Levonorgestrel-releasing intrauterine system vs. usual medical treatment for menorrhagia: An economic evaluation alongside a randomised controlled trial

Objective: To undertake an economic evaluation alongside the largest randomised controlled trial comparing Levonorgestrel-releasing intrauterine device ('LNG-IUS') and usual medical treatment for women with menorrhagia in primary care; and compare the cost-effectiveness findings using two alternative measures of quality of life. Methods: 571 women with menorrhagia from 63 UK centres were randomised between February 2005 and July 2009. Women were randomised to having a LNG-IUS fitted, or usual medical treatment, after discussing with their general practitioner their contraceptive needs or desire to avoid hormonal treatment. The treatment was specified prior to randomisation. For the economic evaluation we developed a state transition (Markov) model with a 24 month follow-up. The model structure was informed by the trial women's pathway and clinical experts. The economic evaluation adopted a UK National Health Service perspective and was based on an outcome of incremental cost per Quality Adjusted Life Year (QALY) estimated using both EQ-5D and SF-6D. Results: Using EQ-5D, LNG-IUS was the most cost-effective treatment for menorrhagia. LNG-IUS costs £100 more than usual medical treatment but generated 0.07 more QALYs. The incremental cost-effectiveness ratio for LNG-IUS compared to usual medical treatment was £1600 per additional QALY. Using SF-6D, usual medical treatment was the most cost-effective treatment. Usual medical treatment was both less costly (£100) and generated 0.002 more QALYs. Conclusion: Impact on quality of life is the primary indicator of treatment success in menorrhagia. However, the most costeffective treatment differs depending on the quality of life measure used to estimate the QALY. Under UK guidelines LNG-IUS would be the recommended treatment for menorrhagia. This study demonstrates that the appropriate valuation of outcomes in menorrhagia is crucial. Copyright: © 2014 Sanghera et al

Herbivory and eutrophication mediate grassland plant nutrient responses across a global climatic gradient

Plant stoichiometry, the relative concentration of elements, is a key regulator of ecosystem functioning and is also being altered by human activities. In this paper we sought to understand the global drivers of plant stoichiometry and compare the relative contribution of climatic vs. anthropogenic effects. We addressed this goal by measuring plant elemental (C, N, P and K) responses to eutrophication and vertebrate herbivore exclusion at eighteen sites on six continents. Across sites, climate and atmospheric N deposition emerged as strong predictors of plot‐level tissue nutrients, mediated by biomass and plant chemistry. Within sites, fertilization increased total plant nutrient pools, but results were contingent on soil fertility and the proportion of grass biomass relative to other functional types. Total plant nutrient pools diverged strongly in response to herbivore exclusion when fertilized; responses were largest in ungrazed plots at low rainfall, whereas herbivore grazing dampened the plant community nutrient responses to fertilization. Our study highlights (1) the importance of climate in determining plant nutrient concentrations mediated through effects on plant biomass, (2) that eutrophication affects grassland nutrient pools via both soil and atmospheric pathways and (3) that interactions among soils, herbivores and eutrophication drive plant nutrient responses at small scales, especially at water‐limited sites

Effectiveness, safety and acceptability of ‘see and treat' with cryotherapy by nurses in a cervical screening study in India

We evaluated a ‘see and treat' procedure involving screening, colposcopy, biopsy and cryotherapy by trained nurses in one-visit in field clinics in a cervical screening study in South India for its acceptability, safety and effectiveness in curing cervical intraepithelial neoplasia (CIN). Women positive on visual inspection with acetic acid (VIA) were advised colposcopy, directed biopsies and cryotherapy if they had colposcopic impression of CIN in one visit by nurses in field clinics supervised by a doctor. Side effects and complications were assessed and cure rates were evaluated with VIA, colposcopy and biopsy if colposcopic abnormalities were suspected. Cure was defined as no clinical or histological evidence of CIN at ⩾6 months from treatment. Of the 2513 women offered ‘see and treat' procedure, 1879 (74.8%) accepted. Of the 1397 women with histologically proved CIN treated with cryotherapy, 1026 reported for follow-up evaluation. Cure rates were 81.4% (752 out of 924) for women with CIN 1; 71.4% (55 out of 77) for CIN 2 and 68.0% (17 out of 25) for CIN 3. Minor side effects and complications were documented in less than 3% of women. ‘See and treat' with cryotherapy by nurses under medical supervision is acceptable, safe and effective for cervical cancer prevention in low-resource settings

Participant recruitment and retention in a pilot program to prevent weight gain in low-income overweight and obese mothers

<p>Abstract</p> <p>Background</p> <p>Recruitment and retention are key functions for programs promoting nutrition and other lifestyle behavioral changes in low-income populations. This paper describes strategies for recruitment and retention and presents predictors of early (two-month post intervention) and late (eight-month post intervention) dropout (non retention) and overall retention among young, low-income overweight and obese mothers participating in a community-based randomized pilot trial called <it>Mothers In Motion</it>.</p> <p>Methods</p> <p>Low-income overweight and obese African American and white mothers ages 18 to 34 were recruited from the Special Supplemental Nutrition Program for Women, Infants, and Children in southern Michigan. Participants (n = 129) were randomly assigned to an intervention (n = 64) or control (n = 65) group according to a stratification procedure to equalize representation in two racial groups (African American and white) and three body mass index categories (25.0-29.9 kg/m², 30.0-34.9 kg/m², and 35.0-39.9 kg/m²). The 10-week theory-based culturally sensitive intervention focused on healthy eating, physical activity, and stress management messages that were delivered via an interactive DVD and reinforced by five peer-support group teleconferences. Forward stepwise multiple logistic regression was performed to examine whether dietary fat, fruit and vegetable intake behaviors, physical activity, perceived stress, positive and negative affect, depression, and race predicted dropout as data were collected two-month and eight-month after the active intervention phase.</p> <p>Results</p> <p>Trained personnel were successful in recruiting subjects. Increased level of depression was a predictor of early dropout (odds ratio = 1.04; 95% CI = 1.00, 1.08; p = 0.03). Greater stress predicted late dropout (odds ratio = 0.20; 95% CI = 0.00, 0.37; p = 0.01). Dietary fat, fruit, and vegetable intake behaviors, physical activity, positive and negative affect, and race were not associated with either early or late dropout. Less negative affect was a marginal predictor of participant retention (odds ratio = 0.57; 95% CI = 0.31, 1.03; p = 0.06).</p> <p>Conclusion</p> <p>Dropout rates in this study were higher for participants who reported higher levels of depression and stress.</p> <p>Trial registration</p> <p>Current Controlled Trials NCT00944060</p

Longer First Introns Are a General Property of Eukaryotic Gene Structure

While many properties of eukaryotic gene structure are well characterized, differences in the form and function of introns that occur at different positions within a transcript are less well understood. In particular, the dynamics of intron length variation with respect to intron position has received relatively little attention. This study analyzes all available data on intron lengths in GenBank and finds a significant trend of increased length in first introns throughout a wide range of species. This trend was found to be even stronger when using high-confidence gene annotation data for three model organisms (Arabidopsis thaliana, Caenorhabditis elegans, and Drosophila melanogaster) which show that the first intron in the 5′ UTR is - on average - significantly longer than all downstream introns within a gene. A partial explanation for increased first intron length in A. thaliana is suggested by the increased frequency of certain motifs that are present in first introns. The phenomenon of longer first introns can potentially be used to improve gene prediction software and also to detect errors in existing gene annotations

Effects of long-term moderate exercise and increase in number of daily steps on serum lipids in women: randomised controlled trial [ISRCTN21921919]

BACKGROUND: This study was designed to evaluate the effects of a 24-month period of moderate exercise on serum lipids in menopausal women. METHODS: The subjects (40–60 y) were randomly divided into an exercise group (n = 14) and a control group (n = 13). The women in the exercise group were asked to participate in a 90-minute physical education class once a week and to record their daily steps as measured by a pedometer for 24 months. RESULTS: Mean of daily steps was significantly higher in the exercise group from about 6,800 to over 8,500 steps (P < 0.01). In the control group, the number of daily steps ranged from 5,700 to 6,800 steps throughout the follow-up period. A significant interaction between the exercise group and the control group in the changes og total cholesterol (TC), high-density lipoprotein cholesterol (HDLC) and TC : HDLC ratio could be observed (P < 0.05). By multiple regression analysis, the number of daily steps was related to HDLC and TC : HDLC levels after 24 months, and the changes in TC and HDLC concentrations. CONCLUSIONS: These results suggest that daily exercise as well as increasing the number of daily steps can improve the profile of serum lipids

Human immunoglobulin G levels of viruses and associated glioma risk

Few consistent etiological factors have been identified for primary brain tumors. Inverse associations to asthma and low levels of varicella-zoster virus, immunoglobulin (Ig) levels in prevalent cases have indicted a role for the immune system in the development of glioma. Because samples from prevalent cases of glioma could be influenced by treatments such as steroids and chemotherapy, we investigated pre-diagnostic samples from three large Scandinavian cohorts. To test the hypothesis that immune response levels to these viruses are associated etiologically with glioma risk, we investigated pre-diagnostic immunoglobulin levels for cytomegalovirus (CMV), varicella-zoster virus (VZV), adenovirus (Ad), and Epstein-Barr virus (EBV) including the nuclear antigen (EBNA1) using plasma samples from 197 cases of adult glioma and 394 controls collected from population-based cohorts in Sweden and Denmark. Low VZV IgG levels were marginally significantly more common in glioma cases than the controls (odds ratio (OR) = 0.68, 95% CI 0.41–1.13) for the fourth compared with the first quartile (p = 0.06 for trend). These results were more prominent when analyzing cases with blood sampling at least 2 years before diagnosis (OR = 0.63, 95% CI 0.37–1.08) (p = 0.03). No association with glioma risk was observed for CMV, EBV, and adenovirus

Visual inspection with acetic acid as a cervical cancer test: accuracy validated using latent class analysis

<p>Abstract</p> <p>Background</p> <p>The purpose of this study was to validate the accuracy of an alternative cervical cancer test – visual inspection with acetic acid (VIA) – by addressing possible imperfections in the gold standard through latent class analysis (LCA). The data were originally collected at peri-urban health clinics in Zimbabwe.</p> <p>Methods</p> <p>Conventional accuracy (sensitivity/specificity) estimates for VIA and two other screening tests using colposcopy/biopsy as the reference standard were compared to LCA estimates based on results from all four tests. For conventional analysis, negative colposcopy was accepted as a negative outcome when biopsy was not available as the reference standard. With LCA, local dependencies between tests were handled through adding direct effect parameters or additional latent classes to the model.</p> <p>Results</p> <p>Two models yielded good fit to the data, a 2-class model with two adjustments and a 3-class model with one adjustment. The definition of latent disease associated with the latter was more stringent, backed by three of the four tests. Under that model, sensitivity for VIA (abnormal+) was 0.74 compared to 0.78 with conventional analyses. Specificity was 0.639 versus 0.568, respectively. By contrast, the LCA-derived sensitivity for colposcopy/biopsy was 0.63.</p> <p>Conclusion</p> <p>VIA sensitivity and specificity with the 3-class LCA model were within the range of published data and relatively consistent with conventional analyses, thus validating the original assessment of test accuracy. LCA probably yielded more likely estimates of the true accuracy than did conventional analysis with in-country colposcopy/biopsy as the reference standard. Colpscopy with biopsy can be problematic as a study reference standard and LCA offers the possibility of obtaining estimates adjusted for referent imperfections.</p