Just Saying…Vaccines Don’t Trigger Inflammatory Bowel Disease

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The other day I was having a fun discussion on words that we may choose before providing information that others might not like.  Some examples:

  • “No offense but”…
  • “Don’t take this the wrong way”…
  • “Just saying”…

A recent report (GP de Chambrun et al. Clin Gastroenterol Hepatol 2015; 13: 1405-15) debunks claims that vaccines increase the risk of inflammatory bowel disease (IBD).  A report by Thompson NP et al (Lancet 1995; 345: 1071-74) suggested that measles vaccination could increase risk of IBD.  In the current study, the researchers examined 11 previous studies for review and meta-analysis.  Vaccines included: BCG, DPT, smallpox, poliomyelitis, pertussis, H1N1,measles, mumps, rubella, and combined MMR.  This study included 2399 patients with IBD and 33,747 controls. Bottomline: “Results of this meta-analysis show no evidence supporting an association between childhood immunization or H1N1 vaccination in adults and risk of developing IBD.” With regard to the measles vaccine in particular, the relative risk was 1.33 (CI 0.31 -5.80) in cohort studies and the relative risk was 0.85 (CI 0.60 -1.20) in case-control studies.

What types of words do you hear people use before saying something someone is not going to like?

Related posts:

Desperate Measures in Refractory IBD

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The often cited, ‘desperate times call for desperate measures,’ resonates in the setting of refractory inflammatory bowel disease (IBD).  [Of course, this saying could be used to justify about anything you want to do.]  For IBD, two recent studies point out potential remedies:

  • SA Merkley, et al. Inflamm Bowel Dis 2015; 21: 1854-59.
  • M Lazzerini, et al. Inflamm Bowel Dis 2015; 21: 1739-49, with editorial by A Bousvaros (1750-51)

In the first study, the authors retrospectively analyzed date from 24 IBD patients who were treated with intravenous immunoglobulin (IVIG) at a dose of 0.4 g/kg/day for 3 days, then 0.4 g/kg once a month. Key findings: 16 (67%) had a response and 3 (12.5%) obtained remission. Measures of improvement included CRP, ESR, Simple Endoscopic Score for Crohn’s disease, and the Harvery-Bradshaw Index. The researchers speculate that IVIG has anti-inflammatory and immunomodulator effects.  In addition, they note that IVIG can be given with concurrent infections.

In the second study, the authors studied thalidomide(1.5-2.5 mg/kg/day) in a double-blind, placebo-controlled randomized pediatric clinical trial in children with refractory active ulcerative colitis. Key findings: at week 8, clinical remission was achieved in 10/12 (83%) of thalidomide arm compared with 2/11 (19%) of control patients.  Then, among control patients who were switched, 8 of 11 (72%) reached remission as well. Peripheral neuropathy and amenorrhea were reported adverse effects. In the accompanying editorial, Dr. Bousvaros notes that there has been some data to suggest thalidomide efficacy in ulcerative colitis since 1979.  However, due to widespread bad publicity related to thalidomide-induced teratogenicity (eg. phocomelia) and side effects including neuropathy, it has not been used with much frequency. He notes that this study, as well, requires replication and speculates that “the primary focus on drug development will focus on newer small molecules and biologics, and this potentially useful medication may be left on the sidelines.” It is worth noting that the authors response (pg 1752) to this editorial was that the stigma of thalidomide is unwarranted and that teratogenicity can be avoided. “No case was observed out of 124,000 patients enrolled in the thalidomide distribution risk management program for more than 6 years.”

Bottomline: Both thalidomide and IVIG may be beneficial to desperate patients (and desperate doctors).  While small trials appear promising, larger trials are needed.  Don’t hold your breath waiting … will they ever happen?

Related blog posts:

ICD-10: Source for humor?

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Like most physicians, I am not terribly excited about the transition to ICD-10.  The increased detail with coding will take longer and be a hassle. However, there is apparently some humor to be derived from the institution of ICD-10.

From HealthcareDive.com: “There are 68,000 billing codes under the new ICD-10 system, as opposed to a paltry 13,000 under the current ICD-9. …Despite the controversy surrounding ICD-10, there is one universally agreed-upon upside to the hyper-specific coding system: Weird and obscure codes that stand for bizarre medical injuries. There’s even an illustrated book, Struck by an Orca: ICD-10 Illustrated.”

Some of the absurd ICD-10 codes from HealthcareDive.com:

  • V97.33XD: Sucked into jet engine, subsequent encounter
  • Y92.146: Swimming-pool of prison as the place of occurrence of the external cause
  • W55.41XA: Bitten by pig, initial encounter​
  • W61.62XD: Struck by duck, subsequent encounter
  • Z63.1: Problems in relationship with in-laws
  • W220.2XD: Walked into lamppost, subsequent encounter
  • Y93.D: V91.07XD: Burn due to water-skis on fire, subsequent encounter​
  • W55.29XA: Other contact with cow, subsequent encounter
  • W22.02XD: V95.43XS: Spacecraft collision injuring occupant, sequela
  • W61.12XA: Struck by macaw, initial encounter
  • R46.1: Bizarre personal appearance

Multiple authorities have weighed in on the issue of which ICD-10 codes are most zany. Here are a few links:

University of South Florida their list includes

  • Knitting and Crocheting (Y93.D1)
  • Pecked by chicken, initial encounter (W61.33XA)

Multibriefs Exclusive their list includes

  • T71.231D Asphyxiation due to being trapped in a discarded refrigerator, accidental
  • V80.730A Animal-rider injured in collision with trolley
  • Z62.1 Parental overprotection
  • T63 Unspecified event, undetermined intent

NY Times: Roughed up by an Orca? There’s a code for that (from 12/29/13) “There are codes for injuries incurred in opera houses and while knitting, and one for sibling rivalry.” This article has some nice graphics, including one of a water skier with the skis on fire.

Another Look at “Step-up” IBD Therapy

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Whether and how long to continue immunomodulators in patients who have undergone a “step-up” treatment to anti-tumor necrosis factor (anti-TNF) therapy remains murky.  This is due to conflicting data from different patient cohorts, changing treatment trends, (e.g. use of drug monitoring to enhance anti-TNF therapy), and different endpoints. With regard to the latter, dual therapy has been clearly more effective in some landmark studies (eg. SONIC, UC SUCCESS); however, there have been ongoing concerns regarding long-term outcomes and adverse effects.

Will more studies help resolve this question? Perhaps, but not today.

A recent study (MT Osterman et al. Clin Gastroenterol Hepatol 2015; 13: 1293-1301) examined a retrospective cohort of new users of anti-TNF therapy for Crohn’s disease in Medicare recipients.  The authors matched 381 combination with infliximab (ie. dual therapy) with 912 users of monotherapy. In addition, the authors did the same with adalimumab with 196 combination users and 505 monotherapy users. In their cohort, combination therapy occurred primarily as a “step-up” treatment after institution of thiopurine therapy.

Results:

  • Key outcome measures were unchanged: rates of surgery (hazard ratio [HR] 1.2, hospitalization HR 0.82, discontinuation of anti-TNF therapy or surgery HR 1.09, and serious infection HR 0.93
  • Opportunistic infections were increased in combination therapy with HR 2.64 and herpes zoster infection was increased with HR 3.16

Take-home message: This study suggests, at least in this elderly population, that once remission is achieved with anti-TNF therapy, discontinuation of thiopurine therapy or use of an alternative immunomodulator therapy may be worthwhile.  At the same time, definitive answers to these type of questions await carefully designed randomized trials.

Related blog posts:

Identifying Anastomotic Ulcers with Capsule Endoscopy

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A retrospective review (LM Bass et al. JPGN 2015; 61: 215-9) showed that capsule endoscopy (CE) can be helpful in identifying anastomotic ulcers among patients with short bowel syndrome and chronic GI blood loss.

This study of 4 patients (& 6 CE procedures) indicated that two of these patients underwent surgery after identifying anastomotic ulcers.  The other common treatment was antibiotics. In the suggested evaluation CE was used after upper/lower endoscopy. The recommended role for patency capsule/small bowel imaging is not clearly spelled out, but should be carefully considered due to the risk of strictures.

“The decision to perform CE is made in conjunction with medical and surgical teams so that, although every effort is made to avoid a situation that may result in a retained capsule, both parents and care teams are prepared.”

Related blog posts:

Why We Should Not Worry That Much About Water Intake

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A recent article in the NY Times rebuts the claim that so many kids are dehydrated: No, You Don’t Have to Drink 8 Glasses of Water a Day

An excerpt:

Prospective studies fail to find benefits in kidney function or all-cause mortality when healthy people increase their fluid intake. Randomized controlled trials fail to find benefits as well, with the exception of specific cases — for example, preventing the recurrence of some kinds of kidney stones. Real dehydration, when your body has lost a significant amount of water because of illness, excessive exercise or sweating, or an inability to drink, is a serious issue. But people with clinical dehydration almost always have symptoms of some sort….

This summer’s rash of stories was inspired by a recent study in the American Journal of Public Health. Researchers used data from the National Health and Nutrition Examination Survey from 2009 to 2012 to examine 4,134 children ages 6 to 19. Specifically, they calculated their mean urine osmolality, which is a measure of urine concentration. The higher the value, the more concentrated the urine…

But as people in this country live longer than ever before, and have arguably freer access to beverages than at almost any time in human history, it’s just not true that we’re all dehydrated.

Some of the key points:

  • Much of the research suggesting that there is an epidemic of under hydration is being funded by companies with a financial interest
  • Water is contained in both foods and other beverages
  • The research standard of urine osmalality >800 mOsm is not used clinically
  • There are no documented health advantages that have been identified in individuals who drink more fluid (except in those with documented history of kidney stones)

Related blog posts:

 

 

 

Does Staying Up All Night Affect Surgery the Next Day?

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According to a recent study (A Govindarajan et al. NEJM 2015; 373: 845-33), the answer is no.  That being said, my preference would be for a well-rested surgeon.

Some of the details:

The authors conducted a retrospective, population-based, matched cohort study in Ontario, Canada.  Twelve procedures were analyzed from 1448 physicians and involving 38,978 patients.  The same physicians had his/her procedures compared when they were done after treating patients from midnight to 7am to when these were done on days that were not preceded by night call.  The physicians included in the study were attending physicians; thus this does not provide insight into whether residents or fellows would perform similarly.

Key finding:

  • No difference in any primary outcome: death, readmission, or complication.  This primary outcome occurred in 22.2% after night call and 22.4% without night call.

Here’s a graph below -which depicts, from top to bottom, odds ratio for cholecystectomy (n=9322 patients, 479 physicians), gastric bypass (n=320 patients, 25 physicians), colon resection (n=2214 patients, 315 physicians), hysterectomy (n=7020 patients, 384 physicians), knee arthroplasty (n-2504 patients, 192 physicians), hip arthroplasty (n=1564 patients, 154 physicians), repair hip fracture (n=1192 patients, 166 physicians), lung resection (n=550 patients, 55 physicians), CABG (n=460 patients, 48 physicians), Spine surgery (n=3456 patients, 104 physicians), Craniotomy (n=1396patients, 66 physicians), Angioplasty (n=8980 patients, 130 physicians)

From NEJM Twitter Feed

From NEJM Twitter Feed

FDA Approves New Drug for Nausea/Vomiting

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FDA Announcement -here’s excerpt:

The U.S. Food and Drug Administration approved Varubi (rolapitant) to prevent delayed phase chemotherapy-induced nausea and vomiting (emesis). Varubi is approved in adults in combination with other drugs (antiemetic agents) that prevent nausea and vomiting associated with initial and repeat courses of vomit-inducing (emetogenic and highly emetogenic) cancer chemotherapy….

“Chemotherapy-induced nausea and vomiting remains a major issue that can disrupt patients’ lives and sometimes their therapy,” said Amy Egan, M.D., M.P.H., deputy director of the Office of Drug Evaluation III in the FDA’s Center for Drug Evaluation and Research. “Today’s approval provides cancer patients with another treatment option for the prevention of the delayed phase of nausea and vomiting caused by chemotherapy.”

Varubi is a substance P/neurokinin-1 (NK-1) receptor antagonist. Activation of NK-1 receptors plays a central role in nausea and vomiting induced by certain cancer chemotherapies, particularly in the delayed phase. Varubi is provided to patients in tablet form.

The safety and efficacy of Varubi were established in three randomized, double-blind, controlled clinical trials where Varubi in combination with granisetron and dexamethasone was compared with a control therapy (placebo, granisetron and dexamethasone) in 2,800 patients receiving a chemotherapy regimen that included highly emetogenic (such as cisplatin and the combination of anthracycline and cyclophosphamide) and moderately emetogenic chemotherapy drugs. Those patients treated with Varubi had a greater reduction in vomiting and use of rescue medication for nausea and vomiting during the delayed phase compared to those receiving the control therapy…

The most common side effects in patients treated with Varubi include a low white blood cell count (neutropenia), hiccups, decreased appetite and dizziness.

Varubi is marketed by Tesaro Inc., based in Waltham, Massachusetts.

Changing Practice Patterns with Pediatric Pancreatitis

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A recent study (FK Szabo et al. J Pediatr 2015; 167: 397-402) supports the practice of early enteral nutrition and aggressive fluid administration with acute pancreatitis. Starting in January 2014, Cincinnati Children’s began using high rates of intravenous fluid and resuming enteral nutrition within 48 hours for children presenting with acute pancreatitis.  This retrospective study assessed this practice in 201 patients and compared with prior experience dating back to 2009. To be included, patients had to have mild acute pancreatitis based on the Atlanta criteria (Gut 2013; 62: 102-11). Exclusion criteria:

  • Severe acute pancreatitis: multiorgan failure, systemic inflammatory response, local pancreatic complications (eg. necrosis, hemorrhage, pseudocyst), or respiratory complications
  • Pancreatitis due to trauma, gallstones or postsurgical

With regard to enteral nutrition (EN), nasoenteric tubes were not placed during the first 48 hours, but preexisting enteral tubes were used. So, most patients were orally fed. With regard to IV fluids, 62% received 1.5-2 times the maintenance IVF during the first 24 hours of admission.  More than 90% of cases received dextrose 5% normal saline. Key Findings:

  • Length of stay was 2.9 days in the early EN group compared with 4.4 days in the NPO group (P <.0001).  It is noted that the NPO group did include 24% with severe acute pancreatitis compared with 6% in the early EN group.
  • The authors did not identify any change in measured outcomes based on high or low volume IVF.

From the discussion:

  • “EN remains an integral part of management which has been associated with a lower incidence of infection, multiorgan failure, lower mortality rates, and a shorter hospital stay in adult patients with AP [acute pancreatitis]”
  • “Our study shows that oral feeds represent a safe and a feasible strategy in mild AP.” There was not an increase in readmission rates within 72 hours of discharge, either.

Because this is a retrospective study, this limits the interpretation of these findings; there could be an element of reverse causation with regard to the outcomes.

My take: Increasing evidence supports the practice of early enteral feedings in mild acute pancreatitis.  The exact IV fluids to use remain unclear, though my preference is lactated ringer’s based on ERCP-induced pancreatitis studies.

Related blog posts:

  • Why an ERCP Study Matters to Pediatric Care | gutsandgrowth This post explains why LR may be best.
  • Nutrition University / gutsandgrowth What are the nutritional management recommendations for acute pancreatitis? Justine Turner indicated that too many centers continue to rely on parenteral nutrition.  Yet, guidelines recommend the use of enteral nutrition due to lower risk of poor outcomes (eg. infections when NPO and on parenteral nutrition). ‘Resting pancreas is not helpful.’ With acute pancreatitis, enzyme secretion is reduced.  Her approach is to start nasogastric (NG) feedings at about 24 hours after presentation, as long as hemodynamically stable.  She indicated that nasojejunal (NJ) feedings can be done if NG is not well-tolerated.  NJ feedings are effective at reducing enzyme secretion.  However, Praveen Goday stated that his practice was often starting with NJ feeds.  “Sometimes there is only one shot” before the ICU team starts HAL.  Both physicians indicated that polymeric formulas were probably acceptable; however, starting with semi-elemental or elemental feedings are often done, again as a practical matter to minimize the likelihood of reverting to parenteral nutrition.
Artist Point, Yellowstone

Artist Point, Yellowstone

1000th Tweet: GI Symptoms Preceding IBD Diagnosis

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Another milestone for this blog: since 2012, the blog has been publicized on twitter; this is the 1000th tweet. It is also 1314th blog post over nearly 4 years.

A recent study (H Singh et al. Clin Gastroenterol Hepatol 2015; 13: 1302-09) indicates that children with inflammatory bowel disease (IBD) were more likely to have gastrointestinal symptoms in each of the 4 years before the diagnosis of IBD than children without IBD.

In this study, the researchers identified all children with IBD from a population-based Manitoba database; Manitoba had a population of 1.27 million in 2012.  651 children were matched with 5950 controls without IBD.  The study’s Table 1 & 2 indicates that children with IBD had increased clinic visits prior to diagnosis:

  • 54-66 months prior: standardized rate ratio for number of ambulatory visits 1.15; & for ≥1 visit due to GI symptoms odds ratio 1.44
  • 42-54 months prior: standardized rate ratio for number of ambulatory visits  1.22; & for ≥1 visit due to GI symptoms odds ratio 2.05
  • 30-42 months prior: standardized rate ratiofor number of ambulatory visits 1.19; & for ≥1 visit due to GI symptoms odds ratio 2.16
  • 18-30 months prior: standardized rate ratio for number of ambulatory visits 1.23; & for ≥1 visit due to GI symptoms odds ratio 2.93
  • 6-18 months prior: standardized rate ratio for number of ambulatory visits  1.15; & for ≥1 visit due to GI symptoms odds ratio 5.23

There was not a clear trend in increased symptoms between those who developed Crohn’s disease compared with Ulcerative Colitis. In addition, the study noted a trend towards decreased colectomy and resective surgery in Crohn’s in the time period 2002-2010 compared with 1987-2001.  One limitation of this study is the few number of pediatric gastroenterologists in Manitoba (only 1 before 2003); the lack of pediatric gastroenterology availability could impact timely diagnosis.

My take: This data shows that GI symptoms still predate diagnosis in many children and indicate a potential for diagnosis delay. The authors note that noninvasive tools like stool calprotectin have not been widely adopted (at least in Manitoba) and could be helpful in reducing diagnostic delays.

Estes Park, Colorado

Estes Park, Colorado