Quitting Smoking Associated with Better Mental Health

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Given the amount of information about the negative consequences of smoking that is currently available, some might say that you would have to be mentally-ill to start smoking.  The good news is that stopping smoking has been associated with improvements in mental health (BMJ 2014; 348: g1151 dii 10.1136/bmj.g1151 -thanks to Mike Hart for this reference).  Free full-text BMJ article PDF

From Abstract:

Design Systematic review and meta-analysis of observational studies.

Eligibility criteria for selecting studies Longitudinal studies of adults that assessed mental health before smoking cessation and at least six weeks after cessation or baseline in healthy and clinical populations.

Results 26 studies that assessed mental health with questionnaires designed to measure anxiety, depression, mixed anxiety and depression, psychological quality of life, positive affect, and stress were included…. the standardised mean differences (95% confidence intervals) were anxiety −0.37 (95% confidence interval −0.70 to −0.03); depression −0.25 (−0.37 to −0.12); mixed anxiety and depression −0.31 (−0.47 to −0.14); stress −0.27 (−0.40 to −0.13). Both psychological quality of life and positive affect significantly increased between baseline and follow-up in quitters compared with continuing smokers 0.22 (0.09 to 0.36) and 0.40 (0.09 to 0.71), respectively). There was no evidence that the effect size differed between the general population and populations with physical or psychiatric disorders.

Conclusions Smoking cessation is associated with reduced depression, anxiety, and stress and improved positive mood and quality of life compared with continuing to smoke. The effect size seems as large for those with psychiatric disorders as those without. The effect sizes are equal or larger than those of antidepressant treatment for mood and anxiety disorders.

Figure 2 shows the relationship of the individual studies and the mental health outcomes.  In every study except one, there was improvement in those who quit smoking, though many of the studies had confidence limits that indicated that the results did not meet statistical significance.

Bottomline: This study indicates that quitting smoking can improve rather than worsen mental health.

Adenoma Detection Rate: Life or Death Quality Measure

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Many physicians bristle at numerous quality measures due to concerns that they may have little relevance to clinical practice or that they are not representative since they measure only a tiny fraction of their work.  For adult gastroenterologists, adenoma detection rate may become a quality measure that will be more difficult to dismiss (NEJM 2014; 370: 1298-306).

Background: In this study, the authors evaluated 314,872 colonoscopies by 136 gastroenterologists by using data from an integrated health care delivery organization.  They determined associations between adenoma detection rate and the risks of colorectal cancer/cancer-related deaths diagnosed 6 months to 10 years after colonoscopy.  Estimates of attributable risk were adjusted for the demographics of the patients, indications for colonoscopy, and coexisting conditions.

Key Results:

  • The adenoma detection rate varied considerably, from 7.4% to 52.5%.
  • 712 colorectal adenocarcinomas were identified during followup, including 255 advanced-stage cancers.
  • 147 deaths from interval colorectal cancer occurred.
  • Among patients of physicians with adenoma detection rates in the highest quintile, compared with patients of physicians in the lowest quintile, the adjusted hazard ratio for any interval cancer was 0.52; it was 0.43 for advanced-stage interval cancer and 0.38 for fatal interval cancer.
  • For each 1% increase in the adenoma detection rate, there was an associated decrease in the risk of cancer by 3%.

Bottomline: Previous studies have shown that spending longer than 6 minutes on a screening colonoscopy increases detection rates.  This study shows that doing a high quality colonoscopy really does alter the outcome.

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Buyer Beware: Supplement at Your Own Risk

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Although I’m a pretty good swimmer, I am always a little uneasy when I see signs that say “Swim at Your Own Risk.” Perhaps, signs like that should accompany ‘dietary supplements’ since they are unregulated and often pose a significant unknown danger.

A fascinating perspective article discusses the myriad of problems with over-the-counter supplements (NEJM 2014; 370: 1277-80).  The article begins by detailing the cases of severe hepatitis and death due to OxyElite Pro, a supplement marketed for weight loss and muscle building.  This agent was linked to 97 patients, 47 required hospitalizations, 3 resulted in liver transplantation (that’s one way to lose weight!), and one death.  An astute liver-transplant surgeon was the first to suspect this supplement.

Since then “nothing has been done to prevent another supplement from causing organ failure or death.”

Key points:

  • Supplement industry: $32 billion spent in U.S. per year on 85,000 different combinations of vitamins, minerals, botanicals, amino acids, probiotics, and other ingredients
  • Supplements do not require premarketing approval.  “Under the Dietary Supplement Health and Education Act of 1994, anything labeled as a dietary supplement is assumed to be safe until proven otherwise.”
  • More than 500 supplements have already been found to be adulterated with pharmaceuticals like anabolic steroids, unapproved antidepressants, banned weight-loss medications, untested sildenafil analogues, and even methamphetamine analogues.
  • The FDAs ability to monitor these supplements is poor.  The MedWatch (https://www.safetyreporting.hhs.gov) is plagued with underreporting and lack of timeliness.  Local health departments have frequently stumbled upon the problem first.

Some common problems with current supplements include the following:

  1. Arrhythmias with agents like Ephedra, horny goat weed, and oleander
  2. Bleeding with Ginkgo
  3. Cancer with anabolic steroids (hepatoma), Beta-carotene (lung cancer), and Vitamin E (prostate cancer)
  4. Hepatotoxicity with numerous supplements including chaparral, comfrey, fo-ti, gerrymander, and kava
  5. Other problems: stroke, kidney stones, panic attacks, rashes, and mood alterations

The perspective notes that a bill in a Senate committee if passed would require that manufacturers register their products and provide some safety information.  This is unlikely to make any significant change.  The author recommends that “every supplement ingredient should undergo rigorous safety testing before marketing.”

Bottomline: when a patient asks you if “this supplement” is OK, the honest answer is nobody knows.

Related blog post:

Living on MARS

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As anyone who follows this blog knows, I really like good acronyms.  MARS which stands for molecular adsorbents recirculating system is another good one.  Data regarding the use of MARS for acute liver failure (ALF) due to Wilson disease in children has been recently reported (JPGN 2014; 58: 160-64, editorial 140-41).

Background: MARS is a form of dialysis to remove albumin-bound toxins via a specialized membrane. MARS has been studied as a potential bridge to liver transplantation or as a support to try to avoid liver transplantation in some cases.

The present study with only four children is not terribly informative.  However, both the article and the editorial provide references on small randomized controlled trials which concur with the conclusions of the authors that “biological and clinical improvement is demonstrated in the MARS treatment group compared with the standard medical treatment group.”  Yet, recent large multicenter randomized controlled trials are inconclusive with regard to whether MARS improves survival.

Bottomline (from editorial): “MARS does not prevent transplantation, and survival outcome post transplantation is unclear.  There is no robust evidence to justify the financial implications of this intervention in a clinical setting. The present role of MARS remains within the research setting.”

Macrolide Antibiotics and Pyloric Stenosis

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It is well-recognized that infants who receive macrolide antibiotics are at increased risk of pyloric stenosis. A recent study (BMJ 2014;348:g1908) indicates that maternal macrolide intake can also increase the risk of pyloric stenosis in their infants.

Link to article from NASPGHAN twitter feed: http://t.co/CnkbdZoRVf

Conclusions Treatment of young infants with macrolide antibiotics was strongly associated with IHPS and should therefore only be administered if potential treatment benefits outweigh the risk. Maternal use of macrolides during the first two weeks after birth was also associated with an increased risk of IHPS. A possible association was also found with use during late pregnancy.

EXTEND & MUSIC: Optimizing Crohn Disease Care

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As noted in recent posts (see links below), there is increased interest in showing direct mucosal healing and achieving optimal drug levels in controlling Crohn disease (CD).

  1. Clin Gastroenterol Hepatol 2014: 12: 414-422.
  2. Clin Gastroenterol Hepatol 2014: 12: 423-431.

The first study examines the rates of deep remission induced by adalimumab.  Deep remission is “defined as the absence of mucosal ulceration and CD Activity Index scores less than 150.”

Design: The data is derived from the EXTEND (EXTend the Safety and Efficacy of Adalimumab Through ENDoscopic Healing) trial.  EXTEND was a 52-week randomized, double-blind, placebo-controlled trial of adalimumab (ADA) for adults (n=135) with moderate to severe ileocolonic CD.  All patients received open-label induction with ADA (160/80 mg at weeks 0/2), then were randomized to ongoing ADA 40 mg every other week or placebo.

Results: Rates of DR were 16% in ADA patients compared with 10% of placebo-treated patients at week 12.  By week 52, 19% of ADA patients were in DR compared with 0% of placebo-treated patients.

Key findings:

  • Analysis showed that shorter disease duration was associated with DR.  One-third of patients with CD for <2 years achieved DR.
  • Patients with DR had better outcomes than those with only mucosal healing (n=8); those with isolated clinical remission (n=19, no mucosal healing), but not DR, had similar outcomes to those with DR.  The associated editorial (pg 432) notes “symptoms will still make patients go to the emergency department, or miss work, or feel miserable, regardless of how good their mucosa looks.”
  • The authors state that during the 40 weeks after early CR, “estimated savings were $6117 for direct medical costs and $4243 for indirect costs” (total $10,360).  This monetary savings may not be offset in clinical practice by ileocolonoscopy which is not only invasive but also expensive.

Conclusion (from the authors): “Before any recommendation to adopt DR as a treatment target, establishing a clear association between achievement of DR and better long-term prognosis is necessary.”  The editorial advises against adopting DR as a treatment goal: “combining symptoms and mucosal healing into 1 end-point should be reconsidered as a measure of response to anti-inflammatory therapies.”

The second study, referenced above, examined plasma concentrations of certolizumab pegol (CZP) and endoscopic outcomes of patients with Crohn disease.

Design: The authors analyzed data (post hoc analysis) from the MUSIC (The Endoscopic MUcoSal Improvement in Patients with Active CD Treated with CZP) study. Adult patients received subcutaneous CZP (400 mg) at weeks 0, 2, and 4 followed by every 4 week treatment for 52 weeks.  Endoscopic evaluation took place at weeks 0, 10, and 54 and CZP concentrations were measured at weeks 8 and 54. At week 10, there were 45 patients analyzed and at week 54, 18 patients.

Key findings:

  • Mean CZP concentrations: 11.1 mcg/mL at week 8 (4 weeks after previous dosing) and 14.9 mcg/mL at week 54 (2 weeks after previous dosing).
  • Higher CZP concentration (by quartile values) correlated with endoscopic response (P=.0016) and remission (P=.0302) at week 10.
  • Among those with the highest CZP values, their 8-week CDEIS (CD Endoscopic Index of Severity) remission rate was 75% (12/16).  Overall, CDEIS remission was noted in 56% (25/45) at week 8.
  • At week 54, endoscopic remission correlated with plasma CZP values (P=.0206).
  • Both high CRP and high body weight inversely correlated with CZP concentrations.

Conclusion from this study: As with other anti-TNF agents, higher serum levels were associated with mucosal healing.  However, the data do not prove causality.  “It is possible that higher trough concentrations at week 8 may be a consequence of mucosal healing” rather than the reverse.

Bottomline: These two studies together show that achieving optimal long-term response correlates with therapeutic drug levels and mucosal healing.  At the same time, these studies along with many other indicate that we have along way to go in order for us to achieve these objectives consistently.

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Camp Weekaneatit for Kids with Celiac

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From my colleague, Jeff Lewis:  “The camp is called Camp Weekaneatit, it is July 13 to July 18, overnight camp, strictly gluten-free so the kids can eat what they want without having to worry.  Its part of Camp Twin Lakes – an organization that hosts tons of medical camps.  We have kids from all over – as far away as California the last two years.  Scholarships are available.”

Anyone who tries to follow a strict gluten-free diet knows how difficult it can be to take a trip outside the home.  This camp lets kids enjoy camp without the worry about the next meal or snack.  Spread the word!

 

CampInformation 

Are you familiar with CMMR-D?

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In a recent review, CMMR-D and Lynch syndrome are reviewed (JPGN 2014; 58: 144-52). The term CMMR-D refers to constitutional mismatch repair deficiency.  This occurs when an individual inherits two MMR gene defects (rather than one gene defect in Lynch syndrome). CMMR-D can occur when a different mutation is inherited from each parent. MMR genes include MLH1, MSH2, MSH6 and PMS2.

Unlike Lynch syndrome when screening for colorectal cancer (CRC) usually starts at age 20 years or 5 years before first CRC in family, with CMMR-D screening recommendations include yearly endoscopic evaluation beginning at age 3 years or at diagnosis.  Complete management guidelines are listed in Table 4.

Digging into the COMMIT Study

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“Lies, damned lies, and statistics” –Mark Twain (who attributed this quote to Benjamin Disraeli)

Using statistics, the recent COMMIT study (Gastroenterol 2014; 146: 681-88) showed that the combination therapy of methotrexate (MTX) and infliximab (IFX) was not more effective than IFX alone. Does this result makes sense? No.

Before getting back to that question, here’s the background: this 50-week study was a randomized, double-blind, placebo-controlled trial with patients assigned to either methotrexate at dose escalated gradually to 25 mg/week (n=63) or placebo (n=62); both groups received a prednisone induction (with tapering starting at week 1) along with IFX (5 mg/kg) at weeks 1, 3, 7, 14, 22, 30, 38, and 46.  Remission was considered to be a CD Activity Index (CDAI) of <150 in individuals off prednisone.  The patients enrolled in this study were on average about 40 years of age and had similar baseline characteristics, including disease duration of more 9 years.

Amazing to me was the fact that nearly 40% of both the treatment and control group included current smokers (since smoking clearly worsens CD).

Key Results:

  • Combination therapy resulted in fewer antibodies to IFX (ATIs): 4% vs. 20% (P=.01)
  • Combination therapy resulted in higher IFX trough levels: 6.35 mcg/mL vs. 3.75 mcg/mL (P=.08); the proportion with detectable trough levels was also higher in the combination group: 52% compared with 46%.
  • Safety was similar.  “No clinically relevant hepatotoxicity was identified.” However, 14 patients did experience an increase in liver enzymes. Infusion-related reactions were infrequent: 1 in combination group, and 3 in IFX monotherapy.
  • At week 14, 76% of combination group achieved prednisone-free remission and 78% of IFX monotherapy.  At week 50, these numbers were 56% and 57% respectively.

Getting back to the question about why this does not add up as a negative study –the combination group had lower ATIs and better IFX drug levels, this usually translates into better response.  As such, the limitations of this study deserve to be scrutinized:

  • Relatively small numbers of patients
  • Objective markers like colonoscopy were not included
  • Short duration of study period.  While a 1 year study is not really all that short, some benefits of medications can take a longer time to appreciate
  • Prednisone induction may have obscured MTX benefit
  • Treatment group had long duration of disease.  Those with shorter disease duration may have a more inflammatory component to their disease and respond more favorably.

Bottomline: this study showed that the combination of MTX/IFX was not statistically-superior to IFX alone.  Given the favorable benefit on ATIs and IFX drug levels, MTX combination may still be useful, particularly in those with more recent onset of IBD.

Plus One More Reference:

Clin Gastroenterol Hepatol 2014; 12: 434-42.  This retrospective study of 425 patients (1975-2012) examined features associated with failure of medical treatment. “Patients prescribed thiopurine or anti-TNF therapy when they have a complicated stage of CD are more likely to require surgery.  Better patient outcomes are achieved by treating CD at early inflammation stages.”

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Only in Kids: Allergies Vary by Region

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From the NIH:  link to full article: http://t.co/QuVzGFPTDb

An excerpt (highlighted for emphasis):

In the largest, most comprehensive, nationwide study to  examine the prevalence of allergies from early childhood to old age, scientists  from the National Institutes of Health report that allergy prevalence is the  same across different regions of the United States, except in children 5 years  and younger.

“Before this study, if you would have asked 10 allergy  specialists if allergy prevalence varied depending on where people live, all 10 of them would have said yes, because allergen  exposures tend to be more common in certain regions of the U.S.,” said Darryl  Zeldin, M.D., scientific director of the National Institute of Environmental  Health Sciences (NIEHS), part of NIH. “This study suggests that people prone to  developing allergies are going to develop an allergy to whatever is in their  environment. It’s what people become allergic to that differs.”

The research appeared online in February in the Journal of  Allergy and Clinical Immunology, and is the result of analyses performed on  blood serum data compiled from approximately 10,000 Americans in the National  Health and Nutrition Examination Survey (NHANES) 2005-2006.

… Among children  aged 1-5, those from the southern U.S. displayed a higher prevalence of  allergies than their peers living in other U.S. regions. ..

“The higher allergy prevalence among the youngest children  in southern states seemed to be attributable to dust mites and cockroaches,”  explained Paivi Salo, Ph.D., an epidemiologist in Zeldin’s research group and  lead author on the paper. “As children get older, both indoor and outdoor  allergies become more common, and the difference in the overall prevalence of  allergies fades away.”

The NHANES 2005-2006 not only tested a greater number of  allergens across a wider age range than prior NHANES studies, but also provided  quantitative information on the extent of allergic sensitization. The survey  analyzed serum for nine different antibodies in children aged 1-5, and nineteen  different antibodies in subjects 6 years and older. Previous NHANES studies used skin prick tests to test for allergies.

The scientists determined risk factors that made a person  more likely to be allergic. The study found that in the 6 years and older  group, males, non-Hispanic blacks, and those who avoided pets had an increased  chance of having allergen-specific IgE antibodies, the common hallmark of  allergies.

Socioeconomic status (SES) did not predict allergies, but  people in higher SES groups were more commonly allergic to dogs and cats,  whereas those in lower SES groups were more commonly allergic to shrimp and  cockroaches.