12 Year Data: Pros and Cons with Bariatric Surgery

Posted on November 30, 2017 by gutsandgrowth

A recent study (TD Adams et al. NEJM 2017; 377: 1143-55) examines outcomes of bariatric surgery after 12 years. The ‘skinny’ on this study is that the weight loss/improved metabolic measures associated with bariatric surgery were very durable but there was a small increased risk of suicide among those undergoing bariatric surgery.

In this study, there were three cohorts:

Surgery group: 418 patients
Nonsurgery group 1: 417 patients. This group had sought surgery but did not receive surgery (often due to insurance coverage) (147 underwent subsequent surgery)
Nonsurgery group 2: 321 patients. This group had not sought surgery (39 underwent subsequent surgery)

Key findings:

At 12 yrs, mean change from baseline body weight was -35 kg in surgery group, compared with -2.9 kg in nonsurgery group 1 and 0 kg in nonsurgery group 2
Of those with type 2 diabetes in the surgery group, type 2 diabetes remitted in 75% at 2 yrs and remained remitted in 51% at 12 yrs.
The surgery group had higher remission rates of hypertension and dyslipidemia as well.
7 deaths by suicide were noted -5 in the surgery group, and 2 in the nonsurgery 1 group but only after the patients had undergone subsequent bariatric surgery

My take: Weight loss and improved metabolic changes at 6 yrs were maintained over the following 6 yrs. It is troubling that the surgery and/or weight loss is associated with suicide in a small number of patients.

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Crisis Developing in Blood Supply

Posted on November 29, 2017 by gutsandgrowth

As noted in a previous blog, Business of Blood in Decline, the number of transfusions are declining. While this is good news, there are a number of worrisome trends that indicate a crisis in the sustainability of the U.S. blood system (HG Klein et al. NEJM 2017; 1485-8).

Some background:

U.S. blood collectors draw 35,000 units a day
Blood transfusion is ordered in 10-15% of all hospitalizations
Less-invasive surgical techniques and other blood-management strategies have reduced demand for blood

So what is the problem?

The U.S. blood supply relies on nonprofit organizations which in turn have relied on blood as a major source of revenue. With reduction in blood demand and increased screening (e.g. for more infections), the cost per unit has increased; yet, due to stiff competition, there has not been a commiserate increase in reimbursement.

57.1% of America’s Blood Centers in December 2016 reported operating with negative margins
90% of the blood supply is estimated to be provided below cost
Due to cost constraints, blood suppliers are less likely to adopt additional measures which could improve patient and donor safety

The authors argue that human blood should not be treated as “just another consumer good.” Strict economic principles undervalues the need of having a safe, available blood supply. While there have not been clinical consequences thus far, the current model is not sustainable.

My take: The financial market of the blood supply is precarious. This needs to be addressed to ensure the availability of blood when we need it.

Briefly noted -related study: EA Gehrie et al. J Pediatr 2017; 189: 227-31. In this study, the authors tested 220 red blood cell units. 15 (6.8%) had detectable drugs:. opiates, benzodiazepines, stimulants, and barbituates. While none of these units would have been disallowed under current FDA regulations, it is possible that these levels could cause reactions in vulnerable populations, like neonates. The authors note that allergens, like peanuts and fish, in blood donations can result in anaphylactic transfusion reactions

The MH Score: Separating primary Hemophagocytic Lymphohistiocytosis from Macrophage Activation Syndrome

Posted on November 2, 2017 by gutsandgrowth

“Sincerity is the key to success. Once you can fake that, you’ve got it made.”

–Groucho Marx

The above quote is not particularly related to this blog post –but I like it.

A recent study (F Minoia et al. J Pediatr 2017; 189: 72-8) provides data supporting a scoring system which helps distinguish primary hemophagocytic lymphohistiocytosis (HLH) from macrophage activation syndrome (MAS).

Background: “By convention, secondary HLH seen in rheumatic disorders is termed macrophage activation syndrome…occurs most commonly in systemic juvenile idiopathic arthritis (sJIA).” Both HLH and MAS are life-threatening, though HLH tends to be more severe. The treatment for the two disorders is much different.

HLH typically develops in the first year of life, though some remain asymptomatic until later. Identification of pathologic mutations (primary HLH is not a single disease) is considered the gold standard, but this “takes weeks to complete and is not available in many resource-limited areas.”

In this study, the authors reviewed clinical features from 362 patients with MAS and 258 patients with HLH to develop a scoring system that more readily distinguished these conditions.The data from 80% of the patients was used to construct the scoring system and then this was validated with the remaining 20%. MH Score:

Age of onset, years: 0 points if >1.6 yr, 37 points if ≤1.6 yr
Neutrophil count, x 10 to the 9th/L: 0 points if >1.4, 37 points if ≤1.4
Fibrinogen, mg/dL: 0 points if >131, 15 points if ≤131
Splenomegaly: 0 points if no, 12 points if yes
Platelet count, x 10 to the 9th/L: 0 points if >78, 11 points if ≤78
Hemoglobin, g/dL: 0 points if >8.3, 11 points if ≤8.3

The age of onset and severe neutropenia are weighted the most heavily as they most heavily influence the odds ratio of having HLH; with multivariate analysis (Table 3), age of onset ≤1.6 yrs had an OR of 40.3, and neutrophil count ≤1.4 had an OR of 39.3. All of the other parameters had OR between 2.9 and 4.4. Hepatomegaly favored HLH as well but was not independently associated with the diagnosis.

How to use this scoring system:

In this cohort, the MH score ranged from 0 to 123. The median value was 97 for HLH and 12 for MAS.
A cutoff of ≥60 yielded a sensitivity of 91% and specificity of 93% for the diagnosis of HLH. Higher values increased the probability of HLH further.

Most laboratory studies were more abnormal with HLH; however, both ferritin elevation and LDH elevation were more pronounced with MAS. Median ferritin was 5353 with MAS and 2910 with HLH. Median LDH was 1230 with MAS compared with 696 with HLH.

This study validated the MH score for distinguishing HLH from MAS associated with sJIA; this can allow early introduction of aggressive treatment and appropriate genetic/immunologic evaluation. The applicability of the MH score for distinguishing HLH from other conditions is unclear. Further prospective evaluation of the MH score is needed.

My take: This is a very helpful study and is likely to influence diagnostic workup and management of these sick patients. Due to the liver and spleen abnormalities, pediatric gastroenterologists need to be able to recognize both HLH and MAS.

Related blog post:

What’s with $1040 -is a fine of $40 more going to make a difference?

FDA Postapproval Studies: ‘You can have pie as long as you do your homework later’

Posted on October 21, 2017 by gutsandgrowth

A recent commentary (S Woloshin et al. NEJM 2017; 377: 1114-7) examines the fate of FDA postapproval studies.

“Both Congress and the Food and Drug Administration (FDA) have sought to accelerate the “availability of new drugs by allowing sponsors to wait to resolve many questions about safety and benefit until after their drugs receive marketing approval.”

However, this commentary points out that many times these studies are never completed. The authors examined these studies since 2009. Key finding:

“After 5 to 6 years, 20% of postapproval studies had not been started, 25% were delayed or ongoing, and 54% had been completed.”

The authors note ‘the slow irregular pace of postapproval studies contrasts starkly with the short, rigid deadlines and other shortcuts used to speed marketing approval.” They suggest that the FDA impose fines and establish shorter deadlines. They indicate that the current administrations stated view that the FDA is ‘slow and burdensome’ could necessitate even more reliance on postapproval studies by loosening the evidence for new medication approvals.

In the same issue, the FDA responds that there have been improvements and that since 2015, “88% of postmarketing requirements overall…were progressing according to their original schedules.”

My take: More rapid approvals will inevitably lead to more medications with unrecognized safety signals. These postapproval studies are crucial in identifying infrequent but important adverse effects.

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America Needs Immigrant (Doctors)

Posted on October 20, 2017 by gutsandgrowth

While anti-immigrant sentiment has become more widespread among many, in medicine it is clear that immigrant physicians play an important role. This is discussed in a recent NY Times article: Why America Needs Foreign Medical Graduates

The key points:

Foreign medical graduates help fill residency training positions that would otherwise be left vacant. Their availability helps many hospitals operate.
Foreign medical graduates disproportionately take positions in primary care, accounting for approximately 40% of primary care physicians.
There is evidence that the care of foreign medical graduates is at least as good as physicians who received their medical degrees in the U.S.

An excerpt:

The American system relies to a surprising extent on foreign medical graduates, most of whom are citizens of other countries when they arrive. By any objective standard, the United States trains far too few physicians to care for all the patients who need them. We rank toward the bottom of developed nations with respect to medical graduates per population…

A 2015 study found that almost a quarter of residents across all fields, and more than a third of residents in subspecialist programs, were foreign medical graduates…

About a quarter of all doctors in the United States are foreign medical graduates.

My take: Physicians from other countries improve the health of our entire country. In addition, many physicians who train in the U.S. return abroad and help improve health in their home countries.

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Physician Team Cohesiveness

Posted on October 17, 2017 by gutsandgrowth

Recently, I attended our medical staff semi-annual meeting. Two speakers (Dr. Usha Sathian and Dr. Lucky Jain) provided some impressive information about the growth of the hospital system’s outreach with ambulatory care services and about the development of Emory/associated institutions’ academic medicine advances. The latter includes graduate medical education, extensive grants, and involvement in more than 1000 current clinical studies. The number of trainees at all levels has grown incredibly. These trainees are much more likely to stay in Georgia than trainees in many other parts of the country.

This growth corresponds to increases in the hospital’s bed capacity and technical abilities. A third speaker, Dr. Joseph Rosenfeld, was honored for being both a community physician and attending physician for 40 years! When he first arrived, there were eight pediatric ICU beds at Egleston Children’s hospital. Now, there has been about an 8-fold increase. The number of hospital beds has more than tripled.

Yet, sadly in my view, only a tiny number of physicians attended this meeting, a fraction that attended when the medical staff was much smaller. Despite the huge increase in staff physicians, there is a dwindling number who attend meetings; this is true for grand rounds as well. When I first arrived in town about 20 years ago, I looked forward to these meetings to engage and meet my colleagues. In addition, due to ever larger number of subspecialists, it is much less frequent that when I rotate on hospital service that I will see the well-known neurologist, pulmonologist, endocrinologist, infectious disease expert and so many others.

I came away from the staff meeting with a tangible feeling that despite the incredible success of the system in developing improved capabilities that the feeling of working together as a team of subspecialists and generalists has diminished. This makes me wonder whether other aspects of modern medicine and the worry over physician burnout are not related to increased isolation of physicians into their specialty silos and to cloistering into our computers and smartphones.

Though I feel grateful to be able to help children in my work, the biggest reason that I chose pediatrics was because of my admiration for the pediatricians I had met and my desire to both emulate their work and to work with them. I think working closely together is one aspect that makes being a pediatric specialist worthwhile.

My take: Experts have recommended “peer support” to prevent burnout and increase job satisfaction. My experience, which I suspect is shared widely, indicates that engaging with our peers is becoming less frequent.

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Great Story -How CAR-T Came About

Posted on October 15, 2017 by gutsandgrowth

While chimeric antigen receptor T-cell (CAR-T) therapy does not have much to do with pediatric gastroenterology, the development of this therapy, described recently (L Rosenbaum NEJM 2017; 377: 1313-5), holds lessons about perseverance and chance that are widely applicable.

CAR-T involves genetically engineering the patient’s own T cells to kill tumor cells. It recently received FDA approval to treat patients up to 25 years of age with relapsed or refractory acute lymphoblastic leukemia.

The story of the survival of Emily Whitehead, the index patient for this therapy, is suitable for Hollywood. The groundwork for this very expensive treatment dates back to 1893 with William Coley’s recognition of the immune system’s potential for treating cancer –he injected streptococcus into an inoperable osteosarcoma and observed tumor shrinkage.

Key Steps in this Story:

University of Pennsylvania’s immunologist Carl June spent his career working on CAR-T. His wife died of ovarian cancer in 2001 and he resolved to develop this emerging immunotherapy that he had wanted for her.
Barbara and Edward Netter provided key funding for this project in 2008. They too had lost a close family member to cancer.
Emily Whitehead nearly died due to CAR-T therapy which triggered cytokine-release syndrome, which was not a recognized entity at the time. In part due to chance, extremely high levels (>1000-fold) of interleukin-6 (IL-6) were detected quickly due to the ability of the institution and prodding by the researchers to their colleagues. This allowed the experimental use of tocilizumab, a monoclonal antibody that targets IL-6.
Her survival helped reenergize this line of research.

My take (borrowed from author): “Therapeutic advances are motivated by more than money –that it’s the hope, vision, and perseverance of both patients and investigators that made this …possible.”

Acute esophageal necrosis ina a 63 year-old that resolved with conservative treatment. “The cause is unknown..[it] occurs most commonly in the distal third of the esophagus, which is hypovascular” often in the setting of chronic disease.

We Are Last in Health Care Among High-Income Countries

Posted on October 8, 2017 by gutsandgrowth

In a recent commentary (EC Schneider, D Squires. NEJM 2017; 377: 901—4) explains why the U.S. Health Care System is last among high-income countries.

Overall, the U.S. “begins with a challenge: its population is sicker and has higher mortality than those of other high-income countries.” The U.S. has a rate of death from “conditions that can be managed and treated effectively (referred to as ‘mortality amenable to health care’) is far higher than in other high-income countries.

Four areas that have to be addressed to help U.S. move from last to first:

U.S. must confront lack of access to health care. The top-ranked countries offer universal insurance coverage with minimal out-of-pocket costs for preventive and primary care.
Underinvestment in primary care. In other countries, a higher percentage of “the professional workforce is dedicated to primary care than to specialty care.”
Administrative inefficiency. “Both patients and professionals In the United States are baffled by the complexity of obtaining care and paying for it.”
Disparities in the delivery of care. This may be mediated in part by a less robust social safety net than other high-income countries. “Social spending [for] stable housing, educational opportunities, nutrition, and transportation may reduce the demand for” many health care services.

My take: It makes me mad that our health care system performs so poorly compared to other countries.

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Firearm Mortality -Tragic Inertia

Posted on October 4, 2017 by gutsandgrowth

When it comes to gun violence, the U.S. is the leader among developed nations. It is sad how that despite the magnitude of this problem there are not significant efforts to mitigate this tragedy.

We know from Australia’s experience that changes in gun laws can make a big difference: Link: Gun Law Reforms and Firearm Mortality, Australia 1979-2013