MS LeBoff et al. NEJM 2022; 387: 299-309. Supplemental Vitamin D and Incident Fractures in Midlife and Older Adults

SR Cummings, C Rosen. NEJM 2022; 387: 368-370. VITAL Findings — A Decisive Verdict on Vitamin D Supplementation

In an ancillary study of the Vitamin D and Omega-3 Trial (VITAL), the investigators tested whether supplemental vitamin D₃ would result in a lower risk of fractures than placebo. Design: VITAL was a two-by-two factorial, randomized, controlled trial with 25,871 participants with a median followup of 5.3 years.

Key findings:

• Supplemental vitamin D₃, as compared with placebo, did not have a significant effect on total fractures (hazard ratio, 0.98), nonvertebral fractures (hazard ratio, 0.97), or hip fractures (hazard ratio, 1.01). 

From the editorial:

• This study reinforces a recent trial which found that Vitamin D supplementation did not significantly improve bone mineral density/structure with high-resolution CT.
• “There is no justification for measuring 25-hydroxyvitamin D in the general population or treating to a target serum level.” Exceptions may include some patients at high-risk for deficiency like persons living in residential settings with little sunlight exposure and those with malabsorptive conditions (eg. celiac disease, cholestatic liver disease).
• “Providers should stop screening for 25-hydroxyvitamin D levels or recommending vitamin D supplements and people should stop taking vitamin D supplements to prevent major diseases or extend life.”

NY Times (7/27/22): Study Finds Another Condition That Vitamin D Pills Do Not Help

“The first part of VITAL, previously published, found that vitamin D did not prevent cancer or cardiovascular disease in trial participants. Nor did it prevent falls, improve cognitive functioning, reduce atrial fibrillation, change body composition, reduce migraine frequency, improve stroke outcomes, protect against macular degeneration or reduce knee pain. Another large study, in Australia, found that people taking the vitamin did not live longer.”

My take: This should be the end of the Vitamin D epidemic. Will it?

Related blog posts:

• What is Driving the Vitamin D Epidemic? (More Testing)
• Why I Don’t Check Vitamin D Levels During IBD Flareups
• How Important Is It to Correct Vitamin D Deficiency in a Critically-Ill Patient?
• What happens to micronutrient levels in the hospital setting? When CRP concentration is >20 mg/L (>2 mg/dL), “plasma concentrations of selenium, zinc, and vitamins A, B-6, C, and D are clinically uninterpretable.
• Common to be “D-ficient” | gutsandgrowth
• Explaining the Vitamin D Paradox | gutsandgrowth
• Why Adding Vitamin D May Not Help IBD | gutsandgrowth
• Understanding Why Vitamin D Deficiency is Not So Common Afterall | gutsandgrowth
• Single High-Dose Oral Vitamin D Therapy … – gutsandgrowth

FW Woodley et al. JPGN Reports. 2022. August 2022 – Volume 3 – Issue 3 – p e209. Open access: Significant Temporal Association of Esophageal Air Events (Supragastric Belches, Air Swallows, and Gastric Belches) With Hiccups: A Case Study in an Adolescent

This report showed a significant temporal association between esophageal air events (EAEs) and hiccups using impedance-pH monitoring (I-pHM). EAEs include air swallows, gastric belching, and supragastric belching

This article reviews physiology of hiccups:

• “Hiccups are physiologically normal but can become pathological when they occur with increasing regularity or for extended periods of time (¹). The occurrence of hiccups is mediated through a reflex arc that consists of 3 basic branches: (1) afferent/sensory limb involving vagal, phrenic, and sympathetic nerves; (2) medulla and possibly the cervical spine (⁸) where central processing occurs; and (3) efferent/motor limb involving motor fibers of phrenic nerves and accessory nerves that innervate the diaphragm and intercostal muscles, respectively (^1,9). A hiccup may be caused by any disturbance that triggers one of these branches (¹).”

Understanding reasons for hiccups may help with treatment:

• “We initially tried treating this patient’s hiccups with acid suppression. When symptoms persisted despite H2 blocker, PPI, and cyproheptadine therapy, I-pHM confirmed minimal GER and allowed us to focus instead on other treatments: behavioral techniques, diaphragmatic breathing, and baclofen.”

My take: It is nice to see a correlation between hiccups and physiology with I-pHM. In some patients, baclofen along with diaphragmatic breathing may be a consideration prior to definitive testing.

Related blog posts:

• Belching, Hiccups and Aerophagia
• Treatment for rumination and belching
• Baclofen for Rumination

Unrelated article (but interesting): Brooks R, Christidis R, Carah N, et al Turning users into ‘unofficial brand ambassadors’: marketing of unhealthy food and non-alcoholic beverages on TikTok. BMJ Global Health 2022;7:e009112.

Key point: This study examines the marketing of unhealthy food and non-alcoholic beverages on TikTok. Videos posted by top food brands frequently feature branding, product images, engagement and celebrities/influencers. These videos reach billions of views.

Several pointers from this bowel sounds episode:

• For thickeners, Dr. Rosen recommends Gelmix for infants with reflux who are breastfed or receiving amino acid formulas. Cereal does not work for breastmilk or amino acid formulas.
• For infants, acid suppression, especially proton pump inhibitors, have not been shown to be effective but could contribute to a higher risk of allergies, infections and possibly bone complications.
• The podcast reviewed the rationale for a time-limited trial of hydrolysates for infants with reflux symptoms due to the overlap of symptoms between reflux and MSPI. However, if it is not effective in several weeks, then it should be stopped.
• Dr. Rosen does use “spit-up formulas” which can help reduce reflux symptoms and potentially help with swallow dysfunction. These are particularly well-suited for NG tubes as additional cereal in other formulas result in clogged NG tubes.
• Several new technologies have helped understand esophageal physiology much better including pH-impedance, high-resolution manometry and FLIP device. PH-impedance can help better categorize reflux symptoms into non-erosive reflux disease, reflux hypersensitivity, and functional heartburn; however, this test is used fairly infrequently at Dr. Rosen’s center as the test is burdensome.
• For older children/teenagers with functional heartburn symptoms, Dr. Rosen most frequent neuromodulator is gabapentin, which may alleviate coughing as well.
• Fundoplications have fallen out of favor and are undertaken much less frequently. The use of blenderized formulas or gastrojejunostomy tubes are often used to manage reflux symptoms in patients with neurologic impairment.
• Other treatments like prucalopride are emerging but quite limited in use in part due to lack of insurance coverage/cost.

Closing points:

• Red throat on ENT exam is not specific for reflux
• Aspiration, not reflux, is a common reason for infants who have coughing or BRUEs
• In infants, nonacid reflux is the main issue, not acid reflux

My take: If you like one of these podcasts, is it proper to say “I liked hearing your bowel sounds?”

If you want to listen to the episode click this link: https://www.buzzsprout.com/581062/10918260 or listen to it on apple podcast, Spotify, or where every you listen to podcasts.

Related article: S Yang et al. J Pediatr 2022; 245: 158-164. Pediatric Prescriptions of Proton Pump Inhibitors in France (2009-2019): A Time-Series Analysis of Trends and Practice Guidelines Impact Key findings:

• Between 2009 and 2019, the PPI prescription rate increased by 41% in the overall pediatric population (+110% in infants)
• There was a a mean PPI prescription rate of 52.5 per 1000 with the highest prescription rate in infants (131.5 per 1000 children)
• There was a seasonal pattern with prescriptions increased in the winter compared with the summer

Related blog posts:

• Acid Suppression for Laryngomalacia -Handed This Article to My ENT Colleagues
• Something Useful for Apparent Life-Threatening Events (ALTEs)
• Blaming Reflux for BRUEs -Not Changing Despite Guideline Recommendations
• Do Acid Blockers Given to Infants Increase the Risk of Allergic Disease?
• 2018 Pediatric Gastroesophageal Reflux Clinical Practice Guidelines
• Clinical evaluation not sensitive for aspiration
• How Many Kids with Reflux have Reflux?
• Better to do a coin toss than an ENT exam to determine reflux
• Hard Data on Blenderized Diets
• Treating reflux does not help asthma | gutsandgrowth
• How Likely is Reflux in Infants with “Reflux-like … – gutsandgrowth
• Which kids who aspirate need a gastrostomy tube?
• No Effect of Proton Pump Inhibitors and Irritability on … – gutsandgrowth
• Even the Experts Agree: pH-MII is a “Flawed Test” | gutsandgrowth

O Zerbo et al. Pediatrics 2022; 150: e2021056021. Open access: Safety of Live-Attenuated Vaccines in Children Exposed to Biologic Response Modifiers in Utero

This large retrospective cohort study (2006-2017) identified 960 infants with in utero biologic medicine exposures (most commonly etanercept, anakinra, adalimumab, and infliximab) among 582,759 infants. Key findings:

• Receipt of live-attenuated rotavirus vaccine in their first year or measles vaccine during their first 24 months were not at increased risk of prespecified adverse events compared to unexposed children
• There was not a significant difference in diarrhea, bloody stools, intussusception, vomiting, encephalitis, myelitis, hepatitis, ataxia, or fevers
• Receipt of the recommended number of doses of rotavirus vaccines in the first year of life was lower among biologic-exposed than among unexposed children (81.00% vs 85.20%, adjusted OR = 0.74)

Examples of guideline recommendations with regard to live-virus vaccination:

“The Toronto Consensus Statements for the Management of Inflammatory Bowel Disease in Pregnancy,” (Gastroenterology. 2016; 150(3):734–757) states the following: “live vaccinations are not recommended within the first 6 months of life in the offspring of women who were on anti-TNF therapy during pregnancy.”

“Inflammatory Bowel Disease in Pregnancy Clinical Care Pathway: A Report From the American Gastroenterological Association IBD Parenthood Project Working Group (Gastroenterology. 2019; 156(5):1508–1524.open access)” states the following: “if the mother is exposed to any biologic therapy, other than certolizumab, during the third trimester of pregnancy (ie, after 27 weeks gestation) avoidance of live vaccines is recommended for the first 6 months of life.”

In their discussion, the authors note that this “provide some reassurance to parents and pediatricians regarding live-attenuated vaccines for children exposed to BRM [biologics] in utero. Professional societies may want to consider reevaluating their live-attenuated vaccines recommendations for these children as new safety data accumulates.”

My take: There are clearly theoretical concerns about biologic-exposures of infants in utero since some are actively transported across the placenta barrier and can remain in infants for up to 12 months after birth. However, this study could not identify significant adverse effects in exposed infants.

I never saw the show, “Office Space.” However, I did see the opening trailer (1 min) recently and it is very funny. YouTube Link: Office Space – Peter’s Original Traffic Scene

MB Wallace et al. Gastroenterol 2022; 162: 295-304. Open access: Impact of Artificial Intelligence on Miss Rate of Colorectal Neoplasia

Design: In a multicenter and multicountry randomized crossover trial, patients (n=230) undergoing CRC screening or surveillance were enrolled in 8 centers (Italy, UK, US), and randomized (1:1) to undergo 2 same-day, back-to-back colonoscopies with or without AI (deep learning computer aided diagnosis endoscopy) in 2 different arms, namely AI followed by colonoscopy without AI or vice-versa.

Key finding: There was an approximately 50% reduction of the miss rate of colorectal neoplasia, mainly due to a decreased miss rate of flat and small lesions.

The editorial (pg 35-38, DK Rex et al. Artificial Intelligence Improves Detection at Colonoscopy: Why Aren’t We All Already Using It?) provides some perspective regarding the study limitations and why AI will not be widely adopted in the near term.

Limitations:

• “Tandem studies are more often positive than parallel design studies.  In a parallel design study, endoscopist bias toward any study arm is mitigated by the clinical and medical-legal demands to protect patients from colorectal cancer in a single withdrawal.”
• “Detection gains for AI are largely for diminutive lesions.³ This is generally true for detection gains from ancillary devices, because powering trials for improved advanced lesion detection is not practical”

Slow Uptake of AI:

• First, other adjunctive detection devices have received approval from the US Food and Drug Administration and then failed to reach widespread use…the limited adoption of this entire category suggests that physicians attach a relatively low price point to the value of detection gains produced by add-on devices…Incorporating detection devices with add-on cost is particularly problematic in US ambulatory surgery centers.”
• The authors indicate that an endoscopy company could add AI to standard equipment as one way to advance use of this technology

My take: AI will likely improve interpretation and usefulness of colonoscopy, whether for cancer surveillance and other reasons. Cost and familiarity are current barriers to early adoption.

Related blog post: #NASPGHAN19 Impact of New Technologies on Patient Health