ABSTRACT
Gastroesophageal reflux disease (GERD) is one of the most prevalent and bothersome functional gastrointestinal disorders worldwide, including in Thailand. After a decade of the first Thailand GERD guideline, physician and gastroenterologist encountered substantially increase of patients with GERD. Many of them are complicated case and refractory to standard treatment. Concurrently, the evolution of clinical characteristics as well as the progression of investigations and treatment have developed and changed tremendously. As a member of Association of Southeast Asian Nations, which are developing countries, we considered that the counterbalance between advancement and sufficient economy is essential in taking care of patients with GERD. We gather physicians from university hospitals, as well as internist and general practitioners who served in rural area, to make a consensus in this updated version of GERD guideline focusing in medical management of GERD. This clinical practice guideline was constructed adhering with standard procedure. We categorized the guideline in to four parts including definition, investigation, treatment, and long-term follow up. We anticipate that this guideline would improve physicians' proficiency and help direct readers to choose investigations and treatments in patients with GERD wisely. Moreover, we wish that this guideline would be applicable in countries with limited resources as well.
Subject(s)
Gastroesophageal Reflux , Consensus , Gastroesophageal Reflux/complications , Gastroesophageal Reflux/diagnosis , Gastroesophageal Reflux/therapy , Humans , Proton Pump Inhibitors/therapeutic use , ThailandABSTRACT
BACKGROUND: Linaclotide, a guanylate cyclase C agonist relieves irritable bowel syndrome with predominant constipation (IBS-C) symptoms, but how it improves pain in humans is unknown. AIMS: To investigate the effects of linaclotide and placebo on the afferent and efferent gut-brain-gut signalling in IBS-C patients, in a randomised clinical trial. METHODS: Patients with IBS-C (Rome III) and rectal hypersensitivity were randomised (2:1) to receive linaclotide (290 µg) or placebo for 10 weeks and undergo bi-directional gut and brain axis assessment using anorectal electrical stimulations and transcranial/transspinal-anorectal magnetic stimulations. Rectal sensations were examined by balloon distention. Assessments included abdominal pain, bowel symptoms and quality of life (QOL) scores. Primary outcomes were latencies of recto-cortical and cortico-rectal evoked potentials. RESULTS: Thirty-nine patients participated; 26 received linaclotide and 13 received placebo. Rectal cortical evoked potentials latencies (milliseconds) were significantly prolonged with linaclotide compared to baseline (P1:Δ 19 ± 6, P < 0.005; N1:Δ 20 ± 7, P < 0.02) but not with placebo (P1:Δ 3 ± 5; N1:Δ 4.7 ± 5,P = 0.3) or between groups. The efferent cortico-anorectal and spino-anorectal latencies were unchanged. The maximum tolerable rectal volume (cc) increased significantly with linaclotide compared to baseline (P < 0.001) and placebo (Δ 29 ± 10 vs 4 ± 20, (P < 0.03). Abdominal pain decreased (P < 0.001) with linaclotide but not between groups. Complete spontaneous bowel movement frequency increased (P < 0.001), and IBS-QOL scores improved (P = 0.01) with linaclotide compared to baseline and placebo. There was no difference in overall responders between linaclotide and placebo (54% vs 23%, P = 0.13). CONCLUSIONS: Linaclotide prolongs afferent gut-brain signalling from baseline but both afferent and efferent signalling were unaffected compared to placebo. Linaclotide significantly improves rectal hypersensitivity, IBS-C symptoms and QOL compared to placebo. These mechanisms may explain the effects of linaclotide on pain relief in IBS-C patients. ClinicalTrials.Gov: Registered at Clinical trials.gov no NCT02078323.
Subject(s)
Abdominal Pain/drug therapy , Brain/drug effects , Intestines/drug effects , Irritable Bowel Syndrome/drug therapy , Peptides/therapeutic use , Abdominal Pain/etiology , Abdominal Pain/microbiology , Adult , Brain/physiology , Constipation/drug therapy , Constipation/etiology , Constipation/microbiology , Female , Gastrointestinal Microbiome/drug effects , Gastrointestinal Microbiome/physiology , Humans , Intestines/physiology , Irritable Bowel Syndrome/complications , Irritable Bowel Syndrome/microbiology , Male , Middle Aged , Placebos , Quality of Life , Rectum/drug effects , Rectum/physiology , Signal Transduction/drug effects , Signal Transduction/physiology , Treatment OutcomeABSTRACT
Constipation is a heterogeneous, polysymptomatic, multifactorial disease. Acute or transient constipation can be due to changes in diet, travel or stress, and secondary constipation can result from drug treatment, neurological or metabolic conditions or, rarely, colon cancer. A diagnosis of primary chronic constipation is made after exclusion of secondary causes of constipation and encompasses several overlapping subtypes. Slow-transit constipation is characterized by prolonged colonic transit in the absence of pelvic floor dysfunction. This subtype of constipation can be identified using either the radio-opaque marker test or wireless motility capsule test, and is best treated with laxatives such as polyethylene glycol or newer agents such as linaclotide or lubiprostone. If unsuccessful, subspecialist referral should be considered. Dyssynergic defecation results from impaired coordination of rectoanal and pelvic floor muscles, and causes difficulty with defecation. The condition can be identified using anorectal manometry and balloon expulsion tests and is best managed with biofeedback therapy. Opioid-induced constipation is an emerging entity, and several drugs including naloxegol, methylnaltrexone and lubiprostone are approved for its treatment. In this Review, we provide an overview of the burden and pathophysiology of chronic constipation, as well as a detailed discussion of the available diagnostic tools and treatment options.
