COVID-19: Failing the Test, What We Know About Aerolization, Georgia DPH Revisions, CDC COVID-19 Projections

Yesterday –E Schneider NEJM commentary (DOI: 10.1056/NEJMp2014836) on how the U.S. has lagged behind other countries in SARS-CoV-2 testing  Full Text: Failing the Test

An excerpt:

Tragically, the United States, unable to match other countries’ response, has tallied the most cases and deaths in the world — and recent data suggest that those tallies are underestimates. Why has the U.S. response been so ineffectual? One key answer is testing, which has been a cornerstone of Covid-19 control elsewhere…

Having failed to test early enough to contain outbreaks, the country has fallen back on two mitigation strategies: accelerating drug and vaccine development and an unprecedented strategy of nonpharmacologic interventions (NPIs) involving draconian school and business closures, stay-at-home orders, and physical distancing

March 16 -May 8, 2020

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T Lewis. Scientific American (May 12):  How Coronavirus Spreads through the Air: What We Know So Far

An excerpt:

According to the U.S. Centers for Disease Control and Prevention and the World Health Organization, the novel coronavirus is primarily spread by droplets from someone who is coughing, sneezing or even talking within a few feet away. But anecdotal reports hint that it could be transmissible through particles suspended in the air…

 “There is not much convincing evidence that aerosol spread is a major part of transmission” of COVID-19, Perlman says. That assessment does not mean it is not occurring, however…

Cowling hypothesizes that many respiratory viruses can be spread through the airborne route—but that the degree of contagiousness is low…

Most researchers still think the new coronavirus is primarily spread via droplets and touching infected people or surfaces. So diligent hand washing and social distancing are still the most important measures people can take to avoid infection.


From AJC: Georgia’s Latest Errors in Reporting COVID-19 Data 

In the latest bungling of tracking data for the novel coronavirus, a recently posted bar chart on the Georgia Department of Public Health’s website appeared to show good news: new confirmed cases in the counties with the most infections had dropped every single day for the past two weeks.

In fact, there was no clear downward trend. The data is still preliminary, and cases have held steady or dropped slightly in the past two weeks.

DPH’s page has led readers to think that cases were dropping dramatically, even though lower case numbers were the result of a lag in data collection.

My take: Though, the number of reported cases has been fairly steady in Georgia, the amount of testing has increased; thus, even if the numbers hold steady, this likely reflects some improvement in the absolute number of infected individuals.


Big Study on Intralesional Steroid Injection for Esophageal Anastomotic Strictures & 8 Truths on COVID-19

A recent retrospective study (PD Ngo et al. JPGN 2020; 70: 462-7) describes the largest published experience with intralesional steroid injection (ISI) for esophageal anastomotic strictures; the population studied in this report were strictures associated with esophageal atresia (EA) repair.

Key Details:

  • 158 patients, 2010-2017, were included
  • 1055 balloon dilatations and 452 ISI+
  • Triamcinolone acetate (10 mg/mL) was injected into the scar tissue “at a typical doses of 1 to 2 mg/kg with a weight-based maximum of 20mg and not >40 mg per procedure (typically 10-20 mg).  The total injected dose was divided into 4 or more injection sites.”
  • Dilatation was performed with controlled radial expansion (CRE) balloons.
  • Prior to dilatation, a brief intraoperative contrast esophagram with half-strength ioversol 68% (Optiray 320) was performed.  This allowed estimation of the anastomotic diameters. In some cases with poor contrast distention, the estimation was completed using the endoscope diameter or biopsy forceps size.

Key findings:

  • The median change in stricture diameter was significantly greater in the ISI+ group compared to the ISI-neg group with stricture dilatation, with an adjusted odds ratio of 3.24
  • The likelihood of ISI injection being helpful was more pronounced with the first three sessions, with a median change of 1 mm compared to 0.5mm (after the first three).  The authors note that after the first 3 ISI+-dilatations, there was not a statistically-significant difference in stricture dilatation between those receiving ISI and those with balloon alone
  • There was no difference in perforation rates with ISI than without
  • The authors noted that patients who received ISI were less likely to be subsequently characterized as refractory

The study has a number of limitations including lack of precision/reproducibility with stricture diameter with dilatation; in addition, it was non-randomized and retrospective.

My take: This study, completed in a highly-specialized center, provides evidence that stricture dilatation following esophageal atresia repair is likely to be more successful with steroid injection.

Related blog posts:

Also, a good read (thanks to 33mail Bryan Vartabedian for this reference): Can We Discuss Flatten-the-Curve in COVID19? My Eight Assertions by JOHN MANDROLA, MD

” I will argue that the cumulative deaths from COVID19 will not be reduced significantly by flatten-the-curve policies. And that this virus will be as dangerous to vulnerable patients in 6 months to a year. We should be allowed to debate this.”

Key points: flattening of the curve does not mean that we will substantially lower the total mortality related to COVID-19 –though hospitals now have had time to avoid being overwhelmed.  The virus is not contained, tests will underperform, new treatments do not help much (thus far), the overall mortality is ~1%, it may be difficult for a vaccine to prove its effectiveness, and COVID-19 (& our response) will likely lead to a large number of deaths not due to COVID-19.

Curbside Humor

Is A Gluten-Free Diet Possible? DOGGIE BAG Study. And Face Mask Use in U.S.

A recent study (JA Silvester et al. Gastroenterol 2020; 158: 1497-99)  examined the diet of 18 participants with celiac disease who endorsed no intentional gluten ingestion.

From BeyondCeliac website: CELIAC DISEASE RESEARCHERS EXAMINE THE CONTENT OF PATIENTS’ DOGGIE BAGS

There are two ways you could interpret the name of the new Doggie Bag study, which investigates how much gluten people with celiac disease are getting in their diets. And each would be correct.

Participants in the study provided portions of all the food they ate over 10 days – what you could think of as the doggie bag you bring home from a restaurant. They also provided stool samples, which might bring to mind the bags dog owners use to clean up after their pets.

Either way, the name reflects the commitment made by 18 celiac disease patients on the gluten-free diet who took part in the 10-day review of all the gluten going in and coming out of their bodies. Urine samples were also collected.

Celiac disease researchers tested all the samples for the presence of gluten immunogenic peptides (GIP) and concluded that 66 percent of the patients trying to follow a strict gluten-free diet showed evidence, by one measure or another, of being exposed to gluten. The amount of gluten varied from .23 milligrams (mg) to more that 40 mg with each exposure. Up to 10 mg of gluten per day is generally considered a safe level of gluten consumption for most people with celiac disease, according to the University of Chicago Celiac Disease Center.

Key findings:

  • 25 of 313 (8%) of food samples from 9 participants had detectable gluten with a median of 11 parts per million
  • 12 of 18 with good or excellent GFD adherence based on standardized self-report were exposed to gluten within the 10-day study period
  • Among the 12 with gluten detected in their diet, 5 (42%) had abnormal TTG IgA antibody levels and 8 (66%) had Marsh 3A histology; in the 6 with no gluten detected, 2 (33%) had abnormal TTG IgA antibody levels and 2 (33%) had Marsh 3A histology

My take: For many patients with celiac disease, a “GFD may be more aspirational than achievable, even by highly committed and knowledgeable individuals.”

Related blog posts:


 

From YouGov survey: The states that are more and less likely to adopt face masks

  • Methodology: The survey is based on the interviews of 89,347 US adults aged 18 and over between March 26-April 29, 2020. All interviews were conducted online and the results have been weighed to be nationally representative.
  • During the course of April, the share of Americans who wore face masks while out in public surged from 17 percent at the start of the month to 63 percent by month’s end
  • A state-by-state analysis reveals some states are significantly more likely to adopt face masks than others. Georgia was ahead of nationwide average during study period (45% compared to 43% nationwide)


 

Disclaimer: This blog, gutsandgrowth, assumes no responsibility for any use or operation of any method, product, instruction, concept or idea contained in the material herein or for any injury or damage to persons or property (whether products liability, negligence or otherwise) resulting from such use or operation. These blog posts are for educational purposes only. Specific dosing of medications (along with potential adverse effects) should be confirmed by prescribing physician.  Because of rapid advances in the medical sciences, the gutsandgrowth blog cautions that independent verification should be made of diagnosis and drug dosages. The reader is solely responsible for the conduct of any suggested test or procedure.  This content is not a substitute for medical advice, diagnosis or treatment provided by a qualified healthcare provider. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a condition

Economic Burden of Inflammatory Bowel Disease, Fewer Operations and Emerging Treatments

Pouillon, L., Travis, S., Bossuyt, P. et al. Head-to-head trials in inflammatory bowel disease: past, present and futureNat Rev Gastroenterol Hepatol (2020). https://doi.org/10.1038/s41575-020-0293-9 (Thanks to KT Park for this reference)

An excerpt:

This Perspective provides an overview of the past, current and future concepts in IBD trial design, with a detailed focus on the role of comparative research and the challenges and pitfalls in undertaking and interpreting the results from such studies.

Related blog posts:

GR Lichenstein et al. Clin Gastroenterol Hepatol 2020; 18: 889-97.  Using Truven MarketScan Insurance Claims data (2008-2015) from more than 160,000 patients with inflammatory bowel disease (IBD), the authors estimated economic burdens from Crohn’s disease (CD) and ulcerative colitis (UC).

  • For CD, lifetime incremental cost was $416,352 on average, but was $707,711 if diagnosis was established between 0-11 years of age. The lifetime costs, $622,056, consisted of $273,056 for outpatient care, $164,298 for inpatient care, $163,722 for pharmacy costs, and $20,979 for emergency room care.
  • For UC, lifetime incremental cost averaged $230,102, but was $369,955 if diagnosis was established between 0-11 years of age. The lifetime costs, $405,496, consisted of $153,670 for outpatient care, $123,190 for inpatient care, $105,142 for pharmacy costs, and $13,493 for emergency room care.
  • The lifetime costs for UC and CD were both greater than that for rheumatoid arthritis ($100,273) and for type 2 diabetes ($89,064).
  • Related blog postIBD Shorts 2020  Cost of IBD Care is Increasing. From Healio Gastro: Chronic inflammatory disease expenditures nearly double over last 2 decades

T Shinagawa et al. Clin Gastroenterol Hepatol 2020; 18: 898-907.  In this study from Japan with 1871 patients with CD, the 5- and 10-year reoperation rates were 23.4% and 48.0% respectively.  However, reoperation rates were significantly lower after 2002 than prior with HR 0.72.  Postoperative use of immunomodulators (OR 0.60) and anti-TNF therapy (HR 0.71) were associated with a reduced the risk of reoperation.

IBD Updates: Depression and Crohn’s Disease, Blood Tests in Pediatric IBD

LW Gaines et al. Inflamm Bowel Dis 2020; 26: 423-8. In this study with 3307 adults with Crohn’s disease (CD) and baseline demographics, CD activity and an affective-cognitive index of depression, the authors used structural equation models to determine the likelihood of whether depression triggers CD activity or whether CD activity triggers depression.  Key findings: “The hypothesis that an affective-cognitive depression predicts patient-reported exacerbation of CD is 218 times more likely to account for the data than the converse.”   (Depression is likely to increase CD activity rather than be due to CD activity).

JJ Ashton et al. Inflamm Bowel Dis 2020; 26: 469-76. Among 256 patients (dx 2013-17) in Southhampton-PIBD database, there were 151 with CD, 95 with UC and 10 IBD-unclassified.  Key findings:

  • 9% presented with all normal blood tests (tests analyzed if available: CRP, ESR, Albumin, platelets, packed cell volume, wbc, ALT)
  • Normal labs were more common with UC compared to CD: 14.4% vs 5.3%

RC Ungaro et al. AP&T; 2020; DOI: 10.1111/apt.15685.  (Thanks to Ben Gold for this reference).  Systematic review with meta-analysis: efficacy and safety of early biologic treatment in adult and paediatric patients with Crohn’s disease. A total of 18 471 patients were studied, with  a median follow-up of 64 weeks (range 10-416). Meta-analysis found that early use of biologics was associated with higher rates of clinical remission (OR 2.10 [95% CI: 1.69-2.60], n = 2763, P < 0.00001), lower relapse rates (OR 0.31 [95% CI: 0.14-0.68], n = 596, P = 0.003) and higher mucosal healing rates (OR 2.37 [95% CI: 1.78-3.16], n = 994, P < 0.00001) compared with late/conventional management. Conclusions: Early biologic treatment is associated with improved clinical outcomes in both adult and paediatric CD patients, not only in prospective clinical trials but also in real-world settings.

RS Boneh et al. Dietary Therapies Induce Rapid Response and Remission in Pediatric Patients With Active Crohn’s Disease Clin Gastroenterol Hepatol (online April 14, 2020, in press) Thanks to KT Park’s Twitter feed for this reference.

  • Methods: We collected data from the multicenter randomized trial of the CD exclusion diet (CDED). We analyzed data from 73 children with mild to moderate CD (mean age, 14.2±2.7 y) randomly assigned to groups given either exclusive enteral nutrition (EEN, n=34) or the CDED with 50% (partial) enteral nutrition (n=39). Patients were examined at baseline and at weeks 3 and 6 of the diet. Remission was defined as CD activity index scores below 10 and response was defined as a decrease in score of 12.5 points or clinical remission. Inflammation was assessed by measurement of C-reactive protein.
  • Results: At week 3 of the diet, 82% of patients in the CDED group and 85% of patients in the EEN group had a dietary remission (DiRe). Median serum levels of C-reactive protein had decreased from 24 mg/L at baseline to 5.0 mg/L at week 3 (P<.001). Among the 49 patients in remission at week 6, 46 patients (94%) had a DiRe and 81% were in clinical remission by week 3. In multivariable analysis, remission at week 3 increased odds of remission by week 6 (odds ratio, 6.37; 95% CI, 1.6–25; P=.008) whereas poor compliance reduced odds of remission at week 6 (odds ratio, 0.75; 95% CI, 0.012–0.46; P=.006).
  • Conclusions: For pediatric patients with active CD, dietary therapies (CDED and EEN) induce a rapid clinical response (by week 3).

Related blog posts:

Disclaimer: This blog, gutsandgrowth, assumes no responsibility for any use or operation of any method, product, instruction, concept or idea contained in the material herein or for any injury or damage to persons or property (whether products liability, negligence or otherwise) resulting from such use or operation. These blog posts are for educational purposes only. Specific dosing of medications (along with potential adverse effects) should be confirmed by prescribing physician.  Because of rapid advances in the medical sciences, the gutsandgrowth blog cautions that independent verification should be made of diagnosis and drug dosages. The reader is solely responsible for the conduct of any suggested test or procedure.  This content is not a substitute for medical advice, diagnosis or treatment provided by a qualified healthcare provider. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a condition

 

AGA Guidelines: Moderate to Severe Ulcerative Colitis

Full Text: JD Feuerstein et al. Gastroenterol 2020; 158: 1450-61. AGA Clinical Practice Guidelines on the Management of Moderate to Severe Ulcerative Colitis

Full Tex PDF: AGA Clinical Practice Guidelines on the Management of Moderate to Severe Ulcerative Colitis

 

Associated articles included the following:

  • Clinical decision support tool (1462-63)
  • PDF: Spotlight (summary -images above) (1464)
  • Technical Review (1465-96)

Key recommendations:

  • 2a. In adult outpatients with moderate to severe UC who are naïve to biologic agents, the AGA suggests using infliximab or vedolizumab rather than adalimumab, for induction of remission. Comment: Patients, particularly those with less severe disease, who place higher value on the convenience of self-administered subcutaneous injection, and a lower value on the relative efficacy of medications, may reasonably chose adalimumab as an alternative
  • 2c. In adult outpatients with moderate to severe UC who have previously been exposed to infliximab, particularly those with primary nonresponse, the AGA suggests using ustekinumab or tofacitinib rather than vedolizumab or adalimumab for induction of remission.
  • 6. In adult outpatients with moderate to severe UC, the AGA suggests early use of biologic agents with or without immunomodulator therapy rather than gradual step up after failure of 5-ASA. Comment: Patients, particularly those with less severe disease, who place higher value on the safety of 5-ASA therapy and lower value on the efficacy of biologic agents or tofacitinib may reasonably chose gradual step therapy with 5-ASA therapy.
  • 10. In hospitalized adult patients with ASUC refractory to intravenous corticosteroids, the AGA suggests using infliximab or cyclosporine

Summary of recommendations:

Related blog posts:

Disclaimer: This blog, gutsandgrowth, assumes no responsibility for any use or operation of any method, product, instruction, concept or idea contained in the material herein or for any injury or damage to persons or property (whether products liability, negligence or otherwise) resulting from such use or operation. These blog posts are for educational purposes only. Specific dosing of medications (along with potential adverse effects) should be confirmed by prescribing physician.  Because of rapid advances in the medical sciences, the gutsandgrowth blog cautions that independent verification should be made of diagnosis and drug dosages. The reader is solely responsible for the conduct of any suggested test or procedure.  This content is not a substitute for medical advice, diagnosis or treatment provided by a qualified healthcare provider. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a condition