• Supreme Court Hears Arguments on Healthcare Law's Individual Mandate
• Higher Vitamin D Status Protects Against Crohn Disease
• This One Goes Out to the Chocoholics: Chocolate Consumption Linked to Lower BMI
• No Safe Pattern of Alcohol Consumption During Pregnancy
• Benefits of Physical Activity After Cancer Treatment
• Alzheimer Disease and Cancer: An Inverse Relation?
• Autism: 1 in 88 U.S. Kids Diagnosed
• FDA Considering Expanding Over-the-counters
• Vaginal Progesterone Use in Pregnant Women with Short Cervix
• NAMS 2012 Position Statement on Postmenopausal Hormone Therapy
• High Intake of White Rice Associated with Excess Risk for Type 2 Diabetes
• Lifestyle Change Improves Mobility in Patients with Type 2 Diabetes
• The Wording of a Radiology Report Makes a Difference
• Clostridium difficile — But from Where?
• Non-HDL Cholesterol Seems a Better Target Than LDL to Gauge Statin Therapy
• Tamoxifen Effective for Ductal Carcinoma in Situ
• Fully Oral Therapy for Symptomatic Pulmonary Embolism
• Does C-Section Increase Risk for Stillbirth in Subsequent Pregnancy?
Supreme Court Hears Arguments on Healthcare Law's Individual Mandate
The U.S. Supreme Court on Tuesday heard oral arguments concerning the constitutionality of the Affordable Care Act's individual mandate. You can listen to (or read a transcript of) the proceedings via the link below.
http://www.supremecourt.gov/oral_arguments/argument_audio_detail.aspx?argument=11-398-Tuesday
http://www.washingtonpost.com/politics/supreme-court-considers-main-constitutional-question-in-health-care-law/2012/03/26/gIQAkyKWdS_story.html
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MM: Here is another benefit of even moderately increasing Vitamin D levels. The levels examined in this study look at a bare minimum blood level of Vitamin D. Important to note is that the article does not recommend a particular target level but it examines the general population that is sorely deficient in Vitamin D. The “highest quartile” is still below 32ng/ml and is therefore still insufficient! In my opinion, the minimum goal for vitamin D and health should be in the 60-80 ng/ml range. It is imperative that people discover what their D levels are. The test for this is 25-hydroxy D. Any other test may provide inappropriate and misleading data.
Gastroenterology 2012 Mar; 142:482
Higher Vitamin D Status Protects Against Crohn Disease
Among women in the Nurses' Health Study, risk was lowest in those with the highest predicted serum 25-hydroxy vitamin D levels.
Previous studies have suggested that lower levels of vitamin D are associated with increased risk for inflammatory bowel disease (IBD). Now, researchers have examined the risk for IBD in 72,719 women who were participating in the Nurses' Health Study. All had previously completed an assessment of diet and lifestyle, from which each participant's predicted 25-hydroxy vitamin D status was derived using a previously validated regression model.
During 1,492,811 person-years of follow-up, Crohn disease was diagnosed in 122 women and ulcerative colitis in 123. Compared with women in the lowest quartile of predicted 25-hydroxy vitamin D levels (median, 22.9 ng/mL), those in the highest quartile (median, 31.8 ng/mL) had adjusted hazard ratios of 0.55 for Crohn disease (P=0.02) and 0.68 for ulcerative colitis (P=0.17).
Comment: Measuring vitamin D levels and recommending supplementation for patients with low levels have become more common in clinical practice; deficiency is often seen in individuals with IBD. Although the present findings do not establish that vitamin D supplementation reduces disease activity in patients with Crohn disease, there doesn't seem to be any downside to elevating levels into the normal range. Clinical trials of supplementation in the treatment for IBD are warranted.
— Douglas K. Rex, MD Published in Journal Watch Gastroenterology March 30, 2012
Citation(s):Ananthakrishnan AN et al. Higher predicted vitamin D status is associated with reduced risk of Crohn's disease. Gastroenterology 2012 Mar; 142:482
http://www.ncbi.nlm.nih.gov/pubmed/22155183?dopt=Abstract
http://www.ncbi.nlm.nih.gov/pubmed/22367731?dopt=Abstract
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MM: Although I am excited about the prospect of losing weight or maintaining weight by increasing my chocolate consumption I am also aware that there have to be pretty strict parameters on how to use this information. A low fat, low sugar chocolate source does not typically sound appealing but we have found viable options. Coco-Pro™De-fatted Chocolate is available at Mark Drugs. It is delicious, only 10 calories per serving and quite satisfying to those who want a “chocolate fix”. Additionally, it is an “approved food” for the HCG and Metabolic Syndrome Weight Management Program. Please ask us for more information or come in and try a sample.
Arch Intern Med 2012; 172: 519-521
This One Goes Out to the Chocoholics: Chocolate Consumption Linked to Lower BMI
Frequent chocolate consumption was associated with lower BMI in a cross-sectional study published in the Archives of Internal Medicine.
Researchers assessed the chocolate intake of roughly 1000 healthy adults via food-frequency questionnaires. Although more frequent chocolate consumption was associated with higher intake of calories and saturated fat relative to less frequent consumption, chocolate intake was linked to lower BMI — even after adjustment for mood scores, activity, calories, and saturated fat.
Based on rodent studies, the authors speculate that catechins, derived from cocoa, may increase mitochondrial biogenesis and capillarity, muscle performance, and lean muscle mass. They conclude: "A randomized trial of chocolate for metabolic benefits in humans may be merited." Sign us up!
Association Between More Frequent Chocolate Consumption and Lower Body Mass Index, Golomb et al. Arch Intern Med.2012; 172: 519-521
http://www.ncbi.nlm.nih.gov/pubmed?term=22450943
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Alcohol Clin Exp Res 2012 Jan 17
No Safe Pattern of Alcohol Consumption During Pregnancy
Risk was highest during the second half of the first trimester.
Since the first clinical description of fetal alcohol syndrome (FAS) nearly 40 years ago, no prospective study has examined the effect of various patterns of prenatal alcohol exposure on risk for the major dysmorphic features associated with the syndrome (smooth philtrum, thin vermillion border, short palpebral fissures, microcephaly, and growth deficiency). To explore this relation, researchers analyzed data from 992 pregnant women with a positive history of alcohol consumption during pregnancy who had enrolled in a prospective study conducted by the California Teratogen Information Service and Clinical Research Program. Data on exposure to 70 teratogens were collected at enrollment and every 3 months during pregnancy. A physical examination of all infants was performed by a dysmorphologist who was blind to prenatal history.
Mean gestational age at enrollment was 13 weeks (age range, 4.4–37.9 weeks). The median average number of binge drinking episodes and daily drinks during the first trimester were significantly associated with all alcohol-related birth outcomes on physical examination, with the exception of short palpebral fissures. The strongest associations were for exposure during the second half of the first trimester. Exposures during the second and third trimesters were also significantly associated with increased risk, but for fewer dysmorphic features. All associations were linear with no evidence of a threshold.
Comment: This is the first prospective study to quantify specific alcohol exposure patterns at various times during pregnancy and risk for dysmorphic facial features and growth deficiencies. An important finding was that there was no evidence for a safe threshold for drinking during pregnancy. The authors conclude decisively, ". . .women who are pregnant should abstain from alcohol throughout pregnancy."
— Martin T. Stein, MD Published in Journal Watch Pediatrics and Adolescent Medicine
February 29, 2012
Citation(s):Feldman HS et al. Prenatal alcohol exposure patterns and alcohol-related birth defects and growth deficiencies: A prospective study. Alcohol Clin Exp Res 2012 Jan 17; [e-pub ahead of print]. (http://dx.doi.org/10.1111/j.1530-0277.2011.01664.x)
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MM: Resuming some level of “normal” exercise activity is a must when treating any illness or disease. There is no question that we can become depressed, withdrawn and inactive when confronted with a diagnosis of cancer but survival rates have improved with the treatment of many of these cancers. Exercise combined with exposure to fresh air, sunlight, nature and other people decreases stress levels, increases endorphins and enhances our body’s immune function. This has a positive effect on mood and apparently on recovery as well.
BMJ 2012 Jan 31; 344:e70
Benefits of Physical Activity After Cancer Treatment
Exercise improved physical function, psychological outcomes, and quality of life in cancer survivors.
Can physical activity mitigate some of the debilitating effects of cancer treatment? To find out, investigators conducted a meta-analysis of 34 randomized, controlled trials in which patients were assigned to physical-activity interventions after their cancer treatment or did not engage in posttreatment exercise regimens. Twenty-two of the trials (65%) included only breast cancer patients; most of the others included patients with various types of cancer. Physical-activity interventions (median duration, 13 weeks) included aerobic exercise and resistance strength training. Exercise intensity, specified in only 13 trials, was usually moderate.
Compared with physical inactivity, exercise interventions were associated with significant improvements in body weight, body-mass index, peak oxygen consumption, peak power output, 6-minute walking distance, bench- and leg-press weight capacity, handgrip strength, fatigue, depression, and some quality-of-life measures.
Comment: This meta-analysis showed that exercise improved the physical function, psychological outcomes, and quality of life in patients who had been treated for cancer. Although most of the trials involved only breast cancer patients and none assessed the effects of physical activity on cancer recurrence or mortality, the findings nevertheless make a compelling case for advising cancer survivors to be physically active.
— Paul S. Mueller, MD, MPH, FACP Published in Journal Watch General Medicine February 23, 2012
Citation(s):Fong DYT et al. Physical activity for cancer survivors: Meta-analysis of randomised controlled trials. BMJ 2012 Jan 31; 344:e70. (http://dx.doi.org/10.1136/bmj.e70)
http://www.ncbi.nlm.nih.gov/pubmed/22294757?dopt=Abstract
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MM: There has long been a theory that cancer risk may be increased by stress and many believe that certain aspects of AD reduce psychological stress. Could this be a mitigating factor in the cancer vs AD relationship? Just another idea that could be considered.
BMJ 2012 Mar 12; 344:e1442
Alzheimer Disease and Cancer: An Inverse Relation?
Framingham data support this biologically plausible phenomenon.
Some evidence suggests that people with Alzheimer disease (AD) have diminished risk for cancer and that cancer survivors have diminished risk for AD. To assess those possibilities, researchers analyzed data from 1278 Framingham Heart Study participants (age 
65; 61% women) without AD at baseline; 14% were cancer survivors. Mean follow-up was 10 years.
Analyses were adjusted for variables such as age, sex, and smoking status. When the reference group consisted of participants without cancer at baseline, risk for incident probable AD was significantly lower among survivors of any cancer (hazard ratio, 0.67) and survivors of smoking-related cancers (HR, 0.26), and nonsignificantly lower among survivors of non–smoking-related cancers (HR, 0.82). Participants who developed probable AD during follow-up had significantly lower risks for subsequent development of any cancer (HR, 0.29), smoking-related cancers (HR, 0.21), and non–smoking-related cancers (HR, 0.31) than patients who did not develop AD.
Comment: In this study population, cancer survivors had a reduced risk for Alzheimer disease and patients with AD had a reduced risk for cancer. As the authors note, their findings are biologically plausible because a genetic propensity for programmed cell death may protect against cancer while promoting neurodegeneration. Although these observations are unlikely to alter clinical practice, they could provide clues in the search for better preventive and therapeutic strategies for both AD and cancer.
— Paul S. Mueller, MD, MPH, FACP
Published in Journal Watch General Medicine March 29, 2012
Citation(s):Driver JA et al. Inverse association between cancer and Alzheimer's disease: Results from the Framingham Heart Study. BMJ 2012 Mar 12; 344:e1442.
(http://dx.doi.org/10.1136/bmj.e1442)
http://www.ncbi.nlm.nih.gov/pubmed/22411920?dopt=Abstract
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Autism: 1 in 88 U.S. Kids Diagnosed
One in 88 children in the U.S. was diagnosed with an autism spectrum disorder in 2008, according to new CDC estimates published in MMWR. This represents an increase of 78% from 2002.
CDC researchers examined autism diagnoses among children aged 8 years in 14 areas of the country using education and health records. Among the reporting areas, Utah had the highest prevalence at 21.2 per 1000, and Alabama had the lowest at 4.8 per 1000.
The largest increases were seen among Hispanic and non-Hispanic black children and among those without intellectual disability. Boys were at greater risk for the disorder — 1 in 54 boys had autism, compared with 1 in 252 girls.
The authors say it is not known to what extent the observed increase is a true increase in autism symptoms versus better awareness and access to services.
http://www.cdc.gov/mmwr/preview/mmwrhtml/ss6103a1.htm?s_cid=ss6103a1_w
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FDA Considering Expanding Over-the-counters
The FDA is considering expanding the list of drugs that can be purchased without a prescription. The agency has discussed whether cholesterol, asthma, migraine, and blood-pressure medications should be sold over-the-counter, a regulatory change intended to lower costs and ease access to drugs for people with chronic ailments. Some have also urged that any expansion of nonprescription drugs include birth control.
The FDA has been discussing ways to enhance pharmacists' roles in chronic treatments or supplement drug labels in an interactive way that helps people determine whether they have a condition and need a drug.
http://www.bloomberg.com/news/2012-03-23/doctors-press-fda-in-push-for-birth-control-without-prescription.html
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Am J Obstet Gynecol 2012 Feb; 206:124.e1
Vaginal Progesterone Use in Pregnant Women with Short Cervix
Treatment with vaginal progesterone significantly reduced rates of preterm birth in women with short cervix with or without prior preterm delivery.
Since 2007, evidence has supported the use of vaginal progesterone to reduce the risk for spontaneous preterm birth in pregnant women with a short cervix. These researchers performed a meta-analysis using individual patient data from five randomized, placebo-controlled trials in asymptomatic women with a sonographically identified short cervix (
25 mm) in the second trimester. The primary outcome was preterm birth (<33 weeks' gestation). Secondary outcomes included preterm birth at other gestational ages, as well as indicators of perinatal and neonatal morbidity.
Data for 775 pregnant women and 827 fetuses met the inclusion criteria. Treatment with vaginal progesterone was associated with a significant 42% reduction in risk for preterm birth at <33 weeks (12% vs. 22%). Risk reduction was also significant when preterm was defined as <28, <30, <34, or <35 weeks. Among women with a singleton pregnancy who had 
1 previous spontaneous preterm birth, treatment was associated with a 44% lower risk for birth before 33 weeks. For twins, there was a trend toward a similar reduction in risk, but it was not statistically significant. Progesterone use was not associated with significant reductions in neonatal and fetal death, but infants of mothers who received progesterone had significantly lower risk for respiratory distress syndrome, low birth weight (<1500 g), and admission to the neonatal intensive care unit. There was no difference in efficacy between doses of 90 to 100 mg/day versus 200 mg/day of progesterone.
Comment: The authors suggest the time is at hand for universal screening of cervical length in pregnant women at 19 to 24 weeks' gestation. However, before such screening is adopted, cost-analysis is warranted — as are further trials of vaginal progesterone in twin gestations.
— Diane J. Angelini, EdD, CNM, FACNM, FAAN, NEA-BC Published in Journal Watch Women's Health March 29, 2012
Citation(s):Romero R et al. Vaginal progesterone in women with an asymptomatic sonographic short cervix in the midtrimester decreases preterm delivery and neonatal morbidity: A systematic review and metaanalysis of individual patient data. Am J Obstet Gynecol 2012 Feb; 206:124.e1. (http://dx.doi.org/10.1016/j.ajog.2011.12.003)
http://www.ncbi.nlm.nih.gov/pubmed/22284156?dopt=Abstract
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Menopause 2012 Mar; 19:257
NAMS 2012 Position Statement on Postmenopausal Hormone Therapy
Data continue to support the benefits of HT for symptom management and fracture risk reduction.
The North American Menopause Society (NAMS) has updated its evidence-based position statement on hormone therapy (HT; last published in 2010) to include interim findings from observational studies and randomized controlled trials. The statement is available at http://www.menopause.org/psht12.pdf.
NAMS continues to emphasize that data support the initiation of HT around the time of menopause as an effective treatment for symptoms and fracture risk reduction, and that risks and benefits should be assessed for each woman. Recognition is growing that the safety profile of systemic HT when used by younger menopausal women (i.e., women in their 50s or within 10 years of menopause onset) is reassuring. The following points are newly included:
- Urinary tract health: Local (i.e., vaginal) estrogen therapy (ET) may benefit some women with overactive bladder.
- Osteoporosis: Low-dose HT effectively maintains or improves bone mineral density.
- Endometrial cancer: Progestogen alone "could be considered" for management of vasomotor symptoms, although no data are available.
- Cognitive decline: HT cannot be recommended at any age for preventing or treating cognitive decline and dementia.
- Premature menopause and primary ovarian failure: Women who experience early menopause (i.e., before age 40) and require bone-loss prevention are "probably best served" by administration of HT or oral contraceptives until they reach natural menopausal age (median, 51), at which time treatment can be reevaluated.
- Dosage and route of administration: All ET administration routes (oral, transdermal, vaginal, and intrauterine) effectively diminish postmenopausal symptoms. Accumulating evidence from observational trials suggests that, compared with standard-dose oral ET, transdermal ET may be associated with lower risk for venous thromboembolism, stroke, and myocardial infarction. Both oral and transdermal combined estrogen-progestogen therapy (EPT) confer protection against endometrial cancer.
- Duration of use: Length of EPT use is limited by increased breast cancer risk associated with 3 to 5 years of use; the more favorable risk–benefit profile of ET (seen during a mean of 7 years of use plus 4 years of follow-up) allows longer-term use.
- Bioidentical hormones: Compounded EPT or ET should not be prescribed unless women are allergic to components of government-approved products.
- HT discontinuation: Vasomotor symptoms have a 50% chance of recurring when HT is discontinued, regardless of age, duration of use, or whether cessation is abrupt or gradual.
— Diane E. Judge, APN/CNP Published in Journal Watch Women's Health March 29, 2012
Citation(s):The North American Menopause Society. The 2012 hormone therapy position statement of the North American Menopause Society. Menopause 2012 Mar; 19:257.
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BMJ 2012 Mar 15; 344:e1454.
High Intake of White Rice Associated with Excess Risk for Type 2 Diabetes
This finding was particularly marked in Asian populations.
White rice — which is almost entirely starch — is the main type of rice eaten worldwide and has a higher glycemic index than other grains. High consumption of foods with high glycemic indexes is associated with excess risk for type 2 diabetes. In this meta-analysis of seven prospective cohort studies, investigators assessed the association between white rice intake and risk for type 2 diabetes mellitus.
Of 352,000 participants, 13,000 developed type 2 diabetes (follow-up range, 4–22 years). Among Asian populations, there was a significant 55% increased risk for type 2 diabetes in the highest category of white rice intake compared with the lowest category. In contrast, among Western populations, a 12% increase in risk was not statistically significant. Combining these populations, each serving per day increment of white rice consumption was associated with an 11% increased risk for type 2 diabetes
Comment: Although this meta-analysis showed that high intake of white rice was associated with excess risk for type 2 diabetes in Asian populations, the association does not prove that rice is more diabetogenic than other starches. For example, mean white rice intake in Asian populations was far higher (3–4 servings daily) than in Western populations (1–2 servings weekly), and rice comprises a smaller proportion of overall glycemic load in Western than in Asian populations. In any case, people should limit their intake of starchy foods and employ other measures (e.g., exercise, weight control) to lower their risk for type 2 diabetes.
— Paul S. Mueller, MD, MPH, FACP Published in Journal Watch General Medicine March 27, 2012
Citation(s):Hu EA et al. White rice consumption and risk of type 2 diabetes: Meta-analysis and systematic review. BMJ 2012 Mar 15; 344:e1454. (http://dx.doi.org/10.1136/bmj.e1454)
http://www.ncbi.nlm.nih.gov/pubmed/22422870?dopt=Abstract
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N Engl J Med 2012 Mar 29; 366:1209.
Lifestyle Change Improves Mobility in Patients with Type 2 Diabetes
Better mobility was related more to weight loss than to better fitness.
Many approaches to lifestyle modification in patients with diabetes result in weight loss and better glycemic control. Researchers looked beyond those outcomes to improvements in mobility. About 5000 adults with type 2 diabetes (mean age, 59; 60% women; mean body-mass index, 36 kg/m2) were randomized to follow an intensive lifestyle-modification program or a diabetes education-and-support program.
By 1 year, mean weekly calorie expenditure was significantly greater in the intensive-intervention group than in the control group (881 kcal vs. 99 kcal), as was mean percentage weight loss (6% vs. 1%). At 4 years, according to a multicomponent annual assessment of mobility-related disability, the percentage of intensive-intervention recipients with good mobility rose from 37% at baseline to 39%, compared with a decline in the control group from 33% to 32%. The percentage with severe or moderate mobility-related disability increased more in the control group (from 37% to 43%) than in the intensive-intervention group (from 33% to 37%). Mobility benefits in the intensive-intervention group were mediated more through weight loss than better fitness.
Comment: These results extend the known benefits of intensive lifestyle modification. On top of metabolic control and weight loss, we can now add improvements in mobility that actually lessen functional disability.
— Thomas L. Schwenk, MD Published in Journal Watch General Medicine March 29, 2012
Citation(s):Rejeski WJ et al. Lifestyle change and mobility in obese adults with type 2 diabetes. N Engl J Med 2012 Mar 29; 366:1209. (http://dx.doi.org/10.1056/NEJMoa1110294)
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Radiology 2012 Mar; 262:941
The Wording of a Radiology Report Makes a Difference
Physicians changed their management of lower back pain after being reminded that LS spine abnormalities on MRI are often meaningless.
When a patient complains of back pain or sciatica, the physician often reacts by ordering a magnetic resonance image (MRI) of the lumbosacral (LS) spine. However, guidelines argue against such a practice, because radiologic LS spine abnormalities are common in asymptomatic individuals and generally should not change first-pass conservative management.
Beginning in 2005, the radiology reporting system at a single U.S. hospital incorporated a statement reminding clinicians of the high prevalence of MRI spine abnormalities in asymptomatic adults. Although the statement was intended to be included in all LS spine MRI reports, only a minority of radiologists used it. To determine whether the statement altered physicians' treatment recommendations, researchers retrospectively evaluated treatment referrals among 237 patients who underwent MRI for uncomplicated lower back pain or radiculopathy. Referrals for physical therapy, steroid injections, and surgical consultations were just as common in the 71 patients whose MRI reports included the reminder as in the 166 whose reports did not. However, patients in the reminder group were significantly less likely to receive a prescription narcotic for pain (7% vs. 22%).
Comment: This clever study is undercut by its small sample size. Still, it suggests that when physicians are reminded of imaging's limitations (and, importantly, have the evidence in black and white to show the patient), they may adjust their treatment behavior. Withholding narcotics does not necessarily mean they took the pain less seriously, but that they simply looked to better means of control.
— Abigail Zuger, MD Published in Journal Watch General Medicine March 29, 2012
Citation(s):McCullough BJ et al. Lumbar MR imaging and reporting epidemiology: Do epidemiologic data in reports affect clinical management? Radiology 2012 Mar; 262:941. (http://dx.doi.org/10.1148/radiol.11110618)
http://www.ncbi.nlm.nih.gov/pubmed/22357893?dopt=Abstract
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PLoS Med 2012 Feb; 9:e1001172
Clostridium difficile — But from Where?
An investigation of Clostridium difficile transmission within hospital wards identified the transmission route in less than 25% of cases.
Clostridium difficile is a leading cause of both healthcare-associated diarrhea and hospital-acquired infection. With today's more-virulent strains, such illness causes considerable morbidity and mortality. Although C. difficile infection (CDI) is almost universally preceded by antibiotic therapy, which may have ended weeks or months before symptom onset (JW Infect Dis Feb 29 2012), the source and transmission route of such infection often cannot be identified.
Now, investigators have published the results of an extensive investigation of C. difficile transmission dynamics in Oxfordshire, U.K. From September 2007 through March 2010, 29,299 unformed stool samples from 14,858 individuals (inpatients and outpatients) were tested by enzyme immunoassay for C. difficile toxins; samples that tested positive were cultured. A total of 1276 C. difficile isolates were subjected to multilocus sequence typing, which revealed 69 distinct strains.
Analysis of hospital admissions and ward-movement data for each patient with CDI, assuming an 8-week maximum infection period and a 12-week maximum incubation period, showed that 66% of cases were not linked to known cases, and only 23% had a credible ward-based source. When the analysis was adjusted for chance meetings of patients within the hospital, only 16% of cases were linked by probable transmission events.
Comment: The results of this sophisticated epidemiologic study contrast with the current view of hospitals as C. difficile transmission "hotspots." Editorialists note that the authors did not consider several potential sources and routes of C. difficile transmission in hospitals, such as intervention suites, other wards, and asymptomatic carriers. Nonetheless, there appear to be additional, as-yet-unidentified reservoirs of infectivity and routes of C. difficile transmission in the community.
— Thomas Glück, MD Published in Journal Watch Infectious Diseases March 28, 2012
Citation(s):Walker AS et al. Characterisation of Clostridium difficile hospital ward–based transmission using extensive epidemiological data and molecular typing. PLoS Med 2012 Feb; 9:e1001172. (http://dx.doi.org/10.1371/journal.pmed.1001172)
http://www.ncbi.nlm.nih.gov/pubmed/22346738?dopt=Abstract
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Non-HDL Cholesterol Seems a Better Target Than LDL to Gauge Statin Therapy
LDL cholesterol levels may not be the best target for statin therapy, according to a JAMA meta-analysis.
Researchers examined patient data from eight randomized trials in which nearly 40,000 patients received statins. They assessed whether non-HDL cholesterol or apolipoprotein B were more predictive of future cardiovascular events than LDL.
Increases of one standard deviation from baseline levels of LDL, apoB, and non-HDL at 1 year were all associated with increased risks for cardiovascular events, but the differences between LDL (and apoB) versus non-HDL were significant. Patients reaching the non-HDL target of 130 mg/dL or less, but not the LDL target of 100 mg/dL or less, were at lower risk than those reaching the LDL target but not the non-HDL target.
The authors conclude: "Non-HDL-C may be a more appropriate target for statin therapy than LDL-C."
http://jama.ama-assn.org/content/307/12/1302.short
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J Clin Oncol 2012 Mar 5
Tamoxifen Effective for Ductal Carcinoma in Situ
In women with estrogen receptor–positive disease, adjuvant tamoxifen reduced risk for subsequent breast cancer.
The National Surgical Adjuvant Breast and Bowel Project (NSABP) B-24 trial showed that women with ductal carcinoma in situ (DCIS) who underwent lumpectomy and whole-breast radiotherapy had significantly lower risk for subsequent breast cancer events when treated for 5 years with adjuvant tamoxifen versus placebo (Lancet 1999; 353:1993). However, patients in this early study were not selected to receive the study drug on the basis of estrogen receptor (ER) status.
Now, researchers have retrospectively evaluated the association between DCIS receptor status and response to adjuvant tamoxifen in 732 of the 1804 patients in the NSABP B-24 trial for whom DCIS tissue was available in a central lab (449 patients) or hormonal status was available at the enrolling institution (283 patients). Of these patients, 76% were ER positive and 66% were PgR positive. Median follow-up time was 14.5 years.
ER-positive patients treated with tamoxifen experienced lower risk for subsequent breast cancer at 10 years (hazard ratio, 0.49; P<0.001) compared with patients receiving placebo. ER-negative patients experienced no benefit from tamoxifen treatment.
Multivariable analysis showed that independent predictors of subsequent breast cancer included treatment status (tamoxifen vs. placebo; HR, 0.64; P<0.003) and younger age at entry (
49 vs. 
50; HR, 0.61; P<0.001).
Comment: For invasive breast cancer, the benefit of adjuvant tamoxifen has been shown in numerous studies to be limited to patients with ER-positive disease. Until publication of the current research, this limitation has also been assumed but not proven to be the case for women with DCIS. DCIS is notably different from invasive carcinoma in that the survival from this disease is already approximately 98% among patients treated with state-of-the-art therapy. Thus, the principal aim of treatment for patients with DCIS is to prevent invasive cancers and development of local recurrence following breast-conserving therapy. The absolute benefit of tamoxifen therapy, therefore, must far outweigh the risks. In this study, a significant benefit of tamoxifen was seen in patients with hormone receptor–positive disease, and the absolute 10-year benefit of tamoxifen versus placebo for the development of any breast cancer event (ipsilateral and contralateral disease) among patients with ER-positive DCIS was 12%. This benefit seems substantially higher than the known potential risks associated with tamoxifen therapy and dictates that clinicians should discuss this therapy with patients who have hormone receptor–positive DCIS. Results from the successor trial to NSABP B-24 (NSABP B-35) reached accrual in 2006 and will be of interest in light of the current findings, given that the study requires positive hormone-receptor status for entry and randomizes patients with DCIS undergoing lumpectomy and radiation therapy to the aromatase inhibitor anastrozole versus tamoxifen.
— Henry Mark Kuerer, MD, PhD, FACS Published in Journal Watch Oncology and Hematology March 27, 2012
Citation(s): Allred DC et al. Adjuvant tamoxifen reduces subsequent breast cancer in women with estrogen receptor–positive ductal carcinoma in situ: A study based on NSABP protocol B-24. J Clin Oncol 2012 Mar 5; [e-pub ahead of print].
(http://dx.doi.org/10.1200/JCO.2010.34.0141)
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N Engl J Med 2012 Mar 26 2011 Aug 8/22; 171:1363
Fully Oral Therapy for Symptomatic Pulmonary Embolism
The efficacy and safety of rivaroxaban was similar to that of enoxaparin plus a vitamin K antagonist.
In a previous study, the oral factor Xa inhibitor rivaroxaban was as effective as standard enoxaparin-warfarin therapy for patients with proximal deep venous thrombosis (JW Gen Med Dec 21 2010). Now, industry-supported researchers have conducted a similar open-label, randomized trial involving nearly 5000 adults with acute symptomatic pulmonary embolism. Patients received either oral rivaroxaban (15 mg twice daily for 3 weeks, followed by 20 mg once daily) or standard therapy (subcutaneously injected enoxaparin followed by warfarin or acenocoumarol). Treatment duration was 3, 6, or 12 months, depending on the treating physician's preference. Exclusion criteria included creatinine clearance <30 mL/minute, clinically significant liver disease, severe hypertension, and need for thrombolytic therapy. Although the trial was open-label, endpoints were adjudicated by a committee blinded to treatment assignment.
The primary efficacy outcome (symptomatic fatal or nonfatal recurrent venous thromboembolism) occurred in 2.1% of rivaroxaban patients and 1.8% of conventionally treated patients, a nonsignificant difference that met specified criteria for noninferiority. Clinically relevant bleeding occurred in 10.3% and 11.4% of patients in the rivaroxaban and standard-therapy groups, respectively; major bleeding (e.g., bleeding that occurred at critical sites, required transfusion, or contributed to death) occurred in significantly fewer rivaroxaban patients than standard-therapy patients (1.1% vs. 2.2%).
Comment: Fully oral therapy with rivaroxaban appears effective and safe for a fairly broad range of patients with pulmonary embolism. However, the drug is currently FDA-approved only for prophylaxis after orthopedic surgery and for stroke prevention in atrial fibrillation.
— Allan S. Brett, MD Published in Journal Watch General Medicine March 26, 2012
Citation(s):Büller HR et al. for the EINSTEIN–PE Investigators. Oral rivaroxaban for the treatment of symptomatic pulmonary embolism. N Engl J Med 2012 Mar 26; [e-pub ahead of print]. (http://dx.doi.org/10.1056/NEJMoa1113572)
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J Midwifery Womens Health 2012 Jan/Feb; 57:12
Does C-Section Increase Risk for Stillbirth in Subsequent Pregnancy?
In a retrospective cohort study, prior cesarean birth was associated with increased risk for antepartum fetal death.
The cesarean birth rate in the U.S. has increased sharply, including for first births, but the effect of prior C-section on risk for stillbirth in a second pregnancy is not clear. For this retrospective cohort study, data on nearly 11,000 women were obtained from a large academic hospital from 1994 to 2002. Women who were pregnant after one prior birth were included unless they had multiple gestations, fetal anomalies, or gestation <24 weeks or >43 weeks in their current pregnancies. Outcomes of second pregnancies were compared based on method of the first birth: vaginal (78%) or cesarean (22%). The primary outcome measure was antepartum fetal death at >24 weeks' gestation in the second pregnancy.
Women whose first delivery was by cesarean were older, shorter, and heavier and more likely to have hypertensive disorders or diabetes by the time of their second pregnancy than women whose first birth was vaginal, but the groups were similar in terms of race, gravidity, and rates of smoking during pregnancy.
The risk for antepartum fetal death in the second pregnancy was significantly greater for the prior-cesarean group than for the vaginal-birth group (0.4% vs. 0.1%). This difference was not evident earlier in pregnancy, but in pregnancies lasting at least 34 weeks, the risk for stillbirth was 0.25% in the cesarean vs. 0.048% in the vaginal group, a difference of 2.02 deaths per 1000 births.
Comment: The findings of this observational study do not necessarily indicate cause and effect, and it seems premature to raise the concern regarding an increased risk for stillbirth among women with a prior cesarean birth among the clinicians or the pregnant women.
— Diane J. Angelini, EdD, CNM, FACNM, FAAN, NEA-BC Published in Journal Watch Women's Health March 8, 2012
Citation(s):Osborne C et al. First birth cesarean and risk of antepartum fetal death in a subsequent pregnancy. J Midwifery Womens Health 2012 Jan/Feb; 57:12.
(http://dx.doi.org/10.1111/j.1542-2011.2011.00142.x)
http://www.ncbi.nlm.nih.gov/pubmed/22251907?dopt=Abstract
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