Good care 24/7

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In hospital settings, there have been concerns about clinical care at night or weekends (see references below).  At least with liver transplantation, 24/7 care appears to be the rule rather than the exception (Liver Transpl 2012; 18: 558-65). 

Using the UNOS database, this study analyzed 94,768 transplants from 1987-2010.  Survival rates at 30, 90, and 365 days for nighttime operations: 96%, 93%, and 86% respectively.  For weekends, the respective rates were 95%, 92%, and 86%.  These rates did not differ from weekday rates.  Graft failure rates were modestly increased for weekend transplants at 365 days (HR 1.05, 95% confidence interval 1.01-1.11) but not for 30 days or 90 days.  In addition, there was no difference in graft failure between nighttime and weekday transplantations.

Additional reference:

  • -Clin Gastroenterol & Hepatol 2009; 7: 296., 303.  n>400,000 discharges.  OR 1.2 for mortality of UGI bleed if on weekend. 
  • NEJM 2001; 345: 663-668.   3,789,917 admissions (in Canada).  Weekend admissions were also associated with significantly higher mortality rates for 23 of the 100 leading causes of death and were not associated with significantly lower mortality rates for any of these conditions.

Proton pump inhibitors–infection risk with cirrhosis

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In a previous post (The Medical Pendulum and Gastroesophageal Reflux), I note that enthusiasm for proton pump inhibitors has started to wane.  In addition, a significant number of reported of potential side effects were referenced.  Another potential adverse effect is increasing the rate of spontaneous bacterial peritonitis (SBP) in patients with cirrhosis (Clin Gastroenterol Hepatol 2012; 10: 422-27).

This retrospective study examined 65 hospitalized cirrhotic patients with paracentesis-proven SBP between 2006-2009 and compared them to 65 contemporaneous hospitalized cirrhotic patients without SBP.   Patients with SBP had a higher incidence of use of PPI within previous 7 days: 71% versus 42%.  Of patients with SBP receiving PPI, the authors state that 68% did not have a documented indication for PPI use.

Additional references/previous posts:

  • –Treating reflux does not help asthma
  • -Risk of Hypomagnesemmia -2011. http://www.fda.gov/drugs/drugsafety/ucm245011.htm
  • –Gastroenterology 2010; 139: 1115.  Review of safety of PPIs.
  • –Gastroenterology 2010; 139: 93. n=167,000. PPIs associated with hip fracture risk, OR 1.3, in patients with other risk factors.
  • –Gastroenterology 2010; 138: 896-904. 5 yrs of PPI -no increase risk in hip/spine fx.
  • –Arch Intern Med 2010; 170: 765-71, 747 (ed). PPI not related to hip fx (n=161,806) women 50-79. INCREASE risk of spine fx, hazard risk 1.47
  • –Arch Intern Med 2010; 170: 772-8. PPIs increase risk of Clostridium difficile infection (hazard ratio 1.42 –42% increase in risk), n=1166.
  • –Arch Intern Med 2010; 170: 784-90. n=101,796. OR 1.74 for daily PPI, OR 2.36 if BID Rx; thus ~70% increase risk of nosocomial infection.
  • –Clin Gastro & Hep 2010; 8: 504. Increased bacterial overgrowth with PPI use.
  • -JAMA 2009; 301: 2120-2128. Use of PPIs associated with INCREASED hospital acquired pneumonia by ~30%. Could result in 180,000 HAP cases/yr with ~33,000 deaths. n+ 63,878 admissions, 52% on PPIs or H2RAs (83% PPIs, 17% H2RAs). H2RAs NOT associated with HAP cases.

Does it make sense to look for parasites in RAP?

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Probably not, in the absence of other symptoms.  A small study from Switzerland shows that treatment of Blastocystis hominis does not help recurrent abdominal pain (RAP) more than placebo (JPGN 2012; 54: 677-79).

This study result is not surprising.  A previous study of 157 RAP pediatric patients (JPGN 2007; 44: 524-26) showed that testing for ova and parasites was unnecessary as the incidence of parasitic infections in this population was not increased in RAP patients compared with controls. In this 2007 study, stool samples were positive for parasitic infection in 15 children, with no difference in prevalence between children with chronic abdominal pain (6/87; 7%) and healthy control children (9/70; 13%).

The current study had 37 patients complete the study.  The pain index (PI) for all patients improved in the study; however, there was no difference between patients who received antibiotics (trimethoprim-sulfa was used as first-line agent) compared to those who received placebo.

Regarding the methodology, the PI was either a visual analog scale with numbers from 0 to 10 or a standardized face scale; the specific scale was determined by the patient age.  Also, among the 20 patients who received antibiotics, 13 continued with B hominis in their stool tests after an initial round of therapy.  Yet the change in pain was virtually identical.  In antibiotic-treated patients, initial PI was 7.1.  After treatment, those with persistent B hominis detected in the stool had a PI of 4.2 whereas those with negative stool specimens had a PI of 4.1.  The placebo patients started with a PI of 7.4; after placebo treatment, a similar proportion cleared the B hominis from their stool –in this group, at the conclusion of the placebo treatment the PI was 2.4; the placebo group with persistent detection of B hominis had a PI of 3.2 at the conclusion of the study.

Although the potential pathogenicity of B hominis in humans remains unclear, it is not unusual in clinical practice for patients with this finding to receive treatment.   Besides trimethoprim-sulfa, metronidazole is frequently administered. Based on this study, placebo would be as helpful as an antibiotic in improving clinical symptoms.

Related blog entries:

What to make of FODMAPs

Pain changes brain

Treating diabetes with surgery

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Two articles in the New England Journal of Medicine point to the role of bariatric surgery in  treating type 2 diabetes in obese patients (NEJM 2012; 366: 1567-76 & 1577-85).  Type 2 diabetes looms as one of “the most challenging contemporary threats to public health.”

The first study was a randomized nonblinded single-center trial with 150 patients; mean BMI 36 with 34% having a BMI less than 35.  Intensive medical therapy was compared to Roux-en-Y gastric bypass or sleeve gastrectomy.  Mean patient age was 49 years. 42% of the gastric bypass group, 37% of the sleeve-gastrectomy group, and 12% of the medical treatment group achieved the primary end-point of a glycated hemoglobin level of ≤6% by the 12 month followup; the average starting glycated (HgbA1C) hemoglobin was 9.2%.  At the conclusion of the study, the average HgbA1C was 6.4, 6.6, and 7.5 respectively in the three groups.

The second study used a similar trial with 60 obese patients; all had BMI >35  At 2 years, diabetes remission occurred in 75% of their gastric bypass group, 95% of their biliopancreatic-diversion group and in no patients receiving intensive medical therapy patients. HgbA1C had similar rates of improvement as the 1st study: 6.3 in gastric-bypass, 4.9 in biliopancreatic-diversion group, and 7.7 in medical-therapy group.

While surgery has risks (see related material below), its benefits are likely to alter future treatment strategies with surgery being contemplated prior to exhausting all medical treatments.

Additional References:

  • -JAMA 2012; 307: 56-65.  Bariatric surgery and long-term cardiovascular events.
  • -JAMA 2011 [doi: 10.1001/jama.2011.817]). Large study failed to show that roux-en-Y gastric bypass prolonged life. n=850 VA pts to 41,244 controls. Same group showed no cost savings during initial 3 yrs: Med Care 2010; 48: 989-98.
  • -NEJM 2011; 365: 1365. Increased frequency of bariatric surgery in adolescents.
  • -NEJM 2009; 361: 445/520. perioperative safety.
  • -NEJM 2007; 357: 741, 753, 818. Bariatric surgery improves mortality rate.
  • NEJM 2007; 356: 2176. Review

Complications from surgery:

  • Early: bowel obstruction, DVT, GI bleed, leaks, pulmonary embolism, wound infection
  • After 30 days: anastomotic stricture, bowel obstruction, gallstones, dehiscence, fistula, Bleeding, Incisional hernia, nutrient deficiencies (iron, B12; calcium, Vit D (w RYGB), folate, B6/riboflavin).
  • Complications from gastric band: food impaction, erosion (now banned in Finland!), band slippage, gastric volvulus, band too tight, port infection
  • Roux-y gastric bypass:
    anastomotic leak 1.2%, anastomotic ulcers/stricture
  • Nutrient Monitoring–every 3months x 3, then yearly: Vitamin A, B12, Folate, Ceruloplasmin, Vit D-25OH, Iron studies, Zinc, thiamine, Selenium, Intact PTH, Mg, PT/PTT
  • Suggested supplements: Calcium c vitamin D 1200-2000mg, Iron at least 18-27mg/day, MVI with zinc/selenium
  • Also if duodenal switch, add Vitamin A 10,000 IU, and Vitamin D3 1200units daily or 50,000 units weeekly, Vitamin K 300 mcg,

Potential nutritional deficiencies:

  • B12, B6 (pyridoxine), Riboflavin (B2), B1 (Thiamine), Folate (B9)
  • Vitamins A,D,E, K
  • Calcium, Copper, Iron, Selenium, Zinc

Recommendations from NASPGHAN Post-Graduate Course 2011:

  • If post-op pain: epigastric –>do EGD & if neg do ‘RUQ w/u’, RUQ –> check U/S, LFTs possibly CT
  • If post-op vomiting –>do EGD
  • If post-op nausea –>Rx PPI and EGD if not improving
  • Anastomotic stricture in stomach –>dilate to 10-12mm in 1 session

Related blog posts (includes additional references)

Cardiovascular disease for the entire family

Staggering cost of obesity

A liver disease tsunami

Lower leptin with physical activity

Disease modifying treatment in IBD

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As noted in this blog (Only one chance to make first impression) and other sites as well, many have argued for early “top down” treatment to try to modify the natural history of Crohn’s disease (CD).  Early in the course of CD when an inflammatory process predominates, theoretically, treatment at this time point can prevent the development of intestinal fibrosis/strictured IBD phenotype.

Support for this approach can now be extrapolated from a mouse model as well (Inflamm Bowel Dis 2012; 18: 460-71).  In this study, the authors eliminated an inflammatory stimulus, Salmonella typhimurium, with levofloxacin treatment.  Treatment was initiated at sequential time points during infection.  Subsequently, the effects of the inflammation on the development of fibrosis was determined by examining histopathology; in addition, the effects on mRNA expression and protein expression were determined.  The time course of a number of cytokines is followed including TNFα, TGFβ, IL12p40, IL-17, IL-1β, and IL-6. While intestinal fibrosis developed even in those with early treatment, early treatment lessened, but did not eliminate, the development of fibrosis.

Since no effective antifibrotics exist and fibrosis may autopropagate even in the absence of inflammation, the authors postulate that early effective treatment has the best opportunity to alter the natural history.

Indomethacin to prevent post-ERCP pancreatitis

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“Take two and call me in the morning” may now apply to the use of indomethacin in preventing post-ERCP pancreatitis.  A multicenter, randomized, placebo-controlled, double-blind clinical trial has shown that rectal indomethacin (two 50 mg suppositories) can reduce the rate of post-ERCP pancreatitis (NEJM 2012; 366: 1414-22).

A total of 602 adult patients were enrolled.  Patient selection favored those at increased risk for post-ERCP pancreatitis (eg. suspicion of sphincter of Oddi dysfunction) and excluded those at low risk for this complication (eg. routine biliary stent exchange, chronic calcific pancreatitis, or a pancreatic head mass).  Other exclusion criteria included active pancreatitis, elevated creatinine (>1.4 mg/dL), active peptic ulcer disease, and those already receiving a NSAID.

The suppositories (or placebo) were administered immediately after ERCP while the patient remained in the procedure room.

Post-ERCP pancreatitis developed in 27 of 295 patients (9.2%) in indomethacin group and in 52 of 307 patients (16.9%) in placebo group.  In addition, moderate-to-severe pancreatitis was reduced as well 4.4% compared with 8.8% respectively.  In addition, there were no increased adverse events in the treatment arm; there was no increased risk of bleeding in particular.

While the mechanism of improvement is unclear, NSAIDs are potent inhibitors of phospholipase A2, cyclooxygenase, and neutrophil-endothelial interactions, all of which are known to play a role in the pathogenesis of acute pancreatitis.

Additional references:

  • -Am J Gastroenterol 2007; 102: 978-83.  Use of indomethacin to reduce pancreatitis after ERCP
  • -Gut 2008; 57: 1262-7.  Meta-analysis of rectal NSAIDs to prevent post-ERCP pancreatitis

Diseases peculiar to children

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In celebration of NEJM’s 200th anniversary, a special series of articles is being published.  A recent one, titled “What we don’t see” makes some useful observations about the history and trajectory of the field of pediatrics (NEJM 2012; 366: 1328-34).

According to the author, most physicians did not consider children as a distinct medical population in the early part of the 19th century.

  • In 1789 Benjamin Rush at the Univ of Pennsylvania gave lectures called “diseases peculiar to children.”
  • William Osler introduced the term “pediatrics” in 1880.
  • While advances in genetics, surgery, neonatology, oncology, and many other disciplines have been very important, infectious diseases have remained the predominant cause of childhood death both in the past and currently.
  • In 2008, causes of childhood death worldwide:  pneumonia 19%, diarrhea 15%, malaria 8%, other infections 26%.  Diarrhea and pneumonia each killed more than 1 million children.
  • Neonatal deaths comprised 41% of all deaths in the first 5 years of life.

Aspirin prophylaxis for colorectal cancer?

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A recent article in The Lancet has provided additional information about the use of aspirin for cancer prevention, especially colorectal cancer (Rothwell PM et al. Lancet 2012; published online March 21. DOI: 10: 1016/S0140-6736 (11)61720-0).  In the commentary on this article (DOI: 10: 1016/S0140-6736 (11)61654-1), the potential benefits of aspirin are placed into context and previous studies are reviewed.  In short, the data from a number of studies suggest that aspirin lowers the risk of cancer.

In Rothwell’s study, which pooled data from 51 randomized trials, aspirin at any dose reduced the risk of non-vascular death by 12% and cancer death by 15%.   Benefit was seen within 3 years for high-dose (>300 mg/day) and after 5 years for low doses (<300 mg).  The cumulative numbers of patients in the reviewed studies was approximately 40,000 in each arm.  These studies were divided and examined under separate categories to assess primary prevention for vascular events and to assess effects on cancer deaths.

Yet, these encouraging results though have not been seen in several large randomized trials; the editorial notes that “the Women’s Health Study (WHS) of 39,876 women treated with alternated day 100 mg aspirin over 10 years and the Physicians’ Health Study (PHS) of 22,071 men treated with alternate-day 325 mg aspirin for 5 years.  After 10-12 years of folllow-up, aspirin was not associated with reduced risk of colorectal cancer.”  In addition, as noted in previous post, ( Who needs aspirin?/Arch Intern Med 2012; 119: 112-8) a large study with over 100,000 patients also did not show reduction in mortality from vascular or non-vascular events.

Whether alternate-day dosing of aspirin (in WHS and PHS studies) undermines its efficacy in preventing cancer is not clear.  Until more data are available, aspirin for chemoprevention is best-suited for those with increased cancer risk (eg. history of colorectal cancer & hereditary cancer syndrome) and low risk of GI bleeding.  Rates of bleeding due to aspirin are about 4% per year and for serious bleeding about 2% per year. In addition, other adverse effects, including macular degeneration, have been reported with aspirin use (Ophthalmology 2012; 119: 112-8).

Additional references:

  • Link to pdf copy of cited article:http://extremelongevity.net/wp-content/uploads/asa-ca.pdf
  • -Lancet 2011; 377: 31-41. Aspirin effect on cancer mortality -decreased by 30-40% (esophageal, gastric, pancreatic, colorectal)
  • -Lancet 2010; 376: 1741 – 1750. Long-term effect of aspirin on colorectal cancer incidence and mortality: 20-year follow-up of five randomised trials. Lowers risk of colon Ca.
  • -JAMA 2009; 302: 649. Aspirin use likely increases survival after dx of colon cancer.
  • -Gastro 2010;138: 2012. Commentary on aspirin for decreasing risk after diagnosis of colon cancer.
  • -NEJM 2007; 356: 2131, 2195. Aspirin can decrease high-expressing COX-2 colon adenoca; not recommended as routine prophylaxis at this time

Who needs aspirin?

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Despite a lot of good press for aspirin with regards to prevention of cardiovascular events and cancer prevention, determining who should take aspirin is quite tricky.  This blog entry will discuss the vascular rationale and a subsequent post will tackle the potential of aspirin for colorectal cancer prevention.

At this time, the cardiovascular disease (CVD) rationale includes preventing myocardial infarction [MI] and stroke.  These are the main determinants of risk/benefit for taking aspirin.  In 2009, guidelines from US Preventive Services Task Force (USPSTF) for taking aspirin were published (Ann Intern Med 2009; 150: 396-404).  The following link can be used to access this article:

http://www.uspreventiveservicestaskforce.org/uspstf09/aspirincvd/aspcvdrs.pdf

The recommendations include the following:

Men <45:  Not encourage aspirin for MI prevention

Women <55: Not encourage aspirin for stroke prevention

Men 45-79:  Encourage aspirin when CVD benefit.  Benefit likely if:

  • 45-59 years, 10 -year CVD risk ≥4%
  • 60-69 years, 10-year CVD risk ≥9%
  • 70-79 years, 10-year CVD risk ≥12%
To calculate 10-year CVD risk: http://www.mcw.edu/calculators.htm
Risk factors: age, high blood pressure, diabetes, smoking, history of CVD, total cholesterol level, and HDL cholesterol level

Women 55-79:  Encourage aspirin when stroke benefit.  Benefit likely if:

  • 55-59 years, 10 -year stroke risk ≥3%
  • 60-69 years, 10 -year stroke risk ≥8%
  • 70-59 years, 10 -year stroke risk ≥11%

To calculate 10 -year stroke risk: http://my.clevelandclinic.org/p2/stroke-risk-calculator.aspx

Risk factors: age, high blood pressure, diabetes, smoking, history of CVD, atrial fibrillation, and left ventricular hypertrophy

In addition, it is noted that aspirin is NOT recommended when other NSAIDs are being administered or if history of GI ulcers/risk of serious GI bleeding.

While these recommendations are a useful starting point and the risk calculators are fascinating, the absolute benefit of aspirin remains unclear.  A recent article on this subject indicates that aspirin may not improve mortality (Arch Intern Med. 2012;172(3):209-216. doi:10.1001/archinternmed.2011.628).  This article reviewed nine large randomized placebo-controlled studies, each with at least 1000 participants.  In total, more than 100,000 patients were described in these studies.  While CVD events were reduced by 10%, there was no reduction in mortality for cardiovascular disease (OR 0.99) or for cancer (OR 0.93) among aspirin takers over a mean of 6 years.  Most of the reduction in CVD events were due to a lower rate of non-fatal MI (OR 0.80).  In addition, there was an increase in significant GI bleeding among patients taking aspirin (OR 1.31)

Due to these results, the authors conclude that routine use as primary prevention is not warranted; “treatment decisions need to be considered on a case-by-case basis.”

Additional reference:

  • –Arch Intern Med 2012;172:217-218.  Aspirin Therapy in Primary Prevention: Comment on “Effect of Aspirin on Vascular and Nonvascular Outcomes”

“Watch for change in the stools”

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Many years ago I noticed the tremendous burden that coin ingestions cause in terms of ER visits and need for endoscopy/anesthesia.  As a result, I contacted the US treasury.  I think if any other product resulted in this many hospitalizations and endoscopic procedures it would be removed from the market.  Well, the treasury stated that the coins are mandated by Congress and any change would need to be initiated in Congress. So, I contacted our Georgia senator and informed the office about the problem.  Apparently, it could be a while before this becomes a priority for him.

Some good news, though, based on a recent article, watchful waiting may be appropriate for many esophageal coins (Emerg Med J 2012; doi: 10.1136/emermed-2011-200958).  (The blog title quote comes from Bill Balistreri who use to say that it was not worth it to take out anything less than a quarter —just watch for change in the stools.)

Acheson J et al performed a retrospective review of esophageal coin ingestions between 2004-2010 (age <16 years).  Among asymptomatic patients who were told to wait 18 hours for a repeat xray, 33 of 37 passed spontaneously.

Exclusion criteria:

  • Previous esophageal disease
  • Previous tracheal disease
  • Coins present >24 hours

All mid-to-lower coins (that were given 18 hours) passed in this study.  The authors note that previous studies had spontaneous passage rates of 30-60%.  Some of the difference may be related to differences in the UK coins compared to coins in US.  In the UK, the authors suggest that patients who are asymptomatic and with no other risk factors should be sent home and reevaluated the next day.

**Before sending them home, make sure the “coin” is not really a button battery by examining the radiograph carefully.

Additional references:

  • -Pediatrics 2005; 116: 752 (editorial), 614-19 (article). 25-30% of coins (esp distal -56%) will pass spontaneously if given time (8-16hrs)–in this randomized study.
  • -Arch Pediatr Adol Med 1999; 153: 1073. 28% of uncomplicated esophageal coins pass c/in 24hrs
  • Emerg Med J doi:10.1136/emermed-2011-200958
    [Link to free full-text EMJ article]