all possible treatment options, i.e., both steroids plus adjuvant therapy for pemphigus and antihistaminic, antibiotics, moisturizer, and lotions for PRIDE complex. The patient was initially admitted for infusion of the first dose of rituximab and later for management of flare-up condition and infusion of the second dose of rituximab infusion. Discussion: The complexity of the management of Pemphigus Vulgaris and PRIDE complex demands adequate monitoring of the patient's anti-cancerous therapy by clinical pharmacists, which can impact the clinical outcomes by providing pharmaceutical care and minimize the economic burden.

Can probiotics stop oral cancer progression?

Data sources Four electronic databases (PubMed, Web of Science, Scopus and PLOS) were queried to identify studies that investigated the effects of probiotics against oral cancer, published in the English language between January 2015 and February 2020.Study selection Randomised controlled trials (RCT) including in vivo and in vitro studies that evaluated the effects of probiotics against oral cancer were included.Data extraction and synthesis The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA-P) 2015 guidelines were followed to conduct this systematic review. Screening of titles, abstracts and full texts was done independently by four authors with disagreements resolved by mutual discussion. Individual studies' year, author, country, as well as strain of probiotics, type of sample, mechanisms of probiotics and outcomes, were analysed by two authors. The methodological quality of the included studies was assessed using the Joanna Briggs Institute (JBI) Critical Appraisal Tools (Checklist for Randomised Controlled Trial) by three authors. Meta-analysis was performed with Review Manager software, Version 5.3 and results were reported in odds ratio. Inconsistency test (I2) was used to examine the heterogeneity between studies.Results From an initial 774 articles, only five met the study eligibility criteria to be included in this review. Two studies used in vivo animal models and three studies conducted in vitro experiments using cancer and normal cell lines. There were no studies on humans. Four probiotics were reported to inhibit oral carcinogenesis; namely, Acetobacter syzygii (A. syzygii), Lactobacillus plantarum (L. plantarum), Lactobacillus salivarius (L. salivarius) Ren and AJ2 (combination of Streptococcus thermophiles, Bifidobacterium breve, Bifidobacterium longum, Bifidobacterium infantis, Lactobacillus acidophilus, Lactobacillus plantarum, Lactobacillus casei, Lactobacillus bulgaricus). Two studies that used L. salivarius Ren were combined quantitatively in a meta-analysis which showed 95% reduction of risk in oral cancer development (OR = 0.05, 95% CI 0.01-0.23; p <0.05).Conclusions Within the limitations of in vivo (animal) and in vitro (cell lines) studies, the authors concluded that the probiotics analysed in this review, especially L. salivarius Ren, seem to play a role in oral cancer inhibition.

Evolutionary analysis of rabies virus using the partial Nucleoprotein and Glycoprotein gene in Mumbai region of India.

Nearly 1.7 million cases of dog bites are reported every year in India and many cases of animal rabies are left unattended and undiagnosed. Therefore, a mere diagnosis of rabies is not sufficient to understand the epidemiology and the spread of the rabies virus (RV) in animals. There is a paucity of information about the evolutionary dynamics of RV in dogs and its biodiversity patterns in India. In total, 50 dog-brain samples suspected of rabies were screened by the nucleoprotein- (N) and glycoprotein- (G) gene PCR. The N and G genes were subsequently sequenced to understand the molecular evolution in these genes. The phylogenetic analysis of the N gene revealed that six isolates in the Mumbai region belonged to a single Arctic lineage. Time-scaled phylogeny by Bayesian coalescent analysis of the partial N gene revealed that the time to the most recent common ancestor (TMRCA) for the sequences belonged to the cluster from 2006.68 with a highest posterior density of 95 % betweeen 2005-2008, which is assigned to Indian lineage I. Migration pattern revealed a strong Bayes factor between Mumbai to Delhi, Panji to Hyderabad, Delhi to Chennai, and Chennai to Chandigarh. Phylogenetic analysis of the G gene revealed that the RVs circulating in the Mumbai region are divided into three lineages. Time-scaled phylogeny by the Bayesian coalescent analysis method estimated that the TMRCA for sequences under study was from 1993 and Indian clusters was from 1962. In conclusion, the phylogenetic analysis of the N gene revealed that six isolates belonged to single Arctic lineages along with other Indian isolates and they were clustered into a single lineage but divided into three clades based on the G-gene sequences. The present study highlights and enhances the current molecular epidemiology and evolution of RV and revealed strong location bias and geographical clustering within Indian isolates on the basis of N and G genes.

Long-Term Risks of Parkinson's Disease, Surgery, and Colorectal Cancer in Patients With Slow-Transit Constipation.

BACKGROUND & AIMS: Long-term outcomes of constipation have not been evaluated fully. We investigated the incidence of Parkinson's disease, constipation-related surgery, and colorectal cancer (CRC) in patients with constipation and slow-transit constipation (STC), followed up for up to 20 years. METHODS: We collected data from 2165 patients (33.1% men; median patient age, 54 y; median symptom duration, 5.0 y) with a diagnosis of constipation (based on Rome II criteria) who underwent an anorectal function test and a colonic transit time study, from 2000 through 2010, at a tertiary university hospital in Seoul, South Korea. The presence of STC was determined from colonic transit time. We used the Kaplan-Meier method to analyze and compare cumulative probabilities of a new diagnosis of Parkinson's disease or CRC according to the presence of STC. The patients were followed up until the end of 2019. RESULTS: During a median follow-up period of 4.7 years (interquartile range, 0.7-8.3 y), 10 patients underwent constipation-related surgery. The cumulative probabilities of constipation-related surgery were 0.7% at 5 years and 0.8% at 10 years after a diagnosis of constipation. Twenty-nine patients (1.3%) developed Parkinson's disease; the cumulative probabilities were 0.4% at 1 year, 1.0% at 5 years, and 2.6% at 10 years after a diagnosis of constipation. At 10 years, 1.3% of patients with STC required constipation-related surgery and 3.5% of patients with STC developed Parkinson's disease; in contrast, none of the patients without STC required constipation-related surgery (P = .003), and 1.5% developed Parkinson's disease (P = .019). In multivariate analysis, patient age of 65 years or older at the diagnosis of constipation (hazard ratio, 4.834; 95% CI, 2.088-11.190) and the presence of STC (hazard ratio, 2.477; 95% CI, 1.046-5.866) were associated independently with the development of Parkinson's disease. Only 5 patients had a new diagnosis of CRC during the follow-up period. The risk of CRC did not differ significantly between patients with vs without STC (P = .575). CONCLUSIONS: In a long-term follow-up study of patients with constipation in Korea, most patients had no severe complications. However, patients older than age 65 years with a new diagnosis of STC might be considered for Parkinson's disease screening.

Efficacy and Safety of Over-the-Counter Therapies for Chronic Constipation: An Updated Systematic Review.

INTRODUCTION: Constipation is commonly treated with over-the-counter (OTC) products whose efficacy and safety remain unclear. We performed a systematic review of OTC therapies for chronic constipation and provide evidence-based recommendations. METHODS: We searched PubMed and Embase for randomized controlled trials of ≥4-week duration that evaluated OTC preparations between 2004 and 2020. Studies were scored using the US Preventive Services Task Force criteria (0-5 scale) including randomization, blinding, and withdrawals. The strengths of evidence were adjudicated within each therapeutic category, and recommendations were graded (A, B, C, D, and I) based on the level of evidence (level I, good; II, fair; or III, poor). RESULTS: Of 1,297 studies identified, 41 met the inclusion criteria. There was good evidence (grade A recommendation) for the use of the osmotic laxative polyethylene glycol (PEG) and the stimulant senna; moderate evidence (grade B) for psyllium, SupraFiber, magnesium salts, stimulants (bisacodyl and sodium picosulfate), fruit-based laxatives (kiwi, mango, prunes, and ficus), and yogurt with galacto-oligosaccharide/prunes/linseed oil; and insufficient evidence (grade I) for polydextrose, inulin, and fructo-oligosaccharide. Diarrhea, nausea, bloating, and abdominal pain were common adverse events, but no serious adverse events were reported. DISCUSSION: The spectrum of OTC products has increased and quality of evidence has improved, but methodological issues including variability in study design, primary outcome measures, trial duration, and small sample sizes remain. We found good evidence to recommend polyethylene glycol or senna as first-line laxatives and moderate evidence supporting fiber supplements, fruits, stimulant laxatives, and magnesium-based products. For others, further validation with more rigorously designed studies is warranted.

Translumbosacral Neuromodulation Therapy for Fecal Incontinence: A Randomized Frequency Response Trial.

INTRODUCTION: Treatments for fecal incontinence (FI) remain unsatisfactory because they do not remedy the underlying multifactorial dysfunction(s) including anorectal neuropathy. The aim of this study was to investigate the optimal dose frequency, clinical effects, and safety of a novel treatment, translumbosacral neuromodulation therapy (TNT), aimed at improving neuropathy. METHODS: Patients with FI were randomized to receive 6 sessions of weekly TNT treatments consisting of 600 repetitive magnetic stimulations over each of 2 lumbar and 2 sacral sites with either 1, 5, or 15 Hz frequency. Stool diaries, FI severity indices, anorectal neurophysiology and sensorimotor function, and quality of life were compared. Primary outcome measure was the change in FI episodes/week. Responders were patients with ≥50% decrease in weekly FI episodes. RESULTS: Thirty-three patients with FI participated. FI episodes decreased significantly (∆ ±95% confidence interval, 4.2 ± 2.8 (1 Hz); 2 ± 1.7 (5 Hz); 3.4 ± 2.5 (15 Hz); P < 0.02) in all 3 groups when compared with baseline. The 1 Hz group showed a significantly higher (P = 0.04) responder rate (91 ± 9.1%) when compared with the 5 Hz group (36 ± 18.2%) or 15 Hz (55 ± 18.2%); no difference was found between the 5 and 15 Hz groups (P = 0.667). Anal neuropathy, squeeze pressure, and rectal capacity improved significantly only in the 1 Hz (P < 0.05) group compared with baseline, but not in other groups. Quality of life domains improved significantly (P < 0.05) with 1 and 5 Hz groups. No device-related serious adverse events were noted. DISCUSSION: TNT significantly improves FI symptoms in the short term, and the 1 Hz frequency was overall better than 5 and 15 Hz. Both anorectal neuropathy and physiology significantly improved, demonstrating mechanistic improvement. TNT is a promising, novel, safe, efficacious, and noninvasive treatment for FI (see Visual Abstract, Supplementary Digital Content 3, http://links.lww.com/AJG/B598).

Effects of Lubiprostone, an Intestinal Secretagogue, on Electrolyte Homeostasis in Chronic Idiopathic and Opioid-induced Constipation.

GOALS: To assess short-term and long-term effects of lubiprostone, a type-2 chloride channel activator, on electrolyte homeostasis. BACKGROUND: Conventional laxatives are associated with electrolyte imbalances. Lubiprostone is a type-2 chloride channel activator approved for treating chronic idiopathic constipation (CIC), opioid-induced constipation (OIC), and constipation-predominant irritable bowel syndrome in women. It induces intestinal fluid secretion, possibly affecting water and electrolyte homeostasis. We investigated short-term and long-term effects of lubiprostone on electrolyte, blood urea nitrogen (BUN), and creatinine levels using pooled data from CIC and OIC patients. STUDY: Data were pooled from 10 CIC and OIC studies-6 double-blind, randomized, placebo-controlled studies and 4 open-label, long-term studies. Total duration of lubiprostone exposure was from 3 weeks (short-term: CIC, 3 to 4 wk; OIC, placebo-controlled, 12 wk) to 48 weeks (long-term: CIC, 24 to 48 wk; OIC, 48 wk). Sodium, chloride, potassium, magnesium, BUN, and creatinine levels were examined at baseline and final assessment. RESULTS: Overall, 3209 patients were assessed. In the double-blind, placebo-controlled studies, there were no clinically meaningful differences in levels of electrolytes, BUN, and creatinine between lubiprostone and placebo groups, and in changes from baseline levels with long-term use of lubiprostone. Analyses of shifts in laboratory values (low/normal/high) at baseline and final assessment showed minimal effects on electrolytes, BUN, and creatinine. CONCLUSIONS: Lubiprostone did not cause clinically meaningful electrolyte imbalances or affect markers of renal function in either the short-term or long-term treatment of CIC or OIC.