Better Outcomes For Women Research Articles

Sex differences in survival of cutaneous melanoma are age dependent

This study identified sex differences in clinical presentation and survival for primary cutaneous melanoma without clinical evidence of metastasis at diagnosis from 1976 to 2008 in southern Germany. Melanoma-specific survival curves and estimated survival probabilities were generated using the Kaplan-Meier method. Multivariate survival analyses were carried out using the Cox modeling. Male patients had significantly thicker and more frequently ulcerated tumors and a lower 10-year disease-specific survival (DSS) and recurrence-free survival probability compared with females among patients of 43 years old or younger (DSS: 86.1 vs. 93.2%, P<0.001) and 44-60 years old (DSS: 83.5 vs. 90.1%, P<0.001). The survival advantage of female patients in terms of 10-year DSS and 10-year recurrence-free survival was not observed after an age of 60 years (P=0.21 and 0.51, respectively). Sex was of prognostic importance for DSS and survival after recurrence [hazards ratio (HR): 1.3; 95% confidence interval (CI): 1.1-1.6; P=0.002 and HR: 1.2; 95% CI: 1.0-1.5; P=0.018, respectively]. Stratified by age groups, sex remained of prognostic importance for DSS only in patients of 43 years or younger, and 44-60 years old (HR: 1.5; 95% CI: 1.0-2.1; P=0.03 and HR: 1.4; 95% CI: 1.1-2.0; P=0.02, respectively). Sex is an independent prognostic factor in surviving melanoma. The sex difference in survival with a better outcome for women is confined to melanoma patients of 60 years and younger. In addition, in younger age groups, male patients present with prognostically unfavorable features of primary melanoma. A female survival advantage is also known for other solid tumors such as colon and lung cancer; however, age dependency has not been studied.

Listening to mental health workers' experiences: Factors influencing their work with women who disclose sexual assault

Women are overrepresented within mental health service-use statistics, and a disproportionate number of them have experienced sexual assault. While mental health workers are often the first point of contact between these women and the mental health system, within the research to date, women have often reported a negative experience of disclosing sexual assault to these workers. This article presents findings from an exploratory Australian study. The aim of the study was to explore factors that influenced how mental health Crisis Assessment and Treatment Service (CATS) workers respond to women who disclose sexual assault in crisis service settings. Fifteen CATS workers were surveyed and the predominantly qualitative data were then analysed using thematic analysis. This article presents two key findings: (i) the majority of participants had not experienced adequate sexual assault training, and seven of the 15 did not feel well equipped to respond to a disclosure of sexual assault; and (ii) they rarely consulted or referred women to specialist sexual assault services, despite recognizing the significant impact of sexual assault on mental health functioning. Recommendations are made for training and increased communication between mental health and sexual assault service systems to ensure better outcomes for women.

Risk of Death Due to Breast Cancer in Women Treated with Selective Serotonin Reuptake Inhibitor Antidepressants and Tamoxifen.

Abstract Background: Tamoxifen is widely prescribed to women with breast cancer, but is a prodrug converted by cytochrome P450 2D6 (CYP 2D6) to its active metabolite endoxifen. Selective serotonin re-uptake inhibitor antidepressants (SSRIs) are commonly co-prescribed with tamoxifen, but inhibit CYP 2D6 to varying degrees and may decrease the effectiveness of tamoxifen.Materials and methods: We conducted a population-based retrospective cohort study of women in Ontario, Canada aged 66 years of age or older who were treated with tamoxifen for breast cancer between 1993 and 2005 and had overlapping SSRI therapy. Following completion of tamoxifen therapy, we modeled the risk of death from breast cancer as a function of the proportion of time on tamoxifen during which each SSRI had been co-prescribed.Results: We identified 24,430 women aged 66 years and older who started tamoxifen therapy during the 13 year study period. Of these, 7489 (30.6%) received at least one antidepressant during tamoxifen therapy. After excluding those treated with no SSRI or with multiple SSRIs, those with poor adherence to tamoxifen therapy, and those with unknown cause of death, the primary analysis included 2430 women. Paroxetine was the most commonly prescribed SSRI (n=630; 25.9%) followed by sertraline (n=541; 22.3%), citalopram (n=467; 19.2%), venlafaxine (n=365; 15.0%) fluoxetine (n=253; 10.4%) and fluvoxamine (n=174; 7.2%). A total of 1074 (44.2%) women died during follow-up and there were 374 (34.8%) breast cancer deaths. After adjustment for age, duration of tamoxifen therapy, and other potential confounders absolute increases of 25%, 50%, and 75% in the percentage of time co-prescribed paroxetine during tamoxifen therapy were associated with 24%, 54% and 91% increases in the risk of death from breast cancer respectively (p&amp;lt;0.05 for each comparison). In contrast, we found no such risk with fluoxetine, sertraline, fluvoxamine or citalopram. We observed a nonsignificant trend toward reduced breast cancer mortality among venlafaxine users, which may reflect the common practice of using venlafaxine for tamoxifen-related hot flashes, a putative predictor of better outcomes in women receiving tamoxifen. We replicated our analyses using death from any cause as the outcome of interest (n=1074). After adjusting for potential confounders, we found that absolute increases of 25%, 50% and 75% in paroxetine exposure during tamoxifen therapy were associated with relative increases of 13%, 28% and 46%, respectively, in the risk of death from any cause. In contrast, we found no such increased risk in all-cause mortality associated with exposure to the other SSRIs in women receiving tamoxifen for breast cancer.Discussion: Paroxetine use during tamoxifen therapy is associated with an increased risk of death due to breast cancer. This supports the hypothesis that paroxetine-mediated CYP 2D6 inhibition can reduce or abolish the beneficial effects of tamoxifen. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 2049.

Women's Mental Health

Abstract Women often have different outcomes and experiences with mental illness compared to men. However, there is still a ‘gender-blind’ approach to the understanding and development of new treatments for mental illness. The emphasis is on women and schizophrenia, depression in women and existing sex differences in anxiety disorders (including phobias, agoraphobia, panic disorder, generalized anxiety disorder and post-traumatic stress disorder). Utilizing gender differences in the onset, course and outcomes of mental illness may enable a better development of best outcomes for women with mental illness.

The CORONIS Trial. International study of caesarean section surgical techniques: a randomised fractional, factorial trial

BackgroundCaesarean section is one of the most commonly performed operations on women throughout the world. Rates have increased in recent years – about 20–25% in many developed countries. Rates in other parts of the world vary widely.A variety of surgical techniques for all elements of the caesarean section operation are in use. Many have not yet been rigorously evaluated in randomised controlled trials, and it is not known whether any are associated with better outcomes for women and babies. Because huge numbers of women undergo caesarean section, even small differences in post-operative morbidity rates between techniques could translate into improved health for substantial numbers of women, and significant cost savings.DesignCORONIS is a multicentre, fractional, factorial randomised controlled trial and will be conducted in centres in Argentina, Ghana, India, Kenya, Pakistan and Sudan.Women are eligible if they are undergoing their first or second caesarean section through a transverse abdominal incision.Five comparisons will be carried out in one trial, using a 2 × 2 × 2 × 2 × 2 fractional factorial design. This design has rarely been used, but is appropriate for the evaluation of several procedures which will be used together in clinical practice. The interventions are:• Blunt versus sharp abdominal entry• Exteriorisation of the uterus for repair versus intra-abdominal repair• Single versus double layer closure of the uterus• Closure versus non-closure of the peritoneum (pelvic and parietal)• Chromic catgut versus Polyglactin-910 for uterine repairThe primary outcome is death or maternal infectious morbidity (one or more of the following: antibiotic use for maternal febrile morbidity during postnatal hospital stay, antibiotic use for endometritis, wound infection or peritonitis) or further operative procedures; or blood transfusion.The sample size required is 15,000 women in total; at least 7,586 women in each comparison.DiscussionImprovements in health from optimising caesarean section techniques are likely to be more significant in developing countries, because the rates of postoperative morbidity in these countries tend to be higher. More women could therefore benefit from improvements in techniques.Trial registrationThe CORONIS Trial is registered in the Current Controlled Trials registry. ISCRTN31089967.

Gender Differences: Implications for Clinical Trials and Practice

Gender Differences: Implications for Clinical Trials and Practice

Why Adjuvant Trastuzumab Led to Better Outcomes in Women with High-Risk HER-2-Positive Breast Cancer

Why Adjuvant Trastuzumab Led to Better Outcomes in Women with High-Risk HER-2-Positive Breast Cancer

Women's mental health: an overview

Women often have different outcomes and experiences with mental illness compared to men. However, there is still a ‘gender-blind’ approach to the understanding and development of new treatments for mental illness. The emphasis is on: women and schizophrenia, depression in women and existing sex differences in anxiety disorders (including phobias, agoraphobia, panic disorder, generalised anxiety disorder and post-traumatic stress disorder). Utilizing gender differences in the onset, course and outcomes of mental illness may enable a better development of best outcomes for women with mental illness.

SWOG/Intergroup 9623: A phase III comparison of intensive sequential chemotherapy to high dose chemotherapy and autologous hematopoietic progenitor cell support (AHPCS) for primary breast cancer in women with ≥4 involved axillary lymph nodes

572 Background: This randomized trial compared intensive sequential chemotherapy using doxorubicin (ADR), paclitaxel (TAX), and cyclophosphamide (CTX) (Arm 1) versus induction chemotherapy with ADR + CTX followed by high dose chemotherapy and AHPCS (transplant) (Arm 2) with respect to disease-free survival (DFS), overall survival (OS), and toxicity. Methods: Patients with resected primary breast cancer with ≥ 4+ nodes were eligible. Arm 1 received 3 doses each of ADR (80 mg/m2), TAX (200 mg/m2), and CTX (3g/m2) given sequentially at 14-day intervals with filgrastim support. Arm 2 received induction ADR (80 mg/m2) + CTX (600 mg/m2) for 4 cycles at q3 week intervals followed by high dose chemotherapy (STAMP I or V) with AHPCS. The primary study outcome was DFS. The planned sample size was 1000 patients, sufficient for a 1-sided 0.025 level test to have 90% power to detect an Arm 1/Arm 2 hazard ratio (HR) of 1.45. Two interim analyses for both positive and negative results were planned at level 0.005. Log-rank and Cox models were used for DFS and OS analysis. Results: 539 eligible patients were enrolled between 7/96–2/01, when accrual was stopped due to poor recruitment. At the second interim analysis in 10/03 the estimated HR was significantly below 1.45 (p=0.001). The decision to report the current result was made. In the analysis of DFS there were 58 and 67 failures in the 271 and 265 patients on Arms 1 and 2, respectively. For OS, there were 36 and 43 deaths in Arms 1 and 2, respectively. The 99% CI for the HR is 0.53–1.32 for DFS and 0.46–1.48 for OS. 4 patients died due to treatment-related toxicity; 1 in Arm 1 and 3 in Arm 2. 59% of patients in Arm 1 experienced grade 4 hematologic toxicity; grade 4 non-hematologic toxicities were rare. In Arm 2, grade 4 hematologic toxicity was 92% during transplant; grade 4 non-hematologic toxicity was 10%. Discussion: Transplantation did not show superior DFS or OS compared to intensive sequential chemotherapy and actually had poorer outcomes. There is no evidence that adjuvant high dose chemotherapy with AHPCS provides better outcomes for women with ≥4 positive nodes. No significant financial relationships to disclose.

Gender as a Prognostic Factor in CLL. Biological Pointers to the Improved Outcome of Women.

Gender is not widely regarded as a prognostic indicator in CLL. However, the combined data from three MRC randomised trials, CLL1, 2 and 3, and two observational studies for patients with Binet stage A, CLL2A and 3A, over a period of 20 years (1978-1998) totalling 2370 patients, showed a significant survival advantage for women (2p<0.0001). Cox regression analysis of the three randomised trials showed that gender, age, stage and response to therapy were independent prognostic variables. The response to treatment for women was also better than for men receiving the same therapies. The LRF CLL4 randomised trial, which started in 1999 shows the same trend. Preliminary results in 444 patients Binet stages A progressive, B and C showed the same CR/Nod.PR for both sexes (43.5%) but a higher PR rate in women (45%) vs men (36.5%) and a lower proportion of women non-responders to first line therapy (11.5% vs 20%). A number of laboratory investigations in CLL4, which included FISH analysis with five probes, VH mutational status, CD38 and ZAP-70 expression by flow cytometry, showed differences between the sexes, which were significant for 17p and 11q deletions combined and CD38, always in favour of women, as shown in Tables 1 and 2.The clinical and laboratory results suggest that CLL is biologically more benign in women. Women have a lower incidence of CLL, an overall higher incidence of stage A (41.7%) than men (27.3%) in CLL 1, 2, 2A, 3 and 3A and respond better to treatment in all the trials. These differences may be underlined by a higher proportion of 13q del as sole abnormality, a lower proportion of 17p (p53 locus) and 11q deletions and lower levels of CD38. Data on VH mutations and ZAP-70 point in the same direction but the number of cases studied is still small. An additional factor that may play a role in the better outcome for women relates to the effect of oestrogen derivatives which are known to target selectively superoxide dismutase and induce cell kill (Huang et al, Nature 407, 390, 2000).Table 1: FISH analysis by gender (Dohner hierarchical model)Abnormality17p del11q delTrisomy 1213q delOthersMen (286)12%19%10%34%25%Women (94)7%13%11%44%25%p value**0.052* = Combined p value < 0.05 (Chi-Square test)Table 2: Other biological markersCD38 negative (<30%)VH mutatedZAP-70 negativeMen173/335 (52% )51/149 (34%)94/192 (49%)Women68/100 (68%)23/52 (44%)42/68 (62 %)p value<0.005NS0.07

Women's Ischemic Syndrome Evaluation: current status and future research directions: report of the National Heart, Lung and Blood Institute workshop: October 2-4, 2002: Section 6: key messages about acute ischemic heart disease in women and recommendations for practice.

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The prognostic impact of karyotypic subgroups in myelodysplastic syndromes is strongly modified by sex.

The prognostic impact of karyotypic patterns in a consecutive series of 389 adult myelodysplastic syndromes (MDS) was investigated. Time period did not significantly influence the survival times. In the analyses, the MDS cases were subdivided into the cytogenetic subgroups used in the International Prognostic Scoring System, i.e. favourable [-Y, del(5q) or del(20q) as single aberrations or normal karyotype, n = 241], poor [-7, del(7q), der(1;7) or complex karyotypes, i.e. > or = three abnormalities, n = 89] and intermediate (other aberrations, n = 59). The survival times correlated well with the prognostic subgroups, confirming that the cytogenetic classification was valid. Expressed as hazard ratios (HRs), with the favourable subgroup as the reference, the intermediate and poor subgroup HRs increased to 1.5 (95% confidence interval, 1.1-2.1) and 3.2 (2.4-4.1) respectively. Sex, age, morphological subtype and smoking habits significantly modified this prognostic impact. Shorter survival was detected for men in the favourable and the intermediate subgroups, but not in the poor prognosis subgroup. Using women in the favourable subgroup as the reference and adjusting for age, the HR for men was 1.6 (1.2-2.1) in the favourable subgroup. Adjusting for smoking habits as well decreased the HR to 1.4 (1.1-2.0) and, when also excluding cases with del(5q) as the sole anomaly, no significant difference could be discerned [HR 1.2 (0.9-1.6], suggesting that the better outcome for women in the favourable subgroup was mainly as a result of the '5q-syndrome' and to smoking habits. In the intermediate subgroup, the corresponding HRs were 3.0 (1.5-6.0) when adjusted for age and 2.7 (1.3-5.5) when also adjusted for smoking habits. Different survival times between men and women have never previously been reported for this MDS group. Although it remains to be elucidated whether environmental and/or constitutional factors cause the observed sex-related difference, these observations have obvious clinical ramifications, not least in designing and evaluating therapy protocols.

Erosion of the rights of pregnant women: In the interest of fetal well-being

T he current interest in fetal well-being has been generated by the hope that the striking advances made in the health care of women during childbearing could be followed by similar improvements in the health of their fetuses. From the end of World War II, maternal mortality has declined dramatically in the United States and other developed countries because of medical progress in controlling the major causes of illness and death in pregnant women, ie, blood loss, infection, and toxemia of pregnancy. Antibiotics, modern blood banking, surgical technology, and improved living conditions made these improvements in outcome possible. The better outcomes for women naturally improved the lot of their fetuses, but there have remained many fetal conditions that were not affected by this indirect approach via improvements in maternal health. With the pregnant woman's health and safety largely secure, medical attention has been more intensively focused on trying to improve the outlook for the fetus directly by making fetal evaluation and, at times, therapy a part of obstetrical care. In addition, it was hoped to improve fetal outcome by reducing unhealthy habits and lifestyles of pregnant women, such as smoking and alcohol consumption, which have an adverse effect on fetal health. Advances in prenatal diagnosis, surveillance, and treatment in the last 25 years have made it possible to consider approaches to fetal problems in utero. Ultrasound, amniocentesis, and fetal surgery have allowed access to the fetus while it is still in the womb. This access to the fetus, however, has been at the expense of invasive procedures through the pregnant woman who must consent for the procedures not only for her unborn child but for herself as well. It was also discovered that common practices of everyday life could have a devastating impact on pregnancy and the fetus. Thus smoking during pregnancy was noted to cause prematurity and low birth weight. Alcohol consumption has resulted in infants with physical and mental problems, appropriately labeled fetal alcohol syndrome. Street drugs have more recently © 1990 by The Jacobs Institute of Women's Health 1049-3867/90/53.50