• Making Human Liver and Blood Vessels from Stem Cells
• Weight Loss and CPAP Recommended in Obstructive Sleep Apnea Guidelines
• Housework as a Sleep Aid During the Menopausal Transition?
• If You Can't Lose Weight, Maintain It
• BMD Testing Every 2 Years May Not Improve Fracture Risk Prediction
• Increase in Deaths Linked to First Line Treatment with Sulfonylureas
• Drug Safety: All Statins Are Not Created Equal
• Statins Improve Clostridium difficile Outcomes
• Why Does Antibiotic Treatment Predispose to Clostridium difficile and Salmonella Infections?
• World Outlook for Alzheimer's care: Costly Now and Certain to Increase
• Is the Prevalence of Dementia Changing?
• Safety of Fluconazole During Pregnancy
• How Safe Are Topical Steroids During Pregnancy?
• Hysterectomy on the Decline in the U.S.
• Testosterone Study Highlights Role of Estrogen in Male Hypogonadism
• Promote Weight Loss in Patients with NAFLD
• Does Screening Mammography Save Lives?
• Most Breast Cancer Deaths Occur in Unscreened Women
• Smoking Cessation: Tips from Former Smokers' Program Helps U.S. Efforts
• FDA Says Inorganic Arsenic in Rice Poses No Immediate Hazard
MM: Although this information was made public well over a year ago, it is still very cool that this work is continuing nad appears to be on a road of success. I truly believe that in my lifetime, we will be able to "grow" fully functional replacement organs
Nature 2013 Jul 25
Making Human Liver and Blood Vessels from Stem Cells
Another step along the path to creating bioidentical organs
A differentiated skin cell can be transformed into the equivalent of a person's own embryonic stem cell (NEJM JW Gen Med Dec 29 2008), a discovery honored with the Nobel Prize in 2012. Once a differentiated cell is converted into an induced pluripotent stem (iPS) cell — an embryonic-like stem cell — it can be induced to turn into whatever cell type is desired. For example, myocytes created from iPS cells theoretically could be infused, find their way to the heart, and replace the function of myocytes killed by a myocardial infarction. Although such cell therapy already is succeeding in animals, creating new organs from iPS cells has been a daunting task. But in two remarkable reports, investigators show that it might be possible.
A team from Harvard created iPS cells from healthy adults; then, they created both endothelial and mesenchymal precursor cells from the iPS cells and cultured them together in mice. After several days, these human cells formed new blood vessels that connected to the animals' own blood vessels and were perfused with the animals' blood.
A Japanese team created human iPS cells; transformed them into liver epithelial, mesenchymal, and endothelial cells; and cultured them together in vitro. The cells started to form buds of vascularized human liver tissue. When these buds were transplanted into the liver or mesentery of mice, they grew and connected to the hosts' blood supply. They produced human albumin and α1-antitrypsin and metabolized drugs — just like human liver.
Comment: From these small successes to making bioidentical replacement organs is a long road. Nevertheless, these remarkable reports likely will encourage many investigators to travel that path.
Citation(s): Samuel R et al. Generation of functionally competent and durable engineered blood vessels from human induced pluripotent stem cells. Proc Natl Acad Sci U S A 2013 Jul 30; 110:12774.
(http://dx.doi.org/10.1073/pnas.1310675110)
Takebe T et al. Vascularized and functional human liver from an iPSC-derived organ bud transplant. Nature 2013 Jul 25; 499:481.
(http://dx.doi.org/10.1038/nature12271)
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Weight Loss and CPAP Recommended in Obstructive Sleep Apnea Guidelines
By Kelly Young
The American College of Physicians has released guidelines on treating obstructive sleep apnea. The recommendations, published in the Annals of Internal Medicine, include the following:
- Weight loss should be encouraged for all overweight and obese patients with obstructive sleep apnea.
- Continuous positive airway pressure (CPAP) is recommended as a first-line treatment.
- Mandibular advancement devices (MADs) are recommended for patients who experience adverse effects with CPAP treatment, those who don't adhere to CPAP, or those who simply prefer MADs.
Current evidence does not support drug therapy for sleep apnea. Evidence is also lacking for the benefits of surgery, so it shouldn't be used as first-line treatment, the group says.
http://annals.org/article.aspx?articleid=1740756
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MM: When the media gets their teeth into an article like this you can bet that there will be smug remarks and in this case, rightfully so. When large numbers of patients are made uncomfortable by a particular condition, it is typical that many will look for solutions. This is likely the history of how old time salesmen could sell snake oil successfully. In this article, the data and methods must be carefully examined as not all groups investigated showed benefit from the activity.
Menopause 2013 Sep; 20:946
Housework as a Sleep Aid During the Menopausal Transition?
For some women with vasomotor symptoms, household physical activity was associated with better-quality sleep.
Nonrestorative sleep, often linked with vasomotor symptoms (VMS), is a common complaint of women during the menopausal transition (NEJM JW Women's Health Aug 9 2012). In a subanalysis of the Study of Women's Health Across the Nation (SWAN), researchers evaluated the impact of leisure and nonleisure physical activity on sleep in 52 women with VMS (52% white; mean age, 58; mean body-mass index, 30 kg/m2). Participants completed physical activity surveys (sports/exercise, household/caregiving during the past 12 months) and sleep diaries (two 48-hour periods, for which they also rated the quality of the previous night's sleep). Wrist-monitored actigraphy provided objective measurements of sleep patterns; other monitors were used to record physiologic VMS.
Black women had more VMS and shorter total sleep time than white women. Participants reporting more leisure-time physical activity reported better-quality sleep. Among white women but not black women, greater household physical activity was associated with better subjective sleep quality. Such nonleisure activity also resulted in better actigraphically measured sleep efficiency, but only for nonobese white women.
Comment: Despite the authors' efforts to control for certain variables, this study subset is small and therefore not readily generalizable. The authors admit that the concept of household physical activity can be very broad and, to some extent, culturally influenced. Before recommendations can be made, more information is needed about mechanisms linking sleep quality to these forms of physical activity.
Citation(s): Lambiase MJ and Thurston RC. Physical activity and sleep among midlife women with vasomotor symptoms. Menopause 2013 Sep; 20:946.
(http://dx.doi.org/10.1097/gme.0b013e3182844110
http://www.ncbi.nlm.nih.gov/pubmed/23531686?access_
num=23531686&link_type=MED&dopt=Abstract
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MM: Losing weight may be a daunting task as is witnessed by the tremendous long term failure and recidivism rate of many weight loss programs. It makes sense that to "sell an idea" make the idea more possible and palatable. The idea of 'arresting the development' of a condition does not seem as impossible as reversing it. Unfortunately simply slowing the further development of obesity does not truly benefit the patient. Fortunately, we have experienced significant, repeated and documented success of weight loss and medical condition improvement with the HCG metabolic Syndrome and Weight Loss Protocol. For more information, please visit www.MarkDrugs.com
JAMA Intern Med 2013 Aug 26
If You Can't Lose Weight, Maintain It
By participating in a structured behavior-modification program, overweight and class 1 obese black women avoided gaining weight.
Obesity and its health consequences affect black women disproportionately. When premenopausal, they typically gain about 1 kg yearly, and few strategies achieve clinically significant weight loss. Preventing this gain in black women who are overweight (body-mass index [BMI], 25.0–29.9 kg/m2) or have class 1 obesity (BMI, 30.0–34.9] — in whom obesity-related morbidity is less common than those with BMI ≥35 — may be a more achievable goal. In the SHAPE program, investigators randomized 194 black women (mean BMI, 30.2; mean age, 35.4) to usual care or a 12-month weight-gain prevention intervention. Most participants had low incomes and less than a college education. Interventions included goal-setting for behavioral change, weekly self-monitoring through automated telephone calls, monthly phone counseling by a dietitian, skills training materials, and a free 12-month YMCA membership.
In intent-to-treat analysis, mean changes in weight and BMI were significantly larger in the intervention group than in the usual-care group (weight, –1.0 vs. +0.5 kg; BMI, –0.3 vs. +0.3 kg/m2). Significantly more intervention participants (62.1% vs. 45.4%) maintained or reduced their baseline weight, without significant changes in waist circumference, blood pressure, or blood glucose or lipid levels. Significant differences persisted or widened at 18-month follow-up.
Comment: “Maintaining current body shape,” as the investigators explained it to the participants, might be more culturally acceptable and less daunting than losing weight to some groups of women. Significant differences persisted 6 months after the intervention ended, suggesting that women continued to make use of weight-control strategies. Although this modest improvement did not alter other cardiovascular risk factors, maintaining their weight prevents women from moving into higher-risk BMI categories. Clinicians might find electronic and community-based resources worth exploring to offer a similar approach
Citation(s): Bennett GG et al. Behavioral treatment for weight gain prevention among black women in primary care practice: A randomized clinical trial. JAMA Intern Med 2013 Aug 26; [e-pub ahead of print].
(http://dx.doi.org/10.1001/jamainternmed.2013.9263)
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BMD Testing Every 2 Years May Not Improve Fracture Risk Prediction
By Kelly Young
The current practice of testing bone mineral density every 2 years in older adults may be too frequent, suggests a JAMA study.
Roughly 800 adults (mean age, 75) underwent two femoral neck BMD tests an average of 3.7 years apart as part of the Framingham Osteoporosis Study. After 10 years of follow-up, the addition of BMD change to a model predicting fracture risk did no better than use of baseline BMD alone. With a second BMD test, the percentage of patients with a hip fracture reclassified as high risk increased only 3.9%, while those with a major osteoporotic fracture who were upgraded to high risk increased 9.7%.
The authors conclude: "The current clinical practice of repeating a BMD test every 2 years to improve fracture risk stratification may not be necessary in all adults 75 years or older untreated for osteoporosis. Further study is needed to determine an appropriate rescreening interval and to identify individuals who might benefit from more frequent rescreening intervals."
http://jama.jamanetwork.com/article.aspx?articleid=1741821
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Increase in Deaths Linked to First Line Treatment with Sulfonylureas
By Larry Husten
First-line treatment with sulfonylureas instead of metformin in people with type 2 diabetes is associated with a significantly elevated risk for death, according to results from an observational study presented at the European Association for the Study of Diabetes (EASD) meeting in Barcelona. (The American College of Physicians recommends metformin as initial drug therapy.)
Examining data from the U.K.'s Clinical Practice Research Datalink, researchers found that between 2000 and 2012, 76,811 patients with type 2 diabetes began glucose-lowering treatment with metformin, while 15,687 began sulfonylureas (which include glipizide, glyburide, and glimepiride). After adjustment for baseline differences, mortality was 58% higher in the sulfonylurea group (44.6 deaths per 1000 patient-years with sulfonylureas versus 13.6 with metformin).
The researchers acknowledge that while "residual confounding and confounding by indication may remain, this study indicates that treatment with first-line monotherapy with sulfonylureas should be reconsidered."
http://www.easdvirtualmeeting.org/resources/3059
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Circ Cardiovasc Qual Outcomes 2013 Jul; 6:390
Drug Safety: All Statins Are Not Created Equal
In a large meta-analysis, simvastatin and pravastatin were safest.
Because statins lower the incidence of adverse cardiovascular and cerebrovascular events — even in low-risk patients — they are used broadly (NEJM JW Gen Med Jun 12 2012). Statins' reported adverse effects include myalgias, myopathy, rhabdomyolysis, transaminitis, and diabetes mellitus. In a meta-analysis of 135 randomized trials (247,000 participants) that involved seven statins (atorvastatin, fluvastatin, lovastatin, pravastatin, rosuvastatin [Crestor], simvastatin, and pitavastatin [Livalo]), investigators evaluated adverse effects associated with statins overall and individually.
The overall rate of statin discontinuation owing to adverse effects was low (6%) for all statins combined. Statins as a class caused no more medication discontinuations, myalgias, creatinine kinase elevations, myopathy, rhabdomyolysis, or cancer than placebo. However, statins significantly increased relative risk for transaminase elevations (by 50%; baseline incidence, 1%) and diabetes (by 9%) compared with placebo.
Simvastatin and pravastatin were associated with best overall tolerability and lowest discontinuation rates. Compared with controls, atorvastatin and rosuvastatin were associated with the highest discontinuation rate because of adverse events; whereas atorvastatin and fluvastatin were associated with higher risks for transaminase elevations (odds ratios, 2.6 and 5.2, respectively). Higher doses of all statins were associated with higher risk for transaminase elevations. Although low doses of simvastatin appeared to be safest, daily doses >40 mg significantly raised risk for creatinine kinase elevation (OR, 4.1) and transaminase elevation (OR, 2.8).
Comment: Clinicians should compare individual statin safety and tolerability profiles to guide prescribing practices and prevent adverse effects. Even a low incidence of adverse effects could amount to many thousands or even hundreds of thousands of patients affected among the >150 million who receive prescriptions annually. Defining who benefits the most from statin therapy remains paramount. Dr. Finn is a hospitalist and the Inpatient Associate Program Director for the Internal Medicine Residency Program at Massachusetts General Hospital in Boston.
Citation(s): Naci H et al. Comparative tolerability and harms of individual statins: A study-level network meta-analysis of 246 955 participants from 135 randomized, controlled trials. Circ Cardiovasc Qual Outcomes 2013 Jul; 6:390.
(http://dx.doi.org/10.1161/CIRCOUTCOMES.111.000071)
http://circoutcomes.ahajournals.org/content/6/4/390?ijkey=
bf65e7f40b077728daf099df2c53118d21143256&keytype2=tf_ipsecsha
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MM: Finally there appears to be a legitimate contribution of statins! The anti-inflammatory effects that have been touted for a while appear to have a beneficial effect when used for a life-threatening infection. Whether this use will prove to be legitimate and worthwhile, only time will tell.
Aliment Pharmacol Ther 2013 Sep; 38:619
Statins Improve Clostridium difficile Outcomes
Use of statins was associated with a 45% higher likelihood of successful treatment with metronidazole among hospitalized patients with C. difficile.
Statins are increasingly recognized to have a positive outcome on a variety of infections, presumably through their anti-inflammatory effect. Does this include Clostridium difficile infection?
To answer this question, researchers in Korea conducted a case-control study involving 1725 consecutive hospitalized patients with diarrhea and positive C. difficile toxin assays, C. difficile cultures, or presence of pseudomembrane on lower endoscopy. After exclusion of 736 patients, researchers compared successful treatment response — resolution of diarrhea and other symptoms within 6 days of receiving metronidazole — between 199 statin users (defined as statin use for ≥12 weeks) and 750 statin nonusers.
In multivariate analysis, successful treatment response to metronidazole was associated with absence of a nasogastric tube, higher serum albumin level, lower serum creatinine level, lower severity score, absence of exposure to proton-pump inhibitors, and exposure to statins (odds ratio, 1.45; 95% confidence interval, 1.02–2.07). Statin users had a lower 60-day recurrence rate than nonusers (3.0% vs. 7.3%; relative risk, 0.39; 95% CI, 0.17–0.93).
Comment: It is unclear whether statins will ever become part of the treatment regimen of patients with Clostridium difficile infection, or perhaps patients with recurrent C. difficile. However, at a minimum, we can encourage patients who are already taking statins to continue doing so during treatment for C. difficile infection.
Citation(s): Park SW et al. The effects of statins on the clinical outcomes of Clostridium difficile infection in hospitalized patients. Aliment Pharmacol Ther 2013 Sep; 38:619.
(http://dx.doi.org/10.1111/apt.12439)
http://www.ncbi.nlm.nih.gov/pubmed/23888883?access_num=
23888883&link_type=MED&dopt=Abstract
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MM: The gist of this article is that antibiotics have an effect on the mutation of certain bacteria that make them resistant and allow them to thrive. The article describes the proposed mechanism of how this actually happens.
Nature 2013 Sep 1
Why Does Antibiotic Treatment Predispose to Clostridium difficile and Salmonella Infections?
These pathogens exploit increased gut sialic acid levels following antibiotic therapy to cause infection.
Antibiotic treatment is a well-known risk factor for the development of Salmonella and Clostridium difficile infections. This effect has been ascribed to antibiotic-induced alterations in the gut microbiota — but what are the underlying mechanisms? In a recent study involving a murine model, researchers in California showed that antibiotic-induced alterations in gut carbohydrates promote the expansion of these enteric pathogens.
To understand growth factors for Salmonella within the gut, the researchers assessed gene expression by Salmonella typhimurium in germ-free mice and in mice colonized with a single Bacteroides species. This work, along with experiments involving mutant S. typhimurium strains, showed that the presence of the carbohydrates fucose and sialic acid strongly influenced the growth of this bacterium. Similar experiments involving C. difficile showed that increased sialic acid levels within the gut lumen promoted growth. Subsequent studies in conventional mice revealed that antibiotic exposure can markedly increase gut sialic acid levels. Wild-type S. typhimurium and C. difficile showed growth expansion in the gut of antibiotic-treated conventional mice, with decreased growth of mutant strains of these organisms that lacked the ability to metabolize sialic acid (both S. typhimurium and C. difficile) or fucose (S. typhimurium only).
Comment: By helping us to understand how antibiotic therapy predisposes to Salmonella and C. difficile infections, this work could lead to the development of new preventive strategies.
Citation(s): Ng KM et al. Microbiota-liberated host sugars facilitate post-antibiotic expansion of enteric pathogens. Nature 2013 Sep 1; [e-pub ahead of print].
(http://dx.doi.org/10.1038/nature12503)
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World Outlook for Alzheimer's care: Costly Now and Certain to Increase
By Joe Elia
If the cost of dementia care in 2010 were a country, it would represent the world's 18th-largest economy, ranked between Turkey and Indonesia, according to Alzheimer's Disease International's annual report.
The report focuses on long-term care, with global costs estimated to nearly double (to US$1.1 trillion) by 2030.
The authors warn against a "pay-as-you-go" approach to paying for dementia care, because "future generations of working age adults will struggle to produce enough to pay" for their parents' care. They also call for better integration of health and social care systems to create "coordinated care pathways."
Observing that caregivers often work at minimum wages (or earn nothing at all in the case of family members), the report recommends better pay and working conditions for them.
http://www.alz.co.uk/research/WorldAlzheimerReport2013.pdf
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Lancet 2013 Jul 16
Is the Prevalence of Dementia Changing?
In England, the prevalence fell from 8.3% to 6.5% during the past 20 years.
Dementia in the growing elder population is an important driver of healthcare costs and a matter of societal concern. Some trends might increase dementia prevalence (e.g., longer lifespan, increasing obesity and diabetes, survival after stroke), whereas others might reduce it (e.g., more-effective prevention of cardiovascular disease, improved early-life education). Between 1989 and 1994, researchers estimated dementia prevalence in three geographic areas in England by interviewing a population-based sample of more than 7500 older adults (age, ≥65). Now, investigators report results of an identical survey in a similar sample from the same areas between 2008 and 2011.The overall prevalence of dementia fell significantly, from 8.3% to 6.5%. In care facilities, dementia prevalence rose from 58% to 73%; however, the proportion of elders living in such facilities declined from 5% to 3%. In both surveys, dementia prevalence was higher in women than in men in care and community settings.
Comment: This rigorous study is a persuasive piece of evidence that, at least in some settings, the prevalence of dementia in elders is declining and might be sensitive to societal efforts to improve education, primary prevention, and healthcare delivery.
Citation(s): Matthews FE et al. A two-decade comparison of prevalence of dementia in individuals aged 65 and older from three geographical areas of England: Results of the Cognitive Function and Ageing Study I and II. Lancet 2013 Jul 16; [e-pub ahead of print].
(http://dx.doi.org/10.1016/S0140-6736(13)61570-6)
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MM: One of the most common questions that I receive from clinicians is some variation of "What is safe during pregnancy?". There is almost always a risk to benefit ratio that must be examined. This exists with conventional medications as well as herbal and nutritional products. Unfortunately there is a lack of published data and documentation with many products so we have to rely upon specific questions to manufacturers that are often side-stepped, anecdotal or personal clinical experience. When we have a stydy that addresses drug side effects, as pharmacists and clinicians, we are especially grateful.
N Engl J Med 2013 Aug 29; 369:830
Safety of Fluconazole During Pregnancy
First-trimester use of typical therapeutic doses of oral fluconazole was not associated with excess risk for birth defects overall, but risk for tetralogy of Fallot was significantly increased.
Vaginal candidiasis is common in pregnant women, who are often given 150-mg oral fluconazole (particularly for recurrent infections). Concern has been raised that higher doses of this medication during the first trimester confer excess risk for birth defects. Danish investigators linked national birth, prescription, and childhood health records to assess the effects of oral fluconazole on risk for birth defects when given at typical cumulative doses (mostly 150 or 300 mg) during the first trimester of pregnancy.
Nearly 1 million live born infants were studied, <1% of whom were exposed to fluconazole during the first trimester. Of these infants, 87% were exposed to <300 mg in total. First-trimester exposure was not associated with excess risk for birth defects overall (adjusted prevalence odds ratio, 1.1), nor with excess risk for 14 of 15 prespecified individual defects previously associated with azole agents. Risk for tetralogy of Fallot, however, was significantly increased (adjusted prevalence OR, 3.2).
Comment: This large, albeit retrospective, cohort study provides welcome safety data for common doses of fluconazole used during pregnancy. Overall risk for birth defects was not elevated, but prevalence of tetralogy of Fallot was higher among fetuses exposed even to low doses of fluconazole. Although absolute incidence of this defect was low among those exposed (an estimated 6.5 excess cases per 10,000 infants), and the possibility of a chance finding was increased given the number of specific defects examined, these data present some cause for restraint. Clinicians should keep in mind that topical preparations for yeast infections are first line, particularly during the first trimester — and these data should sway us away from fluconazole use merely for patients' convenience. On the other hand, for vaginitis refractory to topical therapies, women can be fairly well assured of the safety of this common medication.
Citation(s): Mølgaard-Nielsen D et al. Use of oral fluconazole during pregnancy and the risk of birth defects. N Engl J Med 2013 Aug 29; 369:830.
(http://dx.doi.org/10.1056/NEJMoa1301066)
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MM: In general we try to avoid medications during pregnancy unless absolutely necessary but when a patient is uncomfortable we look for the safest options that will provide the most benefits. This article provides those guidelines and gives not only what may be used, the relative danger of the type of medication and the amount of exposure during a pregnancy that could be a danger.
JAMA Dermatol 2013 Sep 4
How Safe Are Topical Steroids During Pregnancy?
Total dosage of potent topical corticosteroids is related to heightened risk for newborns.
An estimated 6% of pregnant women receive prescription topical corticosteroids (TCS), which are pregnancy risk category C. Animal studies show teratogenic effects, but data are limited and conflicting regarding use in pregnant women. Investigators performed a retrospective cohort study using data from the U.K. National Health Service. They documented type and dosages of TCS prescriptions filled at pharmacies by 2658 pregnant women over a 7-year period, who were matched with 7246 unexposed pregnant controls. Mean dispensed quantity of potent or very potent topical steroids during the whole pregnancy was 64 grams (range, 15–490). Women who received corticosteroids via other routes during pregnancy and those with multiple pregnancy or assisted reproduction were excluded. A subgroup who received TCS during the first trimester was identified (the critical period for fusion of the lip/palate is the 5th–12th gestational week). Other outcomes studied included low birth weight (LBW, <2500 g), preterm delivery (<37 weeks' gestation), fetal death, mode of delivery (vaginal vs. C-section), and low Apgar score (<7 at 5 minutes). Confounding concurrent diseases were noted.
Compared with no TCS use, maternal TCS exposure was not associated with orofacial cleft, LBW, preterm delivery, fetal death, low Apgar score, or mode of delivery. A separate analysis showed a significantly increased risk for LBW when the dispensed amount of potent or very potent TCS exceeded 300 g during the entire pregnancy.
Comment: Risks to the fetus from topical corticosteroid exposure appear to be lower than feared, but a dose-dependent relationship with low birth weight was seen. Many patients do not use up their prescriptions, and unaccounted-for TCS may have been received elsewhere, so the risks for adverse outcomes may be underestimated by this study design. Because LBW seems to correlate with quantity of potent TCS exposure, limited amounts of mild or moderate-strength TCS are safest in pregnant women. When potent or very potent TCS are indicated, the cumulative amount should be kept under 300 g, and fetal growth should be monitored.
Citation(s): Chi C-C et al. Pregnancy outcomes after maternal exposure to topical corticosteroids: A UK population-based cohort study. JAMA Dermatol 2013 Sep 4; [e-pub ahead of print].
(http://dx.doi.org/10.1001/jamadermatol.2013.5768)
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Obstet Gynecol 2013 Aug; 122:233
Hysterectomy on the Decline in the U.S.
New surgical approaches and medical therapies suggest that the trend will continue.
An estimated one in nine U.S. women will have a hysterectomy in her lifetime, typically for benign disease, yet other surgical and medical therapies are now available for women historically treated with hysterectomy. To determine recent trends in hysterectomy use, investigators analyzed Nationwide Inpatient Sample (NIS) data. This database included >1.5 million women aged ≥18 who underwent inpatient hysterectomies between 1998 and 2010. The NIS samples approximately 20% of all U.S. hospital discharges, implying that about 7.5 million U.S. women underwent hysterectomies during that period.
The annual projected number of inpatient hysterectomies rose to a peak of 681,000 in 2002, then fell each year to 433,000 in 2010 — a 36% decline. The proportion of hysterectomies performed abdominally, vaginally, and laparoscopically declined from 1998 to 2010, while the use of robotic surgery increased markedly, from 0.9% in 2008 to 8.6% in 2010. Beginning in 2002, there were sharp declines in the percentages of hysterectomies performed for endometriosis (–65%), benign ovarian mass (–63%), leiomyoma (–48%), pelvic organ prolapse (–39%), and abnormal uterine bleeding (–29%). Hysterectomies for gynecologic cancers increased slightly (9%) between 1998 and 2010. Median hospital case volume fell between 2002 and 2010, indicating minimal market concentration.
Comment: These data probably reflect the growing use of nonsurgical treatments for benign gynecologic disorders. They also suggest that gynecologists (and hospitals) might find it increasingly difficult to acquire and maintain the skills necessary to perform hysterectomies. Further specialization appears likely, with more gynecologists shifting mainly to office practice. The authors note that the exclusion of same-day surgeries from the NIS database could result in underestimation of the number of hysterectomies performed, but this is unlikely to alter the reported trends.
Citation(s): Wright JD et al. Nationwide trends in the performance of inpatient hysterectomy in the United States. Obstet Gynecol 2013 Aug; 122:233.
(http://dx.doi.org/10.1097/AOG.0b013e318299a6cf)
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MM: Since this article came out I have had quite a few calls and e-mails asking for clarification. For this reason I went to an expert on Bio-Identical Hormones, Dr Paul savage, M.D.
Testosterone Study Highlights Role of Estrogen in Male Hypogonadism
By Kelly Young
Androgen deficiency reduces muscle mass and strength in men; estrogen deficiency is associated with increase in fat mass; and deficiencies in both impair sexual function, according to an industry-supported study in the New England Journal of Medicine.
Some 200 healthy men aged 20 to 50 years first received goserelin acetate for suppression of estradiol and testosterone. They were then randomized to various doses (0-10 g) of daily 1% testosterone gel for 16 weeks. Another cohort of 200 men were similarly treated and also given anastrozole daily to inhibit the aromatization of testosterone to estrogen, leading to an estrogen-deficient state.
In the first cohort, patients who received low doses of testosterone saw increases in body fat percentages and reductions in lean mass. In the second cohort, the percentage of body fat increased in all groups as aromatization was blocked. In both cohorts, sexual desire declined and erectile dysfunction worsened with lower doses of testosterone.
The authors conclude: "Our finding ... indicates that estrogen deficiency is largely responsible for some of the key consequences of male hypogonadism and suggests that measuring estradiol might be helpful in assessing the risk of sexual dysfunction, bone loss, or fat accumulation in men with hypogonadism."
http://www.nejm.org/doi/full/10.1056/NEJMoa1206168
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MM: There is no question in my mind that establishing weight control in obese patients with virtually any ailment will show improvement in their various conditions. The body simply functions better when excesses are monitored and limited.
J Hepatol Med 2013 Sep; 59:536
Promote Weight Loss in Patients with NAFLD
In a community-based intervention, 97% of patients who achieved 10% weight loss also achieved disease remission.
Medical therapy for nonalcoholic fatty liver disease (NAFLD) should include weight loss. In a small randomized, controlled trial, a scripted weight-loss program improved NAFLD (NEJM JW Gastroenterol Mar 12 2010). But can such programs work in community-based settings? To find out, researchers conducted a randomized, controlled superiority trial to assess the efficacy of a community-based lifestyle-modification program in Hong Kong to improve NAFLD.
Patients with NAFLD were defined as having elevated liver enzymes and fatty liver (intrahepatic triglyceride content [IHTG] ≥5% on proton-magnetic resonance spectroscopy). Patients with other liver diseases were excluded. Of 154 patients randomized, 77 participated in the intervention — a 12-week, dietitian-led, lifestyle-modification program held at two urban centers open to the public for the management of obesity and related disorders. Sessions were weekly for the first 4 months and monthly thereafter and focused on ways to reduce caloric intake and increase energy expenditure. The control group received general advice on diet and exercise at a hospital medical clinic. The primary outcome was improvement in fatty liver at 12 months, defined as IHTG <5%.Based on intention-to-treat analysis, the intervention group had a higher rate of improvement in NAFLD than controls (7% vs. 2%; P<0.001) and lost more weight (5.6 kg vs. 0.6 kg; P<0.001). Notably, of patients who achieved a 10% reduction in weight, 97% achieved remission of NAFLD.
Comment: Data from this well executed study demonstrate not only that a 10% reduction in weight improves nonalcoholic fatty liver disease, but also that a community-based lifestyle-modification program is effective. Although this study was not designed to assess histologic improvement or long-term benefits of such an intervention, weight loss yields many other health benefits. Until other specific therapies are identified for NAFLD, clinicians should continue to look for effective ways to promote weight loss in their patients.
Citation(s): Wai-Sun Wong V et al. Community-based lifestyle modification programme for non-alcoholic fatty liver disease: A randomized controlled trial. J Hepatol 2013 Sep; 59:536.
(http://dx.doi.org/10.1016/j.jhep.2013.04.013)
http://www.ncbi.nlm.nih.gov/pubmed/23623998?access_num=
23623998&link_type=MED&dopt=Abstract
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Cancer 2013 Sep 9
Does Screening Mammography Save Lives?
Perhaps, but questions remain.
The utility of screening mammography is controversial, particularly for women in their 40s. Investigators from two Boston hospitals assessed mammographic history and cause of death in women who died following invasive breast cancer diagnosed between 1990 and 1999. Interval cancers were defined as symptomatic or palpable tumors presenting <2 years after the prior screening mammogram.
Among 609 deaths from confirmed breast cancer, 29% occurred in women who had been screened (19% screen-detected cancers, 10% interval cancers) and 71% occurred in unscreened women (6% diagnosed >2 years after the last mammogram, 65% never screened). Among women who died from breast cancer versus other causes, median age at diagnosis was 49 versus 72. The authors concluded that regular screening of women younger than 50 would lower mortality from breast cancer.
Comment: In 2009, the U.S. Preventive Services Task Force recommended mammography screening in women beginning at age 50 and continuing biennially until age 74. However, the American Cancer Society and other professional groups have continued to recommend annual screening beginning at age 40, resulting in controversy and confusion (NEJM JW Womens Health Feb 4 2010). Although some might find the present study persuasive, I am concerned about its limitations. Because it was conducted in women with diagnosed breast cancer, outcomes in screened and unscreened populations could not be compared; also, no information was provided about treatment received by screened and unscreened women. Women who have been screened infrequently (or never) probably are considerably less affluent and less educated than those who participate in regular screening. Accordingly, unscreened women are less likely to seek timely medical attention upon finding a palpable breast mass, leading to differences in breast cancer outcomes independent of screening history. For now, I will continue to be flexible in my recommendations about mammograms for average-risk women in their 40s, supporting their individual preferences.
Citation(s): Webb ML et al. A failure analysis of invasive breast cancer. Cancer 2013 Sep 9; [e-pub ahead of print].
(http://dx.doi.org/10.1002/cncr.28199)
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Most Breast Cancer Deaths Occur in Unscreened Women
By Amy Orciari Herman
Nearly three quarters of deaths from breast cancer occur among women who've not undergone mammographic screening, according to a study in Cancer.
Researchers in Massachusetts examined the medical records of some 7300 women who were diagnosed with potentially curable (stages I to III) invasive breast cancer from 1990 through 1999 and followed them through 2007. During that time, there were roughly 600 proven breast cancer deaths — 71% of which occurred among unscreened women. Half of all breast cancer deaths occurred among those younger than 50.
The researchers conclude: "To maximize mortality reduction and life-years gained, initiation of regular screening before age 50 years should be encouraged."
http://onlinelibrary.wiley.com/doi/10.1002/cncr.28199/abstract
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Smoking Cessation: Tips from Former Smokers' Program Helps U.S. Efforts
By Joe Elia
A $54 million national advertising program sponsored and paid for by the federal government is estimated to have helped 100,000 U.S. smokers quit, according to an account in the Lancet.
The 12-week program, called Tips from Former Smokers, recruited former smokers to tell stories about the effects of their smoking-related illnesses on the quality of their lives. Viewers of the campaign were encouraged to call 1-800-QUIT NOW.
To gauge the program's effect, some 3000 smokers and 2200 nonsmokers filled out questionnaires both before the program began and again during the month after it ended. Extrapolating from the survey data, researchers estimate that over three quarters of smokers across the U.S. saw at least one Tips ad. They report that quit attempts during the campaign rose from 31% to 35%, resulting in 1.6 million additional attempts nationwide. Some 220,000 quitters remained abstinent by the end of the campaign, and 100,000 likely quit permanently.
http://www.thelancet.com/journals/lancet/article/PIIS0140-6736%2813%2961686-4/abstract
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FDA Says Inorganic Arsenic in Rice Poses No Immediate Hazard
By Kelly Young
The levels of inorganic arsenic found in rice do not pose a short-term health concern to people, the FDA said in an update to consumers Friday.
The agency made the determination after testing 1300 samples of rice and rice-based foods for arsenic. On average, a serving of rice grains contained 2.6 to 7.2 micrograms of inorganic arsenic. Brown rice averaged closer to the higher end. Processed rice foods contained slightly lower levels.
The FDA recommends that consumers eat a well-balanced diet; eat a variety of grains like wheat, barley, and oats; and consider other options for an infant's first solid food.
The agency is now conducting a risk assessment that will, among other things, examine whether certain populations are at greater risk from arsenic in rice.
http://www.fda.gov/ForConsumers/ConsumerUpdates/ucm352569.htm
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