Events In Women Research Articles

Sex-Related Differences in Metastatic Melanoma Patients Treated with Immune Checkpoint Inhibition.

Simple SummaryImmune checkpoint inhibitors, ICI, have revolutionized the treatment of advanced melanoma. However, given the small number of patients responding to immunotherapy and the high risk for immune-related adverse events, there has been a rising interest in recent publications to identify factors that influence response to immunotherapies, including sex. We aimed at investigating sex-related differences in patients with advanced melanoma treated with ICI by linking the assessment of inflammatory response in peripheral blood, onset of IRAEs during therapy and treatment response in short- and long-term. Men with advanced melanoma showed a significantly better response to immunotherapy in short- and long-term than women. Higher immune activation in peripheral blood before and after initiation ICI might be linked to favorable treatment response during and after ICI in favor of men and decoupled from the onset of IRAEs. Given the significantly higher immunotoxicity and worse outcome experienced by women compared to men the use of ICI should be chosen carefully in women with advanced melanoma.Objectives: We aimed to investigate sex-related differences in patients with advanced melanoma treated with ICI by linking the assessment of inflammatory response in peripheral blood, onset of immune-related adverse events IRAEs during therapy and treatment response in short- and long-term. Methods: For the purpose of this single-center retrospective study metastatic melanoma patients treated with ICI were included. Baseline patient characteristics, blood sample tests and the onset of immune-related adverse events IRAEs were documented based on clinical records. The short-term treatment response was assessed with 18F-2-Fluor-2-desoxy-D-glucose Positron Emission Tomography/Computed Tomography FDG-PET/CT scans performed six months after initiation of ICI. The overall survival OS and progression-free survival PFS were used as endpoints to assess the long-term response to immunotherapy. Results: In total, 103 patients with advanced melanoma (mean age 68 ± 13.83 years) were included, 29 women (mean age 60.41 ± 14.57 years) and 74 men (mean age 65.66 ± 13.34 years). The primary tumor was located on a lower extremity in one out of three women and on the head/neck in one out of three men (p < 0.001). While the superficial spreading (41%) and nodular (36%) melanoma subtypes represented together 77% of the cases in male population, women showed a more heterogenous distribution of melanoma subtypes with the superficial spreading (35%), nodular (23%), acral lentiginous (19%) and mucosal (12%) melanoma subtypes being most frequent in female population (p < 0.001). Most differences between women and men with regards to inflammatory parameters were observed six months after initiation of ICI with a higher median NLR (p = 0.038), lower counts of lymphocytes (p = 0.004) and thrombocytes (p = 0.089) in addition to lower counts of erythrocytes (p < 0.001) and monocytes (p < 0.001) in women towards men. IRAEs were more frequent in women towards men (p = 0.013). Women were more likely to display endocrinological IRAEs, such as thyroiditis being the most frequent adverse event in women. Interestingly IRAEs of the gastrointestinal tract were the most frequent ones in men. Finally, men with advanced melanoma showed a significantly better response to immunotherapy in short- (p = 0.015) and long-term (OS p = 0.015 and PFS p < 0.001) than women. In fact, every fourth man died during the course of the disease, while every second woman did not survive. (p = 0.001). Conclusion: Men with advanced melanoma showed a significantly better response to immunotherapy in short- and long-term than women. Higher immune activation in peripheral blood before and after initiation ICI might be linked to favorable treatment response during and after ICI in favor of men and decoupled from the onset of IRAEs. Given the significantly higher immunotoxicity and worse outcome experienced by women compared to men the use of ICI should be chosen carefully in women with advanced melanoma.

Mortality and major adverse cardiac events in women with breast cancer receiving radiotherapy: a 10-year cohort study of patients and population controls

Abstract Background Treatment for breast cancer (BC) frequently involves radiotherapy. Guidelines recommend screening for cardiac adverse events starting 10 years after radiotherapy. The rationale for recommending this interval is unclear and informed the objective of this study. Objectives Study cardiovascular event rates in the first decade following curative radiotherapy for breast cancer, the time frame before guidelines recommend screening. Methods We performed a monocentric, retrospective study enrolling all women with unilateral BC in 2007–2008, who received radiotherapy as part of their curative treatment. We compared event rates during 10 years follow-up with an age and risk factor-matched control population (FLEMENGHO population). Results We included 1095 BC patients (median age 55y, IQR: 47–66y). Two hundred and eighteen (19.9%) women died. Cancer and cardiovascular mortality accounted for 107 (49.1%) and 22 (10.1%) deaths, respectively. The incidence of coronary artery disease was similar compared to age and risk-matched women [risk ratio 0.75 (95% CI 0.48–1.18)], yet heart failure (HF) [risk ratio 1.97 (95% CI 1.19–3.25)] and atrial fibrillation or flutter (AF) (risk ratio 1.82 (95% CI 1.07–3.08) occurred more often. Age [HR 1.040 (95% CI 1.012–1.069)], tumor grade [HR 1.646 (95% CI 1.103–2.458)], and neo-adjuvant treatment setting [HR 3.079 (95% CI 1.432–6.620)] were risk factors for mortality; hormonal therapy [HR 0.007 (95% CI 0.001–0.042)] proved protective. Risk factors for MACE were mean heart dose [HR 1.079 (95% CI 1.012–1.151], hormonal therapy, history of cardiovascular disease [HR 2.771 (95% CI 1.253–6.126)], and Mayo Clinic Cardiotoxicity Risk Score [HR 2.547 (95% CI 1.538–4.217)]. While mean heart dose [HR 1.141 (95% CI 1.017–1.282)] and cardiovascular history [HR 3.374 (95% CI 1.259–9.043] clearly associated with new onset HF, only a trend towards higher AF burden with increasing mean heart dose could be observed. Conclusions Ten-year mortality following curative treatment for unilateral BC was mainly cancer-related. HF and AF constituted significantly increased risks in the first decade following irradiation. Mean heart dose, pre-existing cardiovascular diseases, and Mayo Clinic Cardiotoxicity Risk Score were risk factors for early cardiac mortality and adverse events and should guide early dedicated cardio-oncological follow-up. Funding Acknowledgement Type of funding sources: None.

Bone Mineral Density as a Predictor of Cardiovascular Disease in Women: A Real-World Retrospective Study

Background: Atherosclerotic cardiovascular disease (ASCVD) in women remains understudied, under-diagnosed, and under-treated. Traditional risk factors affect men’s and women’s hearts differently. However, the current risk stratification tools do not consider such sex-specific factors. We aimed to investigate the utility of bone mineral density (BMD) with dual-energy X-ray absorptiometry (DXA) scoring as a predictor of ASCVD in women. Methods: Data of 1,995 patients who underwent DXA scanning from 2012 to 2014 at multiple centers within our health system were collected through a chart review and using the SlicerDicer tool of Epic electronic medical records (EMR) to identify comorbidities and outcomes. Age, sex, race, history of hypertension (HTN), hyperlipidemia (HLD), diabetes mellitus (DM), body mass index (BMI), and smoking status were noted. The primary outcome was the composite of ASCVD events (stroke, myocardial infarction (MI) and cardiac death). Osteoporosis was defined as a T score of &lt; -2.5, and osteopenia was defined as a combined T score between -1.5 to -2.5 in either hip, one of the femurs or combined. Results: Of the 1,995 female participants who underwent DXA scanning, 245 patients (10.8%) experienced ASCVD events during the mean follow-up of 9 years. After adjusting covariables, women with osteoporosis and combined low BMD have higher odds of the composite ASCVD events compared to normal BMD (odds ratio (OR) 4.60 (2.783 - 7.867), P &lt; 0.0001). Low BMD in each site, the right femur, left femur, and hip is associated with an increased risk of ASCVD events (OR 6.50 (3.637 - 11.608), P &lt; 0.0001; OR 5.07 (3.166 - 8.108), P &lt; 0.000; OR 3.36 (2.127 - 5.312), P &lt; 0.0001, respectively). Osteoporosis is independently linked to a 4.25-fold rise in MI incidence and a 3.64-fold rise in stroke. Osteopenia was not associated with ASCVD events (OR 1.29 (0.754 - 2.204), P = 0.35416). Conclusions: BMD measurement with DXA scan could stratify and predict the risk of ASCVD events in women, with no additional economic strain on healthcare. Further wide-scale studies are needed to utilize this potentially promising predictor and a commonly used test. J Endocrinol Metab. 2022;12(4-5):125-133 doi: https://doi.org/10.14740/jem840

A Study to Identify the Age of Menopause and Its Relation to Socio-Economic Determinants and to Assess the Knowledge and Attitude About the Health Effects of Menopause

Abstract: Menopause is the most prominent event in women’s middle age and marks the end of a women’s reproductive life. Symptoms of menopause are the basis of health care providers and public health professionals to provide adequate medical care, including improving the physiological and psychological state of women. The main objective of the study was to determine age at menopause along with its health consequences and socio-economic determinants affecting the quality of life. A total of 70 women were enrolled in the study. Information was collected from 40-55 years old womens to estimate the age of menopause along with socio-economic determinants and health effects of menopause. Questionnaire was created consisting of socio demographic data, prevalence of menopausal symptoms, knowledge and attitude towards menopaus for data collection. From the study, we found the average age of menopause was 48.5 years, which is higher than other studies conducted in India, reason may be methodological. Psycho-physiological changes were associated with irritability, heart discomfort, anxiety, depressive mood, hot flashes, physical and mental exhaustion, sleep problems. There must be well planned, balanced health education and necessary treatment arrange for the welfare of perimenopause women for better quality of life. The obtained results were analyzed and discussed in detail

Association of obstructive sleep apnoea with cardiovascular events in women and men with acute coronary syndrome.

The impact of sex on the association of obstructive sleep apnoea (OSA) with recurrent cardiovascular events following acute coronary syndrome (ACS) remains uncertain. This study sought to examine the association between OSA and long-term cardiovascular outcomes in women and men with ACS. In this prospective cohort study, we recruited 2160 ACS patients undergoing portable sleep monitoring between June 2015 and January 2020. The primary end-point was major adverse cardiovascular and cerebrovascular event (MACCE), including cardiovascular death, myocardial infarction, stroke, ischaemia-driven revascularisation or hospitalisation for unstable angina or heart failure. After exclusion of patients with failed sleep studies, central sleep apnoea, regular continuous positive airway pressure therapy and loss of follow-up, 1927 patients were enrolled. Among them, 298 (15.5%) were women and 1014 (52.6%) had OSA (apnoea-hypopnoea index ≥15 events·h-1). The prevalence of OSA was 43.0% and 54.4% in women and men, respectively. In 4339 person-years (median 2.9 years, interquartile range 1.5-3.6 years), the cumulative incidence of MACCE was significantly higher in OSA versus non-OSA groups in the overall population (22.4% versus 17.7%; adjusted hazard ratio (HR) 1.29, 95% CI 1.04-1.59; p=0.018). OSA was associated with greater risk of MACCE in women (28.1% versus 18.8%; adjusted HR 1.68, 95% CI 1.02-2.78; p=0.042), but not in men (21.6% versus 17.5%; adjusted HR 1.22, 95% CI 0.96-1.54; p=0.10). No significant interaction was noted between sex and OSA for MACCE (interaction p=0.32). The incremental risk in women was attributable to higher rates of hospitalisation for unstable angina and ischaemia-driven revascularisation. In hospitalised ACS patients, OSA was associated with increased risk of subsequent events, particularly among women. Female patients with ACS should not be neglected for OSA screening and dedicated intervention studies focusing on women with ACS and comorbid OSA should be prioritised.

Cardiometabolic Risk Factors and Incident Cardiovascular Disease Events in Women vs Men With Type 1 Diabetes

The lower risk of cardiovascular disease (CVD) among women compared with men in the general population may be diminished among those with diabetes. To evaluate cardiometabolic risk factors and their management in association with CVD events in women vs men with type 1 diabetes enrolled in the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications (DCCT/EDIC) study. This cohort study used data obtained during the combined DCCT (randomized clinical trial, conducted 1983-1993) and EDIC (observational study, conducted 1994 to present) studies through April 30, 2018 (mean [SD] follow-up, 28.8 [5.8] years), at 27 clinical centers in the US and Canada. Data analyses were performed between July 2021 and April 2022. During the DCCT phase, patients were randomized to intensive vs conventional diabetes therapy. Cardiometabolic risk factors and CVD events were assessed via detailed medical history and focused physical examinations. Blood and urine samples were assayed centrally. CVD events were adjudicated by a review committee. Linear mixed models and Cox proportional hazards models evaluated sex differences in cardiometabolic risk factors and CVD risk over follow-up. A total of 1441 participants with type 1 diabetes (mean [SD] age at DCCT baseline, 26.8 [7.1] years; 761 [52.8%] men; 1390 [96.5%] non-Hispanic White) were included. Over the duration of the study, compared with men, women had significantly lower body mass index (BMI, calculated as weight in kilograms divided by height in meters squared; β = -0.43 [SE, 0.16]; P = .006), waist circumference (β = -10.56 cm [SE, 0.52 cm]; P < .001), blood pressure (systolic: β = -5.77 mm Hg [SE, 0.35 mm Hg]; P < .001; diastolic: β = -3.23 mm Hg [SE, 0.26 mm Hg]; P < .001), and triglyceride levels (β = -10.10 mg/dL [SE, 1.98 mg/dL]; P < .001); higher HDL cholesterol levels (β = 9.36 mg/dL [SE, 0.57 mg/dL]; P < .001); and similar LDL cholesterol levels (β = -0.76 mg/dL [SE, 1.22 mg/dL]; P = .53). Women, compared with men, achieved recommended targets more frequently for blood pressure (ie, <130/80 mm Hg: 90.0% vs 77.4%; P < .001) and triglycerides (ie, <150 mg/dL: 97.3% vs 90.5%; P < .001). However, sex-specific HDL cholesterol targets (ie, ≥50 mg/dL for women, ≥40 mg/dL for men) were achieved less often (74.3% vs 86.6%; P < .001) and cardioprotective medications were used less frequently in women than men (ie, angiotensin-converting enzyme inhibitor or angiotensin II receptor blocker: 29.6% [95% CI, 25.7%-33.9%] vs 40.0% [95% CI, 36.1%-44.0%]; P = .001; lipid-lowering medication: 25.3% [95% CI, 22.1%-28.7%] vs 39.6% [95% CI, 36.1%-43.2%]; P < .001). Women also had significantly higher pulse rates (mean [SD], 75.2 [6.8] beats per minute vs 71.8 [6.9] beats per minute; P < .001) and hemoglobin A1c levels (mean [SD], 8.3% [1.0%] vs 8.1% [1.0%]; P = .01) and achieved targets for tighter glycemic control less often than men (ie, hemoglobin A1c <7%: 11.2% [95% CI, 9.3%-13.3%] vs 14.0% [95% CI, 12.0%-16.3%]; P = .03). These findings suggest that despite a more favorable cardiometabolic risk factor profile, women with type 1 diabetes did not have a significantly lower CVD event burden than men, suggesting a greater clinical impact of cardiometabolic risk factors in women vs men with diabetes. These findings call for conscientious optimization of the control of CVD risk factors in women with type 1 diabetes.

Risk of psychiatric events in women treated with isotretinoin: a self-controlled study with SIDIAP database

ABSTRACT Background Since isotretinoin marketing, reports of psychiatric events have been noted. Howeverto date, a relation between these events and acne or isotretinoin treatment has not been clearly established. Our objective was to analyze the incidence of psychiatric events in women receiving isotretinoin. Methods Self-controlled study including women treated with isotretinoin from July 2014 to December 2018. Data source was SIDIAP, a primary health care-based database from Catalonia, Spain. Risk of psychiatric events was analyzed during the isotretinoin exposure and during the previous and posterior periods of non-exposure. Results We included 4,738 women in the study, 25.3% of them had history psychiatric disorders prior to receiving isotretinoin. During the follow-up, 782 (16.5%) patients were diagnosed with new mental disorders and 925 (19.5%) received new psychotropic drug prescriptions. We found a trend to an increase of new events when the previous non-exposure and the isotretinoin exposure periods were compared, with no significant differences. Incident psychiatric events during isotretinoin exposure was significantly higher in those patients with previous psychiatric history. Conclusions We cannot conclude any causality between acne and isotretinoin and the appearance of new psychiatric events. However, we contribute to the evidence with a more robust methodological approach, which minimizes the effect of confounding variables.

Locoregional relapse after sparing mastectomies and immediate reconstruction in women with breast cancer

IntroductionIn recent years, cultural changes in today's society and improved risk assessment have increased the indication for mastectomies in women with breast cancer. Various studies have confirmed the oncological safety of sparing mastectomies and immediate reconstruction. The objective of this study is to analyze the incidence of locoregional relapses of this procedure and its impact on reconstruction and overall survival. Patients and methodsProspective study of patients with breast carcinoma who underwent a sparing mastectomy and immediate reconstruction. Locoregional relapses and their treatment and their impact on survival were analyzed. ResultsThe study group is made up of 271 women with breast carcinoma treated with a skin-sparing mastectomy and immediate reconstruction. The mean follow-up was 7.98 years and during the same 18 locoregional relapses (6.6%) were diagnosed: 72.2% in the mastectomy flap and 27.8% lymph node. There were no significant differences in the pathological characteristics of the primary tumor between patients with and without locoregional relapse, although the percentage of women with hormone-sensitive tumors was higher in the group without relapse. Patients with lymph node relapse had larger tumors (80% T2-T3) and 60% had axillary metastases at diagnosis, compared to 7.7% of women with skin relapse (p = 0.047). All patients operated on for locoregional relapse preserved their reconstruction. The incidence of metastases and deaths was significantly higher in patients with a relapse, causing a non-significant decrease in overall survival. ConclusionLocoregional relapses are a rare event in women with a sparing mastectomy and immediate reconstruction. Most patients with locoregional relapse can preserve their initial reconstruction through local resection of the tumor and adjuvant and / or neoadjuvant therapies.

Association between cognitive representation of illness and the outcome of patients with premature coronary artery disease

ObjectiveTo assess whether illness perception (IP) in overall and each of its three dimensions (cognitive, emotional and comprehension) have an independent prognostic value in men and women with premature coronary artery disease (CAD). MethodsIn a prospective cohort, 778 patients (370 men and 408 women) with premature CAD(diagnosed in men aged<45 y and women aged<55 y), who had completed brief illness perception questionnaire were followed up for 4 years. Outcome event was defined as composite of all-cause mortality, nonfatal myocardial infarction(MI), repeated revascularization or/and stroke. Analysis was performed for men and women separately. High scores for each item of illness perception indicate positive perception. ResultsAmong men, 90 patients (24.3%) experienced events: 14(3.8%) death, 23(6.2%) nonfatal MI, 9(2.4%) strokes, and 44(11.9%) revascularization. Men with and without event showed no difference regarding the traditional risk factors, depression and anxiety symptoms. Among women, 72(17.6%) had events: 11(2.7%) death, 23(5.6%) nonfatal MI, 7(1.7%) strokes and 31(7.6%) revascularization; who had a lower education, more severe CAD, and more depressive symptoms. After adjustments for potential confounders, overall IP and only its cognitive dimension were significantly associated with the outcome in women:1-score increase in the women's cognitive perception resulted in an 18% decrease in the event (HR = 0.82, 95% CI:0.72 to 0.95; P = 0.007). In the men, this effect remained nonsignificant either for IP or its dimensions. ConclusionsPositive cognitive representation of illness was predictive of a decreased likelihood of mortality and/or cardiovascular events in women with premature CAD. Interventional studies are needed to confirm the results.

Risk of Ocular Adverse Events With Taxane-Based Chemotherapy

Taxane-based chemotherapy agents, such as docetaxel and paclitaxel, are used for treating a wide range of cancers. Although much has been published on adverse events related to taxanes, data on ocular outcomes with these very important drugs are scant. To quantify the risk of 3 mutually exclusive ocular adverse events of epiphora, cystoid macular edema (CME), and optic neuropathy with taxane-based chemotherapy agents by undertaking a large pharmacoepidemiologic study. This retrospective cohort study design used a private health-claims database from the US that captures health information of more than 150 million enrollees. The study team created a cohort of new users of women with cancer who were taking taxane-based chemotherapy (docetaxel or paclitaxel) and new users of tamoxifen as controls. Study members were observed to the first incidence of each of the 3 mutually exclusive outcomes. An analysis of taxane-only users was also undertaken. Tamoxifen (unexposed) and taxanes (ie, paclitaxel and docetaxel) as the exposed. First diagnosis of (1) epiphora, (2) cystoid macular edema (CME), or (3) optic neuropathy ascertained using International Statistical Classification of Diseases and Related Health Problems, Ninth Revision or International Statistical Classification of Diseases and Related Health Problems, Tenth Revision. Among the 18 219 users in the epiphora analysis and optic neuropathy analysis, there were 1824 taxane users (paclitaxel and docetaxel) (age, mean [SD], 62.1 [12.7] years) and 16 395 tamoxifen users (age, mean [SD], 54.6 [12.8] years), respectively. The crude hazard ratio (HR) for epiphora was 5.55 (95% CI, 2.99-10.29) and adjusted HR was 5.15 (95% CI, 2.79-9.54). For optic neuropathy, the crude HR was 4.43 (95% CI, 1.10-17.82) and the adjusted HR was 4.44 (95% CI, 1.04-18.87). Among the 18 433 users in the CME analysis, there were 1909 taxane users (paclitaxel and docetaxel) (age, mean [SD], 62.5 years) and 16 524 tamoxifen users (age, mean [SD], 54.6 years). The crude HR for CME comparing taxane users with tamoxifen users was 1.37 (95% CI, 0.72-2.60) and adjusted HR was 1.33 (95% CI, 0.70-2.53). The HRs for epiphora and CME in the taxane cohort during the time of exposure compared with the period prior to use of the drugs were 2.86 (95% CI, 1.11-7.39) and 2.27 (95% CI, 0.68-7.54), respectively. In a cohort of women who were using taxane chemotherapy agents, there was an association with elevated risk for epiphora, CME, and optic neuropathy. Ophthalmologists and oncologists should be aware of these adverse events in women with breast cancer who receive these drugs.

Clinical relevance of ovarian vein thrombosis and the risk of secondary venous thromboembolic events in women with gynecologic cancers (473)

<b>Objectives:</b> Ovarian vein thrombosis (OVT) is increasingly being identified in women with gynecologic malignancies who undergo surgery. The diagnosis is usually incidental, and the clinical relevance is unclear. Although there is no consensus on the optimal management for OVT, treatments range from observation to anticoagulation. Furthermore, whether OVT places women at increased risk for secondary venous thromboembolism (VTE) events is unknown. This study aimed to identify the incidence of secondary VTE following the initial diagnosis of OVT and the factors that correlate with subsequent VTE. <b>Methods:</b> After IRB approval, a cross-sectional study was conducted among patients diagnosed with OVT from 2012-2020 in a universitybased hospital system. Cases of women with OVT and a cancer diagnosis were identified. The incidence of a secondary VTE and their clinical management with or without anticoagulation was reviewed. Descriptive statistics were performed among the groups to compare baseline characteristics and identify risk factors for secondary VTE. An analysis of cross-sectional imaging was performed to determine if there was an extension of the OVT into the inferior vena cava (IVC) or either renal vein and the length of the clot extension. Numeric variables were compared using the Mann-Whitney U test, and categorical variables were compared using Chi-square or Fischer's exact test. <b>Results:</b> A total of 116 women with OVT and cancer were included. The incidence of secondary VTE was 19% (22 patients). Women with active smoking status or a history of VTE prior to the OVT diagnosis were more likely to develop a secondary VTE (p=0.035 and p=0.021). Women with a history of hormonal contraception or hormone replacement therapy use were less likely to have secondary VTE (p=1). In patients who underwent salpingo-oophorectomy (SO) on the ipsilateral side in which OVT was subsequently diagnosed, the development of secondary VTE event was significantly lower than those OVT patients without prior ipsilateral SO (9.5% vs 30%, p=0.008). Radiographic measurement of OVT extension into the IVC or renal veins was done as both continuous and nominal variables did not confer an increased risk of secondary VTE. Interestingly, there was no difference in the development of secondary VTE in those who were started on anticoagulation in response to OVT diagnosis versus those who were observed (p=0.672). <b>Conclusions:</b> Guidelines for initiating treatment for OVT remain to be determined. Based on our data, women with gynecologic cancer with OVT who are active smokers or have a history of prior VTE are more likely to develop a secondary VTE event. Anticoagulation should be considered for these women. Based on this data, involvement of the IVC or renal vein did not correlate with secondary VTE events and should not be used as a basis for initiating anticoagulation. Patients with OVT diagnosed on the ipsilateral side of prior SO are less likely to develop a secondary VTE. This probably reflects the sequelae of surgery rather than an underlying propensity for thromboembolism.

Contributions of event rates, pre-hospital deaths, and deaths following hospitalisation to variations in myocardial infarction mortality in 326 districts in England: a spatial analysis of linked hospitalisation and mortality data

Myocardial infarction mortality varies substantially within high-income countries. There is limited guidance on what interventions-including primary and secondary prevention, or improvement of care pathways and quality-can reduce myocardial infarction mortality. Our aim was to understand the contributions of incidence (event rate), pre-hospital deaths, and hospital case fatality to the variations in myocardial infarction mortality within England. We used linked data from national databases on hospitalisations and deaths with acute myocardial infarction (ICD-10 codes I21 and I22) as a primary hospital diagnosis or underlying cause of death, from Jan 1, 2015, to Dec 31, 2018. We used geographical identifiers to estimate myocardial infarction event rate (number of events per 100 000 population), death rate (number of deaths per 100 000 population), total case fatality (proportion of events that resulted in death), pre-hospital fatality (proportion of events that resulted in pre-hospital death), and hospital case fatality (proportion of admissions due to myocardial infarction that resulted in death within 28 days of admission) for men and women aged 45 years and older across 326 districts in England. Data were analysed in a Bayesian spatial model that accounted for similarities and differences in spatial patterns of fatal and non-fatal myocardial infarction. Age-standardised rates were calculated by weighting age-specific rates by the corresponding national share of the appropriate denominator for each measure. From 2015 to 2018, national age-standardised death rates were 63 per 100 000 population in women and 126 per 100 000 in men, and event rates were 233 per 100 000 in women and 512 per 100 000 in men. After age-standardisation, 15·0% of events in women and 16·9% in men resulted in death before hospitalisation, and hospital case fatality was 10·8% in women and 10·6% in men. Across districts, the 99th-to-1st percentile ratio of age-standardised myocardial infarction death rates was 2·63 (95% credible interval 2·45-2·83) in women and 2·56 (2·37-2·76) in men, with death rates highest in parts of northern England. The main contributor to this variation was myocardial infarction event rate, with a 99th-to-1st percentile ratio of 2·55 (2·39-2·72) in women and 2·17 (2·08-2·27) in men across districts. Pre-hospital fatality was greater than hospital case fatality in every district. Pre-hospital fatality had a 99th-to-1st percentile ratio of 1·60 (1·50-1·70) in women and 1·75 (1·66-1·86) in men across districts, and made a greater contribution to variation in total case fatality than did hospital case fatality (99th-to-1st percentile ratio 1·39 [1·29-1·49] and 1·49 [1·39-1·60]). The contribution of case fatality to variation in deaths across districts was largest in women aged 55-64 and 65-74 years and in men aged 55-64, 65-74, and 75-84 years. Pre-hospital fatality was slightly higher in men than in women in most districts and age groups, whereas hospital case fatality was higher in women in virtually all districts at ages up to and including 65-74 years. Most of the variation in myocardial infarction mortality in England is due to variation in myocardial infarction event rate, with a smaller role for case fatality. Most variation in case fatality occurs before rather than after hospital admission. Reducing subnational variations in myocardial infarction mortality requires interventions that reduce event rate and pre-hospital deaths. Wellcome Trust, British Heart Foundation, Medical Research Council (UK Research and Innovation), and National Institute for Health Research (UK).

Association between hormone therapy and short-term cardiovascular events in women with spontaneous coronary artery dissection

Introduction and objectivesChanges in sex hormone levels are a known triggering factor for spontaneous coronary artery dissection (SCAD) in women. However, it is unknown whether exposure to exogenous hormone therapy (HT) at the time of SCAD presentation modifies the clinical course of this condition. We investigated the association between HT in female patients presenting with SCAD and short-term clinical outcomes. MethodsWe enrolled consecutive patients presenting with SCAD from the DISCO-IT/SPA (dissezioni spontanee coronariche Italian-Spanish) registry. Women on HT (estrogens, progestagens, or gonadotropins) at the time of presentation were identified, and their clinical characteristics and short-term outcomes were compared with those not receiving active HT. The outcome measure was nonfatal myocardial infarction and/or unplanned percutaneous coronary intervention during the first 28 days after the index catheterization. ResultsOf 224 women presenting with SCAD (mean age 52.0±10.0 years), 39 (17.4%) were currently using HT while 185 (82.6%) were not. No significant differences were noted in the baseline demographics, clinical presentation, angiographic features, or initial treatment received between the 2 groups. All patients on systemic HT (n=36, 92%) discontinued it at the time of diagnosis. The composite outcome occurred in 7 (17.9%) patients with prior HT compared with 14 (7.6%) without (P=.039). After multivariable adjustment, HT remained associated with the composite outcome recorded in the first 28 days of follow-up (HR, 3.53; 95%CI, 1.30-9.61; P=.013). ConclusionsIn women with SCAD, exposure to HT at the time of clinical presentation was associated with short-term recurrent cardiovascular events such as nonfatal myocardial infarction and/or unplanned percutaneous revascularization.

Caught on camera: a video assessment of suspected concussion and other injury events in women's rugby union

ObjectivesThe objective of this study was to identify and report the incidence and mechanisms of suspected injury and concussion in women's rugby union. DesignA cross-sectional video analysis study. MethodsUsing video analysis of non-professional, single-angle footage, cases of suspected injury and concussion were identified and reported, based on content validation and consensus by eight rugby-specific researchers, therapists, and sport medicine physicians. ResultsThere were 225 suspected injuries recorded in 48 games [Suspected injury rate (IR) = 117.5/1000 h (95 % CI;102.6–133.9) or 4.7 suspected injuries per match]. The on-field medical attention IR was 95.0/1000 h (95 % CI;81.7–109.9: 3.8 per game). Suspected concussions accounted for 26 % of injuries (30.8/1000 h: 95 % CI;23.5–39.7: 1.2 per game). The attacking team sustained 64 % of suspected injuries. Permanent removal from play was observed for 29 % of suspected injuries. The most common suspected injury locations were head/neck (28.4 %) and lower extremity (27.6 %). The tackle accounted for 67.1 % of all suspected injuries, with a propensity of 11.2/1000 tackle events (95 % CI;9.5–13.2) or 3.1 tackle-related injuries/game. Of tackle-related injuries, 63.6 % were to the ball carrier while 52.2 % of tackle-related concussions were to the ball carrier. ConclusionThis study adds to the growing body of literature examining women's rugby. The rate of suspected injury is high compared with other studies. It is acknowledged that these are suspected injuries not supported by prospective injury surveillance. The high proportion of suspected injuries that are tackle-related warrants specific attention to identify tackle characteristics associated with injury and concussion.

Sex-related differences in left ventricular remodeling and outcome after alcohol septal ablation in hypertrophic obstructive cardiomyopathy: insights from cardiovascular magnetic resonance imaging

BackgroundAlcohol septal ablation (ASA) has been proven to reverse left ventricular (LV) remodeling in hypertrophic cardiomyopathy (HCM). However, there are no studies on the effect of sex on LV remodeling after ASA. We aimed to investigate whether sex differences affect the process of LV remodeling and outcome after ASA.MethodsA total of 107 patients with obstructive HCM (54 men and 53 women, mean age 51 ± 8 years) were recruited. Cardiovascular magnetic resonance (CMR) was performed at baseline and 16 months after ASA. The extent of late gadolinium enhancement (LGE) was measured.ResultsWomen had a higher indexed LV mass and smaller indexed LV end-systolic volumes than men at the time of ASA. After ASA, both men and women exhibited a regression of LV mass, and the percentage of mass regression was greater in men than women (15.3% ± 4.3% vs. 10.7% ± 1.8%, p < 0.001). In multivariable analysis, male sex, higher reduction of LV outflow tract (LVOT) gradient and lower baseline LV mass index were independently associated with greater LV mass regression after ASA. Kaplan–Meier analysis showed significantly higher cardiovascular events in women than in men (p = 0.015). Female sex [hazard ratio (HR) 3.913, p = 0.038] and LV mass preablation (HR, 1.019, p = 0.010) were independent predictors of cardiovascular outcomes.ConclusionsMales with HCM had favorable reverse remodeling with greater LV mass regression post-ASA than female patients. This favorable LV reverse remodeling might provide a mechanistic explanation for the survival advantage in men.

Predictive ability of six obesity measures to identify 7-year fatal and non-fatal cardiovascular events: A population-based cohort study

BackgroundGlobally, most people die from cardiovascular diseases. We aimed to compare predictive ability of six obesity indices, including body mass index, waist circumference, waist-to-hip ratio, waist-to-height ratio, conicity index, and abdominal volume index, to identify people at risk of fatal and non-fatal cardiovascular events, in a cohort study. MethodsWe studied 5147 participants in a baseline population-based cohort study conducted in northern Iran. The obesity measures were calculated in enrollment phase (2009–2010), and the cardiovascular events were recorded during a 7-year follow-up phase (2010–2017). Receiver operating characteristic (ROC) analyses and Cox hazard regression models were applied, considering the obesity measures as predictors, and the 7-year cardiovascular events as outcomes. Multiple Cox models were adjusted by age, prior history of cardiovascular diseases, chronic kidney diseases, insulin resistance, diabetes mellitus, dyslipidemia, hypertension, and smoking status. ResultsConicity index showed the highest performance in predicting 7-year fatal and non-fatal cardiovascular events with areas under the ROC curve of 0.77 [95% confidence interval: 0.71–0.82], and 0.63 [0.59–0.68] in men, and 0.80 [0.74–0.87], and 0.65 [0.60–0.71] in women, respectively. In multiple Cox models, the obesity measures had no significant associations with cardiovascular events in women. In men, only waist-to-height ratio was independently associated with 7-year non-fatal cardiovascular events (hazard ratio: 1.19 [95% confidence interval: 1.01–1.38]). ConclusionsAlthough waist-to-height ratio had an independent association with 7-year non-fatal cardiovascular events in men, conicity index showed the best ability to predict 7-year fatal and non-fatal cardiovascular events in our study.

WHY THE VAULT BECAME SUPERIOR TO OTHER EVENTS IN WOMEN’S ARTISTIC GYMNASTICS AT THE OLYMPICS?

Critics argue that disciplines in women’s artistic gymnastics are not equal and the vault is generally scored much higher than the uneven bars, balance beam and floor exercise. The aim of this study is to understand why the vault became superior to other women’s events. The data are the official results for the 586 women gymnasts in Qualification at Olympics from 2000 to 2020. The One-Way ANOVA was used to analyze the variance of D-scores, E-scores and F-scores for women gymnasts obtained on each apparatus. Our research shows that disciplines in women’s artistic gymnastics have not been equal for gymnasts when trying to obtain high F-scores in the past 6 Olympics. Among the four women’s events, the vault came to be the one on which gymnasts are more likely to obtain high F-scores after the 2000 Olympics. We indicate that the strength of vault resulted from the introduction of the new vaulting table in 2001 and the new open-ended rules in 2006. Although the two big changes implemented by the International Federation of Gymnastics in the beginning of the new millennium were aimed at improving safety of the vault and fairness of judging, the interplay of the two big changes unintentionally promoted the vault to become the most powerful event in women’s artistic gymnastics. Such unanticipated consequence of purposeful action may constitute the most important element (i.e., imbalance of disciplines) in the sport. Accordingly, this research has the potential to shed new light on not only this important topic of equality between disciplines, but also broader trends in modern artistic gymnastics.

Effect of Aromatic Massage on Somatic Problems among a Cohort of Menopausal Women

Context: Menopause is a significant event in women's lives. It marks the end of a woman's natural reproductive life; it is usually accompanied by symptoms that affect the women's ability to perform their normal daily activities. Massage is one of the non-pharmacological methods that can help women cope with menopausal symptoms.&#x0D; Aim: The study aimed to evaluate the effect of aromatic massage on somatic problems among a cohort of menopausal women.&#x0D; Methods: A comparative quasi-experimental time serial (pre-posttest, study/control) design was used. The study was conducted at outpatient clinics of Ain shams University Maternity Hospital. A purposive sample of 74 menopausal women with menopausal symptoms was recruited in this study and divided randomly into an intervention group (Aromatic massage) and a control group (Massage only). Data were collected through three tools. A structured interviewing questionnaire is divided into three parts: general data, obstetrics, and menstrual history, the Kupperman index (menopausal assessment symptoms tool) to assess somatic menopausal symptoms, and the Visual Analogue Scale to assess the history of menstrual pain degree among menopausal women.&#x0D; Results: It revealed two matched groups of women with a mean age of 47.83±5.23 vs. 49.05±3.98 in the aromatic and massage-only groups, respectively. The pre/post-intervention results revealed a significant improvement in most somatic menopausal symptoms, decreasing the frequency of hot flushes attacks, paresthesia, vertigo, fatigue, myalgia, headache, heart palpitation, and formication in the aromatherapy massage group post-intervention and in the follow up (p&lt;0.05). The comparison between the aromatic and massage-only groups revealed a significant difference between the two groups with a significantly lower mean score in total menopausal somatic symptoms.&#x0D; Conclusion: Aromatic massage with lavender, clary sage, jasmine, and rose dissolved in almond oil was effective in easing somatic menopausal symptoms compared to their pre-intervention level and compared to the massage-only group. The study recommended developing counseling programs for women about aromatic massage therapy at gynecological clinics.

Chronic and Cumulative Adverse Life Events in Women with Primary Ovarian Insufficiency: An Exploratory Qualitative Study.

Background and PurposePrimary ovarian insufficiency (POI) has serious physical and psychological consequences due to estradiol deprivation, leading to increased morbidity and mortality. However, the causes of most POI cases remain unknown. Psychological stress, usually caused by stressful life events, is known to be negatively associated with ovarian function. It is important to explore high-frequency adverse life events among women with POI for future interventions.MethodsForty-three women (mean age=33·8 years) were recruited who were newly- diagnosed with idiopathic POI (FSH levels >40 IU/L) to participate in semi-structured interviews through convenience sampling. The main questions covered by the topic guide were designed to explore adverse life events prior to POI diagnosis. Interviews were audio recorded, transcribed and analyzed thematically. Data were analyzed from June 2019 to August 2020.ResultsAmong the women with POI, mean age at diagnosis of POI was 33·8 years (range from 19 to 39 years), and the average time between the onset of irregular menstruation and POI diagnosis was 2.3 years. These women with POI had a relatively normal menstrual cycle before the diagnosis. A number of stressful life events prior to POI diagnosis were discussed by them as important factors influencing their health. Four core themes emerged: 1) persistent exposure to workplace stress, 2) persistent exposure to family-related adverse life events, 3) sleep problem/disturbance existed in women with POI before diagnosis, and 4) participants’ general cognition and concerns about POI.ConclusionsPersistent exposures to adverse life events related to work stress, family stress and sleep problem existed in women with POI. Our findings are consistent with the hypothesis that adverse life events play a role in the development of POI. Future research should investigate how social environmental factors influence POI disease risks, and whether provision of tailored interventions (i.e. preventing or mitigating impact of adverse life events) aimed at high-risk populations may help prevent new POI cases and improve conditions of women with POI. We gained an in-depth understanding of the experiences of these women via 1:1 qualitative method, and find adverse life events are frequent in women with POI prior to the diagnosis.

Safety, reactogenicity, and immunogenicity of a 2-dose Ebola vaccine regimen of Ad26.ZEBOV followed by MVA-BN-Filo in healthy adult pregnant women: study protocol for a phase 3 open-label randomized controlled trial

BackgroundRisks to mother and fetus following Ebola virus infection are very high. Evaluation of safety and immunogenicity of non-replicating Ebola vaccine candidates is a priority for use in pregnant women. This is the protocol for a randomized, open-label, single-center phase 3 clinical trial of the safety, reactogenicity, and immunogenicity of the 2-dose Ebola vaccine regimen in healthy adult pregnant women. This 2-dose regimen has been shown to be safe, judged effective, and approved in non-pregnant populations.MethodsA total of 2000 adult (≥ 18 years of age) pregnant women will be enrolled from antenatal care facilities in Western Rwanda and randomized (1:1) to receive the 2-dose Ebola vaccine regimen (Ad26.ZEBOV, MVA-BN-Filo (group A)) or control (unvaccinated pregnant women (group B)). The primary objectives are to (1) assess adverse maternal/fetal outcomes in randomized pregnant women up to 1.5 months after delivery and (2) assess adverse neonatal/infant outcomes in neonates/infants born to randomized women up to 3.5 months after birth. The frequency and relatedness of all serious adverse events in women and newborns from randomization or birth, respectively, until study end will be reported. The reactogenicity and unsolicited adverse events of the 2-dose Ebola vaccine regimen in all vaccinated pregnant women (group A) will be reported. We will also assess the immunogenicity of the 2-dose Ebola vaccine regimen in 150 pregnant women who are anticipated to receive both vaccine doses within the course of their pregnancy (a subset of the 1000 pregnant vaccinated women from group A) compared to 150 non-pregnant women vaccinated after delivery (a subset of group B). The persistence of maternal antibodies in 75 infants born to women from the group A subset will be assessed. Exploratory analyses include assessment of acceptability of the 2-dose Ebola vaccine regimen among group A and assessment of maternal antibodies in breast milk in 50 women from group A and 10 controls (women from group B prior to vaccination).DiscussionThis study is intended to support a label variation to relax restrictions on use in pregnant women, a vulnerable population with high medical need.Trial registrationClinicaltrials.gov NCT04556526. September 21, 2020.