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]

Inadequate treatment of anemia in IBD

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In some patients with inflammatory bowel disease (IBD), treatment of anemia associated with IBD sometimes results in more symptomatic benefit than treatment of the IBD.  Yet, anemia remains common in IBD, both in children and adults (Inflamm Bowel Dis 2012; 18: 513-19).

Using a cross-sectional observational study design, a tertiary adult and pediatric IBD center reviewed consecutive clinic patients in April 2009.  The prevalence of anemia was 70% (41/59) children, 42% (24/54) adolescents, and 40% (49/124) adult.  In addition, iron deficiency anemia was more common in the pediatric population: 36/41 children and 20/23 adolescents.  In the adults with anemia, only 55% (27/49) were iron deficient.  One of the key determinants of anemia was disease activity.

Interestingly, among patients with iron deficiency, younger age was inversely associated with treatment with iron therapy: 13% of children, 30% of adolescents, and 48% of adults.

Other important aspects of anemia in IBD:

  • Anemic patients can have quality of life scores as poor as those seen in malignancy
  • Almost all IBD patients will respond to either oral or parenteral iron.  Erythropoetin reserved for patients who do not respond to parenteral iron.

Additional references:

  • -NEJM 2005; 352: 1011. Anemia algorithm.  If transferrin saturation <16%, check ferritin.  If ferritin less than 30, then patient with Fe-deficiency; if >100, anemia of chronic disease.  If 30-100, could check soluble transferrin receptor (level of sTranReceptor/log ferritin < 1 is c/w anemia of chronic disease whereas when > 2, c/w combined Fe-def anemia and anemia of chronic disease)
  • -JPGN 2010; 51: 708. 25-50% still anemic 1yr post IBD diagnosis.
  • -IBD 2007; 13: 1545-53. Guidelines for anemia mgt w IBD. Max oral absorption is 10-20mg/day; thus IV iron often needed. Goal for iron Rx is transferrin saturation of 15-50% and ferritin > 30 mcg/L (>100 if active inflammation). Anemia of chronic disease likely if TS <16% and ferritin > 100. Rec IV iron Rx prior to use of Epo. IV iron effective alone in 70-80%. Epo if no response to IV iron & Hgb <10. Consider folic acid & B12 deficiency if high MCV. AZA/6MP usually associated with pancytopenia not isolated anemia.
  • -Gastroenterology 2011; 141: 846. Ferric carboxymaltose better than iron sucrose (Ferrlecit/Venofer) b/c can use higher dose & give more rapidly.

Picking winners and losers with liver transplantation allocation

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From a pediatric hepatology viewpoint, I’ve always been concerned that scoring systems  do not favor children.  More data is now available relevant to this topic:

  • Goldberg et al. Liver Transplantation 2012; 18: 434-43, editorial: 381-83 
  • Sepulveda et al. Liver Transplantation 2012; 18: 413-422, editorial: 389-90

These articles and the editorials look at the model for end-stage liver disease (MELD) and exceptions for hepatocellular carcinoma (HCC) as well as the issue of split livers to expand the donor pool.

The goals of liver transplantation allocation is to distribute livers to  minimize waiting list mortality, to distribute this valuable resource fairly, and to improve long-term outcomes.  How are we doing?

With regard to HCC, the authors indicate that the current policy is increasing the number of individuals transplanted with this indication.  Before MELD, 4.6% of all transplants were for candidates with HCC.  Between 2002-2007, the number increased to 26%.  This has dramatically improved the outcomes in this previously almost universally fatal disease.

But is the priority afforded by MELD priority unfair?  From 2005-2009, Goldberg et al show that the rate of individuals with HCC removed from the waiting list because of death or disease progression was much lower than non-HCC patients: 4.2% vs. 11% (90-day waitlist outcome).  Patients with HCC with exception points were 2.62 times less likely to die by waiting.  Thus, the authors conclude that allocating 22 MELD points to HCC patients greatly overestimates 90-day mortality.  Other conditions that receive 22 MELD points include candidates with hepatopulmonary syndrome, cholangiocarcinoma, cystic fibrosis, familial amyloidotic polyneuropathy, and portopulmonary syndrome.

Sepulveda et al performed a retrospective review of the experience from split liver transplantation in French adults.  In their cohort of 36 patients who received extended right grafts from split livers, there were increased complications.  Only 21 patients had a relatively easy postoperative course.  Six patients required retransplantation.  Overall survival rate was 84.2% and 77.7% at 1 and 5 years.  Complications were related to ischemia of hepatic segment 4.

In the editorial, Riccardo Superina makes several important points:

  • Many centers have equivalent outcomes for whole and split livers; there is likely a learning curve to improve technique.
  • In the U.S., between 2002-2009, only 288 split livers grafts were performed in adults whereas there were >29,000 whole liver transplants performed.
  • In the U.S. children have the highest mortality rates on the waiting list.  In 2008, 18% of children died without a chance for liver transplantation.
  • In France, allocation policy dictates that livers from all donors less than 30 years old should be directed to children first with the stipulation of liver splitting.  If this policy were adopted in US, it could alleviate the organ shortage for children who are currently most disadvantaged by UNOS (United Network for Organ Sharing) allocation policy.

Related blog posts:

Big gift, how much risk

Sarcopenia, fatigue, and nutrition in chronic liver disease

A liver disease tsunami

Additional references:

  • -Am J Transplant 2010; 10: 1643-48.  HCC patients advantaged with current allocation
  • -Clin Gastro & Hep 2008; 6: 1255. solutble TNF receptor 75 better at predicting mortality risk than MELD>
  • -Gastroenterology 2008; 135: 1568. MELD has changed allocation -less-ill patients now getting higher risk organs.
  • -Liver Transplantation 2006; 12: S128-S136. Guidelines for exceptions (increased status)
  • -Liver Transplantation 2006; 12: 12-15, 40-45. 53% of pediatric livers allocated based on other factors (eg. exception, status 1) than PELD score
  • -Gastroenterology 2003;124: 91-96, 251. MELD scores works fairly well in adults; factors in bilirubin, INR, creatinine.

Lower leptin with physical activity

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Leptin is a cytokine expressed primarily by adipose tissue and helps regulate energy homeostasis in the body.  Higher leptin levels are found in obesity and associated with an increase risk of cardiovascular disease, insulin resistance, and type 2 diabetes.  In a recent study, physical activity, especially vigorous physical activity, has been shown to be negatively associated with leptin levels (J Pediatr 2012; 160: 598-603).

This study was conducted in school settings in 10 European cities from 9 countries (n=902) with ages 12-18 years.  Several fitness tests including handgrip, long jump, and shuttle runs were measured along with serum fasting leptin, insulin, and glucose.

Vigorous activity and fitness test results were associated with lower leptin levels; these findings were maintained when controlling for confounders.  It is not known the exact mechanisms whereby physical activity can lower leptin levels as this finding is independent of total body fat.  The authors note that previous studies have shown some contradictory results; the authors note that this could be related to drawbacks in how some studies measured physical activity.

This study’s information, when combined with previous studies (see below) on hormonal adaptations with weight loss, suggest a reason why exercise is important to maintain weight loss.  Losing weight without exercise could result in increased appetite and make it more difficult to achieve long-term results.  In contrast, physical activity may help maintain weight loss by improving hormonal adaptation.

Additional references:

  • -NEJM 2011; 365: 1597.  Persistence of hormonal adaptations with weight loss.  Due to persistent changes in hormones like leptin & peptide YY, hard to keep wt off -result is increased appetite.
  • -NEJM 2009; 360: 859.  Obesity-wt loss: composition of diet does not seem to be important.  Total calories important.
  • -NEJM 2007; 356: 237.  Leptin receptor deficiency present in 3% of 300 patients with early-onset obesity and hyperphagia.
  • -Pediatrics 2007; 120: suppl 4: S164-S287.
  • -NEJM 2007; 357: 370.  Obestiy spread in social network.
  • -Gastroenterology 2007; 132: 2085-2276.  Special issue on obesity issues.
  • -NEJM 2006; 355: 1593.  Case review on obesity c DDx and mgt.

Diagnosing autoimmune hepatitis

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Criteria for autoimmune hepatitis (AIH) have been simplified over the last decade.  The 2008 AIH criteria have a high sensitivity and specificity in children (Clin Gastroenterol Hepatol 2012; 10: 417-21).

This study examined 238 patients: 41 AIH patients and 197 non-AIH patients.  Among these patients, 37 of the 41 AIH had sufficient data to calculate 2008 score using IgG or globulin & 40 of the 197 of the non-AIH had sufficient data.  Within the 37 AIH patients, 31 had IgG levels; all 37 had either IgG or globulin.  Similarly, among the 40 non-AIH patients, 26 had IgG levels available.

Among AIH patients:  the 1999 criteria categorized 29 of 31 (94%) as definite AIH and 2 of 31 (6%) as probable AIH.  The 2008 criteria: 25  definite AIH, 2 as probable AIH, and 4 were not identified as AIH; all four had fulminant hepatic failure (FHF).

The authors conclude that the simplified 2008 guidelines have high sensitivity/specificity and are easier to use.  Patients with FHF require the 1999 criteria.

  • -Hepatology 2008; 48: 10, 169. Simplified diagnostic criteria: points for autoabs, IgG, histology, & absence of viral hepatitis.

Autoantibodies:

ANA or SMA 1:40                  1
ANA or SMA 1:80
or LKM
or SLA 1:40                           2*

IgG:
IgG >Upper normal limit        1
>1.10 times ULN                   2

Liver histology (evidence of hepatitis is a necessary condition)
Compatible with AIH             1
Typical AIH                            2
Absence of viral hepatitis      2

Scoring Total:

>/=6: probable AIH
>/=7: definite AIH
*Addition of points achieved for all autoantibodies (maximum, 2 points).

Additional references on AIH criteria:

  • -Clinical Gastro & Hep 2011; 9: 57, 3 (editorial). Many AIH meet criteria w/o liver biopsy.
  • AIH 1999 criteria:  Hepatology 2009; 50: 538. diagnosis with scoring system vs. simplified. 1999 criteria more precise. See page 539 for details:

Scoring (points in bold):
if female gender,  +2
if ALP: AST (or ALT) less than 1.5, then +2
if globulin >2 (+3), +2 if >15, +1 if >1
if ANA, >1:80 +3, 1:80 =2, 1:40 +1
if neg viral markers, +3
drug hx neg, +1
if alcohol <25g/d, +2
liver histology: if interface hepatitis +3, lymphoplasmacytic infiltrate +2
if autoimmunity in pt or 1st degree relative, then +2
if response to Rx, +2
Interpretation: if pretreatment >15 definite AIH, 10-15 probable
if posttreatment: >17 definite, 12-17 probable

Additional AIH references:

  • -Gastroenterology 2011; 140: 1980. n=229. in single center, 93% achieved NL ALT w/in 12 months –though still with increased mortality compared to general population.
  • -Liver Tx 2011; 17: 393. 86% 5yr pediatric (n=113) OLTx survival (same as entire cohort)
  • -Hepatology 2010; 53: 926. AIH steroid failures (~20%) more likely to have worse disease at presentation. n=72
  • NAPGHAN 2010 Pointers:  Rx: Typical prednisone dose is 2 mg/kg/day, max 60 mg/day (“Mieli-Vergani regimen”). 90% of patients have dramatic improvement in LFTs within 2 weeks of starting corticosteroids, 80% achieve in remission in ≤18 mos. For the 10-20% failure rate, consider non-adherence to medications or make sure that you have the right diagnosis. Most children with AIH require prolonged or indefinite treatment with steroids, albeit at low dose
  • -Hepatology 2008; 48: 863. n=243. Risk factors for HCC in AIH. Main risk is cirrhosis with HCC occuring ~102 months after cirrhosis develops
  • -Hepatology 2010; 52: 2247. Suggested protocol to minimize steroids: Combined Azathioprine (~1.5/kg in adults) with steroids. Use steroids for 3 months then taper to 5-10mg/day. If doing well, try to d/c steroids at 1 yr of Rx.
  • -JPGN 2010; 51: 524. Use of allopurinol when Azathioprine toxicity (3 cases). Allopurinol dosed between 25mg-50mg and Azathioprine reduced to 0.5-1mg/kg/day.
  • -Hepatology 2008; 48: 10, 169. Simplified dx criteria: points for autoabs, IgG, histology, & absence of viral hepatitis.
  • -Hepatology 2008; 47: 9494-57. Asymptomatic PSC common in AIH –might be higher than 10%.-Clinical Gastro & Hep 2008; 6: 379. genetic factors affecting phenotype of AIH.
  • -Clin Gastro & Hep 2008; 6: 1036. Use of cellcept/mycophenolate for AIH.
  • -JPGN 2006; 43: 635. Use of cyclosporine initially for 6 months, then changing to AZA/steroids, n=84. Goal of CYA trough 250 +/- 50 for 1st 3 months.
  • -Hepatology 2006; 43: (Suppl 1): S132. Nice review.
  • -NEJM 2006; 354: 54. AIH Review.
  • -Clin Gastro & Hepatology 2004; 2: 935. Reviews AIH/PSC criteria in children; use of GGT recommended.

Variability in Inborn Errors of Bile Acid Metabolism

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There is significant variability in the presentation of the most common inborn error of bile acid metabolism, 3β-hydroxy-Δ5-C27-steroid oxidoreductase (3β-HSD) deficiency (Molho-Pessach V et al, Hepatology 2012; 55: 1139-45).  

This report investigated a 24-year-old women from Iran with idiopathic cirrhosis and a strong family history of idiopathic cirrhosis, as well as a 32-year-old first-cousin who had a self-limited liver disease (resolved at age 9).  A genome-wide analysis of 2.4 million single nucleotide polymorphisms was performed in the patient and cousin and compared to a healthy relative.  The investigators were able to identify regions of homozygosity  that was present in the proband and cousin but not the healthy relative; one of these regions corresponded to a gene encoding 3β-HSD.  Subsequent, sequence analysis revealed a specific frameshift mutation and high levels of 3β-hydroxy-Δ5 using mass spectrometry.

For me, this report has two take home points:

  • As with a lot of diseases, 3β-HSD can have variable phenotypic expression and may present beyond infancy.  Its diagnosis remains important because a timely diagnosis allows effective treatment with bile acid replacement.
  • More ‘idiopathic’ diseases will be unmasked with new molecular tools, especially when investigators combine these tools with careful history-taking and family history.

Additional references:

  • w/u for bile acid defects: FAB-MS fast atom bombardment mass spectrometry
    **stop URSO 5 days before test
  • http://www.orpha.net/data/patho/Pro/en/InbornErrorsBileAcidMetabolism-FRenPro11194v01.pdf. Online review article from Heubi JE, et al, reprinted with permission from Thieme Medical Publishers (Seminars Liver Dis. 2007 Aug;27(3):282-294) Homepage at www.thieme.com.“At the Cincinnati Children‘ Hospital Medical Center, more than 130 patients have been identified with defects, accounting for 1% to 2% of the cases of unexplained liver disease in infants and children.”
  • -Gastroenterology 2009; 137: 1310.  Long-term good efficacy of cholic acid for primary defects in bile acid synthesis.
  • -Hepatology 2009; 39: 1403.  Review defects in bile acid synthesis.

When death is on the line

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“Never go against a Sicilian when death is on the line“! –from The Princess Bride

With acetaminophen-induced hepatic failure, King’s College Hospital (KCH) Criteria have been helpful for predicting death.  While the Sequential Organ Failure Assessment (SOFA) was not designed by a Sicilian (to the best of my knowledge), it is more sensitive at predicting death than KCH Criteria (Liver Transplantation 2012; 18: 405-412, & editorial 384-86) .

SOFA measures organ dysfunction by evaluating each of the following on a 0-4 scale: respiratory, hepatic, coagulation, cardiovascular, neurologic, and renal.

In the cited study, 125 consecutive adult patients (mean age 38 years) with acetaminophen-induced acute liver failure were evaluated.  KCH criteria had highest specificity (83%) and lowest sensitivity (47%).  The SOFA score had the best discriminative ability.  A SOFA score >7 during the first 96 hours predicted death or transplantation with a 95% sensitivity and 70.5% specificity.  Other specific predictors of poor outcome included higher lactate levels, worsened coagulation parameters, and need for mechanical ventilation.  In this cohort, 67 (54%) survived with medical management, 35 (28%) died and 23 (18%) received a liver transplant.

While sensitivity and specificity will vary based on pretest probability/specific population, what is clear is that relying on KCH criteria alone would be unwise.

Additional references:

  • -J Pediatr 2011; 159: 813.  Study of ALF in young infants.  38% were indeterminate, ~14% NH, 12% herpes.  n=148. 60% survived w/o OLT, 24% died, 16% OLT
  • -Hepatology 2010; 53: 567.  18% of indeterminate ALF may be due to acetaminophen toxicity.
  • The King’s College Criteria identify two groups of patients that have a poor prognosis with acetaminophen induced liver failure (http://en.wikipedia.org/wiki/King’s_College_Criteria)
  • -J Pediatr 2009; 155:801.  Diagnostic evaluation in ALF  –wide variation.  Often not tested for AIH, wilson’s, HAV, HBV
  • -NEJM 2009; 361: 2105.  Changes in FDA labeling of analgesics.  ~30,000 hospitalizations /yr due to acetaminophen overdose in U.S.  –1/2 inadvertent overdose.  Maximum dose -650mg.
  • -Hepatology 2007; 46: 966.  AASLD public policy.  It is leading cause of acute liver failure in U.S –50% of cases with 30% mortality rate.  500 deaths annually.  10% of cases may occur in those receiving the proper doses. In single year, acetaminophen causes more deaths than all the years of statins.
  • -JAMA 2006; 296: 87-93.  Prospective study of daily 4gm acetaminophen in healthy volunteers.  (stayed at research facility).  ALT >3 ULN in 38%.  Resolved over 6 days.
  • -Liver Transplantation 2006; 12: 682.
    -Hepatology 2005; 42: 1364-72.  74 pts died & 23 needed Tx during  6 yr period at 22 tertiary care centers.  48% of cases were unintentional overdoses.
  • -J Pediatr 2002; 140: 522.  Predictors of outcome p acetaminophen ingestion.

More on magnet ingestions

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Magnet ingestion has been a popular topic this past week on the pediatric GI listserv and follows a recent post on this blog as well (Magnet ingestion –urgent removal needed).  Two useful links are listed below: