Age at menarche and its association with the metabolic syndrome and its components: results from the KORA F4 study

Objective

The metabolic syndrome is a major public health challenge and identifies persons at risk for diabetes and cardiovascular disease. The aim of this study was to examine the association between age at menarche and the metabolic syndrome (IDF and NCEP ATP III classification) and its components.

Design

1536 women aged 32 to 81 years of the German population based KORA F4 study were investigated. Data was collected by standardized interviews, physical examinations, and whole blood and serum measurements.

Results

Young age at menarche was significantly associated with elevated body mass index (BMI), greater waist circumference, higher fasting glucose levels, and 2 hour glucose (oral glucose tolerance test), even after adjusting for the difference between current BMI and BMI at age 25. The significant effect on elevated triglycerides and systolic blood pressure was attenuated after adjustment for the BMI change. Age at menarche was inversely associated with the metabolic syndrome adjusting for age (p-values: <0.001 IDF, 0.003 NCEP classification) and additional potential confounders including lifestyle and reproductive history factors (p-values: 0.001, 0.005). Associations remain significant when additionally controlling for recollected BMI at age 25 (p-values: 0.008, 0.033) or the BMI change since age 25 (p-values: 0.005, 0.022).

Conclusion

Young age at menarche might play a role in the development of the metabolic syndrome. This association is only partially mediated by weight gain and increased BMI. A history of early menarche may help to identify women at risk for the metabolic syndrome.     

A new calibrated bayesian internal goodness-of-fit method: sampled posterior p-values as simple and general p-values that allow double use of the data

Background

Recent approaches mixing frequentist principles with Bayesian inference propose internal goodness-of-fit (GOF) p-values that might be valuable for critical analysis of Bayesian statistical models. However, GOF p-values developed to date only have known probability distributions under restrictive conditions. As a result, no known GOF p-value has a known probability distribution for any discrepancy function.

Methodology/Principal Findings

We show mathematically that a new GOF p-value, called the sampled posterior p-value (SPP), asymptotically has a uniform probability distribution whatever the discrepancy function. In a moderate finite sample context, simulations also showed that the SPP appears stable to relatively uninformative misspecifications of the prior distribution.

Conclusions/Significance

These reasons, together with its numerical simplicity, make the SPP a better canonical GOF p-value than existing GOF p-values.     

Association between Reproductive Factors and Age-Related Macular Degeneration in Postmenopausal Women: The Korea National Health and Nutrition Examination Survey 2010-2012

Purpose

To examine the association between female reproductive factors and age-related macular degeneration (AMD) in postmenopausal women.

Design

Nationwide population-based cross-sectional study.

Methods

A nationally representative dataset acquired from the 2010–2012 Korea National Health and Nutrition Examination Survey was analyzed. The dataset involved information for 4,377 postmenopausal women aged ≥50 years with a fundus photograph evaluable for AMD in either eye. All participants were interviewed using standardized questionnaires to determine reproductive factors including menstruation, pregnancy, parity, lactation, and hormonal use. The association between reproductive factors and each type of AMD was investigated.

Results

The mean age of the study participants was 63.1±0.2 years. Mean ages at menarche and menopause were 16.1±0.0 and 49.2±0.1 years, respectively. The overall prevalence rates of early and late AMD were 11.2% (95% confidence interval [CI], 10.1–12.5) and 0.8% (95% CI, 0.5–1.2), respectively. When adjusted for age, neither smoking nor alcohol use was associated with the presence of any AMD or late AMD. Multivariate logistic regression analysis revealed age (OR, 1.12 per 1 year), duration of lactation (OR, 0.91 per 6 months), and duration of use of oral contraceptive pills (OCP) (OR, 1.10 per 6 months) as associated factors for late AMD. The other variables did not yield a significant correlation with the risk of any AMD or late AMD.

Conclusion

After controlling for confounders, a longer duration of lactation appeared to protect against the development of late AMD. A longer duration of OCP use was associated with a higher risk of late AMD.     

Exogenous and Endogenous Hormones in Relation to Glioma in Women: A Meta-analysis of 11 Case-Control Studies

Background and Objective

Previous investigations of glioma risk in women have focused on oral contraceptive (OC), hormone replacement therapy (HRT), and reproductive factors. However, the results of published studies were inconclusive and inconsistent. Thus, a meta-analysis based on published case-control studies was performed to assess the role of exogenous and endogenous hormones factors in glioma risk.

Methods

The PubMed and EMBASE databases were searched without any restrictions on language or publication year. Reference lists from retrieved articles were also reviewed. We included case-control studies reporting relative risks (RRs) with corresponding 95% confidence intervals (CIs) (or data to calculate them) between oral contraceptive (OC) and hormone replacement therapy (HRT) use, reproductive factors and glioma. Random-effects models were used to calculate the summary risk estimates.

Results

Finally, 11 eligible studies with 4860 cases and 14,740 controls were identified. A lower risk of glioma was observed among women who were ever users of exogenous hormones (OC RR = 0.707, 95% CI = 0.604–0.828; HRT: RR = 0.683, 95% CI = 0.577–0.808) compared with never users. An increased glioma risk was associated with older age at menarche (RR = 1.401, 95% CI = 1.052–1.865). No association was observed for menopause status, parous status, age at menopause, or age at first birth and glioma risk.

Conclusion

The results of our study support the hypothesis female sex hormones play a role in the development of glioma in women. Additional studies are warranted to validate the conclusion from this meta-analysis and clarity the underlying mechanisms.     

Kras Gene Mutation and RASSF1A,FHIT and MGMT Gene Promoter Hypermethylation: Indicators of Tumor Staging and Metastasis in Adenocarcinomatous Sporadic Colorectal Cancer in Indian Population

Objective

Colorectal cancer (CRC) development involves underlying modifications at genetic/epigenetic level. This study evaluated the role of Kras gene mutation and RASSF1A, FHIT and MGMT gene promoter hypermethylation together/independently in sporadic CRC in Indian population and correlation with clinicopathological variables of the disease.

Methods

One hundred and twenty four consecutive surgically resected tissues (62 tumor and equal number of normal adjacent controls) of primary sporadic CRC were included and patient details including demographic characteristics, lifestyle/food or drinking habits, clinical and histopathological profiles were recorded. Polymerase chain reaction - Restriction fragment length polymorphism and direct sequencing for Kras gene mutation and Methylation Specific-PCR for RASSF1A, FHIT and MGMT genes was performed.

Results

Kras gene mutation at codon 12 & 13 and methylated RASSF1A, FHIT and MGMT gene was observed in 47%, 19%, 47%, 37% and 47% cases, respectively. Alcohol intake and smoking were significantly associated with presence of Kras mutation (codon 12) and MGMT methylation (p-value <0.049). Tumor stage and metastasis correlated with presence of mutant Kras codon 12 (p-values 0.018, 0.044) and methylated RASSF1A (p-values 0.034, 0.044), FHIT (p-values 0.001, 0.047) and MGMT (p-values 0.018, 0.044) genes. Combinatorial effect of gene mutation/methylation was also observed (p-value <0.025). Overall, tumor stage 3, moderately differentiated tumors, presence of lymphatic invasion and absence of metastasis was more frequently observed in tumors with mutated Kras and/or methylated RASSF1A, FHIT and MGMT genes.

Conclusion

Synergistic interrelationship between these genes in sporadic CRC may be used as diagnostic/prognostic markers in assessing the overall pathological status of CRC.     

The Impact of Oral Contraceptive Initiation on Young Women’s Condom Use in 3 American Cities: Missed Opportunities for Intervention

Purpose

To describe women’s condom use and assess predictors of consistent condom use and dual method use in the 6 months after the initiation of oral contraception (OC).

Methods

We conducted a planned secondary cohort analysis among women less than 25 years of age initiating oral contraceptives at public family planning clinics in Atlanta, Dallas and New York City, USA, as part of a randomized trial. These clinics provide care to predominantly African American or Hispanic women of low socioeconomic status. Participants completed interviews at enrollment and at 6 months after OC start. We used multivariate logistic regression to assess factors associated with consistent condom and dual method use at 6 months.

Results

1281 participants met the inclusion criteria for this analysis. At enrollment prior to OC start, 28% were consistent condom users. In the six months after initiation of oral contraception, only 14% always used a condom and 4% always used dual methods. In multivariate analysis, receiving basic advice to always use a condom after OC initiation from a provider during the baseline clinic consultation was associated with a 50% increase in the odds of using condoms consistently. Only 28% of participants were given this condom use advice.

Conclusions

This study documents a decline in women’s condom consistent use subsequent to initiation of the oral contraceptive and suggests that opportunities for positive intervention around condom use among women starting hormonal methods are being missed. Basic condom use advice, which is neither time consuming nor resource dependent, was associated with increased consistent use and should be immediately implemented in all family planning services.     

The role of place in shaping contraceptive use among women in Africa

Background

Contraceptive prevalence is low in the African region despite considerable family planning programmatic efforts. This study is the first to examine how community factors shape contraceptive use for married women in an entire region, comparing results across 21 African countries with a DHS in the last 5 years. The analysis builds on previous studies through an examination of the individual, household and community level factors that shape contraceptive use.

Methods

The data used in this analysis were from nationally representative Demographic and Health Surveys completed between 2005 and 2009. A separate multi-level logistic model was fitted for the outcome of current modern contraceptive use in each country.

Results

After controlling for individual and household level factors, community level factors of demographics and fertility norms, gender norms and inequalities, and health knowledge remain significantly associated with contraceptive use, although the magnitude and direction of these community effects varied significantly across countries.

Conclusions

The results highlight the importance of harnessing community level factors in planning interventions for increasing access to and utilization of modern contraceptive methods.     

Association Between Uric Acid Levels and Obstructive Sleep Apnea Syndrome in a Large Epidemiological Sample

Introduction

Recurrent hypoxia, which is associated with obstructive sleep apnea syndrome (OSAS), leads to an increase in the degradation of adenosine triphosphatase into xanthine, which in turn increases uric acid concentrations.

Objective

The current study aimed to determine whether an association exists between OSAS and uric acid levels in the peripheral blood from a representative population of Sao Paulo (Brazil).

Methods

A population-based survey adopting a probabilistic 3-stage cluster sample of Sao Paulo was used to represent the population according to gender, age, and socioeconomic class. A total of 1,042 volunteers underwent polysomnography recordings for OSAS diagnosis, blood pressure assessment, and biochemical blood analysis, and answered questionnaires.

Results

Uric acid levels were correlated with most important risk factors for OSAS, such as AHI, desaturation time and index, minimum oxyhemoglobin saturation (SpO₂), blood pressure, cholesterol, BMI, triglycerides and arousal, and with OSAS itself. Also, uric acid was increased in OSAS volunteers even after controlling for all confounders. Hyperuricemic volunteers presented lower mean and minimum SpO₂ and increased desaturation index. Importantly, minimum SpO₂ was a significant predictor of uric acid levels, which in turn was considered an independent predictor for OSAS in the binary logistic model. However, a ROC curve analysis for establishing cut-off points for uric acid levels as a biomarker of OSAS revealed moderate sensitivity and specificity.

Conclusion

A strong association was found between uric acid levels and OSAS in a representative sample of the population of Sao Paulo. Although they do not qualify for a biomarker alone, uric acid levels may be involved in OSAS severity and should be considered in sleep apnea management in the future.     

Association between Vitamin D Insufficiency and Elevated Serum Uric Acid among Middle-Aged and Elderly Chinese Han Women

Background

Association between vitamin D insufficiency and hyperuricemia has not been reported so far. We aimed to study the association of vitamin D insufficiency with elevated serum uric acid among middle-aged and elderly Chinese Han women.

Methods

We collected data from participants residing in Jinchang district of Suzhou from January to May, 2010. Serum uric acid, 25-hydroxy vitamin D and other traditional biomarkers including fasting plasma glucose and blood lipids were determined in 1726 women aged above 30 years. Association between vitamin D insufficiency and elevated uric acid was analyzed in premenopausal and postmenopausal women, respectively.

Results

Among postmenopausal women, 25-hydroxy vitamin D level of participants with elevated uric acid was lower than that of those with normal uric acid (median [interquartile range]: 35[28–57] vs 40[32–58], µg/L; P = 0.006). Elevated uric acid was more prevalent in participants with vitamin D insufficiency compared to those without vitamin D insufficiency (16.50% vs 8.08%; P<0.001). Association between vitamin D insufficiency and elevated uric acid was not significant among premenopausal women. However, participants with vitamin D insufficiency were more likely to have elevated uric acid compared with those without vitamin D insufficiency among postmenopausal women (OR, 95% CI: 2.38, 1.47–3.87). Moreover, after excluding individuals with diabetes and/or hypertension, the association of vitamin D insufficiency with elevated uric acid was still significant (OR, 95% CI: 2.48, 1.17–5.44).

Conclusions

Vitamin D insufficiency was significantly associated with elevated uric acid among postmenopausal Chinese Han women. This study suggested that a clinical trial should be conducted to confirm the association of vitamin D insufficiency with hyperuricemia.     

Hyperuricemia Is a Risk Factor for the Onset of Impaired Fasting Glucose in Men with a High Plasma Glucose Level: A Community-Based Study

Background

It is not clear whether elevated uric acid is a risk factor for the onset of impaired fasting glucose after stratifying by baseline fasting plasma glucose levels. We conducted a community-based retrospective longitudinal cohort study to clarify the relationship between uric acid levels and the onset of impaired fasting glucose, according to baseline fasting plasma glucose levels.

Methods

We enrolled 6,403 persons (3,194 men and 3,209 women), each of whom was 18–80 years old and had >2 annual check-ups during 2003–2010. After excluding persons who had fasting plasma glucose levels ≥6.11 mM and/or were currently taking anti-diabetic agents, the remaining 5,924 subjects were classified into quartiles according to baseline fasting plasma glucose levels. The onset of impaired fasting glucose was defined as fasting plasma glucose ≥6.11 mM during the observation period.

Results

In the quartile groups, 0.9%, 2.1%, 3.4%, and 20.2% of the men developed impaired fasting glucose, respectively, and 0.1%, 0.3%, 0.5%, and 5.6% of the women developed impaired fasting glucose, respectively (P trend <0.001). After adjusting for age, body mass index, systolic blood pressure, triacylglycerols, high density lipoprotein-cholesterol, creatinine, fatty liver, family history of diabetes, alcohol consumption, and current smoking, uric acid levels were positively associated with onset of impaired fasting glucose in men with highest-quartile fasting plasma glucose levels (adjusted hazard ratio, 1.003; 95% confidence interval, 1.0001–1.005, P = 0.041).

Conclusions

Among men with high fasting plasma glucose, hyperuricemia may be independently associated with an elevated risk of developing impaired fasting glucose.     

Age at Menarche and Natural Menopause and Number of Reproductive Years in Association with Mortality: Results from a Median Follow-Up of 11.2 Years among 31,955 Naturally Menopausal Chinese Women

Background

Studies conducted in Western countries suggest that early age at menarche and early age at menopause are both associated with increased total mortality, but limited data are available for Asian populations. We examined associations of age at menarche and natural menopause and duration of the reproductive span with mortality in a population-based cohort study of Chinese women.

Methods

We evaluated the effects of age at menarche, age at natural menopause, and number of reproductive years on total and cause-specific mortality among 31,955 naturally menopausal Chinese women who participated in the Shanghai Women''s Health Study, a population-based, prospective cohort study.

Results

A total of 3,158 deaths occurred during a median follow-up of 11.2 years. Results from Cox proportional hazards models showed that younger age at menopause (<46.64 years) was associated with higher risk of total mortality (P_trend  = 0.02). Younger age at menarche (<14 years) was associated with higher risk of mortality from stroke (P_trend  = 0.03) and diabetes (P_trend = 0.02) but lower risk of mortality from respiratory system cancer (P_trend  = 0.01). Women with a shorter reproductive span had lower risk of mortality from gynecological cancers (P_trend = 0.03).

Conclusions

Our study found that menstrual characteristics are important predictors of mortality, suggesting an important role of sex hormones in biological aging.     

Association of Serum Uric Acid and Coronary Artery Disease in Premenopausal Women

Objective

To date, no study in the published literature has investigated the role of various serum uric acid (SUA) concentrations in the development of angiographically-proven coronary artery disease (CAD) in premenopausal women. Therefore, the aim of this study was to investigate the role SUA levels may play in the prevalence, severity, and prognosis of CAD in premenopausal women.

Methods

This cross-sectional retrospective study included 607 premenopausal women who had undergone coronary angiography. The CAD diagnosis was based upon stenosis affecting ≥50% of the luminal diameter. Association of the SUA levels with CAD prevalence, severity, and clinical outcomes were assessed by statistical analysis.

Results

In total, 369 (60.8%) of the patients were diagnosed with CAD. The CAD patients had significantly higher SUA levels than those without CAD (5.3±1.9 vs. 4.8±1.7 mg/dL, P = 0.001). The SUA levels were found to be significantly associated with CAD prevalence (P = 0.013). Patients with higher levels of SUA also showed increased rates of multivessel disease and composite end-points, such as major adverse cardiac events. Furthermore, multivariate analysis identified abnormally high levels of uric acid (hyperuricemia) as an independent risk factor for CAD (OR 1.51 (1.11–2.53), P<0.05).

Conclusions

The SUA levels are significantly associated with the prevalence of CAD. The SUA levels may be a predictor for incidence of major cardiovascular events in premenopausal women.     

Theobromine Inhibits Uric Acid Crystallization. A Potential Application in the Treatment of Uric Acid Nephrolithiasis

Purpose

To assess the capacity of methylxanthines (caffeine, theophylline, theobromine and paraxanthine) to inhibit uric acid crystallization, and to evaluate their potential application in the treatment of uric acid nephrolithiasis.

Materials and Methods

The ability of methylxathines to inhibit uric acid nucleation was assayed turbidimetrically. Crystal morphology and its modification due to the effect of theobromine were evaluated by scanning electron microscopy (SEM). The ability of theobromine to inhibit uric acid crystal growth on calculi fragments resulting from extracorporeal shock wave lithotripsy (ESWL) was evaluated using a flow system.

Results

The turbidimetric assay showed that among the studied methylxanthines, theobromine could markedly inhibit uric acid nucleation. SEM images showed that the presence of theobromine resulted in thinner uric acid crystals. Furthermore, in a flow system theobromine blocked the regrowth of post-ESWL uric acid calculi fragments.

Conclusions

Theobromine, a natural dimethylxanthine present in high amounts in cocoa, acts as an inhibitor of nucleation and crystal growth of uric acid. Therefore, theobromine may be clinically useful in the treatment of uric acid nephrolithiasis.     

Serum calcium levels are associated with novel cardiometabolic risk factors in the population-based CoLaus study

Background

Associations of serum calcium levels with the metabolic syndrome and other novel cardio-metabolic risk factors not classically included in the metabolic syndrome, such as those involved in oxidative stress, are largely unexplored. We analyzed the association of albumin-corrected serum calcium levels with conventional and non-conventional cardio-metabolic risk factors in a general adult population.

Methodology/Principal Findings

The CoLaus study is a population-based study including Caucasians from Lausanne, Switzerland. The metabolic syndrome was defined using the Adult Treatment Panel III criteria. Non-conventional cardio-metabolic risk factors considered included: fat mass, leptin, LDL particle size, apolipoprotein B, fasting insulin, adiponectin, ultrasensitive CRP, serum uric acid, homocysteine, and gamma-glutamyltransferase. We used adjusted standardized multivariable regression to compare the association of each cardio-metabolic risk factor with albumin-corrected serum calcium. We assessed associations of albumin-corrected serum calcium with the cumulative number of non-conventional cardio-metabolic risk factors.We analyzed 4,231 subjects aged 35 to 75 years. Corrected serum calcium increased with both the number of the metabolic syndrome components and the number of non-conventional cardio-metabolic risk factors, independently of the metabolic syndrome and BMI. Among conventional and non-conventional cardio-metabolic risk factors, the strongest positive associations were found for factors related to oxidative stress (uric acid, homocysteine and gamma-glutamyltransferase). Adiponectin had the strongest negative association with corrected serum calcium.

Conclusions/Significance

Serum calcium was associated with the metabolic syndrome and with non-conventional cardio-metabolic risk factors independently of the metabolic syndrome. Associations with uric acid, homocysteine and gamma-glutamyltransferase were the strongest. These novel findings suggest that serum calcium levels may be associated with cardiovascular risk via oxidative stress.     

State Variations in Women’s Socioeconomic Status and Use of Modern Contraceptives in Nigeria

Background

According to the 2014 World Population Data Sheet, Nigeria has one of the highest fertility and lowest contraceptive prevalence rates around the world. However, research suggests that national contraceptive prevalence rate overshadows enormous spatial variations in reproductive behavior in the country.

Objective

I examined the variations in women’s socioeconomic status and modern contraceptive use across states in Nigeria.

Methods

Using the 2013 Nigeria Demographic and Health Survey data (n = 18,910), I estimated the odds of modern contraceptive use among sexually active married and cohabiting women in a series of multilevel logistic regression models.

Results

The share of sexually active, married and cohabiting women using modern contraceptives widely varied, from less than one percent in Kano, Yobe, and Jigawa states, to 40 percent in Osun state. Most of the states with low contraceptive prevalence rates also ranked low on women’s socioeconomic attributes. Results of multilevel logistic regression analyses showed that women residing in states with greater shares of women with secondary or higher education, higher female labor force participation rates, and more women with health care decision-making power, had significantly higher odds of using modern contraceptives. Differences in women’s participation in health care decisions across states remained significantly associated with modern contraceptive use, net of individual-level socioeconomic status and other covariates of modern contraceptive use.

Conclusion

Understanding of state variations in contraceptive use is crucial to the design and implementation of family planning programs. The findings reinforce the need for state-specific family planning programs in Nigeria.     

Women's Empowerment and Contraceptive Use: The Role of Independent versus Couples' Decision-Making,from a Lower Middle Income Country Perspective

Introduction

There is little available evidence of associations between the various dimensions of women''s empowerment and contraceptive use having been examined - and of how these associations are mediated by women''s socio-economic and demographic statuses. We assessed these phenomena in Pakistan using a structured-framework approach.

Methods

We analyzed data on 2,133 women who were either using any form of contraceptive or living with unmet need for contraception. The survey was conducted during May - June 2012, with married women of reproductive age (15–49 years) in three districts of Punjab. The dimensions of empowerment were categorized broadly into: economic decision-making, household decision-making, and women''s mobility. Two measures were created for each dimension, and for the overall empowerment: women''s independent decisions, and those taken jointly by couples. Contraceptive use was categorized as either female-only or couple methods on the basis of whether a method requires the awareness of, or some support and cooperation from, the husband. Multinomial regression was used, by means of Odds Ratios (OR), to assess associations between empowerment dimensions and female-only and couple contraceptive methods.

Results

Overall, women tend to get higher decision-making power with increased age, higher literacy, a greater number of children, or being in a household that has superior socio-economic status. The measures for couples'' decision-making for overall empowerment and for each dimension of it showed positive associations with couple methods as well as with female-only methods. The only exception was the measure of economic empowerment, which was associated only with the couple method.

Conclusion

Couples'' joint decision-making is a stronger determinant of the use of contraceptive methods than women-only decision-making. This is the case over and above the contribution of women''s socio-demographic and economic statuses. Effort needs to be made to educate women and their husbands equally, with particular focus on highly effective contraceptive methods.     

Contraceptive use and method preference among women in Soweto, South Africa: the influence of expanding access to HIV care and treatment services

Objective

Preventing unintended pregnancy among HIV-positive women constitutes a critical and cost-effective approach to primary prevention of mother-to-child transmission of HIV and is a global public health priority for addressing the desperate state of maternal and child health in HIV hyper-endemic settings. We sought to investigate whether the prevalence of contraceptive use and method preferences varied by HIV status and receipt of highly active antiretroviral therapy (HAART) among women in Soweto, South Africa.

Methods

We used survey data from 563 sexually active, non-pregnant women (18–44 years) recruited from the Perinatal HIV Research Unit in Soweto (May–December, 2007); 171 women were HIV-positive and receiving HAART (median duration of use = 31 months; IQR = 28, 33), 178 were HIV-positive and HAART-naïve, and 214 were HIV-negative. Medical record review was conducted to confirm HIV status and clinical variables. Logistic regression models estimated adjusted associations between HIV status, receipt of HAART, and contraceptive use.

Results

Overall, 78% of women reported using contraception, with significant variation by HIV status: 86% of HAART users, 82% of HAART-naïve women, and 69% of HIV-negative women (p<0.0001). In adjusted models, compared with HIV-negative women, women receiving HAART were significantly more likely to use contraception while HAART-naïve women were non-significantly more likely (AOR: 2.40; 95% CI: 1.25, 4.62 and AOR: 1.59; 95% CI: 0.88, 2.85; respectively). Among HIV-positive women, HAART users were non-significantly more likely to use contraception compared with HAART-naïve women (AOR: 1.55; 95% CI: 0.84, 2.88). Similar patterns held for specific use of barrier (primarily male condoms), permanent, and dual protection contraceptive methods.

Conclusion

Among HIV-positive women receiving HAART, the observed higher prevalence of contraceptive use overall and condoms in particular promises to yield fewer unintended pregnancies and reduced risks of vertical and sexual HIV transmission. These findings highlight the potential of integrated HIV and reproductive health services to positively impact maternal, partner, and child health.     

Pre-Treatment with Allopurinol or Uricase Attenuates Barrier Dysfunction but Not Inflammation during Murine Ventilator-Induced Lung Injury

Introduction

Uric acid released from injured tissue is considered a major endogenous danger signal and local instillation of uric acid crystals induces acute lung inflammation via activation of the NLRP3 inflammasome. Ventilator-induced lung injury (VILI) is mediated by the NLRP3 inflammasome and increased uric acid levels in lung lavage fluid are reported. We studied levels in human lung injury and the contribution of uric acid in experimental VILI.

Methods

Uric acid levels in lung lavage fluid of patients with acute lung injury (ALI) were determined. In a different cohort of cardiac surgery patients, uric acid levels were correlated with pulmonary leakage index. In a mouse model of VILI the effect of allopurinol (inhibits uric acid synthesis) and uricase (degrades uric acid) pre-treatment on neutrophil influx, up-regulation of adhesion molecules, pulmonary and systemic cytokine levels, lung pathology, and regulation of receptors involved in the recognition of uric acid was studied. In addition, total protein and immunoglobulin M in lung lavage fluid and pulmonary wet/dry ratios were measured as markers of alveolar barrier dysfunction.

Results

Uric acid levels increased in ALI patients. In cardiac surgery patients, elevated levels correlated significantly with the pulmonary leakage index. Allopurinol or uricase treatment did not reduce ventilator-induced inflammation, IκB-α degradation, or up-regulation of NLRP3, Toll-like receptor 2, and Toll-like receptor 4 gene expression in mice. Alveolar barrier dysfunction was attenuated which was most pronounced in mice pre-treated with allopurinol: both treatment strategies reduced wet/dry ratio, allopurinol also lowered total protein and immunoglobulin M levels.

Conclusions

Local uric acid levels increase in patients with ALI. In mice, allopurinol and uricase attenuate ventilator-induced alveolar barrier dysfunction.     

What Do You Know about Reproductive Medicine? – Results of a German Representative Survey

Objective

The use of reproductive medical treatments has become increasingly routine in recent years. This paper reports on a study of how different aspects of modern reproductive medicine are perceived by the German population.

Design

Findings from a nationally representative sample of 2110 men and women aged 18 to 50 are presented. Participants responded to a questionnaire seeking self-report information about attitudes and knowledge regarding different aspects of reproductive medicine.

Results

The majority of respondents had already heard or read something about reproductive medicine; knowledge gaps were prevalent in men and individuals with lower levels of education. The decrease in female fertility usually was underestimated, whereas both the number of involuntarily childless couples and the success rate of reproductive medical treatment were overestimated. One-third of participants would make use of reproductive medicine to have their own child.

Conclusion

This study revealed inadequacies in the knowledge of the German general population regarding reproductive medicine. Despite the low interest and poor knowledge of the topic, a broad acceptance of reproductive medical methods was reported. The results illustrate the need for adequate information transfer regarding female fertility as well as success rate and risks of reproductive medical interventions.     

Oral contraceptives and the risk of gallbladder disease: a comparative safety study

Background

Recent concerns have been raised about the risk of gallbladder disease associated with the use of drospirenone, a fourth-generation progestin used in oral contraceptives. We conducted a study to determine the magnitude of this risk compared with other formulations of oral contraceptives.

Methods

We conducted a retrospective cohort study using the IMS LifeLink Health Plan Claims Database. We included women who were using an oral contraceptive containing ethinyl estradiol combined with a progestin during 1997–2009. To be eligible, women had to have been taking the oral contraceptive continuously for at least six months. We computed adjusted rate ratios (RRs) for gallbladder disease using a Cox proportional hazards model. In the primary analysis, gallbladder disease was defined as cholecystectomy; in a secondary analysis, it was defined as hospital admission secondary to gallbladder disease.

Results

We included 2 721 014 women in the cohort, 27 087 of whom underwent surgical or laparoscopic cholecystectomy during the follow-up period. Compared with levonorgestrel, an older second-generation progestin, a small, statistically significant increase in the risk of gallbladder disease was associated with desogestrel (adjusted RR 1.05, 95% confidence interval [CI] 1.01–1.09), drospirenone (adjusted RR 1.20, 95% CI 1.16–1.26) and norethindrone (adjusted RR 1.10, 95% CI 1.06–1.14). No statistically significant increase in risk was associated with the other formulations of oral contraceptive (ethynodiol diacetate, norgestrel and norgestimate).

Interpretation

In a large cohort of women using oral contraceptives, we found a small, statistically significant increase in the risk of gallbladder disease associated with desogestrel, drospirenone and norethindrone compared with levonorgestrel. However, the small effect sizes compounded with the possibility of residual biases in this observational study make it unlikely that these differences are clinically significant.Oral contraceptives are the most popular mode of birth control among women and are used by about 100 million women worldwide.¹ Long-term use of these drugs has been associated with a variety of serious adverse events, including deep vein thrombosis, stroke and pulmonary embolism.² In addition, both estrogen and progesterone have been shown to play an important role in the formation of gallstones.^3–5 However, the relative risk of gallbladder disease associated with different formulations of oral contraceptives, including newer formulations, is unknown.Recently, there have been concerns expressed in the media about reports of gallbladder disease necessitating cholecystectomy associated with the use of drospirenone, a fourth-generation progestin.⁶ Drospirenone combined with ethinyl estradiol is primarily marketed as Yaz and Yasmin in Canada and the United States and is one of the most prescribed oral contraceptives in North America, with worldwide sales of $2 billion in 2009.⁷ The scientific evidence on the risk of gallbladder disease associated with drospirenone consists of only anecdotal or spontaneous reports in databases of adverse drug events.A possible link between drospirenone and gallbladder disease may lead to cholecystectomy and possible surgical complications.⁸ If there were a substantial risk of gallbladder disease with drospirenone, this might influence its overall risk–benefit ratio and could prompt physicians to prescribe safer alternatives. Given that women using oral contraceptives have been found to be at increased risk of gallbladder disease compared with women not using oral contraceptives,⁴ any excess risk associated with the use of drospirenone merits quantification within the context of a comparative safety study.