427 - GERD Dx and Tx, Fluvoxamine for COVID, “Bumping” You Up

From the Guidelines and the American College of Gastroenterology

1) Diagnosis and Management of Gastroesophageal Reflux Disease

Gastroesophageal reflex disease (GERD) is among the most common diseases seen by gastroenterologists, surgeons, and primary care clinicians. The American College of Gastroenterology (ACG) recently updated their 2013 guideline regarding the evaluation and treatment of GERD, including pharmacologic, lifestyle, surgical, and endoscopic management. In addition, “key concepts and suggestions” for which there is presently insufficient evidence to make recommendations are also provided.

For the purposes of this guideline, GERD is defined as the condition in which the reflux of gastric contents into the esophagus results in symptoms and/or complications. GERD is objectively defined by the presence of characteristic mucosal injury seen at endoscopy and/or abnormal esophageal acid exposure demonstrated on a reflux monitoring study. Recommendations include:

Diagnosis of GERD:

• Recommend an 8-week trial of empiric PPIs once daily before a meal for patients with classic GERD symptoms of heartburn and regurgitation who have no alarm symptoms (strong recommendation, moderate level of evidence).
• Recommend endoscopy as first test for those presenting with dysphagia or other alarm symptoms (weight loss and GI bleeding) and for patients with multiple risk factors for Barrett's esophagus (strong/low).
• Recommend attempting to discontinue the PPIs in patients whose classic GERD symptoms respond to an 8-week empiric trial of PPIs (conditional/low).
• Recommend diagnostic endoscopy, ideally after PPIs are stopped for 2–4 weeks, in those whose classic GERD symptoms do not respond to an 8-week empiric trial of PPIs or whose symptoms return when PPIs are discontinued (strong/low).
• Recommend objective testing for GERD (endoscopy and/or reflux monitoring) in patients who have chest pain without heartburn and who have had adequate evaluation to exclude heart disease (conditional/low).
• Do not recommend barium swallow solely as a diagnostic test for GERD (conditional/low).
• Recommend reflux monitoring be performed off therapy to establish the diagnosis in patients for whom the diagnosis of GERD is suspected but not clear, and endoscopy shows no objective evidence of GERD (strong/low).
• Recommend against reflux monitoring off therapy solely as a diagnostic test in patients known to have endoscopic evidence of Los Angeles (LA) grade C or D reflux esophagitis or in patients with long-segment Barrett's esophagus (strong/low).

Medical Management:

• Recommend weight loss in overweight and obese patients (strong/moderate).
• Suggest avoiding meals within 2–3 hours of bedtime (conditional/low).
• Suggest avoidance of tobacco products/smoking (conditional/low).
• Suggest avoidance of “trigger foods” (conditional/low).
• Suggest elevating head of bed for nighttime (conditional/low).
• Recommend treatment with PPIs over histamine-2-receptor antagonists (H2RA) for healing erosive esophagitis (EE) (strong/high).
• Recommend PPIs for maintenance of healing from EE (strong/moderate).
• Recommend PPI 30–60 minutes before a meal rather than at bedtime (strong/mod).
• For patients with GERD who do not have EE or Barrett's esophagus, and whose symptoms have resolved with PPI therapy, an attempt should be made to discontinue PPIs or to switch to on-demand therapy (conditional/low).
• For patients who require maintenance therapy, the PPIs should be administered in the lowest dose that effectively controls symptoms (conditional/low).
• Recommend against use of a prokinetic agent of any kind unless there is objective evidence of gastroparesis (strong/low).
• Do not recommend sucralfate use for GERD except during pregnancy (strong/low).
• Suggest on-demand or intermittent PPI therapy for heartburn symptom control with non-erosive reflux disease (NERD) (conditional/low).

Notable key concepts and suggestions include:

• There is conceptual rationale for a trial of switching PPIs for patients who have not responded to one PPI. More than one additional trial cannot be supported.
• Evidence is lacking regarding whether abrupt discontinuation of PPIs causes rebound acid hypersecretion and increased symptoms.
• Although GERD may contribute to extraesophageal symptoms, evaluation for other causes should be considered with laryngeal sx., cough, and asthma.
• In patients with refractory symptoms thought to be GERD, PPI therapy should be stopped if off-therapy reflux testing is negative (EGD and pH monitoring) unless another indication for continuing PPIs is present.
• PPIs in and of themselves are not felt to cause osteoporosis, vitamin D or B12 deficiency, or CKD.

Mark’s Comments:

My perception is that there are many patients who are taking PPIs in perpetuity, and sadly, without making lifestyle changes for prevention, it is not surprising that many have a recurrence of symptoms when stopping PPIs. As an “intermittent GERD sufferer” myself, I have been grateful for PPIs, but also mindful that when I do experience significant symptoms, I can immediately trace them back to a specific cause (usually large meal eaten close to bedtime). Perhaps someday I’ll/we’ll learn.

Reference:

Katz P et al. ACG Clinical Guideline for the Diagnosis and Management of Gastroesophageal Reflux Disease. The American Journal of Gastroenterology. Published online November 22, 2021. doi: 10.14309/ajg.0000000000001538. LInk

From the Literature 

2) Fluvoxamine for COVID-19 

Fluvoxamine, a Selective Serotonin Uptake Inhibitor and sigma-1 receptor agonist currently FDA approved for the treatment of obsessive-compulsive disorder, has remained on the lists of potential therapies for COVID-19. The Infectious Disease Society of America still advises that use be confined to randomized controlled trials. 

A report in the Lancet of a randomized, adaptive trial for multiple COVID-19 therapies called “TOGETHER” has recently released its findings on the effectiveness of fluvoxamine for patients with COVID-19.  

• Patients: Adults with outpatient COVID-19 symptoms for 7 days or less with at least one risk factor for severe disease: diabetes, cardiovascular disease, treated hypertension, lung disease, obesity, smoking, history of transplant, stage IV or end-stage kidney disease, immunosuppressive therapy, cancer, or unvaccinated. 
• Intervention: fluvoxamine 100 mg twice a day for 10 days 
• Comparison: placebo twice a day for 10 days 
• Outcomes: Composite endpoint of hospital admission (ED visit + >=6 hours of observation) or hospitalization within 28 days. (Hospital beds in Brazil were scarce during the study, so the outcome had to include what hospitalization could look like) 

The trial was well done – power analysis, masking, randomization, etc. The TOGETHER study is similar to an ongoing omnibus study in the UK (called RECOVERY) where patients are randomized to different investigational treatments as they present with COVID-19 in order to get research done quickly. 

Almost 1500 patients were included. In the intention to treat analysis, there was a 5% reduction in risk of hospitalization (11% fluvoxamine vs. 16% placebo, NNT ~ 20). The authors also did a per-protocol analysis, keeping only those who reported >80% adherence (which compromises some of the validity achieved by randomization). It showed similar reduction in hospitalization but also a decreased risk of death (1/548 in fluvoxamine group and 12/618 in placebo, NNT ~ 56). 

John’s Comments: 

The authors note that these drugs are posited to have an anti-inflammatory effect, which was news to me. I regard this study as encouraging, but I realize that more trials could change these conclusions significantly. The per protocol analysis should be viewed with extreme skepticism as it analyzed <80% of the original cohort. 

Reference: 

Reis G, dos Santos Moreira-Silva EA, Silva DCM, et al. Effect of early treatment with fluvoxamine on risk of emergency care and hospitalisation among patients with COVID-19: the TOGETHER randomised, platform clinical trial. The Lancet Global Health. Published online October 2021:S2214109X21004484. Link 

From PeerR_xMed ( www.PeerRxMed.org )

3) It’s Time to “Bump” You Up

High fives and fist bumps … have a lot to say about the cooperative workings of a team ….” Kraus, Huang, and Keltner (2010)

For those of you who know me, you know expressing encouragement is important to me, and one of my ways of doing so is to share a smiling, look-you-in-the-eye greeting accompanied by a high-five, fist-bump, and/or elbow-bump when I see you.

Since we humans are relational by nature, it should come as no surprise that there is evidence that such physical connection likely helps to improve team performance and promotes cooperation and trust – even at the level of professional athletes. In 2010, Michael Kraus and colleagues published a study titled “Tactile Communication, Cooperation, and Performance: An Ethological Study of the NBA” (Link). Their hypothesis was that in group competition, physical touch would predict increases in both individual and group performance.

They focused their analysis on 12 distinct types of touch that occurred when two or more players were in the midst of celebrating a positive play that helped their team (e.g., making a shot). These celebratory touches included fist bumps, high fives, chest bumps, leaping shoulder bumps, chest punches, head slaps, head grabs, low fives, high tens, full hugs, half hugs, and team huddles

Consistent with their premise, those teams with higher early season touch achieved greater performance for both individuals and teams later in the season, even after accounting for player status, preseason expectations, and early season performance. This success appeared to be explained by greater cooperative behaviors between teammates in the higher-touch groups. And while the authors acknowledged these results were not immediately applicable to other group settings, they did wonder as to how the cumulative effect of such seemingly insignificant acts might enhance group cooperation and performance in other settings.

Depending on the COVID prevalence in your community, you and your team may not yet feel comfortable returning to hand-to-hand contact for connection. If that is the case, elbow bumps are wonderful, and though not a “celebratory touch of choice” by NBA players, seem to be working out quite well for our teams. For those of you who are not ready for physical contact of any kind, here’s elementary school teacher David Jamison, who understands a thing or two about the importance of connection, providing a master class in no-contact full connection (Link). Why not give this a try with a colleague or teammate this week! Doing so would likely “bump you up” for the day, and we could sure all use some of that right now ….

______________

Mark and John

Carilion Clinic Department of Family and Community Medicine

Feel free to forward Take 3 to your colleagues. Glad to add them to the distribution list.

Email: mhgreenawald@carilionclinic.org