Antimullerian hormone and obesity: insights in oral contraceptive users

Background

The study was conducted to examine the impact of oral contraceptives (OCs) on serum antimullerian hormone (AMH) levels by obesity status in reproductive-age women.

Study Design

Ovulatory women, ages 18-35 years, of normal (<25 kg/m²; n=10) and obese (>30 kg/m²; n=10) body mass index (BMI) received a low-dose OC (20 mcg ethinyl estradiol/100 mcg levonorgestrel) for two cycles. Serum samples obtained at several time points during active pill use and hormone-free intervals were analyzed for AMH, follicle-stimulating hormone (FSH), luteinizing hormone (LH), estradiol and inhibin B.

Results

AMH levels did not differ by OC cycle day in either BMI group. On average, AMH levels were 34% lower in the obese group (2.9±2.1 vs. 4.4±1.8 ng/mL, p<.05). Modeling to determine differences in AMH throughout the cycle based on obesity status demonstrated significantly lower levels (p<.05), whereas serum AMH, FSH, LH, estradiol and inhibin B levels revealed no correlations when all time points were included.

Conclusions

In reproductive-age women, serum AMH levels do not appear to fluctuate during OC use, but AMH levels are significantly lower in obese women. Lower levels do not appear to be due to differences in gonadotropin levels or ovarian activity.     

Development of a Diet Index for Older Adults and Its Relation to Cardiovascular Disease Risk Factors: The Elderly Dietary Index

Objective

To develop an index that assesses the degree of adherence to nutritional recommendations for older adults (Elderly Dietary Index [EDI]) and investigate its association with risk factors related to cardiovascular disease (CVD).

Methods

The EDI was constructed using 10 components (ie, questions about the consumption frequency of meat, fish, fruits, vegetables, grains, legumes, olive oil, and alcohol as well as the type of bread and dairy products) according to the Modified MyPyramid for Older Adults and select features of the traditional Mediterranean diet. Scores from 1 to 4 were assigned to all components of the index. The EDI total score had a range between 10 and 40. As a validation procedure, a sample of 668 elderly individuals without known CVD (the MEDIS Study) was used to evaluate the associations between the proposed index and various health outcomes.

Results

The overall mean EDI score was 29.2±3.5. This score implies that study participants were 73% (ie, 29.2/40) adherent to the nutritional recommendations that the EDI evaluates. Regarding the conventional CVD risk factors, it was found that a 1 unit increase in the EDI score is associated with almost 10% lower odds of being obese or hypertensive or having at least one of the investigated CVD risk factors (P<0.001) after controlling for potential confounders.

Conclusions

The suggested EDI may be a useful tool for public health policymakers and other health care professionals to assess diet quality and health status (especially concerning the risk for developing CVD) in older adults.     

Fracture risk in very young women using combined oral contraceptives

Background

Little is known on fracture risk in young women using oral contraceptives.

Study Design

Case-control study (64,548 cases, 193,641 controls).

Results

Overall, no major association with risk of fracture was present. Only in a few age groups a limited increase (OR 1.1-1.5) was seen in those using low average doses (less than one tablet per day — i.e., intermittent use). Neither 20 nor ≥30 mcg per day of ethinylestradiol was associated with risk of fractures, while changing from 20 to ≥30 mcg per day or vice versa was associated with a limited increase in fracture risk (OR 1.1-1.4) in some age groups.

Conclusions

In general, use of oral contraceptives in young women did not seem to be associated with an increased risk of fractures. The isolated increase seen in some strata with low average doses may be linked to factors associated with discontinuation of oral contraceptives rather than pharmacological effects.     

Real-world effectiveness of a German school-based intervention for primary prevention of anorexia nervosa in preadolescent girls

Objective

Anorexia nervosa (‘AN’) is notoriously difficult to treat, has high mortality rates, and has a prevalence peak in 15-year-old girls. We developed a German school-based intervention program (‘PriMa’) for the primary prevention of AN in preadolescent girls and assessed the effects in a sample of Thuringian girls.

Method

Intervention involved nine guided lessons with special posters and group discussions. A parallel controlled trial with pre-post measurements and a three-month follow-up was conducted in 92 Thuringian schools (n = 1553 girls) in 2007 and 2008. Primary outcomes were conspicuous eating behavior, body self esteem, and AN-related knowledge.

Results

After adjusting for the girls' ages and the type of school, we observed significant improvements in the areas of knowledge (d = .24) and body self esteem (d = .29), but not for eating behavior.

Conclusion

The PriMa intervention provides an efficient and practical model to increase AN-related protection factors.     

Interest in health screening as a predictor of long-term overall mortality: multilevel analysis of a Japanese national cohort study

Background

In Japan, screening programmes have been widely implemented as a public health practice. We investigated the effect of the area-level interest in health screening on mortality using data from a large cohort in Japan.

Methods

A baseline survey was conducted between 1988 and 1990 among 110,792 residents of 45 areas, aged 40-79 years. Area-level interest in health screening was defined as the proportion of people with high and moderate interest in health screening in an area. Multilevel Poisson regression was employed in a two-level structure of individuals nested within the areas. During 15 years of follow-up (1,035,617 person-years), 13,184 deaths were observed.

Results

The reduction in mortality rate was (a) 2% in both men (p = 0.009) and women (p = 0.038) for each percent increase in area-level interest in screening, and (b) 10% in men (p = 0.001) and 9% in women (p = 0.001) for individual attendance to screening in the year before follow-up. There was no interaction between area-level interest in screening, individual-level attendance at screening and overall mortality.

Conclusion

Area-level and individual interest for health screening appear to be independent predictor of 15-year mortality in this national Japanese study. The present findings may support public health practices to promote knowledge and participation in screening programmes.     

Strengthening the reliability and credibility of observational epidemiology studies by creating an Observational Studies Register

Objective

To evaluate the need for the creation of a system in which observational epidemiology studies are registered; an Observational Studies Register (OSR).

Study Design and Setting

The current scientific process for observational epidemiology studies is described. Next, a parallel is made with the clinical trials area, where the creation of clinical trial registers has greatly restored and improved their credibility and reliability. Next, the advantages and disadvantages of an OSR are compared.

Results

The advantages of an OSR outweigh its disadvantages.

Conclusion

The creation of an OSR, similar to the existing Clinical Trials Registers, will improve the assessment of publication bias and will provide an opportunity to compare the original study protocol with the results reported in the publication. Reliability, credibility, and transparency of observational epidemiology studies are strengthened by the creation of an OSR. We propose a structured, collaborative, and coordinated approach for observational epidemiology studies that can provide solutions for existing weaknesses and will strengthen credibility and reliability, similar to the approach currently used in clinical trials, where Clinical Trials Registers have played a key role in strengthening their scientific value.     

Changes in abortion provider practices in response to the Partial-Birth Abortion Ban Act of 2003

Background

The April 2007 Supreme Court Gonzalez v. Gonzalez v. Carhart decision upheld the Partial-Birth Abortion Ban Act of 2003. We conducted a pilot study that measured the impact of the ban in one state with a diverse pool of second-trimester abortion providers.

Study Design

A survey was administered via telephone to key informants at each facility in Massachusetts where second-trimester abortions are performed in order to assess clinical and administrative changes following the Supreme Court decision.

Results

Five hospital-based practices introduced injections to induce fetal demise prior to dilation and evacuation for later second-trimester abortions. One site stopped providing dilation and evacuation abortions in the absence of fetal or maternal indications, and another significantly decreased its volume of procedures. Training opportunities were decreased, and costs at three facilities increased.

Conclusions

The Partial-Birth Abortion Ban Act of 2003 resulted in a range of practice changes in Massachusetts, particularly in hospitals. These changes reflect adherence to legal and policy mandates and not the availability of new scientific evidence. Further study to assess the impact of the ban in states with fewer providers is warranted.     

Validation of an Australian electronic food frequency questionnaire to measure polyunsaturated fatty acid intake

Objective

To develop and validate a simple non-invasive method that estimates the intakes of omega-3 and omega-6 polyunsaturated fatty acids (PUFA) in a healthy adult population.

Methods

A new electronic PUFA food frequency questionnaire (FFQ) was validated by comparison with a 3-d weighed food record and blood biomarkers (erythrocytes and plasma) using the method of triads model and tested for reproducibility. Healthy subjects were recruited from the local Illawarra Region, New South Wales, Australia.

Results

The PUFA FFQ adequately estimated intakes for eicosapentaenoic acid, docosahexaenoic acid, total long chain omega-3 PUFA, linoleic acid, total omega-6 PUFA, and total PUFA, which were comparable with results from the 3-d food record. Eicosapentaenoic acid, docosahexaenoic acid, and total long chain omega-3 showed high validity coefficients for erythrocytes (and plasma) 0.92 (0.87), 0.69 (0.64), and 0.78 (0.73) (P < 0.05), respectively. Spearman’s rank correlation coefficients ranged from 0.48 to 0.76 when the PUFA FFQ was tested for reproducibility (P < 0.05).

Conclusion

The electronic PUFA questionnaire was found to be reproducible and is a valid tool to assess PUFA intakes in a healthy adult population.     

Predictors of Dietary Change and Maintenance in the Women’s Health Initiative Dietary Modification Trial

Objective

To identify predictors of dietary change to and maintenance of a low-fat eating pattern (<20% energy from fat, ≥5 servings fruits/vegetables daily, and ≥6 servings grains daily) among a cohort of postmenopausal women. Candidate predictors included intrapersonal, interpersonal, intervention program characteristics, and clinical center.

Design

Longitudinal study within the Women’s Health Initiative Dietary Modification Trial. Dietary change was evaluated after 1 year of participation in the Women’s Health Initiative Dietary Modification Trial, and dietary maintenance after 3 years.

Subjects

Postmenopausal women aged 50 to 79 years at baseline who were randomized to the intervention arm of the Women’s Health Initiative Dietary Modification Trial (n=19,541).

Statistical analysis

Univariate and multivariate linear regression analysis was performed and associations evaluated between candidate predictors and each of the three dietary goals: percent energy from fat, fruit/vegetable servings, and grain servings.

Results

Year 1 (change) predictors of percent energy from fat (P<0.005) included being younger (β=2.12; 70 to 79 years vs 50 to 59 years), more educated (β=-.69; college vs high school), more optimistic (β=-.07), attending more sessions (β=-.69), and submitting more self-monitoring records (β=-.74). At year 3 (maintenance), the predictors of percent energy from fat (P<0.005) included attending more sessions (β=-.65) and submitting more self-monitoring scores (β=-.71). The analytic model predicted 22% of the variance in fat intake at year 1 and 27% at year 3 (P<0.01).

Conclusions

The strongest predictors of dietary change and maintenance were attending intervention sessions and self-monitoring dietary intake. Novel was the finding that optimism predicted dietary change.     

Antioxidant activity and hepatoprotective effects of whey protein and Spirulina in rats

Objectives

The aims of the present study were to evaluate the antioxidant, radical scavenging, and metal-chelating activity of whey protein concentrate (WPC) and Spirulina alone or in combination in vitro and to evaluate their hepatoprotective effects against CCl₄ in vivo.

Methods

Five concentrations (20, 40, 60, 80, and 100 mg/100 mL) of WPC, Spirulina, and their combination were tested in vitro. In the in vivo study, eight groups of male rats comprised the control group and the groups treated with WPC, Spirulina alone, or in combination with or without CCl₄ were used.

Results

The in vitro study showed that WPC and Spirulina showed antioxidant, radical scavenging, and metal-chelating activities in dose-dependent manner. The in vivo study showed that both agents succeeded in preventing liver damage induced by CCl₄. This prevention was more pronounced in rats receiving the combination of WPC and Spirulina.

Conclusion

Whey protein concentrate and Spirulina have free radical scavenging properties and antioxidant activity.     

The antitumor immunopreventive effects of a DNA vaccine against CYP26a1 on mouse breast carcinoma

Background

CYP26a1, which functioned mainly as a retinoic acid (RA) catabolic enzyme, has been shown to be oncogenic and to support cell survival in many breast carcinoma cells.

Objectives

The purpose of the study was to investigate the antitumor effect of a DNA vaccine targeting CYP26a1 on breast tumors development in mice which highly express CYP26a1 and to further clarify its potential mechanism.

Methods

After three times immunization of the DNA vaccine, the BALB/c mice were inoculated with the engineered 4T1 breast cancer cells expressing CYP26a1. Primary tumors were measured every 4 days after tumor cell inoculation. The primary tumors were surgically removed and weighted after 30 days of inoculation. The anti-CYP26a1 antibody titer of the antiserum was measured by an enzyme-linked immunosorbent assay (ELISA). The effect of the vaccine on apoptosis of the primary tumor was determined by terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL). Apoptosis-related proteins in primary tumor were detected by Western blotting. The expression of the Th1 and Th2 type cytokines was detected by RT-PCR.

Results

The vaccine could elicit the production of anti-CYP26a1 antibody and significantly inhibit the growth of the primary tumor compared to the control groups (p < 0.05). The vaccine induced the apoptosis of the primary tumor with the increase in expression of apoptosis-related proteins p53, Caspase3 and Fas. Furthermore, the vaccine increased the expression of the Th1 cytokine, but not the expression of Th2 cytokine.

Conclusion

Our study shows that the vaccine targeting CYP26a1 significantly inhibits the primary tumor growth and progression by activating the apoptosis pathway and by eliciting both humoral and cellular immune responses.     

Meta-analyses of small numbers of trials often agree with longer-term results

Objective

Many systematic reviews include only a few studies. It is unclear whether recommendations based on these will be correct in the longer term; hence, this article explores whether meta-analyses give reliable results after only a few studies.

Study Design and Setting

Cumulative meta-analysis of data from 65 meta-analyses from 18 Cochrane systematic reviews was carried out. Various measures of closeness to the pooled estimate from all trials after three and five trials were included. Changes during the accumulation of evidence were noted.

Results

The 95% confidence interval included the final estimate in 72% of meta-analyses after three studies and in 83% after five studies. It took a median of four (interquartile range: 1.25-6) studies to get within 10% of the final point estimate. Agreement between the results at three and five studies and the final estimate was not predicted by the number of participants, the number of events, τ², or I². Estimates could still change substantially after many trials were included.

Conclusion

Many of the conclusions drawn from systematic reviews with small numbers of included studies will be correct in the long run, but it is not possible to predict which ones.     

Risk of smoking and body mass index for incidence of diabetes mellitus in a rural Japanese population

Objective

To assess the risk of smoking, body mass index (BMI), and both for incidence of diabetes in a rural Japanese population.

Method

This study was a 10.1-year cohort study of 2070 men and 3802 women aged 40-69 years without diabetes at baseline who underwent a health check-up at one central hospital in Nagano Prefecture. Participants were classified according to a combination of smoking status and BMI. Participants were followed from 1990 to 2006. The incidence of diabetes was determined from fasting and random levels of plasma glucose, HbA_1c levels or being under medical treatment for diabetes.

Results

Diabetes developed in 595 of the participants during 59,111 person-years of follow-up. In men, the multivariable-adjusted hazard ratios for incidence of diabetes compared with non-smokers of normal weight were as follows: 3.36 (2.02-5.60) in current smokers with normal weight and 1.70 (0.87-3.34) and 3.93 (2.22-6.96) in obese non-smokers and obese current smokers, respectively. In men the population-attributable fraction of diabetes onset due to current smoking, obesity and both were 22.0%, 2.5% and 11.2%, respectively.

Conclusion

Regardless of BMI, smoking is an important risk factor for diabetes in male populations with a high prevalence of smoking.     

Population studies of the effectiveness of mammographic screening

Objective

To examine population data to see whether survival from breast cancer has improved differentially in screened and unscreened women and examine published studies on mammographic screening to determine whether there is evidence that screening is no longer effective.

Methods

Data was reviewed on trends in breast cancer specific survival among women participating and not participating in the British Columbia Breast Screening Program. Population studies of mammographic screening published between 2000 and 2010 with breast cancer mortality as the outcome were also reviewed.

Results

Breast cancer specific survival in British Columbia improved more in screening participants than non-participants, HR = 0.74 (0.58,0.93) between the periods 1990-4 and 2000-4. Among the published studies of mortality between 2000 and 2010 selected from different jurisdictions all had found a reduction in breast cancer mortality although this was not always statistically different from zero. Studies had used a range of designs and evaluative methods which may have contributed to the magnitude of the effect reported.

Conclusion

No evidence was found in the British Columbia data and the published studies reviewed, that treatment or other changes, had caused mammographic screening to become ineffective.     

Comorbidity scores for administrative data benefited from adaptation to local coding and diagnostic practices

Objective

The Charlson and Elixhauser indices are the most commonly used comorbidity indices with risk prediction models using administrative data. Our objective was to compare the original Charlson index, a modified set of Charlson codes after advice from clinical coders, and a published modified Elixhauser index in predicting in-hospital mortality.

Study Design and Setting

Logistic regression using two separate years of administrative hospital data for all acute nonspecialist public hospitals in England.

Results

For all admissions combined, discrimination was similar for the Charlson index using the original codes and weights and the Charlson index using the original codes but England-calibrated weights (c = 0.73), although model fit was superior for the latter. The new Charlson codes improved discrimination (c = 0.76), model fit, and consistency of recording between admissions. The modified Elixhauser had the best performance (c = 0.80). For admissions for acute myocardial infarction and chronic obstructive pulmonary disease, the weights often differed, although the patterns were broadly similar.

Conclusion

Recalibration of the original Charlson index yielded only modest benefits overall. The modified Charlson codes and weights offer better fit and discrimination for English data over the original version. The modified Elixhauser performed best of all, but its weights were perhaps less consistent across the different patient groups considered here.     

Development of a meat frequency questionnaire for use in diet and cancer studies

Objective

To develop a meat frequency questionnaire to assess dietary heterocyclic amine intake. The meat frequency questionnaire is designed to obtain information on meat types, cooking methods, and doneness preferences that predict heterocyclic amine concentrations in different meats.

Design

Total and specific meat intakes were determined by a standard food frequency questionnaire (FFQ) and compared with that determined by the meat frequency questionnaire.

Subjects/setting

Three-hundred fourteen African-American males participating in a clinic-based study of prostate disease and heterocyclic amine intake were administered the two questionnaires in a cancer education center prior to undergoing screening evaluations for prostate disease.

Main outcome measures

Fried, broiled, and grilled vs total meat intake was assessed using the meat frequency questionnaire vs FFQ, respectively. Specific meat items included in the meat frequency questionnaire were evaluated as factors potentially explaining discrepancies in meat intake estimated using the two questionnaires. Seasonal variation in meat intake was also examined.

Statistical analysis

Correlation coefficients for intake of total meat and individual meat groups determined by FFQ vs meat frequency questionnaire were calculated. Seasonal differences in meat and estimated heterocyclic amine intakes were evaluated by t test, adjusted for multiple comparisons.

Results

Meat intakes determined by the two questionnaires were well-correlated (Pearson r=0.69); however, total meat assessed by the meat frequency questionnaire exceeded total meat assessed by the FFQ in 30% of participants. Total energy and intake of heterocyclic amine−associated meat were greatest when the meat frequency questionnaire was administered during winter months.

Conclusions

The heterocyclic amine meat frequency questionnaire provided a fractional measure of total meat intake and identified specific heterocyclic amine-containing meat items underreported in a standard FFQ.     

The quality of safety reporting in trials is still suboptimal: survey of major general medical journals

Objective

To evaluate whether the quality of reporting harms improved after the publication of the Extension of the Consolidated Standards of Reporting Trials (CONSORT) statement and predictors that influence the safety reporting in randomized controlled trials (RCTs)

Study Design and Setting

Systematic survey of published RCTs assessing drugs. In MEDLINE, we identified 228 RCTs published in Annals of Internal Medicine, British Medical Journal, Journal of American Medical Association, The Lancet, and The New England Journal of Medicine in 2003 and 2006.

Results

The reporting of harms have improved over time both in quality and extent of space. However, the mean score as an overall measure of adequacy in reporting harms was 0.58 in 2003 and increased to 0.67 in 2006, indicating a moderate safety reporting. Safety was more adequate in trials with statistically significant results for efficacy, private funding, primary harms outcome, and anti-infective, antineoplasmatic, or immunosuppressive agents.

Conclusion

The use of the Extension of the CONSORT statement may be associated with improving the quality of safety reporting in RCTs, but there are still deficiencies that need to be corrected to use quantitative objective evidence for harms in performing meta-analyses and making therapeutic decisions.