Prevalence of Rome IV Functional Bowel Disorders in Adults (US, UK, Canada) & Largest Study to Date on Hydroxychloroquine for COVId-19

OS Palsson et al. Gastoenterol 2020; 158: 1262-73.  The authors note that the switch from Rome III to Rome IV criteria reduces the prevalence of IBS by half, but increases the prevalence of functional constipation and functional diarrhea.

Full text PDF: Prevalence of Rome IV Functional Bowel Disorders Among Adults in the United States, Canada, and the United Kingdom

Abstract

BACKGROUND & AIMS:

Little is known about the population prevalence or demographic distributions of Rome IV functional bowel disorders (FBDs) or their effects on quality of life. We examined these in a multinational survey.

METHODS:

We analyzed data from a population-based [online] survey of adults in the United States, Canada, and United Kingdom (5931 valid responders; 49.2% female; mean age, 47.4 years; range, 18-92 years). The survey included the Rome IV Diagnostic Questionnaire, Rome III irritable bowel syndrome (IBS) and constipation questions, and the SF-8 quality of life questionnaire.

RESULTS:

The prevalence values of census-adjusted Rome IV FBDs were similar among the 3 countries; ranges were: 4.4%-4.8% for IBS, 7.9%-8.6% for functional constipation, 3.6%-5.3% for functional diarrhea, 2.0%-3.9% for functional bloating or distention, 1.1%-1.9% for opioid-induced constipation, 7.5%-10.0% for unspecified FBDs, and 28.6%-31.7% for any Rome IV FBD. FBDs were less common in older individuals, and all except functional diarrhea were more common in women. IBS was only half as prevalent by Rome IV as by Rome III criteria (4.6% vs 9.0% overall), primarily due to higher Rome IV minimum pain frequency. Functional diarrhea and functional constipation were more prevalent by Rome IV than Rome III criteria. Subjects with FBD had significant reductions in quality of life and reported more gastrointestinal doctor consultations than other subjects.

CONCLUSIONS:

More than 1 in 4 adults in the general population meet the Rome IV criteria for FBDs. These disorders affect quality of life and increase use of gastrointestinal health care. The switch from Rome III to Rome IV criteria reduces the prevalence of IBS by half, but increases the prevalence of functional constipation and functional diarrhea.

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From @EricTopol: Just published @TheLancet The largest study of hydroxychloroquine shows a significant increase in death (~35%) and >2-fold increase of serious heart arrhythmias. ~96,000 patients, ~15,000 on HCQ or CQ from 671 hospitals, 6 continents.


More Jokes:

Drunk Driving Deaths Fall, Unexpected Problem Related to “Frozen” Movie, and Hydroxychloroquine Trial

Briefly noted: Gen Surgery News: Drunk Driving Deaths Fall Thanks to Ride-Sharing Services

“Retrospective analysis of a Level I trauma center has found a direct correlation between the introduction of ride-sharing services and a decline in alcohol-related motor vehicle accidents. Over the six-year study period, the percentage of motor vehicle collisions that were related to alcohol decreased from 39% to 29% with the availability of ride-sharing apps such as Uber and Lyft….

As Dr. Friedman explained, alcohol-related motor vehicle collisions account for approximately 30% of all U.S. traffic fatalities. …a total of 1,474 patients were involved in alcohol-related motor vehicle collisions during the study period. Average annual alcohol-related traffic accidents and fatalities decreased with the availability of ride-sharing services, said Dr. Friedman, who noted that the biggest impact was observed in the 21- to 24-year-old group.”


A young girl swallowed her “Frozen” movie earring –next time instead of swallowing it, she should ‘let it go’


NEJM Full Text: Observational Study of Hydroxychloroquine in Hospitalized Patients with Covid-19

“Hydroxychloroquine-treated patients were more severely ill at baseline than those who did not receive hydroxychloroquine (median ratio of partial pressure of arterial oxygen to the fraction of inspired oxygen, 223 vs. 360)….[However] in this observational study involving patients with Covid-19 who had been admitted to the hospital, hydroxychloroquine administration was not associated with either a greatly lowered or an increased risk of the composite end point of intubation or death. Randomized, controlled trials of hydroxychloroquine in patients with Covid-19 are needed.”

Freedom from Composite End Point of Intubation or Death. The shaded areas represent pointwise 95% confidence intervals.


 

Autoimmune Hepatitis Outcomes, Grand Rounds on Splenomegaly, Hydroxychloroquine for SARS-CoV-2 & Zantac Warning

Here’s a commentary explaining why hydroxychloroquine is NOT proven effective:

Annals of Internal Medicine -Link: A Rush to Judgment? Rapid Reporting and Dissemination of Results and Its Consequences Regarding the Use of Hydroxychloroquine for COVID-19

Some of the key points:

  • While the study suggested more rapid clearance of SARS-CoV-2 virus at day 6 in those treated with hydroxychloroquine/azathioprine (n=20), the authors excluded 6 from the treatment group including one patient who died and three who were transferrred to the ICU.  In addition, the treatment group had a lower viral load at the start of treatment.
  • Other viral infections, including influenza, have also had in vitro data suggesting efficacy with hydroxychloroquine but this did not translate into clinical efficacy in clinical trials.
  • “The hydroxychloroquine shortage not only will limit availability to patients with COVID-19 if efficacy is truly established but also represents a real risk to patients with rheumatic diseases who depend on HCQ for their survival.”

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A Di Giorgio et al (J Pediatr 2020; 218: 121-9) provide long-term data (median f/u of 14.5 years) from a retrospective review on 83 children with autoimmune hepatitis (AIH, n=54)/autoimmune sclerosing cholangitis (ASC, n=29). Median age at presentation, between 2000-2004 was 12.1 years

Key findings:

  • 29% had histologic evidence of cirrhosis at diagnosis
  • At a median followup of 14.5 years, 99% were alive, 11 underwent transplantation.  In those who underwent transplantation, 5-year and 10-year survival was 95% and 88% respectively.
  • ASC was associated with IBD in 73% of cases, compared to 33% of AIH patients.
  • Treatment: 95% of all patients had normalization with transaminases with immunosuppressive treatment (most commonly azathioprine with prednisone 2.5-5 mg/day). ASC patients also received ursodeoxycholic acid 15-20 mg/kg/day.
  • Immunologic remission: 47% achieved immunologic remission which required normal IgG levels and negative/low ANA/SMA <1:20 in addition to normal transaminases.
  • Liver transplantation was needed in 28% of ASC compared to 9% of AIH patients; overall, 83% experienced 15-year transplant-free survival. Median age of those needing a liver transplant was 19.3 years.
  • Immunosuppression withdrawal was attempted in 12 patients after a median of 4.5 years of treatment.  9 were able to stay off immunosuppression.
  • An increase in case frequency was noted during the last 4 decades at this center, from 3.6 cases/year to 5.4 case/year.
  • Four patients had isolated infrequent autoantibodies of anti-SLA (n=3) nad antiLC-1 (n=1). SLA =liver soluble antigen, LC-1 =liver cytosol antibody type 1.  Thus, in those with suspected AIH/ASC, testing for these autoantibodies is important in ~5%.
  • Pathology: 18% did not have classical features of interface hepatitis.  Instead, some had lymphocytic/lymphoplasmocytic infiltrate without spillover into the parenchyma.
  • Progression from AIH to ASC occurred in 3 patients on followup cholangiography.
  • ASC would have been overlooked in 41% if one relied on pathology alone -reaffirming need for biliary imaging.

My take: This article has a number of useful points and with an overarching message that long-term outcomes are good for children with AIH/ASC.

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B Freiberg et al. 2020; 218: 221-31. This grand rounds describes the extensive workup of a 12 year old with splenomegaly ultimately due to splenic vein stenosis.  The report provides a nice review of hepatologic, hematologic, infectious, and other causes of splenomegaly as well as a work-up algorithm. (look for everything).

Initial evaluation per algorithm should start with CBC/d, retic, blood smear, liver biochemistries, GGT, coags, EBV VCA IgM, CMV IgM, Parvovirus IgM, and complete abdominal ultrasound with doppler.

Hepatologic causes of splenomegaly include the following:

  • cirrhosis with portal hypertension
  • autoimmune hepatitis/autoimmune sclerosing cholangitis
  • congenital hepatic fibrosis
  • hepatoportal sclerosis
  • nodular regenerative hyperplasia
  • storage disease and inborn errors of metabolism which includes lipidosis (Gaucher, Niemann-Pick), mucopolysaccharidoses, defects in carbohydrate metabolism (galactosemis, hereditary fructose intolerance), sea-blue histiocyte syndrome
  • anatomic disorders: portal/splenic thrombosis, Budd-Chiari, cysts, hamartomas, hemangiomas, hematoma, peliosis

Other causes of splenomegaly: infecions, hematologic-oncologic, and rheumatic disorders

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The U.S. Food and Drug Administration today announced it is requesting manufacturers withdraw all prescription and over-the-counter (OTC) ranitidine drugs from the market immediately. This is the latest step in an ongoing investigation of a contaminant known as N-Nitrosodimethylamine (NDMA) in ranitidine medications (commonly known by the brand name Zantac). The agency has determined that the impurity in some ranitidine products increases over time and when stored at higher than room temperatures and may result in consumer exposure to unacceptable levels of this impurity. As a result of this immediate market withdrawal request, ranitidine products will not be available for new or existing prescriptions or OTC use in the U.S.

New FDA testing and evaluation prompted by information from third-party laboratories confirmed that NDMA levels increase in ranitidine even under normal storage conditions, and NDMA has been found to increase significantly in samples stored at higher temperatures, including temperatures the product may be exposed to during distribution and handling by consumers. The testing also showed that the older a ranitidine product is, or the longer the length of time since it was manufactured, the greater the level of NDMA. These conditions may raise the level of NDMA in the ranitidine product above the acceptable daily intake limit.

Bill Gates: What We Need to Do Now for COVID-19, False-negative testing & Article Describing 3 Stages of Infection

A recent commentary in Washington Post by Bill Gates states clearly what we need to do now to improve the outcome of this pandemic. Link (may be behind paywall) : Bill Gates: Here’s how to make up for lost time on covid-19

  1. Nationwide stay-at-home.  Given mobility in country, having some states policies lessens the effectiveness of individual state mandates. “Because people can travel freely across state lines, so can the virus. The country’s leaders need to be clear: Shutdown anywhere means shutdown everywhere. Until the case numbers start to go down across America — which could take 10 weeks or more — no one can continue business as usual or relax the shutdown. Any confusion about this point will only extend the economic pain, raise the odds that the virus will return, and cause more deaths.”
  2. Much more testing and quicker turnaround.  This would allow more effective isolation policies and help determine if/when we are truly making progress.
  3. Nationwide coordination for ventilators/supplies.  Competition between states is counterproductive
  4. Preparation for making billions of doses of vaccine (when available)

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From NY TimesIf You Have Coronavirus Symptoms, Assume You Have the Illness, Even if You Test Negative

An excerpt:

Current coronavirus tests may have a particularly high rate of missing infections. The good news is that the tests appear to be highly specific: If your test comes back positive, it is almost certain you have the infection… From a technical standpoint, under ideal conditions, these tests can detect small amounts of viral RNA.  In the real world, though, the experience can be quite different, and the virus can be missed.

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Thanks to Ben Gold for the following article: COVD-19 Illness in Native and Immunosuppressed States: A Clinical-Therapeutic Staging Proposal (HK Siddiqi, MR Mehra. J Heart Lung Transplantation) available at jhltonline.org

This article describes three stages of COVID-19 and associated laboratory/clinical findings.

  1. I -Early stage.  “In patients who can keep the virus limited to this stage of COVID-19, prognosis and recovery is excellent”
  2. II-Pulmonary involvement (IIa) without and (IIlb) with hypoxia
  3. III-Systemic Hyperinflattion

And a reason to wary of hydroxychloroquine in its use for COVID-19: