FDA approves Amjevita (Humira biosimilar)

Posted on November 26, 2016 by gutsandgrowth

On 9/23/16: FDA approved Amjevita (Humira biosimilar)

Excerpt:

The U.S. Food and Drug Administration today approved Amjevita (adalimumab-atto) as a biosimilar to Humira (adalimumab) for multiple inflammatory diseases.

Amjevita is approved for the following indications in adult patients:

moderately to severely active rheumatoid arthritis;
active psoriatic arthritis;
active ankylosing spondylitis (an arthritis that affects the spine);
moderately to severely active Crohn’s disease;
moderately to severely active ulcerative colitis; and
moderate to severe plaque psoriasis.

…Amjevita is biosimilar to Humira. It has been approved as a biosimilar, not as an interchangeable product.

Fort Knox, Maine

Finding Residual Hepatitis C Virus in Liver Explants

Posted on November 25, 2016 by gutsandgrowth

A recent report (M Gambato et al. Gastroenterol 2016; 151: 633-6) provides some insight into the importance of the presence of residual hepatitis C virus (HCV) RNA in the liver of patients undergoing liver transplantation.

The authors note that many patients with cirrhosis due to HCV do not complete a full course of antiviral therapy before liver transplantation as the waiting time is unpredictable. The authors studied whether there was HCV RNA in the liver of 39 of these patients and tried to assess whether its presence was associated with relapse after liver transplantation.

Background:

Only 6 patients (15%) had completed treatment prior to liver transplantation.
Most patients (68%) had undetectable serum HCV RNA.
Treatment was most commonly sofusbuvir/ribavirin (n=30)

Key findings:

HCV RNA was detected in 26 of 39 liver explants (67%). Higher levels were detected in those who had received a shorter course of treatment at time of liver transplantation. Interestingly, HCV RNA was also detected in 2 (20%) of controls who had an SVR after completing an interferon-free treatment regimen.
33 of 39 (85%) achieved a post-transplantation virologic response (pTVR) and 6 (15%) had recurrent HCV infection. Thus, the persistence of HCV RNA in liver explant did not preclude pTVR.
Among the 26 patients with residual HCV RNA in the liver explant, a HCV RNA concentration was higher in the 4 patients that relapsed (23 vs 3 median copies/mcg total RNA).
Another unexpected finding was that among the 6 who relapsed, two had undetectable HCV RNA in liver explant –both patients carried mutations which could have rendered treatment less effective. The authors note that HCV RNA could have been present at concentrations below detection or distributed unevenly (which could have affected testing).

The authors speculate that the presence of HCV RNA may have been sequestered in membranous webs which allowed the virus to avoid degradation/host defenses.

My take (borrowed from the authors): The presence of HCV RNA in the liver explant does not seem to be associated with treatment failure/virologic relapse after liver transplantation, except in case with high concentrations.

Maine’s oldest lighthouse: Portland Head Light

Portland Head Light

Academic Performance After Anesthesia

Posted on November 24, 2016 by gutsandgrowth

A new study provides some reassurance that anesthesia at a young age is unlikely to cause harm (little to no effect) in most children.

Full text: P Glatz et al. JAMA Pediatrics, Published online November 7, 2016. doi:10.1001/jamapediatrics.2016.3470: Association of Anesthesia and Surgery During Childhood with Long-Term Academic Performance

Findings In this cohort study among 33 514 exposed children, exposure to surgery with anesthesia before age 4 years was associated with 0.41% lower school grades and 0.97% lower IQ test scores, with no difference in school grades with regard to age. The overall difference was markedly less than the differences associated with sex, maternal educational level, or month of birth during the same year.

Comment: Despite efforts to control for indications which of themselves could impact the results, it is quite possible that the small changes detected in this study are a result of confounding factors rather than due to the anesthetic itself.

My take (from the authors): “Exposure to anesthesia and surgery before age 4 years is associated with a small difference in academic performance or cognitive performance in adolescence on a population level. The magnitude of this association should be interpreted in light of potential adverse effects of postponing surgery.”

Related blog post: More evidence of anesthetic neurotoxicity

Understanding Why Vitamin D Deficiency is Not So Common Afterall

Posted on November 23, 2016 by gutsandgrowth

An excellent commentary (JE Marrison et al. NEJM 2016; 375: 1817-20) throws a bunch of cold water on the idea that there is a massive vitamin D deficiency pandemic. The main contention of the authors is that physicians, and by extension patients, focus too closely at specific thresholds which are poorly understood.

They explain the term “Estimated Average Requirement” (EAR) which is the median of the distribution of human requirements. Whereas, the RDA or recommended daily allowance “reflects the estimated requirement for people at the highest end of the distribution.” So, at least 97.5% of people will have a requirement below the RDA. However, due to Vitamin D’s importance, particularly with bone health, “the EAR is set at 400 IU per day for persons 1 to 70 years of age and 600 IU per day for persons older than 70.”

Other key points:

The EAR and RDA assume minimal to no sun exposure.
The RDAs of 600 IU/day and 800 IU/day correspond to 25(OH)D level of 16 ng/mlL and 20 ng/mL.
“A common misconception is that the RDA functions as a ‘cut point’ and that the entire population must have a serum 25(OH)D level above 20 ng per millimeter to achieve good bone health.”
“Approximately half the population has a requirement of 16 ng per milliliter (the EAR) or less.”
“Many studes establish ‘inadequacy’ using the RDA, though it is actually at the upper end of the spectrum of human need.” Thus, most people who are labelled as deficient are misclassified.
Using correct methodology, the authors assert that 13% of Americans 1-70 years are ‘at risk’ and <6% are deficient (with 25(OH)D < 12.5 ng/mL.

The problem with excessive Vitamin D testing and excessive treatment:

If 97.5% of the population has levels of Vitamin D exceeding 20 ng/mL, there are likely to be adverse effects in addition to increased costs of testing/treating.

Who to screen?

Those with risk factors for vitamin D deficiency: osteoporosis, osteomalacia, malabsorption, medications that can affect vitamin D metabolism (eg. anticonvulsants), or institutionalization
“For healthy patients, routine screening is not recommended by most medical organizations.” Though, the authors do recommend that “the RDA will nearly always meet the needs of generally healthy people.”

My take: This article makes a good argument for less testing along with avoidance of overprescribing vitamin D. Nevertheless, for healthy people taking the RDA for vitamin D is quite sensible.

Related blog posts:

Disclaimer: These blog posts are for educational purposes only. Specific dosing of medications/diets (along with potential adverse effects) should be confirmed by prescribing physician/nutritionist. 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.

Victoria Chimes -Maine’s Ship on their state quarter

Guidelines for Esophageal Atresia-Tracheoesophageal Fistula

Posted on November 22, 2016 by gutsandgrowth

From a NASPGHAN-ESPGHAN working group of surgeons and pediatric gastroenterologists. a recent guideline (U Krishan et al JPGN 2016; 63: 550-70) regarding esophageal atresia (EA) and tracheoesophageal fistula (TEF) has made 36 specific statements and graded the evidence for these recommendations.

On GERD:

Low level evidence: The authors recommended starting PPIs in the neonatal period and continuing them “up to the first year of life or longer, depending on persistence of GERD.”
High level evidence: pH monitoring is useful in evaluating the severity of acid reflux in patients with EA. Low level evidence: pH-impedance monitoring is useful to evaluate and correlate non-acid reflux in selected patients.
High level evidence: “Endoscopy with biopsies is mandatory for routine monitoring of GERD in patients with EA.” The authors recommend evaluation (pH, impedance, and/or endoscopy) at time of stopping anti-acid treatment and during long-term follow-up. Specifically, with low level of evidence, the authors advocate for one endoscopy after stopping PPI therapy, one before age 10 years, and one at transition to adulthood.”
High level evidence: Fundoplication has accepted role, despite dysmotility, in patients with recurrent anastomotic strictures and poorly controlled GERD despite maximal PPI therapy. Full evaluation prior to fundoplication is recommended.

Other Statements:

Low level evidence: the authors recommend regular multidisciplinary evaluation, the authors note that symptoms of aspiration during swallowing may be identical to GERD symptoms, and evaluation of dysphagia with EGD/UGI.
High level evidence: ENT evaluation may disclose other anatomic abnormalities
Low level evidence: The authors recommend that anastomotic strictures be excluded in symptomatic children and that there is no “evidence that routine screening and dilatation” is necessary in asymptomatic patients.
Low level evidence: Management of EA patients with eosinophilic esophagitis (EoE) should follow the treatment of EoE in non-EA patients.
High level evidence: Incidence of Barrett’s esophagus is increased in adults with EA.
No level evidence: Potential treatments for recurrent strictures: steroids, mitomycin C, stents, and endoscopic knife.

While some these recommendations noted above are based on low level evidence, it is worthwhile for experts to provide their opinions. At the same time, there are some completely useless statements included in the guidelines, like those that suggest tailoring the treatment to the underlying problem. For example: “Statement 19: We recommend tailoring management of post-fundoplication dysphagia to the underlying mechanism(s).” Another useless statement: “Statement 21: No data are available on the most efficacious methods of avoiding feeding disorders in children with EA. However, the committee recommends a multidisciplinary approach to prevent and treat feeding difficulties.” (very low level evidence). In my view, shortening the number of recommendations, mainly by eliminating the useless ones, would have been helpful.

My take: Despite my view that about 20% of the recommendations are useless (Statements 17, 19, 21, 25, 26A & 26B, 31, and 34), the overall guideline is helpful and it is still worthwhile for experts to provide their recommendations.

Related blog posts:

Rockland Harbor Lighthouse

In the News: UCSF Soda Ban

Posted on November 21, 2016 by gutsandgrowth

NY Times: Putting Sugary Soda Out of Reach

An excerpt:

Last year, U.C.S.F. removed sugar-sweetened beverages from every store, food truck and vending machine on its campus. Even popular fast-food chains on the campus, like Subway and Panda Express, have stopped selling Sprite, Coca-Cola and their sugary brethren at the university’s request….

“We’re a public health institution, and there’s something not right about us making money off of products that we know are making people sick,” said Laura Schmidt, a professor at the medical school who spearheaded the beverage initiative…

Nationwide, at least 30 medical centers have restricted the sale of soda and full-calorie sports drinks, including the Cleveland Clinic in Ohio and the University of Michigan Health System…

the beverage industry argues that the strategy is flawed. It points out that obesity rates have been climbing even as America’s soda intake has declined in recent years. And it says that focusing blame on soda alone, rather than calories from all foods, is misguided.

Related blog posts:

Good News from the Bad News Department: Outcomes of Intestinal Transplantation in Patients with Crohn’s Disease

Posted on November 20, 2016 by gutsandgrowth

Briefly noted: A recent retrospective study (BN Limketkai et al. Clin Gastroenterol Hepatol 2016; 14: 1574-81) examined outcomes of 142 patients with Crohn’s disease (CD) out of a total of 1115 cases of intestinal transplantation. The authors examined the Scientific Registry of Transplant Recipients. Since intestinal transplantation would be a very undesirable outcome in patients with CD, I titled this post as coming from the “Bad News Department.” The good news is that in the last 15 years, patients with CD disease do not appear to have worsened outcomes compared to patients without CD. Overall, during the period 1990-2014, the risk of graft failure was higher, mainly due to the initial 10 years. Graft failure was 18.6% at 1 year, 38.7% at 5 years, and 49.2% at 10 years in patients with CD compared with 14.1%, 32.1% and 41.0% in non-CD patients. The cumulative risk of death at 10 years for CD patients was 59.7%.

My take: It is good that intestinal transplantation outcomes for CD patients are now similar to all patients. In addition, intestinal transplantation outcomes are improving. Nevertheless, there is still a high death rate over 10 years.

World Toilet Day and Poo-ems

Posted on November 19, 2016 by gutsandgrowth

Thanks to my favorite blog reader for pointing me towards this NPR piece:

World Toilet Day: Read Winning Poo Haikus About Diarrheal Disease

An excerpt:

That’s the idea behind Poo Haiku, a competition created by Defeat DD, a campaigndedicated to the eradication of diarrheal disease.

Although everybody’s had the runs, it’s not something most folks talk about, says Hope Randall, digital communications officer for PATH’s Center for Vaccine Innovation and Access, which created DefeatDD to bring together resources on vaccines, nutrition, oral rehydration therapy, sanitation and more…

this winning entry from Kat Kelley of the Global Health Technologies Coalition, which references a recent study published in The Lancet:

Just six pathogens
But eighty percent of kids’
Diarrheal deaths….

Check out all of the poo-ems, including some videos, by searching for the hashtag #poohaiku on Twitter.

My take: Today is World Toilet Day -a great day to write your own poo-em. 2.4 billion people do not have access to a toilet.

World Toilet Day this year is November 19th (today).

Sandy Springs

iPatient and Physician Work Circa 2016

Posted on November 18, 2016 by gutsandgrowth

An interesting commentary (DI Rosenthal, A Verghese. NEJM 2016; 375: 1813-5) provides a closer glimpse into the meaning and nature of physicians’ work at this time.

Key points:

Medical students and residents spend 40-50% of their day in front of a computer & much of the rest of their day on the phone (coordinating care).
Time spent with patients “has remained stable over the past six decades.”
Flipping through the electronic record before seeing patients is commonplace but can lead to a ‘framing bias.’
“Our attention is so frequently diverted from the lives, bodies, and souls of the people entrusted to our care”…”despite all the rhetoric about ‘patient-centered care,’ the patient is not at the center of things.”
The authors equate the digital representation of the patient as an ‘iPatient.’
Physicians are “resentful of the time required to transcribe and translate information.”
Higher satisfaction is associated with perceptions of higher quality of care.
The authors advocate working on “rebuilding our practices and physical spaces to promote human connections that can sustain us — between physicians and patients, physicians and physicians, and physicians and nurses.”

My take: The authors provide a closer glimpse of the problem showing how our digital health has hindered meaningful interactions that go to the heart of medicine –to provide comfort and care.

Related blog posts:

Neighborhood tree a few weeks ago

Autism Drugs: Fat and Happy?

Posted on November 17, 2016 by gutsandgrowth

“The reason fat people are happy is that their nerves are well protected.”
– Luciano Pavarotti

It is not uncommon to see kids with behavioral problems that are also obese. Many times, medications which help improve behavioral problems may contribute to obesity by increasing appetite.

A recent study (K Shedlock et al. J Pediatr 2016; 178: 183-7) provides some insight into this issue. In this retrospective study, using the Military Health System database (2000-2013) with 48,762 individuals with autism spectrum disorder and with 243,810 matched controls, children with autism spectrum disorder (ASD) had significantly higher rates of obesity with OR 1.85 along with obesity-related conditions. These conditions include type 2 diabetes, hypertension, hyperlipidemia, and NAFLD/NASH.

Key points:

In children with ASD, mood stabilizers, antipsychotics, antiepileptic drugs, and selective serotonin reuptake inhibitors (SSRIs) were associated with obesity. Mood stabilizers had the greatest risk in this study, with adjusted OR of 1.41; the other medications had fairly small risk with adjusted ORs between 1.13 to 1.16.
When kids with ASD develop complications like NAFLD/NASH or hyperlipidemia, they may be less likely to adhere with recommended lifestyle changes. This can be due to sensory aversions and social deficits.

My take: Children with autism spectrum disorder are likely at increased risk for obesity at baseline; some of the medications to treat behavior problems may contribute to obesity, though they may be partly an epiphenomenon or a marker of a more severe autism spectrum disorder.

Portland Head Light