In postmenopausal women with osteoporosis, denosumab significantly improved trabecular bone score (TBS), an index of trabecular microarchitecture

Background/Purpose: The trabecular bone score (TBS), a novel graylevel texture index determined from lumbar spine DXA scans, correlates with 3D parameters of trabecular bone microarchitecture known to predict fracture. TBS may enhance the identification of patients at increased risk for vertebral fracture independently of bone mineral density (BMD) (Boutroy JBMR 2010; Hans JBMR 2011). Denosumab treatment for 36 months decreased bone turnover, increased BMD, and reduced new vertebral fractures in postmenopausal women with osteoporosis (Cummings NEJM 2009). We explored the effect of denosumab on TBS over 36 months and evaluated the association between TBS and lumbar spine BMD in women who had DXA scans obtained from eligible scanners for TBS evaluation in FREEDOM. Methods: FREEDOM was a 3-year, randomized, double-blind trial that enrolled postmenopausal women with a lumbar spine or total hip DXA T-score __2.5, but not __4.0 at both sites. Women received placebo or 60 mg denosumab every 6 months. A subset of women in FREEDOM participated in a DXA substudy where lumbar spine DXA scans were obtained at baseline and months 1, 6, 12, 24, and 36. We retrospectively applied, in a blinded-to-treatment manner, a novel software program (TBS iNsightR v1.9, Med-Imaps, Pessac, France) to the standard lumbar spine DXA scans obtained in these women to determine their TBS indices at baseline and months 12, 24, and 36. From previous studies, a TBS _1.35 is considered as normal microarchitecture, a TBS between 1.35 and _1.20 as partially deteriorated, and 1.20 reflects degraded microarchitecture. Results: There were 285 women (128 placebo, 157 denosumab) with a TBS value at baseline and _1 post-baseline visit. Their mean age was 73, their mean lumbar spine BMD T-score was _2.79, and their mean lumbar spine TBS was 1.20. In addition to the robust gains in DXA lumbar spine BMD observed with denosumab (9.8% at month 36), there were consistent, progressive, and significant increases in TBS compared with placebo and baseline (Table & Figure). BMD explained a very small fraction of the variance in TBS at baseline (r2_0.07). In addition, the variance in the TBS change was largely unrelated to BMD change, whether expressed in absolute or percentage changes, regardless of treatment, throughout the study (all r2_0.06); indicating that TBS provides distinct information, independently of BMD. Conclusion: In postmenopausal women with osteoporosis, denosumab significantly improved TBS, an index of lumbar spine trabecular microarchitecture, independently of BMD.

Trends in lung cancer among young European women: the rising epidemic in France and Spain.

Lung cancer mortality in young women in the European Union (EU) has steadily increased until the mid 1990 s and has levelled off thereafter, but trends have been heterogeneous in various countries. We analyzed therefore age-standardized trends in lung cancer mortality in young women (20-44) for the 6 major European countries, using joinpoint regression. In the early 1970s the highest lung cancer mortality in young women was in the UK (2.1/100,000). UK rates, however, steadily declined and in 2000-2004 they were the lowest of all 6 major EU countries (1.2/100,000). The second lowest rate in 2000-2002 was in Italy, whose rates remained around 1.1/100,000 between 1970 and 1994, and increased to 1.4 thereafter. In Germany and Poland, lung cancer rates in young women rose from 0.8-1.0/100,000 in the early 1970s to 1.7-1.9 in the mid 1990 s and levelled off during the last decade. Major rises over recent years were observed in France (from 0.8/100,000 in 1985-1989 to 2.2 in 2000-2003) and in Spain (from 0.8 in the 1985-1989 to 1.7 in 2000-2004). Thus, France showed both the highest rate observed over the last 3 decades and the largest rise over the last 2 decades. Since recent trends in the young give relevant information to the likely future trends in middle age, the female lung cancer epidemic is likely to expand in southern Europe from the current rates of 5.0/100,000 in Spain and 7.7 in France to approach 20/100,000 within the next 2-3 decades. Urgent interventions for smoking cessation in women are therefore required.

Women at home, at school and in the factory. The particular discourse of domesticity done by the Spanish Escuela Economista (1861-1909)

The texts by the Spanish Economist School (second half of the 19th century) contain an assessment of the role of women in the economy and society that is transgressor in front of the prevailing discourse that defended a unique and exclusive role for all women: being at home and a mother. Most members of that economic trend defended female work in the factories, basing themselves on wage arguments and even asked for a professional training for those who in many cases could not even write and read for the fact of being a woman. The texts of those economists give new ideas about the economic and social role of women in a Spain dominated by a discourse that denied the necessity of female work for the working families.

Six years of denosumab treatment in postmenopausal women with osteoporosis: results from the first three years of the freedom extension

Background/Purpose: Denosumab (DMAb) is an approved therapy for the treatment of postmenopausal women with osteoporosis at increased risk for fracture. A favorable risk/benefit profile was demonstrated in the pivotal, 3-year FREEDOM trial (Cummings et al NEJM 2009). The open-label, active-treatment FREEDOM Extension study is investigating the efficacy and safety of DMAb for up to 10 years. The Extension trial enrolled women who had received DMAb or placebo in FREEDOM and provides an opportunity to evaluate the long-term efficacy and safety of continuous DMAb treatment (long-term group), and to replicate the DMAb findings observed in FREEDOM (cross-over group). Here, we report the results from the first 3 years of the Extension, representing up to 6 continuous years of DMAb exposure.Methods: During the Extension, each woman is scheduled to receive 60 mg DMAb every 6 months and supplemental calcium and vitamin D daily. For the analyses reported here, women from the FREEDOM DMAb group received 3 more years of DMAb for a total of 6 years of exposure (long-term group) and women from the FREEDOM placebo group received 3 years of DMAb exposure (cross-over group).Results: Of the 5928 women eligible for the Extension, 4550 (77%) enrolled (N_2343 long-term; N_2207 cross-over). In the long-term group, further significant mean increases in bone mineral density (BMD) occurred 4044 for cumulative 6-year gains of 15.2% at the lumbar spine and 7.5% at the total hip (Figure). During the first 3 years of DMAb treatment during the Extension, the cross-over group had significant mean gains in BMD at the lumbar spine (9.4%) and total hip (4.8%), similar to those observed in the long-term DMAb group during the first 3 years of FREEDOM (lumbar spine, 10.1%; total hip, 5.7%). Serum CTX was rapidly and similarly reduced after the 1st (cross-over) or 7th (long-term) DMAb dose with the characteristic attenuation observed at the end of the dosing period. In the cross-over group, yearly incidences of new vertebral and nonvertebral fractures were lower than in the FREEDOM placebo group. Fracture incidence remained low in the long-term group. Incidences of adverse events (AEs) and serious AEs did not increase over time with DMAb treatment. There were 2 subjects with AEs adjudicated to ONJ in the cross-over group and 2 in the long-term group. Both cases in the cross-over group healed completely and without further complications; 1 of these subjects continues to receive DMAb. Both women in the long-term group continue to be followed. No atypical femur fractures have been observed to date. Figure. Percent changes in bone mineral density during FREEDOM and the Extension Conclusion: DMAb treatment for 6 continuous years (long-term group) remained well tolerated, maintained reduced bone turnover, and continued to significantly increase BMD. Fracture incidence remained low. DMAb treatment for 3 years in the cross-over group reproduced the original observations in FREEDOM.

Women and Cancer in Ireland: 1994-2001

Although prevention is the primary aim of cancer control, early diagnosis and effective treatment are also central to reducing disability and death from cancer. Research in Ireland and internationally has shown major differences between women in the stage (extent) of their cancer when first diagnosed, in access to screening, and in the type of treatment received. These factors have also been shown to determine the rate of cure of cancers and the length of survival for those not cured. Many countries, including Ireland, have developed cancer policies in the past decade, with the aim of improving access, and ensuring that all cancer patients have appropriate, and evidence-based, treatment. These changes have major implications for women in Ireland, for example in the provision of breast and cervical screening programmes and in the expansion of specialist treatment centres for breast cancer. This is a publication of the Women’s Health Council. Read the report (PDF, 1.37mb) Read the Summary (PDF, 120kb)

Cardiovascular Disease in Women

Cardiovascular disease (CVD) is the leading cause of mortality in men and women on a global basis. CVD affects men and women equally but evidence suggests that it is neither diagnosed as readily, nor treated as effectively, in women. In Ireland between 2001 and 2005, an average of 2,484 women died each year from ischaemic heart disease (including myocardial infarction (MI)). (2) Yet, women seem largely unaware of their risk of developing cardiovascular disease, retaining the perception that CVD is predominantly a man's disease.

Five Years Of Denosumab Treatment In Women With Postmenopausal Osteoporosis: Preliminary Results From The Freedom Extension Study

Aims: The pivotal FREEDOM study evaluated the effi cacy and safety of 3 years' denosumab treatment in women with postmenopausal osteoporosis (PMO).1 Since osteoporosis is a chronic condition requiring long-term therapy, FREEDOM was extended to further elucidate the safety and effi cacy of long-term denosumab administration. We present data from the fi rst 2 years of this extension, representing up to 5 years' continuous exposure to denosumab.Methods: Patients who completed FREEDOM were eligible for the extension. Women continued to receive (long-term group), or started after 3 years' placebo (cross-over group), denosumab 60 mg sc every 6 months and daily calcium and vitamin D. These data refl ect 5 years' (long-term) or 2 years' (cross-over) continuous denosumab treatment. Effi cacy measures include changes in BMD from extension study baseline and bone turnover markers (BTM). P-values are descriptive.Results: Of the 83.0% of subjects who completed FREEDOM, 70.2% (N = 4550) agreed to participate in the extension (long-term: 2343; cross-over: 2207). In the long-term group, there were further signifi cant gains (P < 0.0001) in BMD in years 4 and 5: 1.9% and 1.7% at the lumbar spine to a total of 13.7% from FREEDOM baseline and 0.7% and 0.6% at the total hip to a total of 7.0%. During their fi rst 2 years' denosumab treatment, women in the cross-over group had signifi cant improvements in lumbar spine (7.9%) and total hip BMD (4.1%) (P < 0.0001). Serum C-telopeptide (CTX) was rapidly reduced following denosumab dosing in both groups, with the characteristic attenuation of CTX reduction observed at the end of the dosing interval. A low incidence of new vertebral and nonvertebral fractures was reported for both groups. The denosumab safety profi le did not change over time.Conclusions: Denosumab treatment for up to 5 years in women with PMO remains well tolerated, maintains reduction of BTMs and continues to significantly increase BMD.Reference1. Cummings. NEJM 2009;361:756.

Prevalence of oral hairy leukoplakia and epithelial infection by Epstein-Barr virus in pregnant women and diabetes mellitus patients: cytopathologic and molecular study

Oral hairy leukoplakia (OHL) is generally reported in patients with severe immunosuppression, except for a few cases in individuals with moderate degree of immunodeficiency. It is a white lesion that appears mainly in the lateral border of the tongue, caused by Epstein-Barr virus (EBV). The nuclear changes caused by EBV (Cowdry A inclusion, ground glass and nuclear beading), observed in cytopathology, are specific and enough for the definitive diagnosis of OHL, independent of the identification of the virus. Here we investigated the prevalence of OHL and the presence of EBV-DNA in the lateral borders of the tongue from 90 pregnant women, 90 diabetes mellitus (DM) patients, 30 healthy individuals (negative group) and 30 HIV+ with OHL (positive group). Smears were analyzed by cytopathology and polymerase chain reaction (PCR). A case of subclinical OHL and candidiasis was identificated in a DM patient by cytopathologic analysis. PCR results demonstrated EBV-DNA in 65% of the pregnant women, in 35% of DM patients, and in 20% of the healthy individuals. We concluded that DM patients can develop OHL with a low prevalence. Furthermore, the prevalence of the EBV in lateral border of the tongue is larger in pregnant women than in healthy individuals.

Sexually transmitted infections, bacterial vaginosis, and candidiasis in women of reproductive age in rural Northeast Brazil: a population-based study

Population-based data on sexually transmitted infections (STI), bacterial vaginosis (BV), and candidiasis reflect the epidemiological situation more accurately than studies performed in specific populations, but such data are scarce. To determine the prevalence of STI, BV, and candidiasis among women of reproductive age from a resource-poor community in Northeast Brazil, a population-based cross sectional study was undertaken. All women from seven hamlets and the centre of Pacoti municipality in the state of Ceará, aged 12 to 49 years, were invited to participate. The women were asked about socio-demographic characteristics and genital symptoms, and thereafter examined gynaecologically. Laboratory testing included polymerase chain reaction (PCR) for human papillomavirus (HPV), ligase chain reaction (LCR) for Chlamydia trachomatis and Neisseria gonorrhoeae, ELISA for human immunodeficiency virus (HIV), venereal disease research laboratory (VDRL) and fluorescent treponema antibody absorption test (FTA-ABS) for syphilis, and analysis of wet mounts, gram stains and Pap smears for trichomoniasis, candidiasis, and BV. Only women who had initiated sexual life were included in the analysis (n = 592). The prevalences of STI were: HPV 11.7% (95% confidence interval: 9.3-14.7), chlamydia 4.5% (3.0-6.6), trichomoniasis 4.1% (2.7-6.1), gonorrhoea 1.2% (0.5-2.6), syphilis 0.2% (0.0-1.1), and HIV 0%. The prevalence of BV and candidiasis was 20% (16.9-23.6) and 12.5% (10.0-15.5), respectively. The most common gynaecological complaint was lower abdominal pain. STI are common in women in rural Brazil and represent an important health threat in view of the HIV pandemic.

Association of the presence of residual anti-Toxoplasma gondii IgM in pregnant women and their respective family groups in Miracema, Northwest Rio de Janeiro, Brazil

The seroprevalence of toxoplasmosis in 832 pregnant women in Miracema, Rio de Janeiro, was determined and 75.1% (625) and 2.0% (17) were anti-Toxoplasma gondii IgG and IgM positive, respectively. Out of the 17 IgM positive pregnant women, only one had low avidity IgG corresponding to the acute phase of the infection. All the other women presented with high avidity IgG and also presented with residual IgM anti-T. gondii. Of this sample, 106 received home visits (this includes 11 family nuclei of pregnant women with residual IgM anti-T. gondii, 68 nuclei of only IgG positive pregnant women and 27 nuclei of pregnant women with no antibodies to anti-T. gondii), resulting in 267 individuals visited. Out of these 267 individuals, 21 were positive for IgG and IgM anti-T. gondii and were candidates for the IgG avidity test. All of them presented with high avidity IgG and residual IgM. Five of these IgM+ individuals were (5/238; 2.1%) relatives of IgM negative pregnant women. The other 16 (16/29; 55.2%) were relatives of IgM+ pregnant women who were positive for residual IgM anti-T. gondii. This association was statistically significant (p = 0.0000). The analysis presented herein raises questions regarding the presence of residual IgM anti-T. gondii such as genetic determinants or even constant antigenic stimuli for the same family cluster.

Malaria in pregnant women living in areas of low transmission on the southeast Brazilian Coast: molecular diagnosis and humoural immunity profile

Studies on autochthonous malaria in low-transmission areas in Brazil have acquired epidemiological relevance because they suggest continued transmission in what remains of the Atlantic Forest. In the southeastern portion of the state of São Paulo, outbreaks in the municipality of Juquitiba have been the focus of studies on the prevalence of Plasmodium, including asymptomatic cases. Data on the occurrence of the disease or the presence of antiplasmodial antibodies in pregnant women from this region have not previously been described. Although Plasmodium falciparum in pregnant women has been widely addressed in the literature, the interaction of Plasmodium vivax and Plasmodium malariae with this cohort has been poorly explored to date. We monitored the circulation of Plasmodium in pregnant women in health facilities located in Juquitiba using thick blood film and molecular protocols, as well as immunological assays, to evaluate humoural immune parameters. Through real-time and nested polymerase chain reaction, P. vivax and P. malariae were detected for the first time in pregnant women, with a positivity of 5.6%. Immunoassays revealed the presence of IgG antibodies: 44% for ELISA-Pv, 38.4% for SD-Bioline-Pv and 18.4% for indirect immunofluorescence assay-Pm. The high prevalence of antibodies showed significant exposure of this population to Plasmodium. In regions with similar profiles, testing for a malaria diagnosis might be indicated in prenatal care.

Variation of transaminases, HCV-RNA levels and Th1/Th2 cytokine production during the post-partum period in pregnant women with chronic hepatitis C.

This study analyses the evolution of liver disease in women with chronic hepatitis C during the third trimester of pregnancy and the post-partum period, as a natural model of immune modulation and reconstitution. Of the 122 mothers recruited to this study, 89 were HCV-RNA+ve/HIV-ve and 33 were HCV-RNA-ve/HIV-ve/HCVantibody+ve and all were tested during the third trimester of pregnancy, at delivery and post-delivery. The HCV-RNA+ve mothers were categorized as either Type-A (66%), with an increase in ALT levels in the post-partum period (>40 U/L; P<0.001) or as Type-B (34%), with no variation in ALT values. The Type-A mothers also presented a significant decrease in serum HCV-RNA levels in the post-delivery period (P<0.001) and this event was concomitant with an increase in Th1 cytokine levels (INFγ, P = 0.04; IL12, P = 0.01 and IL2, P = 0.01). On the other hand, the Type-B mothers and the HCV-RNA-ve women presented no variations in either of these parameters. However, they did present higher Th1 cytokine levels in the partum period (INFγ and IL2, P<0.05) than both the Type-A and the HCV-RNA-ve women. Cytokine levels at the moment of delivery do not constitute a risk factor associated with HCV vertical transmission. It is concluded that differences in the ALT and HCV-RNA values observed in HCV-RNA+ve women in the postpartum period might be due to different ratios of Th1 cytokine production. In the Type-B women, the high partum levels of Th1 cytokines and the absence of post-partum variation in ALT and HCV-RNA levels may be related to permanent Th1 cytokine stimulation.

Relevant gender differences in epidemiological profile, exposure to first antiretroviral regimen and survival in the Spanish AIDS Research Network Cohort.

BACKGROUND The possible differences in the disease spectrum and prognosis of HIV infection in women and men is a major point of concern. Women are under-represented in randomized clinical trials and in some cohorts. Discordant results have often been obtained depending on the setting. METHODS We assessed gender differences in clinical and epidemiological features, antiretroviral treatment (ART) exposure and survival in two multicentre cohorts of HIV-positive subjects in Spain: CoRIS-MD and CoRIS. Competing risk regression models were used to assess gender effect on time to start ART and time to first ART change, and a Cox regression model to estimate gender effect on time to death. RESULTS Between January 1996 and December 2008, 1,953 women and 6,072 men naive to ART at study entry were included. The trend analysis over time showed the percentage of women in the younger (<20 years) and older (>50 years) strata increased significantly (P<0.001) from 0.5% and 1.8% in 1996 to 4.9% and 4.2% in 2008, respectively. By competing risk analysis women started ART earlier than men (adjusted subhazard ratio [ASHR] 1.21, 95% CI 1.11, 1.31) in CoRIS cohort, while in CoRIS-MD none of these differences were observed. In both cohorts women showed a shorter time to the first ART change (ASHR 1.10, 95% CI 1.01, 1.19). Pregnancy and patient's/physician's decisions as reasons for changing were more frequent in women than in men in CoRIS. In the Cox regression model, gender was not associated with differences in survival. CONCLUSIONS In two large cohorts in Spain, we observed relevant gender differences in epidemiological characteristics and antiretroviral exposure outcomes, while survival differences were not attributable to gender.

Freedom Trial First-Year Extension: Results from 4 Years of Denosumab Exposure in Women with Postmenopausal Osteoporosis

Aims: To investigate the long-term efficacy and safety of denosumab (DMAb) for the treatment of postmenopausal women with osteoporosis in an open-label extension to the 3-year FREEDOM study.1Methods: All women who completed the FREEDOM study were eligible to enter a long-term open-label extension (up to 10 years). After providing informed consent, participants received 6-monthly subcutaneous injections of DMAb (60 mg). Here we report data from the first year of followup. For women randomized to DMAb in the FREEDOM study ('long-term group'), this represents up to 48 months of DMAb exposure (eight 6-monthly injections). For those randomized to placebo ('de novo group') the data are from up to 12 months of exposure (two injections). All participants continued to take calcium (1 g) and vitamin D (≥400 IU) supplements daily. Changes in bone mineral density (BMD) and bone turnover markers (BTM) are reported for subjects enrolled in the extension. No formal statistical testing was planned for this interim report. P-values are descriptive.Results: Overall, 4,550 eligible women (70.2%) who completed the FREEDOM study entered the open-label extension study (long-term, n=2,343; de novo, n=2,207). During the first year of the extension, lumbar spine (LS) BMD in the long-term group further increased by 2.0% (12.1% increase vs. FREEDOM baseline at 48 months), and total hip (TH) BMD further increased by 0.8% (6.5% increase at 48 months) (p<0.0001 for both BMD gains during year 4; Fig. 1). During the first year of the extension, LS and TH BMD increased by 5.4% and 3.0%, respectively in the de novo group (both p<0.0001). After DMAb initiation, serum C-telopeptide (CTX) in the de novo group decreased rapidly and similarly to the long-term group (Fig. 2). Reductions in BTMs continue to attenuate at the end of the dosing interval as previously reported. Adverse event (AE) rates were similar (70.4% of women in the longterm group and 67.9% in the de novo group). Serious Aes were also similar (9.8% and 11.2% of women, respectively). During year 4, osteoporotic nonvertebral fractures were reported in 31 women in the long-term group and 51 in the denovo group.Fig. 1. Percentage change in BMD with denosumab for4 years (long-term) or 1 year (de novo)Fig. 2. Percentage change in sCTX over timeConclusions: These interim results suggest that continuation of DMAb treatment through 48 months is associated with further significant increases in spine and hip BMD with sustained reduction of bone turnover. The de-novo treatment group results confirm the first year active treatment findings previously reported1.Acknowledgements: Amgen Inc. sponsored this study. Figure ©2010, American Society for Bone and Mineral Research, used by permission, all rights reserved. Disclosure of Interest: H. Bone Grant/Research Support from: Amgen, Eli Lilly, Merck, Nordic Bioscience, Novartis, Takeda Pharmaceuticals, Consultant/Speaker's bureau/ Advisory activities with: Amgen, Merck, Takeda Pharmaceuticals, Zelos, S. Papapoulos Consultant/Speaker's bureau/ Advisory activities with: Amgen, Merck, Novartis, Lilly, Procter and Gamble, GSK, M.-L. Brandi Grant/Research Support from: MSD, GSK, Nycomed, NPS, Amgen, J. Brown Grant/Research Support from: Abbott, Amgen, Bristol Myers Squibb, Eli Lilly, Pfizer, Roche, Consultant/ Speaker's bureau/Advisory activities with: Abbott, Amgen, Eli Lilly, Novartis, Merck, Warner Chilcott,, R. Chapurlat Grant/Research Support from: Servier, Sanofi-Aventis, Warner-Chilcott, Novartis, Merck, Consultant/Speaker's bureau/Advisory activities with: Servier, Novartis, Amgen, E. Czerwinski: None Declared, N. Daizadeh Employee of: Amgen Inc., Stock ownership or royalties of: Amgen Inc., A. Grauer Employee of: Amgen Inc., Stock ownership or royalties of: Amgen Inc., C. Haller Employee of: Amgen Inc., Stock ownership or royalties of: Amgen Inc., M.-A. Krieg: None Declared, C. Libanati Employee of: Amgen Inc., Stock ownership or royalties of: Amgen Inc., Z. Man Grant/Research Support from: Amgen, D. Mellström: None Declared, S. Radominski Grant/Research Support from: Amgen, Pfizer, Roche, BMS, J.-Y. Reginster Grant/Research Support from: Bristol Myers Squibb, Merck Sharp & Dohme, Rottapharm, Teva, Lilly, Novartis, Roche, GlaxoSmithKline, Amgen, Servier, Consultant/Speaker's bureau/ Advisory activities with: Servier, Novartis, Negma, Lilly,Wyeth, Amgen, GlaxoSmithKline, Roche, Merckle, Nycomed, NPS, Theramex, UCB, Merck, Sharpe & Dohme, Rottapharm, IBSA, Genvrier, Teijin, Teva, Ebewee Pharma, Zodiac, Analis, Theramex, Novo-Nordisk, H. Resch: None Declared, J. A. Román Grant/Research Support from: Roche, Pharma, C. Roux Grant/Research Support from: Amgen, MSD, Novartis, Servier, Roche, Consultant/ Speaker's bureau/Advisory activities with: Amgen, MSD, Novartis, Servier, Roche, S. Cummings Grant/ Research Support from: Amgen, Lilly, Consultant/Speaker's bureau/Advisory activities with: Amgen, Lilly, Novartis, Merck