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Obesity is a modifiable risk factor for urinary incontinence. This study randomly assigned overweight and obese women with urinary incontinence to an intensive 6-month weight-loss program or to a structured education program. More intervention-group participants had clinically relevant reductions in the frequency of episodes of any incontinence, stress incontinence, and urge incontinence. This study randomly assigned overweight and obese women with urinary incontinence to an intensive 6-month weight-loss intervention or to a structured education program. More intervention-group participants had clinically relevant reductions in the frequency of episodes of any incontinence, stress incontinence, and urge incontinence. Urinary incontinence affects more than 13 million women in the United States and has been associated with profound adverse effects on quality of life 1 , 2 ; an increased risk of falls, fractures, 3 and nursing-home admissions 4 ; and more than $20 billion in estimated annual direct health care costs. 5 Observational studies suggest that obesity is a strong risk factor for urinary incontinence, 6 – 9 and preliminary studies suggest that weight loss may have a beneficial effect on urinary incontinence in obese patients. 10 – 14 Reductions in urinary incontinence have been observed in morbidly obese women who have had dramatic weight loss after bariatric . . .

In this multicenter, placebo-controlled, randomized trial of postmenopausal women at high risk for a coronary event, raloxifene had no significant effect on the risk of primary coronary events, reduced the risk of invasive breast cancer and vertebral fractures, and increased the risk of fatal stroke and venous thromboembolism. A decision whether to use raloxifene for the prevention of breast cancer or vertebral fractures should be individualized, weighing benefits against potential risks. In postmenopausal women at high risk for a coronary event, raloxifene had no significant effect on the risk of primary coronary events, reduced the risk of invasive breast cancer and vertebral fractures, and increased the risk of fatal stroke and venous thromboembolism. Raloxifene is a nonsteroidal selective estrogen-receptor modulator (SERM) that binds to the estrogen receptor, leading to estrogen-agonist effects in some tissues and estrogen-antagonist effects in others. 1 Raloxifene therapy has been associated with improvement in the levels of serum lipoprotein cholesterol, 2 , 3 fibrinogen, 3 and homocysteine. 4 The favorable effect of raloxifene on markers of cardiovascular risk, coupled with evidence from observational studies that treatment with estrogen was associated with a reduced risk of coronary heart disease (CHD) in postmenopausal women, 5 , 6 led to the design of the Raloxifene Use for The Heart (RUTH) trial to determine the effect of raloxifene on clinical . . .

Different outcomes among patients hospitalized for bleeding after starting anticoagulation could influence choice of anticoagulant. We compared length of hospitalization, proportion of Intensive Care Unit (ICU) admissions, ICU length of stay, and 30- and 90-day mortality for adults with atrial fibrillation hospitalized for bleeding after starting warfarin, dabigatran, or rivaroxaban. An US commercial database of 38 million members from 1 November 2010 to 31 March 2014 was used to examine adults with atrial fibrillation hospitalized for bleeding after starting warfarin (2,446), dabigatran (442), or rivaroxaban (256). Outcomes included difference in mean total length of hospitalization, proportion of ICU admissions, mean length of ICU stay, and all-cause 30- and 90-day mortality. Warfarin users were older and had more comorbidities. Multivariable regression modeling with propensity score weighting showed warfarin users were hospitalized 2.0 days longer (95% CI 1.8-2.3; p < 0.001) than dabigatran users and 2.6 days longer (95% CI 2.4-2.9; p < 0.001) than rivaroxaban users. Dabigatran users were hospitalized 0.6 days longer (95% CI 0.2-1.0; p = 0.001) than rivaroxaban users. There were no differences in the proportion of ICU admissions. Among ICU admissions, warfarin users stayed 3.0 days (95% CI 1.9-3.9; p < 0.001) longer than dabigatran users and 2.4 days longer (95% CI 0.9-3.7; p = 0.003) than rivaroxaban users. There was no difference in ICU stay between dabigatran and rivaroxaban users. There were no differences in 30- and 90-day all-cause mortality. Rivaroxaban and dabigatran were associated with shorter hospitalizations; however, there were no differences in 30- and 90-day mortality. These findings suggest bleeding associated with the newer agents is not more dangerous than bleeding associated with warfarin.

Associations have been reported of the seven-repeat (7R) allele of the human dopamine receptor D4 (DRD4) gene with both attention-deficit/hyperactivity disorder and the personality trait of novelty seeking. This polymorphism occurs in a 48-bp tandem repeat in the coding region of DRD4, with the most common allele containing four repeats (4R) and rarer variants containing 2-11. Here we show by DNA resequencing/haplotyping of 600 DRD4 alleles, representing a worldwide population sample, that the origin of 2R-6R alleles can be explained by simple one-step recombination/mutation events. In contrast, the 7R allele is not simply related to the other common alleles, differing by greater than six recombinations/mutations. Strong linkage disequilibrium was found between the 7R allele and surrounding DRD4 polymorphisms, suggesting that this allele is at least 5-10-fold \"younger\" than the common 4R allele. Based on an observed bias toward nonsynonymous amino acid changes, the unusual DNA sequence organization, and the strong linkage disequilibrium surrounding the DRD4 7R allele, we propose that this allele originated as a rare mutational event that nevertheless increased to high frequency in human populations by positive selection.

Randomized trials of postmenopausal hormone therapy have found differing effects on fasting glucose levels. No trial has evaluated the effect of hormone therapy on diabetes incidence. To evaluate the effect of hormone therapy on fasting glucose level and incident diabetes. Randomized, double-blind, placebo-controlled trial. 20 U.S. clinical centers. 2763 postmenopausal women with coronary heart disease who were followed for 4.1 years. At baseline, 734 women had diabetes, 218 women had impaired fasting glucose, and 1811 women were normoglycemic; the 2029 women without diabetes were followed for incident diabetes. 0.625 mg of conjugated estrogen plus 2.5 mg of medroxyprogesterone acetate daily, or placebo. Fasting glucose level was measured at baseline, at year 1, and at the end of the trial. Incident diabetes was defined by self-report of diabetes or disease complication, fasting glucose level of 6.9 mmol/L or greater (> or =126 mg/dL), or initiation of therapy with diabetes medication. Fasting glucose levels increased significantly among women assigned to placebo but did not change among women receiving hormone therapy. The incidence of diabetes was 6.2% in the hormone therapy group and 9.5% in the placebo group (relative hazard, 0.65 [95% CI, 0.48 to 0.89]; P = 0.006). The number needed to treat for benefit to prevent one case of diabetes was 30 (CI, 18 to 103). Changes in weight and waist circumference did not mediate this effect. In women with coronary disease, hormone therapy reduced the incidence of diabetes by 35%. This observation provides important insights into the metabolic effects of postmenopausal hormones but is insufficient to recommend the use of hormones for secondary prevention of heart disease.

A 51-year-old woman is having frequent and distressing hot flushes that interfere with her work and sleep, and vaginal dryness that makes sexual intercourse uncomfortable. She is otherwise healthy. How should her case be managed? A 51-year-old woman is having frequent and distressing hot flushes that interfere with her work and sleep, and vaginal dryness that makes sexual intercourse uncomfortable. How should her case be managed? Foreword This Journal feature begins with a case vignette highlighting a common clinical problem. Evidence supporting various strategies is then presented, followed by a review of formal guidelines, when they exist. The article ends with the author's clinical recommendations. Stage A 51-year-old woman has frequent and distressing hot flushes that interfere with her work and sleep, and vaginal dryness that makes sexual intercourse with her husband uncomfortable. She is otherwise healthy. How should her case be managed? The Clinical Problem Menopausal Transition All healthy women transition from a reproductive, or premenopausal, period, marked by regular ovulation and cyclic menstrual bleeding, to a postmenopausal period, marked by amenorrhea (Table 1). The onset of the menopausal transition is marked by changes in the menstrual cycle and in the duration or amount of menstrual flow. 1 Subsequently, cycles are missed, but the pattern . . .

▪ Abstract  Multiple observational studies suggest a marked reduction in risk of coronary heart disease (CHD) associated with postmenopausal estrogen use. A new meta-analysis presented here extends these results to estrogen plus progestin regimens. Although the findings from observational studies are strong and consistent, and there are several plausible mechanisms by which estrogen might reduce risk for CHD, most of the known biases would tend to exaggerate estrogen's benefit. Further, estrogen therapy clearly increases risk for endometrial hyperplasia and cancer, venous thromboembolic events and gallbladder disease, and long-term use probably also increases the risk of breast cancer. Therefore, until findings from randomized trials confirm and quantitate the benefit of estrogen therapy for prevention of CHD, we believe it should not be recommended to all postmenopausal women.

Evaluation of the safety of hormonal preparations for the treatment of female sexual dysfunction is important to assess the benefit-to-risk profile of these drugs and has been strongly encouraged by the Food and Drug Administration. LibiGel (Biosante Pharmaceuticals, Inc., Lincolnshire, IL), a low-dose testosterone gel, is under development for the treatment of hypoactive sexual desire disorder (HSDD) in oophorectomized women. To evaluate the long-term effects of LibiGel on risk for cardiovascular (CV) events, breast cancer, and general safety, a randomized, placebo-controlled clinical study using a novel adaptive design to optimize sample size and power is being conducted. The primary end point of the BioSante LibiGel Safety Study (BLISS) is a composite of CV events including death, nonfatal myocardial infarction, nonfatal stroke, coronary revascularization, hospitalized unstable angina, and venous thromboembolic events. Breast cancer is a coprimary end point. Postmenopausal women (both surgically and naturally) with HSDD and increased risk for CV events will be followed up for up to 5 years postrandomization with an interim data analysis for regulatory approval after the last woman enrolled has been on therapy for at least 12 months. Determination of the number of subjects to enroll is based on an adaptive design that uses interim data to estimate the predictive probability of study success. In agreement with the Food and Drug Administration, LibiGel will be declared safe if the upper limit of the 97.2% CI of the hazard ratio is ≤2.0 or the upper bound of the 97.2% CI for the absolute difference between CV event rates per 100 person-years is ≤1% and the observed hazard ratio is ≤2.0. The BLISS study will define the CV safety profile of low-dose testosterone therapy in the formulation of LibiGel for postmenopausal women with HSDD, and the trial design may provide a paradigm for studies that aim to document long-term safety when the proposed outcome under study is an uncommon adverse event.

Introduction Adaptive statistical iterative reconstruction (ASIR) can decrease image noise, thereby generating CT images of comparable diagnostic quality with less radiation. The purpose of this study is to quantify the effect of systematic use of ASIR versus filtered back projection (FBP) for neuroradiology CT protocols on patients’ radiation dose and image quality. Methods We evaluated the effect of ASIR on six types of neuroradiologic CT studies: adult and pediatric unenhanced head CT, adult cervical spine CT, adult cervical and intracranial CT angiography, adult soft tissue neck CT with contrast, and adult lumbar spine CT. For each type of CT study, two groups of 100 consecutive studies were retrospectively reviewed: 100 studies performed with FBP and 100 studies performed with ASIR/FBP blending factor of 40 %/60 % with appropriate noise indices. The weighted volume CT dose index (CTDI vol ), dose–length product (DLP) and noise were recorded. Each study was also reviewed for image quality by two reviewers. Continuous and categorical variables were compared by t test and free permutation test, respectively. Results For adult unenhanced brain CT, CT cervical myelography, cervical and intracranial CT angiography and lumbar spine CT both CTDI vol and DLP were lowered by up to 10.9 % ( p  < 0.001), 17.9 % ( p  = 0.005), 20.9 % ( p  < 0.001), and 21.7 % ( p  = 0.001), respectively, by using ASIR compared with FBP alone. Image quality and noise were similar for both FBP and ASIR. Conclusion We recommend routine use of iterative reconstruction for neuroradiology CT examinations because this approach affords a significant dose reduction while preserving image quality.

Objective The developmental trajectory of attention-deficit hyperactivity disorder (ADHD) is variable. Utilizing a longitudinally assessed sample, we investigated the contribution of susceptibility gene variants, previously implicated through pooled or meta-analyses, to the developmental course of Attention-Deficit Hyperactivity Disorder over time. Methods 151 children (aged 6–12) who met diagnostic criteria for ADHD were assessed using research diagnostic interviews during childhood and 5 years later in adolescence. Severity was defined as total number of ADHD symptoms at baseline and reassessment. Association with variants at DRD4 , DRD5 , and the dopamine transporter gene, DAT was analyzed using linear regression. Results As expected, affected individuals showed a decline in ADHD severity over time. The DRD4 48 bp VNTR 7-repeat and DRD5 CA(n) microsatellite marker 148 bp risk alleles were associated with persistent ADHD. Those possessing the DRD4 7 repeat risk allele showed less of a decline in severity at reassessment than those without the risk allele. Conclusions Those carrying the DRD4 7 risk allele showed greater symptom severity at follow-up and less ADHD reduction over time. These findings support the hypothesis that some susceptibility genes for ADHD also influence its developmental course.