COVID-19 severity and cardiovascular outcomes in SARS-CoV-2-infected patients with cancer and cardiovascular disease

BackgroundData regarding outcomes among patients with cancer and co-morbid cardiovascular disease (CVD)/cardiovascular risk factors (CVRF) after SARS-CoV-2 infection are limited.ObjectivesTo compare Coronavirus disease 2019 (COVID-19) related complications among cancer patients with and without co-morbid CVD/CVRF.MethodsRetrospective cohort study of patients with cancer and laboratory-confirmed SARS-CoV-2, reported to the COVID-19 and Cancer Consortium (CCC19) registry from 03/17/2020 to 12/31/2021. CVD/CVRF was defined as established CVD or no established CVD, male ≥ 55 or female ≥ 60 years, and one additional CVRF. The primary endpoint was an ordinal COVID-19 severity outcome including need for hospitalization, supplemental oxygen, intensive care unit (ICU), mechanical ventilation, ICU or mechanical ventilation plus vasopressors, and death. Secondary endpoints included incident adverse CV events. Ordinal logistic regression models estimated associations of CVD/CVRF with COVID-19 severity. Effect modification by recent cancer therapy was evaluated.ResultsAmong 10,876 SARS-CoV-2 infected patients with cancer (median age 65 [IQR 54–74] years, 53% female, 52% White), 6253 patients (57%) had co-morbid CVD/CVRF. Co-morbid CVD/CVRF was associated with higher COVID-19 severity (adjusted OR: 1.25 [95% CI 1.11–1.40]). Adverse CV events were significantly higher in patients with CVD/CVRF (all p<0.001). CVD/CVRF was associated with worse COVID-19 severity in patients who had not received recent cancer therapy, but not in those undergoing active cancer therapy (OR 1.51 [95% CI 1.31–1.74] vs. OR 1.04 [95% CI 0.90–1.20], p_interaction <0.001).ConclusionsCo-morbid CVD/CVRF is associated with higher COVID-19 severity among patients with cancer, particularly those not receiving active cancer therapy. While infrequent, COVID-19 related CV complications were higher in patients with comorbid CVD/CVRF. (COVID-19 and Cancer Consortium Registry [CCC19]; NCT04354701).     

The burden of traumatic brain injury from low-energy falls among patients from 18 countries in the CENTER-TBI Registry: A comparative cohort study

BackgroundTraumatic brain injury (TBI) is an important global public health burden, where those injured by high-energy transfer (e.g., road traffic collisions) are assumed to have more severe injury and are prioritised by emergency medical service trauma triage tools. However recent studies suggest an increasing TBI disease burden in older people injured through low-energy falls. We aimed to assess the prevalence of low-energy falls among patients presenting to hospital with TBI, and to compare their characteristics, care pathways, and outcomes to TBI caused by high-energy trauma.Methods and findingsWe conducted a comparative cohort study utilising the CENTER-TBI (Collaborative European NeuroTrauma Effectiveness Research in TBI) Registry, which recorded patient demographics, injury, care pathway, and acute care outcome data in 56 acute trauma receiving hospitals across 18 countries (17 countries in Europe and Israel). Patients presenting with TBI and indications for computed tomography (CT) brain scan between 2014 to 2018 were purposively sampled. The main study outcomes were (i) the prevalence of low-energy falls causing TBI within the overall cohort and (ii) comparisons of TBI patients injured by low-energy falls to TBI patients injured by high-energy transfer—in terms of demographic and injury characteristics, care pathways, and hospital mortality. In total, 22,782 eligible patients were enrolled, and study outcomes were analysed for 21,681 TBI patients with known injury mechanism; 40% (95% CI 39% to 41%) (8,622/21,681) of patients with TBI were injured by low-energy falls. Compared to 13,059 patients injured by high-energy transfer (HE cohort), the those injured through low-energy falls (LE cohort) were older (LE cohort, median 74 [IQR 56 to 84] years, versus HE cohort, median 42 [IQR 25 to 60] years; p < 0.001), more often female (LE cohort, 50% [95% CI 48% to 51%], versus HE cohort, 32% [95% CI 31% to 34%]; p < 0.001), more frequently taking pre-injury anticoagulants or/and platelet aggregation inhibitors (LE cohort, 44% [95% CI 42% to 45%], versus HE cohort, 13% [95% CI 11% to 14%]; p < 0.001), and less often presenting with moderately or severely impaired conscious level (LE cohort, 7.8% [95% CI 5.6% to 9.8%], versus HE cohort, 10% [95% CI 8.7% to 12%]; p < 0.001), but had similar in-hospital mortality (LE cohort, 6.3% [95% CI 4.2% to 8.3%], versus HE cohort, 7.0% [95% CI 5.3% to 8.6%]; p = 0.83). The CT brain scan traumatic abnormality rate was 3% lower in the LE cohort (LE cohort, 29% [95% CI 27% to 31%], versus HE cohort, 32% [95% CI 31% to 34%]; p < 0.001); individuals in the LE cohort were 50% less likely to receive critical care (LE cohort, 12% [95% CI 9.5% to 13%], versus HE cohort, 24% [95% CI 23% to 26%]; p < 0.001) or emergency interventions (LE cohort, 7.5% [95% CI 5.4% to 9.5%], versus HE cohort, 13% [95% CI 12% to 15%]; p < 0.001) than patients injured by high-energy transfer. The purposive sampling strategy and censorship of patient outcomes beyond hospital discharge are the main study limitations.ConclusionsWe observed that patients sustaining TBI from low-energy falls are an important component of the TBI disease burden and a distinct demographic cohort; further, our findings suggest that energy transfer may not predict intracranial injury or acute care mortality in patients with TBI presenting to hospital. This suggests that factors beyond energy transfer level may be more relevant to prehospital and emergency department TBI triage in older people. A specific focus to improve prevention and care for patients sustaining TBI from low-energy falls is required.

In a cohort study, Fiona Lecky and colleagues investigate the factors associated with traumatic brain injury resulting from low energy falls compared with injuries from high energy transfer mechanisms among patients across Europe and Israel.     

Pooling analysis reveals that galectin-1 is a reliable prognostic biomarker in various cancers

Galectin-1 is reported to be upregulated in various human cancers. However, the relationship between galectin-1 expression and cancer prognosis has not been systematically assessed. In this study, we searched PubMed, Web of Science, and Embase to collect all relevant studies and a meta-analysis was performed. We found that increased galectin-1 expression was associated with tumor size (odds ratio [OR] = 1.75; 95% confidence interval [CI]: 1.06–2.89; p = 0.029), clinical stage (OR = 3.89; 95% CI: 2.40–6.31; p < 0.001), and poorer differentiation (OR = 1.39; 95% CI: 1.14–1.69; p = 0.001), but not with age (OR = 1.07; 95% CI: 0.82–1.39; p = 0.597), sex (OR = 0.89; 95% CI: 0.74–1.07; p = 0.202), or lymph node metastasis (OR = 2.57; 95% CI: 0.98–6.78; p = 0.056). In addition, we found that high galectin-1 expression levels were associated with poor overall survival (HR = 2.12; 95% CI: 1.71–2.64; p < 0.001). The results were further validated using The Cancer Genome Atlas data set. Moreover, high galectin-1 expression was significantly associated with disease-free survival (hazard ratio [HR] = 1.60; 95% CI: 1.17–2.19; p = 0.003), progression-free survival (HR = 1.93; 95% CI: 1.65–2.25; p < 0.001), and cancer-specific survival (HR = 1.82; 95% CI: 1.30–2.55; p < 0.001). Our meta-analysis demonstrated that galectin-1 might be a useful common biomarker for predicting prognosis in patients with cancer.     

Risk of Breast Cancer in Females With Hypothyroidism: A Nationwide,Population-Based,Cohort Study

ObjectivesThe results of studies investigating the relationship between breast cancer and hypothyroidism vary greatly from study to study. In this study, we analyzed a large and reliable, population-based database to gain a better understanding of the correlation.MethodsThis retrospective cohort study analyzed patients with hypothyroidism between January 1, 2000 and December 31, 2012 (hypothyroidism cohort) from the Longitudinal Health Insurance Database 2000 in Taiwan. For each woman with hypothyroidism, 1 woman without a history of breast cancer was randomly selected from the Longitudinal Health Insurance Database 2000 and frequency matched (1:4) with women without hypothyroidism by age and index year of hypothyroidism. The study outcome was the diagnosis of breast cancer during a 12-year follow-up period.ResultsIn this study, 6665 women with hypothyroidism and 26 660 women without hypothyroidism were identified. The hypothyroidism cohort had a significantly higher risk of breast cancer than the nonhypothyroidism cohort (adjusted hazard ratio [aHR] 1.69 [95% CI, 1.15-2.49]; P = .01), especially in the group aged 40 to 64 years (aHR 2.07 [95% CI, 1.32-3.23]; P = .01). Women in the hypothyroidism cohort taking levothyroxine for a duration ˃588 days showed a significantly decreased risk of breast cancer (aHR 0.37 [95% CI, 0.19-0.71]; P = .003).ConclusionWomen with hypothyroidism are at a higher risk of breast cancer than those without hypothyroidism. Levothyroxine may reduce the risk of breast cancer in a woman with hypothyroidism.     

Plasmodium vivax Malaria in Pregnant Women in the Brazilian Amazon and the Risk Factors Associated with Prematurity and Low Birth Weight: A Descriptive Study

Introduction

Plasmodium vivax is the most prevalent malaria species in the American region. Brazil accounts for the higher number of the malaria cases reported in pregnant women in the Americas. This study aims to describe the characteristics of pregnant women with malaria in an endemic area of the Brazilian Amazon and the risk factors associated with prematurity and low birth weight (LBW).

Methods/Principal Findings

Between December 2005 and March 2008, 503 pregnant women with malaria that attended a tertiary health centre were enrolled and followed up until delivery and reported a total of 1016 malaria episodes. More than half of study women (54%) were between 20–29 years old, and almost a third were adolescents. The prevalence of anaemia at enrolment was 59%. Most women (286/503) reported more than one malaria episode and most malaria episodes (84.5%, 846/1001) were due to P. vivax infection. Among women with only P. vivax malaria, the risk of preterm birth and low birth weight decreased in multigravidae (OR, 0.36 [95% CI, 0.16–0.82]; p = 0.015 and OR 0.24 [95% CI, 0.10–0.58]; p = 0.001, respectively). The risk of preterm birth decreased with higher maternal age (OR 0.43 [95% CI, 0.19–0.95]; p = 0.037) and among those women who reported higher antenatal care (ANC) attendance (OR, 0.32 [95% CI, 0.15–0.70]; p = 0.005).

Conclusion

This study shows that P. vivax is the prevailing species among pregnant women with malaria in the region and shows that vivax clinical malaria may represent harmful consequences for the health of the mother and their offsprings particularly on specific groups such as adolescents, primigravidae and those women with lower ANC attendance.     

Hysterectomy and risk of epithelial ovarian cancer by histologic type,endometriosis, and menopausal hormone therapy

BackgroundThis nationwide, register-based case-control study investigated the association between hysterectomy and risk of epithelial ovarian cancer according to histology and by history of endometriosis and menopausal hormone therapy (MHT) use.MethodsFrom the Danish Cancer Registry, all women registered with epithelial ovarian cancer at age 40–79 years during 1998–2016 were identified (n = 6738). Each case was sex- and age-matched to 15 population controls using risk-set sampling. Information on previous hysterectomy on benign indication and potential confounders was retrieved from nationwide registers. Conditional logistic regression was used to calculate odds ratios (ORs) with 95% confidence intervals (CIs) for the association between hysterectomy and ovarian cancer according to histology, endometriosis, and use of MHT.ResultsHysterectomy was not associated with risk of epithelial ovarian cancer overall (OR=0.99; 95% CI 0.91 –1.09) but was associated with reduced risk of clear cell ovarian cancer (OR=0.46; 95% CI 0.28–0.78). In stratified analyses, decreased ORs associated with hysterectomy were seen in women with endometriosis (OR=0.74; 95% CI 0.50–1.10) and in non-users of MHT (OR=0.87; 95% CI 0.76–1.01). In contrast, among long-term MHT users, hysterectomy was associated with increased odds for ovarian cancer (OR=1.20; 95% CI 1.03–1.39).ConclusionHysterectomy was not associated with epithelial ovarian cancer overall but with reduced risk of clear cell ovarian cancer. Our findings may suggest a reduced risk of ovarian cancer after hysterectomy in women with endometriosis and in MHT non-users. Interestingly our data pointed to an increased ovarian cancer risk associated with hysterectomy among long-term users of MHT.     

The impact of a delayed sleep–wake schedule on depression is greater in women – A web-based cross-sectional study in Japanese young adults

Sleep-related problems, such as symptoms of insomnia, daytime sleepiness, shorter sleep duration, or a delayed sleep–wake schedule, are known to be risk factors for depression. In general, depression is more prevalent in women than in men, but sleep-related problems do not necessarily show similar gender predominance. Hence, it can be speculated that the impact of sleep-related problems on the development process of depression differs between genders; however, so far, few studies have focused on this issue. The aim of this study was to clarify gender differences in the rates of depression of people with the above sleep-related problems, and to examine gender differences in factors associated with depression in Japanese young adults. A web-based questionnaire survey comprising assessments of demographic variables, sleep-related variables (bed time, wake time, sleep onset latency, frequency of difficulty in initiating sleep and that in maintaining sleep, i.e. symptom components of insomnia, and daytime sleepiness), and the 12-item version of the Center for Epidemiologic Studies Depression Scale was administered to 2502 participants (males:females?=?1144:1358, age range?=?19–25 years). Female predominance in the rate of depression was observed only in subjects with a delayed sleep–wake schedule (χ²₍₁₎?=?15.44, p?<?0.001). In men, daytime sleepiness and difficulty in initiating sleep were significantly associated with depression (odds ratio [OR]?=?2.39, 95% confidence interval [CI]?=?[1.69, 3.39], p?<?0.001; OR?=?3.50, 95% CI?=?[2.29, 5.35], p?<?0.001, respectively), whereas in women, significant associations were found between depression and a delayed sleep–wake schedule (OR?=?1.75, 95% CI?=?[1.28, 2.39], p?<?0.001), daytime sleepiness (OR?=?2.13, 95% CI?=?[1.60, 2.85], p?<?0.001), and difficulty in initiating sleep (OR?=?4.37, 95% CI?=?[3.17, 6.03], p?<?0.001). These results indicate that in younger generations, the impact of a delayed sleep–wake schedule on the development of depression is greater in women; specifically, women are vulnerable to depression when they have an eveningness-type lifestyle, which is possibly attributable to the female-specific intrinsic earlier and shorter circadian rhythm. These results suggest the necessity of gender-based approaches to treating sleep-related problems for alleviating or preventing depressive symptoms in young adults.     

Effect of early adverse events on response and survival outcomes of advanced melanoma patients treated with vemurafenib or vemurafenib plus cobimetinib: A pooled analysis of clinical trial data

This study aimed to evaluate the impact of early adverse events on overall survival (OS), progression‐free survival (PFS) and objective response within a pooled secondary analysis of participants treated with first‐line vemurafenib or vemurafenib plus cobimetinib in the clinical trials BRIM3 and coBRIM. The study included 583 participants who received vemurafenib monotherapy and 247 who received vemurafenib plus cobimetinib. Adverse events requiring vemurafenib/cobimetinib dose adjustment within the first 28 days of therapy were significantly associated with OS (hazard ratio (HR) [95% CI]: dose reduced/interrupted = 0.79 [0.65–0.96]; drug withdrawn = 1.18 [0.71–1.96]; p = 0.032), PFS (HR [95% CI]: dose reduced/interrupted = 0.82 [0.67–0.99]; drug withdrawn = 1.58 [0.97–2.58]; p = 0.017) and objective response (odds ratio (OR) [95% CI]: dose reduced/interrupted = 1.35 [0.99–1.85]; drug withdrawn = 0.17 [0.06–0.43]; p = <0.001). Arthralgia occurring within the first 28 days of vemurafenib or vemurafenib plus cobimetinib therapy was also significantly associated with favourable OS (p = 0.026), PFS (p = 0.042) and objective response (p = 0.047).     

DEPRESSED MOOD IN THE WORKING POPULATION: ASSOCIATIONS WITH WORK SCHEDULES AND WORKING HOURS

The impact of working time arrangements (WTA) on health has been studied extensively. Still, little is known about the interrelation between work schedules, working hours, and depressed mood. For work schedules, the underlying assumptions regarding depressed mood refer to a disturbance of social and biological rhythms, whereas for working hours, the assumptions relate to workload and work capacity. Conversely, depressed mood may urge an employee to adjust his/her work schedule and/or number of working hours/week (h/wk). The aim of this study was to assess the association between work schedule and working hours with depressed mood. Using baseline data from the Maastricht Cohort Study, depressed mood in day work was compared with depressed mood in different shiftwork schedules (n?=?8843). Within day work, several categories of working h/wk were studied in association with depressed mood (n?=?7217). The association between depressed mood and several aspects of overtime was assessed separately. Depressed mood was measured with a dichotomous item: “Did you feel down every day over the last two weeks?” Separate logistic regression analyses were conducted for men and women, with adjustments for potential confounders. The odds ratio (OR) for depressed mood was greater for men involved in shiftwork than for men only involved in day work (three-shift OR?=?2.05 [95% confidence interval, CI 1.52–2.77]; five-shift OR?=?1.34 [95% CI 1.00–1.80]; irregular-shift OR?=?1.79 [95% CI 1.27–2.53]). In female employees, five-shift work was associated with a higher prevalence of depressed mood (OR?=?5.96 [95% CI 2.83–12.56]). Regarding the number of working h/wk, men working <26?h/wk had a higher prevalence of depressed mood than men working 36–40?h/wk (OR?=?2.73 [95% CI 1.35–5.52]). After conducting trend analyses, a significant decreasing trend was found in men, whereas an increasing trend was found in women working a high number of hours. Furthermore, a dose-response relationship was present in men regarding the number of overtime h/wk. This study showed that different work schedules and working hours are associated with depressed mood. Shiftwork was related to a higher prevalence of depressed mood than day work. The association was more pronounced for male employees. Regarding the number of working h/wk, male and female employees showed an opposite trend in depressed mood. Because of the possibility of a healthy worker effect and the possibility of a reciprocal relationship between WTA and depressed mood, the reported relation might be underestimated. This study has illustrated that occupational physicians, who deal with depressed mood among workers, should carefully consider the impact of WTA. (Author coorespondence: Karolien.Driesen@epid.unimaas.nl)     

Predictors of depressive symptoms post-acute coronary syndrome

Objective: We examined the influence of gender on the prevalence of acute coronary syndrome (ACS) and the severity of depressive symptoms post-ACS.Methods: Patients received a Zung self-assessment questionnaire at hospital discharge for unstable angina (UA) or acute myocardial infarction (AMI) and returned it by mail. Major depressive symptoms were diagnosed based on a summed depressive symptoms (SDS) score of >50. Depressive symptomatology was modeled by stepwise multivariable logistic regression with the following predictors: gender, age, hypertension, diabetes mellitus, history of smoking, hypercholesterolemia, peripheral vascular disease, prior stroke, prior myocardial infarction (MI), and prior percutaneous coronary intervention or coronary artery bypass graft surgery. We also modeled severity of depressive symptoms via stepwise multiple linear regression with the same predictor variables.Results: A total of 944 patients were surveyed: 716 men and 228 women, mean (SD) age, 67 (13) years and 71 (12) years, respectively. Of these patients, 250 (35%) men and 103 (45%) women had depressive symptoms (P = 0.005). No significant difference was observed between men and women in rates of cardiac catheterization; severity of coronary artery disease; treatment with antiplatelet agents, β-blockers, angiotensin-converting enzyme inhibitors, or statins; or percutaneous or surgical revascularization rates during or post-ACS. Significant predictors of the presence of depressive symptoms were female gender (odds ratio [OR] = 1.64; 95% CI, 1.19-1.28), diabetes mellitus (OR = 1.42; 95% CI, 1.03-1.97), prior MI (OR = 1.56; 95% CI, 1.15-2.20), and smoking (OR = 1.41; 95% CI, 1.01-1.97). Variables significantly associated with a higher severity of depressive symptoms were female gender, prior MI, smoking, and stroke. Men with prior MI had significantly higher mean (SD) SDS scores than did men without prior MI in all age groups (48.4 [11] vs 44.6 [11], respectively; P < 0.001). In addition, significantly more men with prior MI had depressive symptoms compared with those without prior MI (45% vs 32%; P = 0.001). However, prior MI did not appear to affect SDS scores in women (49.1 [12] for prior MI vs 48.5 [12] for no prior MI; P = NS), and there was no significant difference in the percentage of women who had depressive symptoms with or without a history of prior MI. Depressive symptoms were much more severe in women with UA (SDS = 49.0 [12]) compared with women with AMI (SDS = 45.0 [12]; P = NS), or men with AMI (45.0 [12]; P = 0.004) or UA (46.0 [11]; P = 0.007) (analysis of variance, P = 0.003).Conclusions: Female gender is a significant independent predictor of depressive symptoms and their severity post-UA and post-AMI. History of prior MI is associated with a higher frequency and severity of depressive symptoms in men. These findings call for routine screening for depressive symptoms in men with prior MI and in women who present with ACS.     

Sex/gender and socioeconomic differences in the predictive ability of self-rated health for mortality

Background

Studies have reported that the predictive ability of self-rated health (SRH) for mortality varies by sex/gender and socioeconomic group. The purpose of this study is to evaluate this relationship in Japan and explore the potential reasons for differences between the groups.

Methodology/Principal Findings

The analyses in the study were based on the Aichi Gerontological Evaluation Study''s (AGES) 2003 Cohort Study in Chita Peninsula, Japan, which followed the four-year survival status of 14,668 community-dwelling people who were at least 65 years old at the start of the study. We first examined sex/gender and education-level differences in association with fair/poor SRH. We then estimated the sex/gender- and education-specific hazard ratios (HRs) of mortality associated with lower SRH using Cox models. Control variables, including health behaviors (smoking and drinking), symptoms of depression, and chronic co-morbid conditions, were added to sequential regression models. The results showed men and women reported a similar prevalence of lower SRH. However, lower SRH was a stronger predictor of mortality in men (HR = 2.44 [95% confidence interval (CI): 2.14–2.80]) than in women (HR = 1.88 [95% CI: 1.44–2.47]; p for sex/gender interaction = 0.018). The sex/gender difference in the predictive ability of SRH was progressively attenuated with the additional introduction of other co-morbid conditions. The predictive ability among individuals with high school education (HR = 2.39 [95% CI: 1.74–3.30]) was similar to that among individuals with less than a high school education (HR = 2.14 [95% CI: 1.83–2.50]; p for education interaction = 0.549).

Conclusions

The sex/gender difference in the predictive ability of SRH for mortality among this elderly Japanese population may be explained by male/female differences in what goes into an individual''s assessment of their SRH, with males apparently weighting depressive symptoms more than females.     

Sex differences in intraventricular hemorrhage rates among very low birth weight newborns

Background: The influence of male or female sex on newborn outcomes has been recognized for >30 years. Several studies have observed higher mortality and morbidity in males than in females. It is not clear how this sex difference is sustained in postnatal complications such as intraventricular hemorrhage (IVH), especially in very low birth weight (VLBW) newborns.Objective: This study examined possible sex-related differences in IVH rates among VLBW neonates.Methods: In a retrospective observational study conducted in Hospital Privado, Córdoba, Argentina, data from 332 consecutive VLBW newborns in a 12-year period were reviewed. Maternal factors, labor and delivery characteristics, and neonatal parameters, including the results of cranial ultrasound examination to detect IVH, were compared for males and females. Bivariate and multivariate logistic regression analyses were performed.Results: A total of 322 VLBW newborns were included, 168 males and 154 females. Compared with female neonates, male neonates had a higher risk of overall IVH (26.8% vs 9.7%; odds ratio [OR] = 3.4 [95% CI, 1.8–6.4]; P < 0.001) and for grades III or IV on the Papile scale (16.1% vs 1.9%; OR = 9.6 [95% CI, 2.9–32.5]; P < 0.001). In the multivariate logistic regression model, male sex sustained the association with a greater risk of IVH (OR = 6.8 [95% CI, 3.8–12.0]).Conclusions: IVH was significantly associated with male sex in these VLBW newborns. Because other factors affect these differences, further research is required.     

TNFAIP3 gene polymorphisms confer risk for Behcet’s disease in a Chinese Han population

The tumor necrosis factor alpha-inducible protein 3 (TNFAIP3) gene polymorphisms have recently been reported to be associated with the susceptibility to several immune-related diseases. This study was performed to evaluate the potential association of TNFAIP3 polymorphisms with Behcet’s disease (BD) in a Chinese Han population. Five single-nucleotide polymorphisms (SNPs), rs10499194, rs610604, rs7753873, rs5029928, and rs9494885 of TNFAIP3 were genotyped in 722 BD patients and 1,415 healthy controls using a PCR-restriction fragment length polymorphism assay. Allele and genotype frequencies were compared between patients and controls using the χ ² test. The results showed a significantly increased prevalence of the rs9494885 TC genotype and C allele in BD patients compared with controls (Bonferroni corrected p (p _c) = 1.83 × 10^?10, odds ratio (OR) [95 % CI] 2.03 [1.65–2.49]; p _c = 8.35 × 10^?10, OR [95 % CI] 1.81 [1.51–2.18], respectively).The frequency of the TT genotype and T allele of rs9494885 was markedly lower in BD patients than that in controls (p _c = 1.23 × 10^?10, OR [95 % CI] 0.50 [0.40–0.61]; p _c = 8.35 × 10^?10, OR [95 % CI] 0.55 [0.46–0.66], respectively). For rs10499194, a higher frequency of the CC genotype (p _c = 0.015, OR [95 % CI] 1.96 [1.30–2.97]) and C allele (p _c = 0.005, OR [95 % CI] 1.92 [1.28–2.90]), and a lower frequency of the TC genotype (p _c = 0.015, OR [95 % CI] 0.51 [0.34–0.77]) and T allele (p _c = 0.005, OR [95 % CI] 0.52 [0.35–2.97]) were found in BD patients. Concerning rs7753873, a higher frequency of the AC genotype (p _c = 0.015, OR [95 % CI] 1.49 [1.17–1.91]) and C allele (p _c = 0.025, OR [95 % CI] 1.39 [1.11–1.76]), and a lower frequency of the AA genotype (p _c = 0.03, OR [95 % CI] 0.68 [0.53–0.87]) and A allele (p _c = 0.025, OR [95 % CI] 0.72 [0.57–0.91]) were observed in BD patients. This study identified one strong risk SNP rs9494885 and two weak risk SNPs rs10499194 and rs7753873 of TNFAIP3 in Chinese Han BD patients.     

Interaction with angiotensin-converting enzyme-encoding gene in female infertility: Insertion and deletion polymorphism studies

Angiotensin-converting enzyme (ACE), a key enzyme in the renin– angiotensin–aldosterone system, converts angiotensin I to angiotensin II. Ethnic origin should be carefully considered in studies pertaining to ACE I/D genotype and disease etiology. This study was evaluated between the ACE gene I/D polymorphism and female infertility in the Saudi population. Out of a A total of 300 women who participated in this study genomic DNA samples from the 150 infertile and 150 fertile women’s were isolated who has participated in this study. Genomic DNA was isolated using an Invitrogen kit according to the manufacturer’s protocol, and D allele specific primers were used for amplification by polymerase chain reaction. Electrophoresis was carried out on a 2% agarose gel. The mean age and BMI of the cases and controls were similar (p > 0.05), and a significant association was noted between the family history and female infertility (p = 0.0001). The D allele (OR: 1.67 [95% CI: 1.18–2.35], p = 0.003), DD genotype (OR: 2.46 [95% CI: 1.20–5.02], p = 0.01) and dominant model (OR: 1.97 [95% CI: 1.00–3.88], p = 0.04) were significantly associated with female infertility or fertility. The results of this study show that the ACE polymorphism plays an important role in female infertility in the Saudi population.     

Symptoms of a first acute myocardial infarction in women and men

Background: Many studies have compared women and men for symptoms of acute myocardial infarction (AMI), but findings have been inconsistent, largely because of varying inclusion criteria, different study populations, and different methods.Objective: The purpose of this study was to analyze gender differences in symptoms in a well-defined, population-based sample of women and men who experienced a first AMI.Methods: Information on symptoms was collected from the medical charts of all patients with a first AMI, aged 25 to 74 years, who had taken part in the INTERGENE (Interplay Between Genetic Susceptibility and Environmental Factors for the Risk of Chronic Diseases) study. INTERGENE was a population-based research program on risk factors for cardiovascular disease. Medical charts were reviewed for each patient to determine the symptoms of AMI, and the prevalence of each symptom was compared according to sex.Results: The study included 225 patients with a first AMI: 52 women and 173 men. Chest pain was the most common symptom, affecting 88.5% (46/52) of the women and 94.8% (164/173) of the men, with no statistically significant difference between the sexes. Women had significantly higher rates of 4 symptoms: nausea (53.8% [28/52] vs 29.5% [51/173]; age-adjusted odds ratio [OR] = 2.78; 95% CI, 1.47–5.25), back pain (42.3% [22/52] vs 14.5% [25/173]; OR = 4.29; 95% CI, 2.14–8.62), dizziness (17.3% [9/52] vs 7.5% [13/173]; OR = 2.60; 95% CI, 1.04–6.50), and palpitations (11.5% [6/52] vs 2.9% [5/173]; OR = 3.99; 95% CI, 1.15–13.84). No significant gender differences were found in the proportions of patients experiencing arm or shoulder pain, diaphoresis, dyspnea, fatigue, neck pain, abdominal pain, vomiting, jaw pain, or syncope/lightheadedness. No significant differences were found in the duration, type, or location of chest pain. The medical charts listed numerically more symptoms in women than in men; 73.1% (38/52) of the women but only 48.0% (83/173) of the men reported >3 symptoms (age-adjusted OR = 3.26; 95% CI, 1.62–6.54).Conclusions: Chest pain is the most common presenting symptom in both women and men with AMI. Nausea, back pain, dizziness, and palpitations were significantly more common in women. Women as a group displayed a greater number of symptoms than did men.     

Maternal vitamin B-6 and folate status and risk of oral cleft birth defects in the Philippines

BACKGROUND: Vitamin deficiencies induce oral clefts in animal experiments, but the role of specific nutrients in human oral clefts is uncertain. METHODS: Associations between maternal vitamin B-6 and folate status and risk of nonsyndromic cleft lip, with or without cleft palate (CL/P), were examined in case-control studies at two sites in the Philippines--Negros Occidental and Davao. Cases were mothers of affected children and control mothers were those who had no children with oral clefts. RESULTS: The risk of having a CL/P-affected child increased with increasing tertile of vitamin B-6 deficiency in both Negros Occidental and Davao (odds ratios [ORs] and 95% confidence intervals [CIs] for sites combined = 1.0 [reference], OR, 2.94; 95% CI, 1.51-5.73; OR, 4.98; 95% CI, 2.56-9.67). Poor B-6 status had a stronger association with CL/P among mothers with lower versus higher plasma folate levels. Increasing tertiles of plasma folate were marginally associated with an increased risk of clefts in both sites combined (1.0 [reference]; OR, 1.58; 95% CI, 0.93-2.68; OR, 1.59; 95% CI, 0.94-2.70). Increasing tertiles of erythrocyte folate were associated with a decreased risk of CL/P in Negros Occidental (1.0 [reference]; OR, 0.34; 95% CI, 0.13-0.90; OR, 0.46; 95% CI, 0.20-1.09) and an increased risk in Davao (1.0 [reference]; OR, 1.23; 95% CI, 0.54-2.81; OR, 4.85; 95% CI, 2.24-10.50). The inconsistent associations between folate status and CL/P risk appeared to be a result of statistical interaction between folate, vitamin B-6, and case-control status that produced different results in study areas of higher versus lower prevalence of vitamin B-6 deficiency. CONCLUSIONS: Poor maternal vitamin B-6 status was consistently associated with an increased risk of CL/P at two sites in the Philippines. Folate-CL/P associations were inconsistent and may be related to the vitamin B-6 status or other characteristics of the populations under study.     

Association of the -14C/G MET and the -765G/C COX-2 gene polymorphisms with the risk of chronic rhinosinusitis with nasal polyps in a Polish population

Chronic rhinosinusitis with nasal polyps is strongly associated with other diseases, including asthma and allergy. The following study tested the association of the -765 G/C polymorphism of cyclooxygenase-2 (COX-2) encoding gene and the -14C/G polymorphism of protooncogen MET (MET) encoding gene with a risk of chronic rhinosinusitis with nasal polyps in a Polish population. One hundred ninety-five patients of chronic rhinosinusitis with nasal polyps as well as 200 sex-, age-, and ethnicity-matched control subjects without chronic sinusitis and nasal polyps were enrolled in this study. Among the group of patients, 63 subjects were diagnosed with allergy and 65 subjects with asthma, respectively. DNA was isolated from peripheral blood lymphocytes of patients as well as controls, and gene polymorphisms were analyzed by restriction fragment length polymorphism-polymerase chain reaction (RFLP-PCR). Ten percent of the samples have been confirmed by a second method single-strand conformation polymorphism (SSCP)-PCR. We reported that the -765 G/C COX-2 (odds ratio [OR] 7.79; 95% confidence interval [CI] 4.88-12.4, p<0.001) and the -14C/G MET (OR 2.83; 95% CI 1.74-4.61, p<0.001) were associated with an increased risk of chronic rhinosinusitis with nasal polyps among analyzed group of patients. Moreover, the group of patients without allergy or asthma indicated the association of the -765 C/G (OR 7.25; 95% CI 4.38-12.1, p<0.001 and OR 7.61; 95% CI 4.47-12.6, p<0.001) genotype of the COX-2 as wells as the -14C/G (OR 2.47; 95% CI 1.46-4.17, p<0.001 and OR 2.59; 95% CI 1.54-4.37, p<0.001) genotype of MET with an increased risk of chronic rhinosinusitis with nasal polyps. Finally, it was also found that the selected group of patients with allergy or asthma indicated a very strong association of the -765 G/C (OR 5.64; 95% CI 2.91-10.9 and OR 4.74; 95% CI 2.49-9.03, p<0.001, respectively) genotype of the COX-2 with an increased risk of chronic rhinosinusitis with nasal polyps. Thus, our results suggest that COX-2 and MET gene polymorphisms may have deep impact on the risk of rhinosinusitis nasal polyp formation, which may also depend on asthma or allergy. Our results showed that the -765 G/C polymorphism of COX-2 gene and the -14C/G polymorphism of the MET gene may be associated with the risk of chronic rhinosinusitis with nasal polyps in a Polish population.     

Women tolerate drug therapy for coronary artery disease as well as men do,but are treated less frequently with aspirin, β-blockers,or statins

Background: Women have worse morbidity, mortality, and health-related quality-of-life outcomes associated with coronary artery disease (CAD) compared with men. This may be related to underutilization of drug therapies, such as aspirin, β-blockers, angiotensin-converting enzyme (ACE) inhibitors, or statins. No studies have sought to describe the relationship of gender with adverse reactions to drug therapy (ADRs) for CAD in clinical practice.Objective: The aim of this study was to determine the prevalence of ADRs associated with common CAD drug therapies in women and men in clinical practice.Methods: In a cohort of consecutive outpatients with CAD, detailed chart abstraction was performed to determine the use of aspirin, β-blocker, ACE inhibitor, and statin therapy, as well as the ADRs reported for these treatments. Baseline clinical characteristics were also determined to identify the independent association of gender with use of standard drug treatments for CAD.Results: Consecutive patients with CAD (153 men, 151 women) were included in the study. Women and men were observed to have a similar prevalence of cardiac risk factors and comorbidities, except that men had significantly higher prevalence of atrial fibrillation (30 [19.6%] men vs 15 [9.9%] women; P = 0.03) and significantly lower mean (SD) high-density lipoprotein cholesterol concentrations (45 [16] mg/dL for men vs 55 [19] mg/dL for women; P < 0.001). No significant differences were observed between the sexes in the prevalence of ADRs; however, significantly fewer women than men were treated with statins (118 [78.1%] vs 139 [90.8%], respectively; P = 0.003). After adjusting for clinical characteristics, women were also found to be less likely than men to receive aspirin (odds ratio [OR] = 0.164; 95% CI, 0.083–0.322; P = 0.001) and β-blockers (OR = 0.184; 95% CI, 0.096-0.351; P = 0.001).Conclusions: Women and men experienced a similar prevalence of ADRs in the treatment of CAD; however, women were significantly less likely to be treated with aspirin, β-blockers, and statins than were their male counterparts. To optimize care for women with CAD, further study is needed to identify the cause of this gender disparity in therapeutic drug use.