• Endometriosis Linked to Increased Risk for Inflammatory Bowel Disease
• FDA Lacks Authority to Protect Public Health from Drug Shortages Says the GAO
• Vitamin D Lowers Fracture Risk, but Its Effects on Cancer and CVD Aren't
• Ketoconazole-loaded Lollipops Could Boost Oral Thrush Compliance
• Louisiana Warns of Ameba Infections Linked to Improper Neti Pot Use
• Rectal Cancer Incidence Rose After Radiation Therapy for Prostate Cancer
• Case Report: Gastric Banding Complications May Present as Pulmonary Symptoms
• Is Acetaminophen a Culprit in Asthma?
• TMP-SMX Is Another Option for Treatment of Acute Osteomyelitis
• New Antibiotic Strategies
Endometriosis Linked to Increased Risk for Inflammatory Bowel Disease
Women with endometriosis face increased risk for a subsequent diagnosis of inflammatory bowel disease (IBD), according to a study published in Gut.
Using a national Danish database, researchers examined outcomes among some 38,000 women who were diagnosed with endometriosis from 1977 through 2007. During an average follow-up of 13 years, 228 women were diagnosed with ulcerative colitis and 92 with Crohn disease — corresponding to risk increases of 50% and 60%, respectively, compared with the general population. The association between endometriosis and IBD was apparent even 20 years after the diagnosis of endometriosis.
The authors say the observed association "may be explained by shared immunological features between endometriosis and IBD, or it may reflect a hitherto little appreciated impact of endometriosis treatment on future risk of IBD."
http://gut.bmj.com/content/early/2011/12/04/gutjnl-2011-301095.abstract
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FDA Lacks Authority to Protect Public Health from Drug Shortages
Says the GAO
In a report by the Government Accountability Office, the director said Congress should consider establishing a requirement for drug manufacturers to report to FDA any changes that could affect the supply of drug products. (The question is what happens after the FDA is informed? Actually, FDA actions result in some of the drug shortages we are currently experiencing.)
http://www.gao.gov/assets/590/586979.pdf
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Vitamin D Lowers Fracture Risk, but Its Effects on Cancer and CVD Aren't
Two reviews on vitamin D appearing in the Annals of Internal Medicine point to its role in lowering fracture risk, but say little is known about its effect on cardiovascular disease and cancer.
One review, undertaken to help the U.S. Preventive Services Task Force draft recommendations, concludes that vitamin D, combined with calcium supplements, reduces fracture risk in older adults. The effect is greater among institutionalized adults than among those living in the community or among postmenopausal women. The reviewers point to conflicting findings on whether vitamin D might decrease (or even increase) the risk for cancer and thus could draw no conclusions.
The other review points to research linking hypovitaminosis D with cardiovascular disease, but says that several confounders may be at work in the association. The review concludes that "no clear evidence indicates that vitamin D supplementation has a role to play in the prevention of cardiovascular disease."
http://www.annals.org/content/155/12/827.abstract
http://www.annals.org/content/155/12/820.abstract
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Ketoconazole-loaded Lollipops Could Boost Oral Thrush Compliance
Oral thrush can commonly occur in bottle-fed babies and is also a problem for older children and adults. Antifungal compounds can treat the disorder but, especially among children, a pleasant delivery form is desirable. A current study in the International Journal of Life Sciences Biotechnology and Pharma Research states:
"Attractive, taste masking formulations are the need of the hour. In the present study ketoconazole sweetened lollipops were designed for the effective treatment of oral thrush in children".
The 3g lollipops each contained 15 mg of ketoconazole. A hydrophilic polymer was added to increase the retention time of the drug in the mouth.
"Stability studies at ambient temperatures show that the formulations were found to have uniform drug content up to 3 months", the researchers wrote.
(Editor's Note: Compounding pharmacists have known this for many, many years!!!!)
http://www.in-pharmatechnologist.com/Materials-Formulation/Drug-loaded-lollipops-could-boost-oral-thrush-compliance
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Louisiana Warns of Ameba Infections Linked to Improper Neti Pot Use
Two people in Louisiana have died this year from primary amebic meningoencephalitis after using tap water to irrigate their sinuses with neti pots, prompting the state's health department to remind consumers to use only distilled, sterile, or boiled water in neti pots. To avoid infections caused by Naegleria fowleri, the CDC also recommends thoroughly rinsing neti pots after each use and letting the devices air dry completely.
http://new.dhh.louisiana.gov/index.cfm/newsroom/detail/2332 http://new.dhh.louisiana.gov/index.cfm/newsroom/detail/2332
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MM: It’s maddening that we should choose to treat a cancer such as prostate that is rarely life threatening with a treatment that may induce a cancer that is frequently life threatening such as colon cancer. We must always be aware of the potential risk vs benefit of any treatment. Remember the pledge taken by all health practitioners, “First, Do No Harm.”
Ann Surg 2011 Dec; 254:947
Rectal Cancer Incidence Rose After Radiation Therapy for Prostate Cancer
Excess 10-year risk was roughly one case per 100 men.
A U.S. study demonstrated an increased risk for rectal cancer following external-beam radiation therapy for prostate cancer (JW Gen Med May 3 2005). Now, Israeli researchers have analyzed data from their national cancer registry to address this issue.
Of nearly 30,000 men with prostate cancer diagnosed between 1982 and 2005, 2163 received radiation therapy (either external-beam or brachytherapy), and 26 of these men received subsequent diagnoses of rectal cancer. Compared with the age-adjusted incidence of rectal cancer in the entire Israeli male population, the incidence was significantly higher in the radiation-therapy group (standardized incidence ratio, 1.8). This increase would correspond roughly to one additional case per 100 men during 10 years of follow-up. In contrast, patients who underwent radical prostatectomy did not have excess risk for rectal cancer.
Comment: Radiation therapy for prostate cancer appears to raise risk for rectal cancer, although the absolute excess risk is fairly low. This potential complication should be factored into decisions about prostate cancer treatment.
— Allan S. Brett, MD Published in Journal Watch General Medicine December 22, 2011
Citation(s):Margel D et al. Radiation therapy for prostate cancer increases the risk of subsequent rectal cancer. Ann Surg 2011 Dec; 254:947.
(http://dx.doi.org/10.1097/SLA.0b013e3182382fd5)
http://www.ncbi.nlm.nih.gov/pubmed/22107741?dopt=Abstract
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Case Report: Gastric Banding Complications May Present as
Pulmonary Symptoms
A Lancet case report shows that gastric banding can have late complications that present as pulmonary symptoms.
Investigators report on a 49-year-old woman who underwent gastric banding and some 18 months later presented with symptoms of a pulmonary infection that were not resolved with use of antibiotics. Examination with CT of the chest showed a cavitating lesion in the left upper lobe of the lung. The lesion and the patient's symptoms completely resolved after the gastric band was emptied.
The authors conclude: "Patients who have undergone laparoscopic adjustable gastric banding should have chest radiography or thoracic CT scan, or both, if they present with respiratory symptoms."
http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(11)61517-1/fulltext
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MM: As medical professionals and parents we have long been with the understanding that aspirin is contraindicated and acetaminophen is acceptable for children with asthma. This now seems to be challenged. It’s good to be aware of these potential complications so that we can make informed decisions rather than assumptions when comforting our children and grandchildren.
Pediatrics 2011 Dec; 128:1181.
Is Acetaminophen a Culprit in Asthma?
Positive associations exist between acetaminophen use and asthma in children.
During the past decade, epidemiologic studies have shown a positive association between acetaminophen use and asthma prevalence and severity in adults and children. In a special article in Pediatrics, a pediatric pulmonologist reviews these data.
Results from a large international study showed a significant threefold higher risk for current asthma in 6- and 7-year-olds who took acetaminophen at least once per month. The authors of this study assert that if acetaminophen does indeed exacerbate asthma, it would account for about 40% of the population-attributable risk for severe asthma symptoms. But what if children with asthma are just more likely to take acetaminophen, or have viral infections that lead to both asthma symptoms and acetaminophen use? In the Boston University Fever Study, researchers randomized febrile children (age range, 6 months–12 years) to receive acetaminophen or ibuprofen for fever. In the subset of children with asthma, those who received acetaminophen were twice as likely to have a subsequent outpatient asthma visit as those who received ibuprofen.
Also noted in the review are studies that have shown dose-response associations, the observation that asthma prevalence and acetaminophen sales have increased in tandem during recent decades, and a plausible mechanism of action by which acetaminophen could increase susceptibility to asthma by depleting airway mucosal glutathione.
Comment: The author of this review draws conclusions from observational data as well as a pediatric randomized controlled trial suggesting that acetaminophen use contributes to asthma exacerbations in individuals and to increased asthma prevalence in the general pediatric population. Although the author of the review now discourages acetaminophen use in children with asthma or a family history of asthma, he raises the possibility that confounding variables might explain some or all of the associations. I agree that acetaminophen use is often unnecessary and fueled by "fever phobia" and that inappropriate dosing can be a problem. However, I would like to see additional experimental studies in children with asthma before I subscribe to "acetaminophen phobia."
— Cornelius W. Van Niel, MD Published in Journal Watch Pediatrics and Adolescent Medicine December 21, 2011
Citation(s):McBride JT. The association of acetaminophen and asthma prevalence and severity. Pediatrics 2011 Dec; 128:1181. http://www.ncbi.nlm.nih.gov/pubmed/22065272?dopt=Abstract
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Pediatr Infect Dis J 2011 Dec; 30:1019
TMP-SMX Is Another Option for Treatment of Acute Osteomyelitis
Treatment with oral trimethoprim-sulfamethoxazole was successful even for MRSA osteomyelitis in children.
Transitioning from intravenous (IV) to oral antibiotic therapy for acute hematogenous osteomyelitis hastens the return to normal activities in children. However, emergence of methicillin-resistant Staphylococcus aureus (MRSA) limits the choice of an oral agent. Clindamycin has a good track record for treatment of MRSA osteomyelitis, but its use is limited by its unpalatable taste and increasing S. aureus resistance. MRSA resistance to trimethoprim-sulfamethoxazole (TMP-SMX) is rare. These investigators report their experience using TMP-SMX for treatment of 20 patients (age, 
18 years) with proven or presumed osteomyelitis caused by S. aureus.
In most cases, patients did not receive TMP-SMX as initial IV therapy but rather as the oral transition drug. Median duration of treatment with TMP-SMX was 40 days; 11 patients received TMP-SMX for most of the treatment duration (median, 31 days). Forty percent of patients experienced adverse effects (rash, neutropenia, and emesis). Erythema multiforme was not reported. All 20 patients were cured at the end of therapy.
Comment: This small, retrospective case series provides the first published data to show good outcomes in patients with MRSA osteomyelitis treated with TMP-SMX. Oral TMP-SMX is easy to administer and palatable for young children, making it an excellent oral treatment option for children with S. aureus resistant to clindamycin or those with methicillin-susceptible S. aureus and β-lactam allergy. More patients in this series had rash than in my experience. Patients should be counseled to contact their physicians at the first sign of rash.
— Peggy Sue Weintrub, MD Published in Journal Watch Pediatrics and Adolescent Medicine December 21, 2011
Citation(s):Messina AF et al. Trimethoprim-sulfamethoxazole therapy for children with acute osteomyelitis. Pediatr Infect Dis J 2011 Dec; 30:1019
http://www.ncbi.nlm.nih.gov/pubmed/21817950?dopt=Abstract
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MM: Drug resistance of microorganisms is a worldwide acknowledged problem and previous studies have indicated that this is nothing new. Recently a study was published demonstrating that bacteria recovered from permafrost that was over 30,000 years old demonstrated antibiotic resistance. It good to know that we may have alternatives coming in our arsenal to combat and cope with life threatening infection.
Science 2011 Nov 18; 334:982
New Antibiotic Strategies
Starvation responses and hydrogen sulfide production appear to be novel targets for defeating antibiotic-tolerance mechanisms.
With antibiotic resistance increasing and the rate of drug development decreasing, treatment of bacterial infections is becoming ever more difficult. New classes of antibiotic agents are desperately needed. Researchers have now identified two mechanisms that confer antibiotic tolerance in bacteria and could serve as targets for new drugs.
Nguyen and colleagues investigated the bacterial response to starvation, based on the observation that nutrient deprivation — which is common in biofilms — results in tolerance to multiple antibiotic classes. In studies comparing wild-type Pseudomonas aeruginosa to a mutant P. aeruginosa lacking two genes (relA and spoT) that are upregulated during nutrient deprivation, the researchers found that growth responses were similar between the strains in the presence of normal and restricted nutrients. However, when nutrients were restricted, the number of bacteria killed by ofloxacin decreased by ~2300-fold with the wild-type strain but only by ~34-fold with the mutant strain. When grown in biofilms, the mutant strain was at least 1000 times more susceptible to ofloxacin, meropenem, colistin, and gentamicin than the wild-type strain; this susceptibility was reversed by restoring the genes. In mouse models of intraperitoneal and subcutaneous infection, ofloxacin was more effective against the mutant than the wild-type bacteria. Detailed investigation revealed that the mutant strains had altered pro-oxidant and antioxidant responses to starvation. Increased antibiotic susceptibility was also noted in a mutant Escherichia coli relA- and spoT-deficient strain.
Shatalin and colleagues noted that most, if not all, sequenced bacterial genomes contain genes related to hydrogen sulfide (H2S) production. Having established that nitric oxide protects some gram-positive bacteria against antibiotics, these researchers wondered whether H2S might have similar activity. They studied strains of Bacillus anthracis, P. aeruginosa, Staphylococcus aureus, and E. coli in which endogenous H2S production was inactivated genetically or chemically and found increased susceptibility to multiple antibiotic classes. The addition of exogenous H2S restored antibiotic susceptibility in these mutant strains. Further study showed that, like nitric oxide, H2S protects bacterial cells against the oxidative stress that contributes to the activity of multiple antibiotic classes.
Comment: These studies raise hope for new classes of compounds that enhance the killing efficacy of current antibiotics by targeting mechanisms that bacteria use to tolerate oxidative stress. The ability to kill nutritionally restricted bacteria in biofilms could be of particular relevance to the management of prosthetic device and bone infections, potentially shortening the duration of antibiotic treatment.
— Richard T. Ellison III, MD Published in Journal Watch Infectious Diseases December 21, 2011
Citation(s):Nguyen D et al. Active starvation responses mediate antibiotic tolerance in biofilms and nutrient-limited bacteria. Science 2011 Nov 18; 334:982
http://www.ncbi.nlm.nih.gov/pubmed/22096200?dopt=Abstract
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