Tracking down a serial killer

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Truth be told, I really do like the murder mystery genre.  In medicine, that particular type of drama is usually absent.  Nevertheless, it is fascinating when epidemiologists can track down an agent responsible for multiple deaths and widespread illness.  The latest example: Listeria monocytogenes (NEJM 2013; 369:  944-53).

This recent report isolated Listeria monocytogenes as the agent responsible for 147 outbreak-related cases in 28 states; there were 33 deaths.  The investigators used multistage epidemiological, trace-back, and environmental studies.  Molecular finger printing of the cases identified five distinct patterns which defined the outbreak cases. By comparing the outbreak cases to sporadic cases using the “Listeria initiative,” the authors were able to determine that uncut cantaloupe ingestion was much more common among the outbreak-related cases.  Subsequently, the source of the contaminated cantaloupe were traced back to a Colorado  farm that had switched to a different cleaning method in 2011.

Other data:

  • Only 7 cases (5%) were pregnancy-associated; 1 miscarriage occurred
  • The median age was 77 years in this cohort.
  • Most of the deaths were in the elderly, with only 2 deaths occurring in individuals less than 60
  • 143 patients required hospitalization

While this report discussed 147 outbreak-related cases, there were undoubtedly many more outbreak-related cases which were unidentified due to milder illness.

Bottomline: this report provides a framework for identifying outbreaks of contaminated produce.  It reinforces the need for good agricultural practices to minimize food borne-pathogen infections. It is a good read.

Related blog posts:

PPIs in Neonates –Helpful?

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Acid suppression in infants has not been proven to be effective in reducing gastroesophageal reflux (GER) symptoms. In a systemic review, this was thought to be either “because the symptoms are not caused by GER or if due to GER, because the symptoms are caused by volume reflux, rather than acidity.”  This quote is noted in the background information of another study which came to the same conclusion (J Pediatr 2013; 163: 692-8).

The pharmaceutical-supported study enrolled neonates (n=52) at 3 centers with gestational ages between 28-44 weeks.  Half of the participants were randomized to esomeprazole (0.5 mg/kg/day) and half placebo.  GER symptoms that were required for enrollment included any 2 of the following:

  • apnea with or without bradycardia
  • apnea with or without oxygen desaturations
  • irritability/pain
  • vomiting/gagging

Participants underwent extensive testing with video monitoring, esophageal pH & impedance testing, and cardiorespiratory monitoring.  They were followed for 14 days.

Findings:

  • There were no significant differences in any GERD-related signs and symptoms.
  • The esomeprazole group had improvement in acid reflux parameters on testing at 7 days, including number of reflux episodes (35 –>23) and mean percent time with pH<4.0.  The latter change was -10.7% was statistically significant (p= .0017) compared to placebo group which had an increase in time with pH<4.0 (2.2% increase).
  • No new safety signals were identified.

Despite its widespread usage, the authors had difficulty enrolling a larger cohort.  The small sample size was one of the study’s limitations along with the 14-day study period.  This limitation also precludes conclusions regarding the safety of these medications in neonates.

Bottomline: this study adds to the growing body of evidence that proton pump inhibitors (PPIs) are not effective in infants with so-called ‘signs and symptoms of reflux.’  PPIs are effective at reducing acid exposure and could be helpful in proven mucosal disease (eg. esophagitis and gastritis).

Related blog entries:

When you gotta go…looking for a clean bathroom

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According to consumer advice guru, Clark Howard, clean bathrooms are a necessity for businesses and now there are mobile apps (eg. SitorSquat) to help people find them.  For patients with GI disorders, this app may be very helpful as well.

Here’s the link from Clark Howard:

Clark Howard: Valued workers translate into a company’s success …

An excerpt:

“Now USA Today reports that dirty bathrooms can hurt business in some very direct ways. Nearly 50 percent of restaurant patrons who experience a dirty bathroom will tell friends. Almost three in 10 restaurant patrons won’t give a place a second chance if they encounter a dirty bathroom. And if you’re a restaurant owner, remember, this is the era of the smartphone where customers are taking pictures of your dirty bathroom and sharing it on social media.

Of course, when you gotta go, you gotta go. That’s why several different smartphone apps like SitorSquat have been developed (for both Android and iOS), pointing you to the nearest clean bathrooms.”

For IBD patients, sometimes taking your own toilet can be helpful, here’s a link to portable products:

Top 5 Portable Toilets – IBD – About.com

Graphic Ads Motivate Smokers to Quit

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From NY Times (coverage of Lancet article), those graphic anti-smoking ads seem to be helping.
http://nyti.ms/18RT9Kq

An except:

For almost two decades, Lisha Hancock smoked between one and two packs of cigarettes a day…..

Then she saw a graphic television commercial featuring a former smoker, Terri Hall, who developed head and neck cancer. The widely seen advertisement shows Ms. Hall inserting a set of false teeth and placing a small speaker inside a hole in her neck.

“It scared me because I had always had problems with my throat,” said Ms. Hancock, 38, who lives in Kentucky. “When I saw that, it made me realize that there are other types of cancer besides lung cancer, and that really hit home for me.”

The ad prompted her to give up smoking about eight months ago, using a combination of an exercise and healthful eating regimen along with nicotine lozenges, and she has not had a cigarette since. But Ms. Hancock may be just one of thousands of Americans who quit smoking after seeing the commercial featuring Ms. Hall, which was part of a series of antismoking ads put out by the federal government last year. The campaign, called Tips From Former Smokers, was notable both for its raw images and because it marked the first time that the government directly attacked the tobacco industry in paid, nationwide advertisements.

According to a new study published on Monday in The Lancet, the ads may have prompted more than 100,000 Americans to give up smoking for good. (emphasis added by blog)

The study, led by a team at the Centers for Disease Control and Prevention, surveyed 5,300 Americans before and after the campaign, including 3,000 smokers. The paid ads ran for three months beginning in March, just after the New Year resolution season, when the percentage of smokers trying to quit is typically on the decline.

The researchers found that over all, four of five of smokers had seen the commercials, and the percentage who reported trying to quit rose by 12 percent. Of those who tried to quit, about 13 percent remained abstinent after the campaign had ended.

Using census data, the researchers estimated that as many as 1.6 million smokers nationwide attempted to quit as a result of the ad campaign. Most smokers require several attempts before they give up cigarettes for good, so only a fraction of those who were motivated by the campaign would have succeeded. The ads were expected to spur about 50,000 smokers to quit permanently, but the Lancet study estimated that twice that number were successful….

Historically, about half of the nation’s 45 million smokers try to quit every year, and yet cessation rates hover around 5 percent annually. Public health officials have long been telling smokers that cigarettes shave years off your life, contributing to more than 400,000 deaths every year.

The new campaign went in a different direction, focusing not on death but on quality of life. The creators of the campaign used focus groups and feedback from smokers to develop sobering ads showing real smokers with amputations, paralysis and disfigurement from heart and lung surgeries.

“I think the fact that you may die is not highly motivating to people,” Dr. Frieden said. “The fact that the remainder of your life may be very unpleasant is, and that’s what the data shows. Not only do smokers die about ten years younger than most people, but they feel about ten years older than their age.”

The campaign last year cost about $54 million and was paid for by the Affordable Care Act. …. Dr. Frieden said the money, which is only a fraction of the $8 billion the tobacco industry spends on marketing and promotion every year, was well spent.

“This is a campaign that has literally saved tens of thousands of lives,” he said. “We would like to be able to have hard-hitting campaigns like this on the air year round. The tobacco industry spends what we spent on this campaign in three days.”

Related blog posts:

Hospital-based Antimicrobial Stewardship

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While there has been growing recognition of antibiotic resistance, the efforts to implement strategies to preserve the effectiveness of our current antibiotics have not been embraced by enough stakeholders.  A recent review provides insight into the antibiotic stewardship (AS) programs that are being implemented by pediatric hospitals (JAMA Pediatrics; 2013; 167: 859-66).  Thanks to Ben Gold for sharing this reference.

AS goals are to “optimize clinical outcomes while minimizing unintended consequences of antimicrobial use, including toxicity, the selection of pathogenic organisms, and the emergence of resistance.”  Five specific goals:

  • timely management of antimicrobial therapy -prompt initiation when indicated, avoid when not indicated (eg. viral illness)
  • appropriate antibiotic selection -minimize redundant antibiotic coverage
  • appropriate antibiotic administration and de-escalation of therapy -reassess after 48-72 hrs whether to discontinue antibiotics, monitor levels when needed
  • use of available expertise and resources at point of care
  • transparent monitoring of antimicrobial data usage

Adoption of AS programs has been accelerating in the past few years.  “A recent survey of 43 children’s hospitals showed that 16 institutions (37%) ..currently have an established AS  program supported by full-time equivalents for a pediatric infectious diseases physician and/or clinical pharmacist.”  Another 15 (35%) are in the preparatory stage of implementing an AS program.

Potential barriers for AS programs:

  • Lack of funding or time –these programs have been reported to yield cost savings
  • Lack of hospital leadership
  • Concerns about physician autonomy

Potential outcome variables to measure:

  • Reduction in adverse events
  • Improved (?) antibiotic resistance trends
  • Reduction (?) in C difficile rates

The authors note that on a national level that AS programs have not been mandated. However, multiple societies, including the Infectious Diseases Society and the Society for Healthcare Epidemiology of America, have recommended their widespread adoption.

Bottomline: Improving hospital antibiotic usage with the use of AS programs will help reduce antibiotic resistance, but it is the tip of the iceberg when it comes to addressing this issue (see related blog posts below).

Related blog entries:

Do antivirals lower the risk of Hepatocellular Carcinoma in HBV?

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Meaningful endpoints of therapy are often difficult to demonstrate in clinical studies due to the length of followup that may be needed.  For patients infected with hepatitis B virus (HBV), most clinical studies use surrogate biologic, virologic and histologic markers rather than endpoints like hepatocellular carcinoma (HCC) and death.  In addition, long-term randomized trials with untreated controls are difficult to justify given the success of current treatments in improving these surrogate markers.

A recent Japanese study (Hepatology 2013; 58: 98-107 and editorial pg 18) reports data on a large entecavir-treated cohort (n=472) which was matched with a historical control (retrospective control group, n=1143).  The authors used propensity score matching to eliminate any baseline differences.

Findings:

  • Cumulative incidence of HCC rate at 5 years was 3.7% (for entecavir group) and 13.7% (for controls)
  • Using regression analysis and adjusting for known HCC risk factors, patients treated with entecavir had a hazard ratio of 0.37 for developing HCC.
  • Patients with more risk factors for HCC (eg. older, more active disease, cirrhosis) obtained greater benefit from entecavir treatment (shown in Figure 4 in manuscript)
  • The authors also showed that entecavir-treated patients also had less risk of developing HCC than lamivudine-treated patients
  • Entecavir-treated patients had low rates of resistance (0.8%) at 3.2 years of treatment

Take-home message: suppression of viral replication in HBV cirrhosis patients reduces but does not eliminate the risk of HCC.  In noncirrhotic patients, the magnitude of risk reduction is less.  Thus, patients with active disease should be treated.

Causes of Death with Hepatitis B in U.S.

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A recent study followed 6,689 patients with hepatitis B virus (HBV) between 1996-2005 and analyzed causes of death (Hepatology 2013; 58: 21-30, editorial pg 6). This study used a large prospectively-collected database.

The patients were all part of Kaiser Permanente Northern California health plan.  Patients were not eligible if they were coinfected with HIV or HCV.  Causes of death were divided into HBV-related (eg. decompensated cirrhosis [DCC], hepatocellular carcinoma [HCC]) and other causes, including cancer and cardiovascular.

Among this cohort, 68.3% were Asian-Pacific Islander (API) descent, and 11.8% were white (non-hispanic); the remainder were other or unknown descent.  The cohort had a mean age of 41 years.

Findings:

  • Males had higher overall 10-year death rates than females for total deaths (8.9% versus 4.1%) and for HBV-related deaths (4.8% versus 1.2%).
  • 46.7% of all deaths were HBV-related.
  • Death rate rose with increasing age; approximately 40% of deaths after age 40 were HBV-related.
  • Among HBV-related deaths, the death rate from HCC was twice the rate of DCC
  • “We did not find that subjects of API descent origin were at higher risk of death from HBV-related complications.”  This was unexpected because presumably “they are often infected in childhood and therefore have disease of longer duration.”
  • Limitations included absence of data on alcohol, cigarettes and coffee.  In addition, the study period occurred when treatment options for HBV were more limited.

The accompanying editorial notes wide variability in mortality outcome data depending on the study setting.   “Studies in patients with incidentally detected HBV infection, mostly conducted in blood donors in Western countries, tend to portray a benign course…with…their incidence of complications of chronic liver disease, HCC, or liver-related mortality is not significantly higher than that in hepatitis B surface antigen-negative healthy controls.”  In China, the lifetime risk for an infected patient to die from an HBV-related cause “has been estimated to be up to 50% in men and 15% in women.”

Related blog posts:

Growth after Liver Transplantation

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A retrospective chart review of patients from Australia and Japan who underwent liver transplantation between 1985-2004 provides some insight into the growth potential after liver transplantation (J Pediatr 2013; 163: 537-42).  The study included height data from 98 patients and weight data from 104 patients.

Study characteristics:

  • 58% were Australian and 42% were Japanese
  • 76 of 98 patients were transplanted for biliary atresia
  • 47% were younger than 2 years at the time of transplantation
  • Measurements were recorded pre-transplant, 1, 5, 10 and 15 years later

Findings:

  • Height recovery continued for at least 10 years to reach the 26th percentile (Z-score -0.67) 15 years after transplant.  Australian patients had better height recovery, reaching the 47th percentile (Z-score -0.06).
  • Weight recovery was most pronounced in 1st year after transplantation but also continued for 15 years.
  • The median height, weight, and BMI Z-scores are listed in Table II for all time periods
  • Those most malnourished and growth impaired at transplant exhibited the most catchup but remained significantly shorter and smaller 15 years later.

While the Australian patients had better growth in this study, this may be attributable to the fact that nearly all the Japanese in this study were transplanted before 1996 whereas Australian patients were transplanted over the entire period of the study.  Improvements in post-operative management with improved immunosuppressive treatment regimens (eg. reduced steroids) may have played a role.

Take-home message:  Most pediatric liver transplantation patients can expect to be normal-sized adults.  Those who are very malnourished at the time of transplantation, though, are likely to have some reduction in growth potential.

Related blog posts:

Immunization Recommendations from CDC 2013

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The following was copied from the ImproveCareNow Circle Newsletter (conta.cc/145rO5T):

The Centers for Disease Control and Prevention (CDC) offers easy-to-print schedules for regular childhood immunizations and “maintenance”. These are good resources for parents and patients to keep track of their vaccine schedule. You can access them here:

It is important to note: Patients taking immunosuppressant drugs (such as prednisone, 6MP, Methotrexate, biologic agents like Remicade or Enbrel) CANNOT receive a “live vaccine” because they can become ill as a result of the vaccine. This is especially important during fall when the flu vaccine is recommended. The intranasal flu vaccine (flu mist) is a live vaccine and should NOT be given to patients taking immunosuppressant drugs.

Yearly flu [injection] shots are encouraged for kids with IBD because the flu can be very serious in someone taking immunosuppressant drugs or who has a chronic illness.  Also, because the flu is a viral infection it can stimulate the immune system and could cause a flare.

Related blog link:

Protecting the most vulnerable | gutsandgrowth