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Practice Question #1
A 45-year-old woman diagnosed with irritable bowel syndrome with diarrhea presents to your clinic. Her diarrhea is well controlled with loperamide, but her abdominal pain persists.
Her primary care provider previously prescribed dicyclomine, but this did not improve her abdominal pain symptoms.
What is the next best medication to treat her abdominal pain?
A. Amitriptyline
B. Codeine/acetaminophen
C. Hydrocodone
D. Meloxicam
Correct answer:
A. Amitriptyline
Commentary:
Amitriptyline is a tricyclic antidepressant medication that functions as a central neuromodulator. A systematic review of randomized controlled trials of 6-12 weeks’ duration showed a modest improvement in global symptom relief and abdominal pain in patients with IBS treated with tricyclic anti-depressants. Opioid medications and nonsteroidal anti-inflammatory medications are not recommended to treat abdominal pain in patients with IBS.
Practice Question #2
A 52-year-old man with hypertension and diabetes mellitus type 2 is referred to you for 8 months of troublesome regurgitation and heartburn. He has a body mass index of 29 kg/m2.
He had minimal relief with single-dose proton pump inhibitor (PPI) therapy before breakfast and partial response with double-dose PPI therapy taken before breakfast and before dinner. Regurgitation after dinner and at bedtime is his most troublesome symptom.
What is the next best step in management?
A. Counsel on weight management
B. Increase PPI to quadruple dose
C. Perform gastric emptying study
D. Refer for bariatric surgery evaluation
E. Switch PPI to before bedtime
Correct answer:
A. Counsel on weight management
Commentary:
This presentation represents typical symptoms of gastroesophageal reflux disease that are not responsive to an optimized regimen of PPI therapy.
Management of refractory gastroesophageal reflux disease symptoms begins with optimizing lifestyle and weight loss.
Quadruple-dose PPI therapy has no established role. A gastric emptying study would be recommended if gastroparesis was suspected.
This patient does not meet criteria for bariatric surgery as his body mass index is less than 30 kg/m2.
PPI therapy optimization with before-meal dosing (30-60 min before breakfast for single-dose therapy and before breakfast and dinner for double-dose therapy) would be the next step after weight management.
Summary content
7 Key Takeaways
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Developed a paper-based colorimetric sensor array for chemical threat detection.
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Can detect 12 chemical agents, including industrial toxins.
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Production cost is under 20 cents per chip.
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Utilizes dye-loaded silica particles on self-adhesive paper.
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Provides rapid, simultaneous identification through image analysis.
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Inspired by the mammalian olfactory system for pattern recognition.
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Future developments include a machine learning-enabled reader device.
The guidelines emphasize four-hour gastric emptying studies over two-hour testing. How do you see this affecting diagnostic workflows in practice?
Dr. Staller: Moving to a four-hour solid-meal scintigraphy will actually simplify decision-making. The two-hour reads miss a meaningful proportion of delayed emptying; standardizing on four hours reduces false negatives and the “maybe gastroparesis” purgatory that leads to repeat testing. Practically, it means closer coordination with nuclear medicine (longer slots, consistent standardized meal), updating order sets to default to a four-hour protocol, and educating front-line teams so patients arrive appropriately prepped. The payoff is fewer equivocal studies and more confident treatment plans.
Metoclopramide and erythromycin are the only agents conditionally recommended for initial therapy. How does this align with what is being currently prescribed?
Dr. Staller: This largely mirrors real-world practice. Metoclopramide remains the only FDA-approved prokinetic for gastroparesis, and short “pulsed” erythromycin courses are familiar to many of us—recognizing tachyphylaxis limits durability. Our recommendation is “conditional” because the underlying evidence is modest and patient responses are heterogeneous, but it formalizes what many clinicians already do: start with metoclopramide (lowest effective dose, limited duration, counsel on neurologic adverse effects) and reserve erythromycin for targeted use (exacerbations, bridging).
Several agents, including domperidone and prucalopride, received recommendations against first-line use. How will that influence discussions with patients who ask about these therapies?
Dr. Staller: Two points I share with patients: evidence and access/safety. For domperidone, the data quality is mixed, and US access is through an FDA IND mechanism; you’re committing patients to EKG monitoring and a non-trivial administrative lift. For prucalopride, the gastroparesis-specific evidence isn’t strong enough yet to justify first-line use. So, our stance is not “never,” it’s just “not first.” If someone fails or cannot tolerate initial therapy, we can revisit these options through shared decision-making, setting expectations about benefit, monitoring, and off-label use. The guideline language helps clinicians have a transparent, evidence-based conversation at the first visit.
The guidelines suggest reserving procedures like G-POEM and gastric electrical stimulation for refractory cases. In your practice, how do you decide when a patient is “refractory” to medical therapy?
Dr. Staller: I define “refractory” with three anchors.
1. Adequate trials of foundational care: dietary optimization and glycemic control; an antiemetic; and at least one prokinetic at appropriate dose/duration (with intolerance documented if stopped early).
2. Persistent, function-limiting symptoms: ongoing nausea/vomiting, weight loss, dehydration, ER visits/hospitalizations, or malnutrition despite the above—ideally tracked with a validated instrument (e.g., GCSI) plus nutritional metrics.
3. Objective correlation: delayed emptying on a standardized 4-hour solid-meal study that aligns with the clinical picture (and medications that slow emptying addressed).
At that point, referral to a center with procedural expertise for G-POEM or consideration of gastric electrical stimulation becomes appropriate, with multidisciplinary evaluation (GI, nutrition, psychology, and, when needed, surgery).
What role do you see dietary modification and glycemic control playing alongside pharmacologic therapy in light of these recommendations?
Dr. Staller: They’re the bedrock. A small-particle, lower-fat, calorie-dense diet—often leaning on nutrient-rich liquids—can meaningfully reduce symptom burden. Partnering with dietitians early pays dividends. For diabetes, tighter glycemic control can improve gastric emptying and symptoms; I explicitly review medications that can slow emptying (e.g., opioids; consider timing/necessity of GLP-1 receptor agonists) and encourage continuous glucose monitor-informed adjustments. Pharmacotherapy sits on top of those pillars; without them, medications will likely underperform.
The guideline notes “considerable unmet need” in gastroparesis treatment. Where do you think future therapies or research are most urgently needed?
Dr. Staller: I see three major areas.
1. Truly durable prokinetics: agents that improve emptying and symptoms over months, with better safety than legacy options (e.g., next-gen motilin/ghrelin agonists, better-studied 5-HT4 strategies).
2. Endotyping and biomarkers: we need to stop treating all gastroparesis as one disease. Clinical, physiologic, and microbiome/omic signatures that predict who benefits from which therapy (drug vs G-POEM vs GES) would transform care.
3. Patient-centered trials: larger, longer RCTs that prioritize validated symptom and quality-of-life outcomes, include nutritional endpoints, and reflect real-world medication confounders.
Our guideline intentionally highlights these gaps to hopefully catalyze better trials and smarter referral pathways.
Dr. Staller is with the Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston.