• Estrogen Therapy and Breast Cancer Risk: More from the Women's Health Initiative
• FDA Approves New GERD Treatment
• Good and Bad News for Vitamin D in African-Americans with Cutaneous Lupus Erythematosus
• Does High HbA1c During Pregnancy Predict Postpartum Glucose Abnormalities?
• Cognitive Decline Accelerates After Hospitalization in the Elderly
• Tranexamic Acid, a Cheap Generic That Slows Bleeding, Not Widely Used in U.S.
• Frequent Use of Nonaspirin NSAIDs May Raise Risk for Inflammatory Bowel Disease
• PPI-Associated Clostridium difficile Infection
• Fecal Transplantation Works for C. difficile Colitis
• About 10% of Parents Report Sleep Problems in Young Children
• Fitness and Overweight: How Do They Contribute to Cardiovascular Risk?
• Managing Drug Therapies as Alzheimer Disease Progresses
• A Raised Risk for NMSC in Patients with Inflammatory Bowel Disease
• Smoking Is Associated with Increased Risk for Nonmelanoma Skin Cancer
• Staph in the Family
• Job Satisfaction, Burnout, and Worklife Balance Among Hospitalists
• Omega-3s May Fight Breast Cancer Fatigue
MM: Well, here is the most perplexing and confusing report from the WHI that I have seen to date. First we discover that the study was stopped prematurely because women were dying of breast cancer associated with oral CEE’s. Now this study says in effect, “No. Oral CEE’s DECREASE the risk of breast cancer.” Which is it?
My opinion, based on the overall peer reviewed literature is that oral estrogens carry the greatest risk and transdermal or intra-vaginal remain significantly safer and beneficial.
Lancet Oncol 2012 Mar 7
Estrogen Therapy and Breast Cancer Risk: More from the Women's Health Initiative
Incidence of and mortality from breast cancer were clearly lower than in women who received placebo.
A key finding of the Women's Health Initiative (WHI) Estrogen-Alone postintervention follow-up published in April 2011 (JW Womens Health Apr 5 2011) was persistently lower risk for invasive breast cancer among women with hysterectomies who used oral conjugated equine estrogen (CEE) for a median of 5.9 years. Now, WHI investigators report details about breast cancer incidence and mortality after a median follow-up of 11.8 years.
Compared with placebo, CEE was associated with lower incidence of invasive breast cancer (annual incidence, 0.27% vs. 0.35%; hazard ratio, 0.77; P=0.02). The level of breast cancer protection associated with CEE did not vary by duration of use during the intervention phase or the postintervention phase. Prevention of breast cancer was even more pronounced (HR, 0.68) when the analysis was restricted to participants most adherent to study medication. Among women with breast cancer diagnoses, both overall mortality and breast-cancer–related mortality were significantly lower in the CEE arm (HR, 0.62 and 0.37, respectively). CEE use did not lower risk for breast cancer in subgroups with histories of benign breast disease or first-degree family histories of breast cancer. However, breast cancer protection associated with CEE use did not vary by Gail model risk scores.
Comment: Although many observational studies have reported modestly elevated risk for breast cancer in women who use estrogen therapy, this could be because, in practice, women who use any hormone therapy undergo more screening mammograms than nonusers. In contrast, in this trial, screening frequencies were similar in conjugated equine estrogen and placebo users during and following the intervention phase. These findings should reassure women who use estrogen to manage menopausal symptoms or to prevent osteoporosis that this medication does not increase breast cancer risk; the findings also remind clinicians that we must distinguish estrogen-only from estrogen-progestin therapy as we help our patients make sound decisions about hormone therapy.
— Andrew M. Kaunitz, MD Published in Journal Watch Women's Health March 22, 2012
Citation(s):Anderson GL et al. Conjugated equine oestrogen and breast cancer incidence and mortality in postmenopausal women with hysterectomy: Extended follow-up of the Women's Health Initiative randomised placebo-controlled trial. Lancet Oncol 2012 Mar 7; [e-pub ahead of print]. (http://dx.doi.org/10.1016/S1470-2045(12)70075-X)
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FDA Approves New GERD Treatment
The FDA has approved a new device to treat symptoms of gastroesophageal reflux disease in patients who have not responded to traditional medical therapy.
The LINX Reflux Management System is a surgically-placed string of magnetic titanium beads that is placed at the lower esophageal sphincter. When a person swallows, the device expands to accommodate the liquid or food. Once the food passes, the device keeps a weak lower esophageal sphincter closed, thus preventing material from flowing back into the esophagus.
Common side effects of the LINX device include difficulty and pain on swallowing, chest pain, vomiting, and nausea. Patients with LINX should not undergo MRI procedures.
http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm296923.htm
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MM: The real point here is that people of color are at increased risk of being vitamin D deficient as their skin darkens and that although 25% of participants in these studies were taking vitamin D supplemtation, about half of all participants were vitamin D deficient. This means that both higher doses are necessary across the board than those that are recommended and that regular vitamin D level testing should be a standard part of office visits and general exams
Br J Dermatol 2012 Feb; 166:372
Good and Bad News for Vitamin D in African-Americans with Cutaneous Lupus Erythematosus
Photoprotective measures by African-American CLE patients did not reduce vitamin D concentrations, but half of all African-Americans had deficient levels.
Patients with cutaneous lupus erythematosus (CLE) are counseled to apply sunscreens and to avoid sun exposure as much as possible — recommendations that undeniably protect against disease flares. However, sun exposure promotes vitamin D synthesis, and previous findings show that CLE patients are prone to vitamin D deficiency, presumably related to photoprotective measures. Because little is known about vitamin D levels in African-American CLE patients, investigators compared the vitamin D status of 25 African-American CLE patients and 26 African-Americans without CLE, all Fitzpatrick skin types V and VI, with white or Latino individuals with and without CLE, skin types I–IV.
Mean vitamin D levels were equivalent in the African-American populations (52.0±18.5 nmol/L with CLE vs. 54.8±21.2 nmol/L without; P=0.62); 48% of both groups were vitamin D insufficient by the Institutes of Medicine definition (<50 nmol/L). African-American CLE patients were more likely than the non-CLE group to employ photoprotective behaviors and ate more vitamin D–fortified foods. About 25% of participants in either group took vitamin D supplements. White and Latino CLE patients had vitamin D levels slightly lower than whites and Latinos without CLE, but the difference was not statistically significant. When stratified by Fitzpatrick skin type, those with types I and II had the highest average vitamin D levels and those with skin types V and VI had the lowest.
Comment: The news is mixed for African-American patients with cutaneous lupus erythematosus. Although photoprotective measures did not reduce their vitamin D concentrations relative to healthy African-American controls, nearly half of all African-American participants were vitamin D deficient. African-Americans and CLE patients should be monitored for vitamin D insufficiency. Vitamin D supplements can be prescribed for those with low levels. It should be noted that the study was conducted in Texas, where ambient sun exposure is high compared with many other geographic regions. Whether the similar vitamin D levels found in these African-American patients with and without CLE would also be found in more-northern locations is unknown.
— Craig A. Elmets, MD Published in Journal Watch Dermatology March 23, 2012
Citation(s): Word AP et al. 25-Hydroxyvitamin D levels in African-American and Caucasian/Hispanic subjects with cutaneous lupus erythematosus. Br J Dermatol 2012 Feb; 166:372.
http://www.ncbi.nlm.nih.gov/pubmed/21966891?dopt=Abstract
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MM: The bottom line is that many women resort to comfort foods during pregnancy that tend to be high in carbohydrates and saturated fats. This can have a negative impact on the mom, the child and the post-partum mom. Greater emphasis and direction must be focused on providing expecting moms with information and knowledge as well as encouragement to focus on a more appropriate pregnancy diet.
Obstet Gynecol 2012 Mar; 119:566
Does High HbA1c During Pregnancy Predict Postpartum Glucose Abnormalities?
Patients with highest HbA1c at diagnosis of gestational diabetes mellitus were more likely to develop abnormal glucose tolerance after delivery.
As many as 60% of women with gestational diabetes mellitus (GDM) will develop type 2 diabetes within 5 to 10 years postpartum. Can glycosylated hemoglobin (HbA1c) testing help identify those at greatest risk? Investigators conducted a retrospective cohort study of pregnant women with GDM treated at two clinics in a diabetes and pregnancy program in North Carolina from November 2000 through April 2010. HbA1c tests were performed within 4 weeks of GDM diagnosis, and women were encouraged to undergo a 2-hour 75-g oral glucose tolerance test 6 weeks after delivery. Overall, 62% of the 277 women who provided data from both tests were nonwhite and overweight or obese (body-mass index 
25 kg/m2) and 80% were using insulin or oral hypoglycemics.
The overall prevalence of any postpartum glucose abnormality (impaired fasting glucose, impaired glucose tolerance, or type 2 diabetes) at a median of 7 to 8 weeks after delivery was 42%. Women in the highest quartile (HbA1c 
6.2%) had nearly fourfold higher risk for postpartum glucose abnormality than women in the lowest HbA1c quartile. However, this outcome was driven by those with the most severe GDM, since effects diverged when stratified by treatment modality. Among women who breast-fed, more were in the lowest than the highest HbA1c quartile, but this finding was not statistically significant.
Comment: Strengths of this study are its size, diversity, and detailed information on treatment modalities. However, socioeconomic data were limited and no data on physical exercise were collected. Glycosylated hemoglobin testing is not universally employed during pregnancy for various reasons, including questions about the effect of pregnancy-associated metabolic changes on HbA1c levels and how to interpret HbA1c values in pregnant women. Nonetheless, HbA1c levels determined at the time of gestational diabetes mellitus diagnosis might be useful for identifying those women at highest risk for abnormal glucose metabolism postpartum.
— Diane J. Angelini, EdD, CNM, FACNM, FAAN, NEA-BC Published in Journal Watch Women's Health March 22, 2012
Citation(s):Katon J et al. Hemoglobin A1c and postpartum abnormal glucose tolerance among women with gestational diabetes mellitus. Obstet Gynecol 2012 Mar; 119:566.
http://www.ncbi.nlm.nih.gov/pubmed/22353955?dopt=Abstract
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Cognitive Decline Accelerates After Hospitalization in the Elderly
Elderly community-dwelling people show an accelerated decline in cognitive function after hospitalization, according to a Neurology study.
Researchers followed nearly 1900 elderly people living in a Chicago neighborhood. Participants underwent brief cognitive testing every 3 years, and information about hospitalizations was obtained from Medicare records.
Compared with testing before hospitalization, those who were hospitalized at least once experienced a 2.4-fold increase in the rate of global cognitive decline. People with more severe illnesses and longer hospital stays showed faster declines, but hospitalization itself remained an independent predictor of the accelerated decline.
The authors speculate that better primary prevention of problems leading to late-life hospitalizations may be a way to reduce cognitive decline. They point out that "lack of detailed data about the course of [each subject's] hospitalization made it difficult to discern the basis of the association."
http://www.neurology.org/content/early/2012/03/21/WNL.0b013e31824d5894.abstract
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Tranexamic Acid, a Cheap Generic That Slows Bleeding, Not Widely Used in U.S.
Colleagues may mention an article in the New York Times that questions the slow adoption of tranexamic acid to reduce trauma-related bleeding in the nation's emergency rooms. The Times' curbside diagnosis is that the drug, being generic, offers few opportunities for profit.
The CRASH-2 trial, a 2010 study published in the Lancet, convinced the British and U.S. military to adopt tranexamic acid, according to the Times. CRASH-2 showed significant drops in all-cause and bleeding-related mortality as compared with placebo.
The Times points to hospitals in New York, Chicago, San Francisco, and Atlanta that are "moving toward using it, probably within two months."
Asked to comment, Dr. Ron M. Walls, editor-in-chief of Journal Watch Emergency Medicine, wrote: "With the evidence from CRASH-2, it is hard to imagine what any thoughtful clinician might be waiting for."
http://www.nytimes.com/2012/03/21/health/tranexamic-acid-cheap-drug-is-found-to-staunch-bleeding.html?_r=1
http://crash2.lshtm.ac.uk/
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Ann Intern Med 2012 Mar 6; 156:350
Frequent Use of Nonaspirin NSAIDs May Raise Risk for Inflammatory Bowel Disease . . . but the effect was small
Aspirin and other nonsteroidal anti-inflammatory drugs (NSAIDs) are known to disrupt the intestinal epithelial barrier. This disruption may alter the interaction between gut microbes and immune cells and, secondarily, may raise risk for inflammatory bowel disease (Crohn disease [CD] or ulcerative colitis [UC]). To assess this potential relation, researchers analyzed data from 76,795 women participating in the Nurses' Health Study who, in 1990 (when mean age was 57), answered questions about use of aspirin and other NSAIDs.
During 18 years of follow-up, 123 new cases of CD and 117 new cases of UC were documented. Aspirin use was not significantly associated with the incidence of these conditions. Use of other NSAIDs for 
15 days per month showed a small but statistically significant association with incident CD and UC (age-adjusted absolute increases of 6 and 7 cases per 100,000 person-years, respectively, compared with nonuse of NSAIDs). In multivariate analysis, the association failed to meet significance for CD but remained significant for UC.
Comment: Frequent use of nonsteroidal anti-inflammatory drugs, but not of aspirin, was associated with a small increase in absolute risk for incident ulcerative colitis in this study. However, as the authors note, the magnitude of this risk was so small that it probably should not influence decisions about prescribing NSAIDs. One possibility, dismissed as unlikely by the authors, is that some of these cases represented NSAID enteropathy (which can occur in the small bowel and colon) and not inflammatory bowel disease.
— Jamaluddin Moloo, MD, MPH Published in Journal Watch General Medicine March 22, 2012
Citation(s): Ananthakrishnan AN et al. Aspirin, nonsteroidal anti-inflammatory drug use, and risk for Crohn disease and ulcerative colitis: A cohort study. Ann Intern Med 2012 Mar 6; 156:350. (http://www.annals.org/content/156/5/350.full)
http://www.ncbi.nlm.nih.gov/pubmed/22393130?dopt=Abstract
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Rockville, MD: Food and Drug Administration; Feb 8 2012
PPI-Associated Clostridium difficile Infection
The FDA recently alerted healthcare professionals and patients that use of proton-pump inhibitors may increase the risk for Clostridium difficile–associated diarrhea.
On reviewing published studies and information from the FDA's Adverse Event Reporting System, the FDA warned the public that use of proton-pump inhibitors (PPIs) may increase the risk for Clostridium difficile–associated diarrhea (CDAD). Although the strength of the association varied widely among studies, most studies found risk for C. difficile infection or disease to be 1.4 to 2.75 times higher in patients with PPI exposure than in those without. Many of the patients affected also had other risk factors, such as antibiotic use, older age, or certain comorbid conditions.
PPIs (and possibly histamine-2 antagonists) alter the gastric pH and can allow overgrowth of C. difficile. Several of these agents are now sold over the counter, without need for a prescription.
Patients taking PPIs should be advised to seek medical care promptly if they experience watery diarrhea that does not improve, abdominal pain, and fever. Those found to have C. difficile infection may require replacement of fluid and electrolytes and may need to discontinue or change a prescribed antimicrobial therapy. Uncommon but serious complications include kidney failure, toxic megacolon, bowel perforation, and even death.
Comment: The literature suggests that PPI use increases risk for several problems in addition to C. difficile infection — for example, nosocomial pneumonia, drug–drug interactions (because PPIs decrease absorption of several antimicrobial and antiretroviral agents), and electrolyte imbalances. The effects of dose and duration are not entirely clear, but using the lowest dose for the prescribed indication — and for no longer than necessary — makes sense.
Unfortunately, PPIs are often prescribed without good reason, such as for stress-ulcer prophylaxis in patients who don't qualify for this therapy. Furthermore, once started, these medications are often continued indefinitely. Over-the-counter availability of PPIs compounds the risk for adverse events by decreasing clinician oversight and, potentially, patient awareness of such risk.
— Lynn L. Estes, PharmD Published in Journal Watch Infectious Diseases February 22, 2012
Citation(s): FDA Drug Safety Communication. Clostridium difficile-associated diarrhea can be associated with stomach acid drugs known as proton pump inhibitors (PPIs). Rockville, MD: Food and Drug Administration; Feb 8 2012. (http://www.fda.gov/Drugs/DrugSafety/ucm290510.htm
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MM: C. difficile is a tough customer and although fecal transplantation may be a last resort attempt at treatment, it has been demonstrated repeatedly to be an effective one with few negative side effects
Gastroenterology 2012 Mar; 142:490
Fecal Transplantation Works for C. difficile Colitis
The largest series to date supports the effectiveness of this approach for refractory disease.
Patients who suffer from protracted Clostridium difficile colitis despite receiving oral antibiotic therapy, often for months, have become a challenge for physicians all over the world. Unlike most treatments for C. difficile infection (CDI), fecal transplantation is said to be remarkably effective in eradicating disease, but most of the published evidence for its success is anecdotal. Now, Finnish researchers present the largest series to date of CDI patients treated with fecal transplantation.
The investigators reviewed data from 70 adults (mean age, 73; 86% outpatients) who had received up to 12 courses of antibiotics for CDI; most had received 3 to 6 courses. Most stool donors were close relatives of the patient. Transplantations were performed using a uniform protocol, which involved bowel preparation with an oral polyethylene glycol solution, followed by an infusion of stool into the cecum via colonoscope.
Three months after transplantation, 66 of the 70 patients reported complete resolution of symptoms. The four who did not respond all had the virulent 027 strain of C. difficile as well as other serious medical illnesses; all died within 3 months of transplantation. In the year following transplantation, four additional patients relapsed; two were treated successfully with antibiotics, and two received another fecal transplant. No complications of transplantation were reported.
Comment: No other C. difficile treatment achieves anything like the 94% eradication rate reported in this study, even in patients with relatively mild disease. Fecal transplantation would probably become the gold-standard treatment for CDI if the logistics of arranging it were not so daunting. Unfortunately, without an organized protocol in place, it is still out of reach for most practitioners.
— Abigail Zuger, MD Published in Journal Watch General Medicine March 22, 2012
Citation(s):Mattila E et al. Fecal transplantation, through colonoscopy, is effective therapy for recurrent Clostridium difficile infection. Gastroenterology 2012 Mar; 142:490.
(http://dx.doi.org/10.1053/j.gastro.2011.11.037)
http://www.ncbi.nlm.nih.gov/pubmed/22155369?dopt=Abstract
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MM: Possible causes of sleep disturbances are environmental and food sensitivities. These can be reduced with a combination of Probiotics and Vitamin D3. Both of these items reduce inflammation and stabilize the immune system. As there is a predominance of both Vitamin D inadequacy and dysbiosis throughout the North American population, it is sensible that the addition of these could improve sleep cycles in infants and toddlers just as they have the potential of doing in adults with the same problems.
Pediatrics 2012 Feb; 129:e276
About 10% of Parents Report Sleep Problems in Young Children
However, responses to a general screening question could miss some symptoms and behaviors.
Primary care pediatricians are tasked with identifying and evaluating caregiver concerns regarding children's sleep. To examine sleep problems in young children, researchers in Ohio prospectively followed a birth cohort of 359 children (64% white) and administered sleep questionnaires to their mothers when the children were ages 6, 12, 24, and 36 months. The questionnaires were based on validated sleep instruments and included a single, nonspecific screening question ("Do you think [child's name] has problems sleeping?"), as well as specific questions about eight sleep-behavior domains.
At each time point, about 10% of mothers, regardless of race or family income, reported that their child had a sleep problem. Parent report of an overall sleep problem was significantly associated with longer time to fall asleep, more night awakenings, and shorter 24-hour sleep duration at all ages; with restless sleep and nightmares or night terrors at ages 12, 24, and 36 months; with loud snoring at 12 months; and with not sleeping in one's own bed at 24 months. Lower-income families reported longer time for children to fall asleep and shorter 24-hour sleep duration than higher-income families, but the same rate of overall sleep problems. Children with a reported overall sleep problem in infancy were three times more likely to have reported sleep problems at age 36 months than infants whose mothers did not report an overall sleep problem.
Comment: The prevalence of problems in the specific sleep domains were not reported, but it is notable that some sleep behaviors that pediatricians might consider problematic — such as loud snoring and cosleeping — generally were not associated with parent reports of an overall sleep problem. Pediatricians who quickly ask, "Any problems with sleep?" might miss some relevant symptoms and details. A comprehensive sleep questionnaire that detects specific sleep problems that are either detrimental to young children's health or of concern to caregivers could be useful.
— Cornelius W. Van Niel, MD Published in Journal Watch Pediatrics and Adolescent Medicine March 21, 2012
Citation(s): Byars KC et al. Prevalence, patterns, and persistence of sleep problems in the first 3 years of life. Pediatrics 2012 Feb; 129:e276.
http://www.ncbi.nlm.nih.gov/pubmed/22218837?dopt=Abstract
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J Am Coll Cardiol 2012 Feb 14; 59:665
Fitness and Overweight: How Do They Contribute to Cardiovascular Risk?
Improvements in one measure somewhat — but not completely — offset deteriorations in the other.
Controversy surrounds the relative contributions of changes in weight and fitness to cardiovascular risk. In this longitudinal cohort study, 3148 adults underwent at least three preventive medical examinations over a 27-year period at a single U.S. clinic. Fitness was measured by maximal exercise stress testing; body-mass index and percent body fat were proxies for fatness (a term used by the authors throughout their article). Researchers analyzed the effect of changes in these measures between the first and second examinations on the subsequent development of risk factors.
During a mean follow-up of approximately 6 years after the second examination, 24%, 14%, and 19% of participants developed hypertension, metabolic syndrome, and hypercholesterolemia, respectively. Increasing fatness and decreasing fitness were both associated with increased risks for all three outcomes — even after adjusting for each other and other potential confounders (see table). Stable or increased fitness attenuated, but did not fully compensate for, the detrimental effects of increased fatness; similarly, reduction in fatness attenuated the detrimental effects of loss of fitness.
Comment: In this analysis, both increased fatness and reduced fitness were associated with increased risks for hypertension, hypercholesterolemia, and metabolic syndrome, even when accounting for other factors. However, improvements in fitness attenuated the effects of increased body-mass index and percent body fat, and vice versa. The ideal, then, is to motivate our patients to both maintain a normal body weight and improve their fitness level, not just one or the other.
— Kirsten E. Fleischmann, MD, MPH Published in Journal Watch General Medicine March 20, 2012
Citation(s):Lee D-C et al. Changes in fitness and fatness on the development of cardiovascular disease risk factors: Hypertension, metabolic syndrome, and hypercholesterolemia. J Am Coll Cardiol 2012 Feb 14; 59:665.
(http://dx.doi.org/10.1016/j.jacc.2011.11.013)
http://www.ncbi.nlm.nih.gov/pubmed/22322083?dopt=Abstract
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N Engl J Med 2012 Mar 8; 366:893
Managing Drug Therapies as Alzheimer Disease Progresses
After several years of donepezil therapy, donepezil (Aricept®)(but not memantine(Namenda®) conferred modest benefits.
A man with Alzheimer disease (AD) has been taking donepezil (Aricept or a generic), and his dementia is progressing. Do you continue or stop the drug? Do you substitute or add memantine (Namenda)? To answer these questions, U.K. researchers conducted a partially industry-supported, randomized, placebo-controlled trial involving 295 community-dwelling patients with moderate-to-severe AD (mean Mini-Mental State Exam [MMSE] score, 9 out of 30) who had received donepezil for several years. Patients were assigned to continue donepezil alone, stop donepezil and start memantine, take both drugs, or take neither drug.
During 1 year of follow-up, MMSE scores and activities-of-daily-living scores indicated deterioration in all four groups. Patients who continued donepezil alone had significantly less deterioration on these scores than patients who stopped donepezil; the MMSE difference of 2 points was considered clinically important by prespecified criteria. Memantine was also associated with statistically less deterioration than no memantine on both scores, but differences were small and not considered clinically important. Adding memantine to donepezil had no benefit over donepezil monotherapy. Neither drug significantly influenced important secondary outcomes: caregivers' assessment of patients' quality of life and caregivers' own psychological symptoms.
Comment: After several years of treatment with donepezil, patients with moderate-to-severe Alzheimer disease appeared to derive cognitive benefit from continuing this drug; substituting or adding memantine was not fruitful. However, neither drug significantly affected outcomes that are important from the caregiver's perspective. Drug therapies for AD clearly have some measurable benefits, but their overall impact on most patients and families remains limited.
— Allan S. Brett, MD Published in Journal Watch General Medicine March 20, 2012
Citation(s):Howard R et al. Donepezil and memantine for moderate-to-severe Alzheimer's disease. N Engl J Med 2012 Mar 8; 366:893. (http://dx.doi.org/10.1056/NEJMoa1106668)
http://www.ncbi.nlm.nih.gov/pubmed/22397651?dopt=Abstract
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Gastroenterology 2011 Nov; 141:1612
A Raised Risk for NMSC in Patients with Inflammatory Bowel Disease
Patients who receive azathioprine or 6-mercaptopurine for inflammatory bowel disease have a greater risk for developing nonmelanoma skin cancer.
Azathioprine is known to raise the risk for nonmelanoma skin cancer (NMSC) in organ transplant recipients, but it has been considered safe in patients without transplanted organs or multiple immunosuppressive therapies. Azathioprine is often prescribed as a steroid-sparing agent for inflammatory bowel disease (IBD) and for many dermatologic disorders, including blistering diseases and chronic idiopathic eczemas. In two recent studies, investigators assessed whether such patients are at increased risk for NMSC.
Researchers in Canada made use of a Manitoba database to compare NMSC incidence in 9618 IBD patients and 91,738 controls. The IBD patients had an increased risk for developing basal cell carcinomas (BCCs) compared with controls (hazard ratio, 1.20), and thiopurine users had an increased risk for squamous cell carcinomas (SCCs) (HR, 5.40). In an analysis of IBD patients, thiopurine use was associated with SCC development (odds ratio, 20.52).
Researchers in France performed a prospective, observational cohort study of 19,486 patients with IBD and matched their observations of these patients against data from a national cancer registry. They found that the risk for NMSC increased with age, but that exposure to thiopurine immunosuppressives was associated with increased NMSC risk at any age (HR, 5.9 for current users and 3.9 for past users). These hazard ratios were unchanged after adjustment for use of other immunosuppressive agents, including methotrexate, mycophenolate mofetil, cyclosporin, and tumor necrosis factor (TNF) antagonists.
The author of an accompanying editorial notes that there are no guidelines for surveillance or prevention of NMSC in IBD patients. He adds that although NMSC might cause deformity and disability, it is rarely lethal. He concludes that the formulation of guidelines for secondary prevention of NMSC in patients with IBD should be considered.
Comment: Patients with inflammatory bowel disease appear to have a raised risk for developing nonmelanoma skin cancer. Whether the NMSCs, particularly SCCs, that develop in IBD patients are more aggressive is not resolved by these studies. It is likely that concomitant use of TNF antagonists enhances the thiopurine-associated risk and increases the aggressive behavior of NMSC in IBD patients.
— Jeffrey P. Callen, MD Published in Journal Watch Dermatology February 17, 2012
Citation(s):Singh H et al. Increased risk of nonmelanoma skin cancers among individuals with inflammatory bowel disease. Gastroenterology 2011 Nov; 141:1612
http://www.ncbi.nlm.nih.gov/pubmed/21806945?dopt=Abstract
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Cancer Causes Control 2011 Nov 19
Smoking Is Associated with Increased Risk for Nonmelanoma Skin Cancer
Smoking is associated with risk for squamous cell carcinoma in both men and women, but especially among women.
Previous studies examining the association between smoking and nonmelanoma skin cancer (NMSC) have produced mixed results. Investigators conducted a case-control study comparing patients who had basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) with a control group of individuals attending a skin cancer detection screening. The analysis controlled for variations in skin, eye, and hair color; alcohol consumption; history of blistering sunburn; occupational sun exposure; and tanning ability. The control population was examined for skin cancer and those with skin cancer were eliminated.
A history of ever smoking was associated with SCC but not with BCC. A dose-dependent curve associated greater risk for SCC with more cigarettes smoked per day and with higher number of pack-years of smoking. Analyzed by sex, the data showed a greater SCC risk in women than in men (relative risk, 3.00 for women, 1.97 for men). Whether persons who quit smoking lowered their risk for NMSC was not ascertained.
Comment: Limitations to this study include recall bias, but this is a powerful piece of work in a clinical setting. One of the study's major strengths is that investigators examined the control population, thereby eliminating a confounding factor should controls have otherwise undetected nonmelanoma skin cancer. Bottom line: Smoking is associated with risk for squamous cell carcinoma in both men and women, but especially among women. Thus, we have yet another reason to encourage smoking cessation.
— Jeffrey P. Callen, MD Published in Journal Watch Dermatology February 10, 2012
Citation(s):Rollison DE et al. Case–control study of smoking and non-melanoma skin cancer. Cancer Causes Control 2011 Nov 19; [e-pub ahead of print].
(http://dx.doi.org/10.1007/s10552-011-9872-y)
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Clin Infect Dis 2012 Mar 15; 54:743
Staph in the Family
Decolonizing household contacts reduces everyone's chances of infection.
Intractable skin and soft-tissue (SST) abscesses caused by Staphylococcus aureus have become a scourge for adult and pediatric patients alike. Some evidence indicates that transmission from colonized household members may contribute to the high recurrence rate of these infections.
Researchers assigned children with SST S. aureus infections who were confirmed carriers to one of two treatment groups. In one group, only the child followed a 5-day decolonization regimen with topical mupirocin and chlorhexidine. In the other group, all household members were asked to follow the same regimen.
After a month, about half the index children in each group were still colonized with S. aureus, and colonization rates remained similar between groups at 3, 6, and 12 months. However, at 3 months, the cumulative recurrence rate of SST infections was significantly lower in the children whose households had been decolonized, and it remained so for the duration of the study (52% vs. 72% at 1 year). In the first 6 months of the study, the household-decolonization group had fewer SST infections reported by household members than the other group did, but by a year, that difference had disappeared.
Comment: Treating household members for presumptive S. aureus carriage seems to make a difference when the infection enters a household (presumably by reducing the index case's exposure to "new" strains of S. aureus rather than by reducing endogenous colonization). Some experts now suggest that this low-risk intervention become part of routine clinical practice, whereas others, citing the expense of mupirocin and the risk of resistance with widespread use, opt to reserve it for patients with multiple or severe infections.
— Abigail Zuger, MD Published in Journal Watch General Medicine March 20, 2012
Citation(s): Fritz SA et al. Household versus individual approaches to eradication of community-associated Staphylococcus aureus in children: A randomized trial. Clin Infect Dis 2012 Mar 15; 54:743. (http://dx.doi.org/10.1093/cid/cir919)
http://www.ncbi.nlm.nih.gov/pubmed/22198793?dopt=Abstract
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J Hosp Med 2012 Jan 23
Job Satisfaction, Burnout, and Worklife Balance Among Hospitalists
A national survey indicates that job satisfaction is high, compensation schemes differ among practice models, and burnout is not uncommon.
The fast-paced nature of hospital medicine has raised concerns that burnout and job turnover are widespread among hospitalists. The rapid growth and relative youth of our specialty might also lead to ambiguity in the professional function of hospitalists to patients and within organizations. The last examination of the effects of these factors on hospitalists was in 1999. Now, the Society of Hospital Medicine (SHM) Career Satisfaction Task Force reports the results of a 2009–2010 national worklife survey.
The survey instrument borrowed elements of the Physician Worklife Survey and was expanded to include issues relevant to hospitalists. Paper surveys were mailed to a stratified sample of 4315 hospitalists in the SHM database, followed by an electronic survey to available e-mail addresses.
Of 3105 eligible hospitalists, 776 (25%) responded; 7% were pediatric hospitalists and 5% were subspecialists. The median age of respondents was 42, 33% were women, 78% worked full time, 44% were employed by a hospital, and mean experience was 7 years. Overall, 63% reported high job satisfaction (4 or 5 on a 5-point Likert scale). Most respondents rated high satisfaction in their relationships with staff (80%), colleagues (76%), practice leaders (75%), and patients (63%). In contrast, fewer hospitalists reported high satisfaction with workload (44%), available personal time (28%), compensation (28%), autonomy (17%), and organizational climate (11%). In regression analyses, all satisfaction domains were positively associated with overall job satisfaction with the exception of workload, which was negatively associated with job satisfaction. Nevertheless, burnout was not uncommon (30%) and was more frequent among hospitalists who were planning to reduce work hours, leave their clinical situation, or abandon direct patient care within the next few years.
Analysis of the data according to five practice models revealed that academic hospitalists had more nonclinical work hours, fewer billable encounters, and earned significantly less than other hospitalists (averaging US$60,000 less than the highest paid hospitalists). Overall job satisfaction and burnout rates did not differ among the practice models.
Comment: A gross comparison with other studies demonstrates job satisfaction levels and burnout rates comparable to other specialties. Sampling challenges (hospitalists changing hospitals, higher response rate among SHM members) are recognized limitations of these data. Nevertheless, the results suggest that most hospitalists experience professional fulfillment at a level consistent with other types of physicians.
— Grace C. Huang, MD Published in Journal Watch Hospital Medicine March 5, 2012
Citation(s):Hinami K et al. Job characteristics, satisfaction, and burnout across hospitalist practice models. J Hosp Med 2012 Jan 23 (http://dx.doi.org/10.1002/jhm.1907); [e-pub ahead of print].
Hinami K et al. Worklife and satisfaction of hospitalists: Toward flourishing careers. J Gen Intern Med 2012 Jan; 27:28.
http://www.ncbi.nlm.nih.gov/pubmed/21773849?dopt=Abstract
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Omega-3s May Fight Breast Cancer Fatigue
Higher blood levels of omega-3s linked to less inflammation and fatigue; opposite trend seen for women with high omega-6/omega-3 ratios by Craig Weatherby
We’ve reported many times on connections between omega-3 and omega-6 fatty acids and breast cancer. There’s substantial evidence that omega-3 fatty acids tend to curb cancer growth and enhance the efficacy of chemo and radiation treatment (Baracos VE et al. 2004; Wendel M et al. 2009; Spencer L et al. 2009; Bougnoux P et al. 2010).
(Omega-3s may also enhance the preventive benefits of tamoxifen … see “Fish Fats May Boost Breast Cancer Drug”.)
However, we lack clinical evidence of efficacy, and epidemiologic studies have produced mixed results (Signori C et al. 2009; Sala-Vila A, Calder PC 2011).
On the plus side, a study among 56,007 French women found that breast cancer risk was lower among women whose estimated omega-3 intake was in the top one-fifth (Thiébaut AC et al. 2009). Conversely, the risk of breast cancer in the French women was higher among those in the top one-fifth of estimated omega-6 intake.
Now, the unusually meaningful results of a new study show that breast cancer patients with higher blood levels of omega-3s suffer less inflammation and fatigue than their peers. The opposite trend was seen for women with higher omega-6/omega-3 ratios, who showed higher levels of inflammation and more fatigue.
Importantly, these associations reflect the actual blood levels of these fats, and do not rely on estimates of omega-6 and omega-3 blood levels based on diet questionnaires. The study was led by Catherine M. Alfano, Ph.D., of the Office of Cancer Survivorship at the National Cancer Institute.
Connections seen between blood fats and fatique, inflammation
Dr. Alfano and an international group of colleagues recruited 633 breast cancer survivors (Alfano CM et al. 2012). The women gave blood samples 30 months after diagnosis and took standard fatigue assessment tests 39 months after diagnosis. The participants’ blood was analyzed for markers of chronic and acute inflammation … C-reactive protein (CRP) and serum amyloid A protein, respectively. (To learn about inflammation and tumor growth, see “Breast Cancer Linked to Inflammation”.)
As the authors reported, their results indicated that the women with higher intake of omega-3s had lower inflammation (CRP) levels and less physical fatigue. After adjusting the results to account for other factors, breast cancer survivors with high CRP [inflammation ] levels were almost twice (1.8 times) as likely to experience fatigue. And the women with higher blood levels of omega-6 fatty acids relative to omega-3s had higher CRP levels and were more than twice (2.6 times) as likely to suffer from fatigue.
As the NCI-led team wrote, “Considering the high prevalence of fatigue among cancer survivors, effective treatment could have a significant health impact.” They proposed that “Future studies should test whether omega-3 supplementation may reduce fatigue among significantly fatigued breast cancer survivors.” (Alfano CM et al. 2012)
Sources: Alfano CM, Imayama I, Neuhouser ML, Kiecolt-Glaser JK, Wilder Smith A, Meeske K, McTiernan A, Bernstein L, Baumgartner KB, Ulrich CM, Ballard-Barbash R. Fatigue, Inflammation, and ω-3 and ω-6 Fatty Acid Intake Among Breast Cancer Survivors. J Clin Oncol. 2012 Mar 12. [Epub ahead of print]. Baracos VE, Mazurak VC, Ma DW. n-3 Polyunsaturated fatty acids throughout the cancer trajectory: influence on disease incidence, progression, response to therapy and cancer-associated cachexia. Nutr Res Rev. 2004 Dec;17(2):177-92. Bougnoux P, Hajjaji N, Maheo K, Couet C, Chevalier S. Fatty acids and breast cancer: sensitization to treatments and prevention of metastatic re-growth. Prog Lipid Res. 2010 Jan;49(1):76-86. Epub 2009 Aug 26. Review. Sala-Vila A, Calder PC. Update on the relationship of fish intake with prostate, breast, and colorectal cancers. Crit Rev Food Sci Nutr. 2011 Oct-Nov;51(9):855-71. Review. Signori C, El-Bayoumy K, Russo J, Thompson HJ, Richie JP, Hartman TJ, Manni A. Chemoprevention of breast cancer by fish oil in preclinical models: trials and tribulations. Cancer Res. 2011 Oct 1;71(19):6091-6. Epub 2011 Sep 20. Review. Spencer L, Mann C, Metcalfe M, Webb M, Pollard C, Spencer D, Berry D, Steward W, Dennison A. The effect of omega-3 FAs on tumour angiogenesis and their therapeutic potential. Eur J Cancer. 2009 Aug;45(12):2077-86. Epub 2009 Jun 1. Review. Thiébaut AC, Chajès V, Gerber M, Boutron-Ruault MC, Joulin V, Lenoir G, Berrino F, Riboli E, Bénichou J, Clavel-Chapelon F. Dietary intakes of omega-6 and omega-3 polyunsaturated fatty acids and the risk of breast cancer. Int J Cancer. 2009 Feb 15;124(4):924-31. Wendel M, Heller AR. Anticancer actions of omega-3 fatty acids--current state and future perspectives. Anticancer Agents Med Chem. 2009 May;9(4):457-70. Review.
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