High-density lipoprotein metrics during midlife and future subclinical atherosclerosis in women: the SWAN HDL study.

OBJECTIVE: The clinical utility of high-density lipoprotein cholesterol (HDL-C) in risk classification is limited, especially in midlife women. Novel metrics of HDL may better reflect this risk. We clustered a comprehensive profile of HDL metrics into favorable and unfavorable clusters and assessed how these two clusters are related to future subclinical atherosclerosis (carotid intima media thickness [cIMT], interadventitial diameter [IAD], and carotid plaque presence) in midlife women. METHODS: Four hundred sixty-one women (baseline age: 50.4 [2.7] years; 272 White, 137 Black, 52 Chinese) from the Study of Women's Health Across the Nation HDL ancillary study who had baseline measures of HDL cholesterol efflux capacity (HDL-CEC), lipid contents (HDL-phospholipids [HDL-PL] and HDL triglycerides [HDL-Tg]), and HDL particle (HDL-P) distribution and size, followed by carotid ultrasound (average 12.9 [SD: 2.6] years later), were included. Using latent cluster analysis, women were clustered into a favorable (high HDL-CEC, HDL-PL, large and medium HDL-P, less HDL-Tg and small HDL-P, larger size) or an unfavorable HDL cluster (low HDL-CEC, HDL-PL, large and medium HDL-P, more HDL-Tg, and small HDL-P, smaller size) and then linked to future subclinical atherosclerosis using linear or logistic regression. RESULTS: The favorable HDL cluster was associated with lower cIMT, IAD, and odds of carotid plaque presence. These associations were attenuated by body mass index, except in Chinese women where the association with cIMT persisted (0.72 [0.63, 0.83]). CONCLUSIONS: The association between favorable HDL clusters and a better postmenopausal subclinical atherosclerosis profile is largely explained by body mass index; however, racial/ethnic differences may exist.

Low-density lipoprotein subclasses over the menopausal transition and risk of coronary calcification and carotid atherosclerosis: the SWAN Heart and HDL ancillary studies.

OBJECTIVE: Perimenopausal women experience a steep increase in low-density lipoprotein cholesterol (LDL-C) that is related to a higher risk of carotid plaque later in life. Low-density lipoprotein subclasses have been linked to cardiovascular diseases beyond LDL-C, promising a better risk stratification. We aim to characterize changes in LDL subclasses and assess their associations with presence of coronary artery calcium (CAC score ≥10) and carotid intima-media thickness (cIMT) over the menopausal transition (MT) and by menopause stage. METHODS: Nuclear magnetic resonance spectroscopy LDL subclasses were measured for a maximum of five time points. Coronary artery calcification and cIMT were measured for a maximum of two time points. LOESS (locally weighted regression with scatter smoothing) plots, linear mixed-effects models, and generalized estimating equations were used for analyses. RESULTS: The study included 471 women (baseline: age, 50.2 ± 2.7 years; 79.0% premenopausal/early perimenopausal), of whom 221 had data on CAC or cIMT. Low-density lipoprotein subclasses increased over the MT, whereas intermediate density-lipoprotein particles declined. In adjusted models, higher total LDL particles (LDL-P) and apolipoprotein B were associated with greater CAC prevalence and greater cIMT. Although none of the associations were modified by menopause stage, higher LDL-C, apolipoprotein B, and total LDL-P were associated with greater cIMT during the perimenopause or postmenopause stages, whereas higher LDL-C and small LDL-P were associated with greater CAC prevalence, mainly during perimenopause. CONCLUSIONS: During the MT, women experience significant increases in LDL subclasses found to be related to greater cIMT levels and CAC prevalence. Whether these changes could better predict future risk of hard cardiovascular disease events beyond LDL-C remains a research question to address.

The independent associations of anti-Müllerian hormone and estradiol levels over the menopause transition with lipids/lipoproteins: The Study of Women's health Across the Nation.

BACKGROUND: The menopause transition (MT) is linked to adverse changes in lipids/lipoproteins. However, the related contributions of anti-Müllerian hormone (AMH) and estradiol (E2) are not clear. OBJECTIVE: To evaluate the independent associations of premenopausal AMH and E2 levels and their changes with lipids/lipoproteins levels [total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), apolipoprotein B (apoB) and apolipoprotein A-1 (apoA-1)] over the MT. METHODS: SWAN participants who transitioned to menopause without exogenous hormone use, hysterectomy, or bilateral oophorectomy with data available on both exposure and outcomes when they were premenopausal until the 1st visit postmenopausal were studied. RESULTS: The study included 1,440 women (baseline-age:mean±SD=47.4±2.6) with data available from up to 9 visits (1997-2013). Lower premenopausal levels and greater declines in AMH were independently associated with greater TC and HDL-C, whereas lower premenopausal levels and greater declines in E2 were independently associated with greater TG and apo B and lower HDL-C. Greater declines in AMH were independently associated with greater apoA-1, and greater declines in E2 were independently associated with greater TC and LDL-C. CONCLUSIONS: AMH and E2 and their changes over the MT relate differently to lipids/lipoproteins profile in women during midlife. Lower premenopausal and/or greater declines in E2 over the MT were associated with an atherogenic lipid/lipoprotein profile. On the other hand, lower premenopausal AMH and/or greater declines in AMH over the MT were linked to higher apo A-1 and HDL-C; the later found previously to be related to a greater atherosclerotic risk after menopause.

The Association of Inflammatory Factors With Peripheral Neuropathy: The Study of Women's Health Across the Nation.

PURPOSE: Previous work has focused on the role of diabetes in peripheral neuropathy (PN), but PN often occurs before, and independently from, diabetes. This study measures the association of cardiometabolic and inflammatory factor with PN, independent of diabetes. METHODS: Study of Women's Health Across the Nation participants (n = 1910), ages 60 to 73 (mean 65.6) were assessed for PN by symptom questionnaire and monofilament testing at the 15th follow-up visit (V15). Anthropometric measures and biomarkers were measured at study baseline approximately 20 years prior, and C-reactive protein (CRP) and fibrinogen were measured longitudinally. Log-binomial regression was used to model the association between metabolic syndrome (MetS), obesity (≥35 body mass index), CRP, and fibrinogen with PN, adjusting for sociodemographic and health behavior measures. RESULTS: Baseline MetS [prevalence ratio (PR) 1.79, 95% CI (1.45, 2.20)], obesity [PR 2.08 (1.65, 2.61)], median CRP [PR 1.32 per log(mg/dL), (1.20, 1.45)], and mean fibrinogen (PR 1.28 per 100 mg/dL, (1.09, 1.50)] were associated with PN symptoms at V15. After excluding participants with baseline diabetes or obesity, MetS [PR 1.59 (1.17, 2.14)] and CRP [PR 1.19 per log(mg/dL), (1.06, 1.35)] remained statistically significantly associated with PN. There was a negative interaction between MetS and obesity, and the association between these conditions and PN was mediated by CRP. CONCLUSIONS: Cardiometabolic factors and inflammation are significantly associated with PN, independent of diabetes and obesity. CRP mediates the relationship of both obesity and MetS with PN, suggesting an etiological role of inflammation in PN in this sample.

Predictors of Respiratory Support Use in Emergency Department Patients With COVID-19-Related Respiratory Failure.

BACKGROUND: Given the known downstream implications of choice of respiratory support on patient outcomes, all factors influencing these decisions, even those not limited to the patient, warrant close consideration. We examined the effect of emergency department (ED)-specific system factors, such as work load and census, on the use of noninvasive versus invasive respiratory support. METHODS: We conducted a multi-center retrospective cohort study of all adult subjects with severe COVID-19 requiring an ICU admission from 5 EDs within a single urban health care system. Subject demographics, severity of illness, and the type of respiratory support used were obtained. Using continuous measures of ED census, boarding, and active management, we estimated ED work load for each subjects' ED stay. The subjects were categorized by type(s) of respiratory support used: low-flow oxygen, noninvasive respiratory support (eg, noninvasive ventilation [NIV] and/or high-flow nasal cannula [HFNC]), invasive mechanical ventilation, or invasive mechanical ventilation after trial of NIV/HFNC. We used multivariable logistic regression to examine system factors associated with the type of respiratory support used in the ED. RESULTS: A total of 634 subjects were included. Of these, 431 (70.0%) were managed on low-flow oxygen alone, 108 (17.0%) on NIV/HFNC, 54 (8.5%) on invasive mechanical ventilation directly, and 41 (6.5%) on NIV/HFNC prior to invasive mechanical ventilation in the ED. Higher severity of illness and underlying lung disease increased the odds of requiring invasive mechanical ventilation compared to low-flow oxygen (odds ratio 1.05 [95% CI 1.03-1.07] and odds ratio 3.47 [95% CI 1.37-8.78], respectively). Older age decreased odds of being on invasive mechanical ventilation compared to low-flow oxygen (odds ratio 0.96 [95% CI 0.94-0.99]). As ED work load increased, the odds for subjects to be managed initially with NIV/HFNC prior to invasive mechanical ventilation increased 6-8-fold. CONCLUSIONS: High ED work load was associated with higher odds on HFNC/NIV prior to invasive mechanical ventilation.

Genome-wide and transcriptome-wide association studies of mammographic density phenotypes reveal novel loci.

BACKGROUND: Mammographic density (MD) phenotypes, including percent density (PMD), area of dense tissue (DA), and area of non-dense tissue (NDA), are associated with breast cancer risk. Twin studies suggest that MD phenotypes are highly heritable. However, only a small proportion of their variance is explained by identified genetic variants. METHODS: We conducted a genome-wide association study, as well as a transcriptome-wide association study (TWAS), of age- and BMI-adjusted DA, NDA, and PMD in up to 27,900 European-ancestry women from the MODE/BCAC consortia. RESULTS: We identified 28 genome-wide significant loci for MD phenotypes, including nine novel signals (5q11.2, 5q14.1, 5q31.1, 5q33.3, 5q35.1, 7p11.2, 8q24.13, 12p11.2, 16q12.2). Further, 45% of all known breast cancer SNPs were associated with at least one MD phenotype at p < 0.05. TWAS further identified two novel genes (SHOX2 and CRISPLD2) whose genetically predicted expression was significantly associated with MD phenotypes. CONCLUSIONS: Our findings provided novel insight into the genetic background of MD phenotypes, and further demonstrated their shared genetic basis with breast cancer.

Lowered progesterone metabolite excretion and a variable LH excretion pattern are associated with vasomotor symptoms but not negative mood in the early perimenopausal transition: Study of Women's Health Across the Nation.

OBJECTIVE: The menopausal transition is characterized by progressive changes in ovarian function and increasing circulating levels of gonadotropins, with some women having irregular menstrual cycles well before their final menstrual period. These observations indicate a progressive breakdown of the hypothalamic-pituitary-ovarian axis often associated with an increase in menopausal symptoms. Relationships between vasomotor symptoms (VMS) and depressed mood and sleep as well as a bidirectional association between VMS and depressed mood in mid-life women have been reported, but the endocrine foundations and hormone profiles associated with these symptoms have not been well described. Our objective was to determine the relationship between daily urinary hormone profiles and daily logs of affect and VMS during the early perimenopausal transition. STUDY DESIGN: SWAN, the Study of Women's Health Across the Nation, is a large, mutli-ethnic, multisite cohort study of 3302 women aged 42-52 at baseline, designed to examine predictors of health and disease in women as they traversed the menopause. Inclusion criteria were: an intact uterus and at least one ovary present, at least one menstrual period in the previous three months, no use of sex steroid hormones in the previous three months, and not pregnant or lactating. A subset (n = 849) of women aged 43-53 years from all study sites in the first Daily Hormone Study collection were evaluated for this substudy. OUTCOME MEASURES: We measured daily VMS, and urinary hormones: follicle stimulating hormone (FSH), luteinizing hormone (LH), pregnanediol glucuronide (PdG) and estradiol (estrone conjugate, E1C). RESULTS: A variable pattern of LH and negative LH feedback were the hormone patterns most strongly associated with increased VMS. In contrast, no hormone pattern was significantly related to negative mood. CONCLUSION: Fluctuations of LH associated with low progesterone production were associated with VMS but not negative mood, suggesting different endocrine patterns may be related to increased negative mood than to the occurrence of VMS.

The Story of Wall Shear Stress in Coronary Artery Atherosclerosis: Biochemical Transport and Mechanotransduction.

Coronary artery atherosclerosis is a local, multifactorial, complex disease, and the leading cause of death in the US. Complex interactions between biochemical transport and biomechanical forces influence disease growth. Wall shear stress (WSS) affects coronary artery atherosclerosis by inducing endothelial cell mechanotransduction and by controlling the near-wall transport processes involved in atherosclerosis. Each of these processes is controlled by WSS differently and therefore has complicated the interpretation of WSS in atherosclerosis. In this paper, we present a comprehensive theory for WSS in atherosclerosis. First, a short review of shear stress-mediated mechanotransduction in atherosclerosis was presented. Next, subject-specific computational fluid dynamics (CFD) simulations were performed in ten coronary artery models of diseased and healthy subjects. Biochemical-specific mass transport models were developed to study low-density lipoprotein, nitric oxide, adenosine triphosphate, oxygen, monocyte chemoattractant protein-1, and monocyte transport. The transport results were compared with WSS vectors and WSS Lagrangian coherent structures (WSS LCS). High WSS magnitude protected against atherosclerosis by increasing the production or flux of atheroprotective biochemicals and decreasing the near-wall localization of atherogenic biochemicals. Low WSS magnitude promoted atherosclerosis by increasing atherogenic biochemical localization. Finally, the attracting WSS LCS's role was more complex where it promoted or prevented atherosclerosis based on different biochemicals. We present a summary of the different pathways by which WSS influences coronary artery atherosclerosis and compare different mechanotransduction and biotransport mechanisms.

Vasomotor symptoms and lipids/lipoprotein subclass metrics in midlife women: Does level of endogenous estradiol matter? The SWAN HDL Ancillary Study.

BACKGROUND: A greater frequency of vasomotor symptoms (VMSs) has been associated with higher low-density lipoprotein cholesterol (LDL-C), but the association with high-density lipoprotein cholesterol (HDL-C) remains unclear. Endogenous estradiol (E2) levels are associated with both VMS and lipid levels and thus may confound such associations. OBJECTIVES: To assess the relationship of VMS frequency with HDL-C, LDL-C, and lipoprotein concentrations (HDL and LDL particles [HDL-P; LDL-P]) and lipoprotein sizes in midlife women and to evaluate whether these associations are explained by E2. METHODS: Participants were from the Study of Women's Health Across the Nation (SWAN) HDL ancillary study who had both nuclear magnetic resonance (NMR) spectroscopy lipoprotein subclass metrics and self-reported frequency of VMS measured 2-5 times over the menopause transition. VMS frequency was categorized into none, 1-5 days (infrequent), or ≥6 days (frequent) within the past 2 weeks. RESULTS: We evaluated 522 women [at baseline: mean age 50.3 (SD: 2.8) years; infrequent VMS: 29.8%, frequent VMS: 16.5%]. Adjusting for potential confounders except E2, frequent VMS was associated with smaller HDL size [ß(SE): -0.06 (0.03); P = .04] and higher concentrations of LDL-C [ß(SE): 3.58 (1.77); P = .04] and intermediate LDL-P [ß(SE): 0.09 (0.05); P = .04] than no VMS. These associations were largely explained by E2, all P's > .05. CONCLUSIONS: Frequent VMSs were associated with smaller HDL size and higher concentrations of LDL-C and intermediate LDL-P. These associations were explained by endogenous E2. Whether treating frequent VMS with exogenous E2 could simultaneously improve lipids/lipoproteins profile should be assessed in future studies.

Validation and Comparison of Tools for Selecting Individuals to Screen for Barrett's Esophagus and Early Neoplasia.

BACKGROUND & AIMS: Guidelines suggest endoscopic screening of individuals who are at increased risk for Barrett's esophagus (BE) and esophageal adenocarcinoma. Tools based on clinical factors are available for identifying patients at risk, but only some have been validated. We aimed to compare and validate available tools. METHODS: We performed a prospective study of 1241 patients, ages 40 to 79 years, presenting either for their first esophagogastroduodenoscopy (EGD) or their first endoscopic therapy of early neoplastic BE, from April 2015 through June 2018. We calculated risk scores for 6 previously published tools (the Gerson, Locke, Thrift, Michigan BE pREdiction Tool [M-BERET], Nord-Trøndelag Health Study [HUNT], and Kunzmann tools). We also investigated the accuracy of frequency and duration of gastroesophageal reflux disease (GERD), using data from a randomly selected 50% of patients undergoing their first EGD. We compared the ability of all these tools to discriminate patients with BE and early neoplasia from patients without BE, using findings from endoscopy as the reference standard. RESULTS: BE was detected in 81 of 1152 patients during their first EGD (7.0%). GERD symptoms alone identified patients with BE with an area under the receiver operating characteristic curve (AuROC) of 0.579. All of the tools were more accurate in identifying patients with BE than the frequency and duration of GERD (AuROC for GERD, 0.579 vs range for other tools, 0.660-0.695), and predicted risk correlated well with observed risk (calibration). The AUROCs of the HUNT tool (0.796), the M-BERET (0.773), and the Kunzmann tool (0.763) were comparable in discriminating between patients with early neoplasia (n = 94) vs no BE. Each tool was more accurate in discriminating BE with early neoplasia than GERD frequency and duration alone (AuROC, 0.667; P < .01). CONCLUSIONS: The HUNT, M-BERET, and Kunzmann tools identify patients with BE with AuROC values ranging from 0.665 to 0.695, and discriminate patients with early neoplasia from patients without BE with AuROC values ranging from 0.763 to 0.796. These tools are more accurate than frequency and duration of GERD in identifying individuals at risk for neoplastic BE.

Antimullerian Hormone and Impending Menopause in Late Reproductive Age: The Study of Women's Health Across the Nation.

BACKGROUND: A test that helps predict the time to the final menstrual period (FMP) has been sought for many years. OBJECTIVE: To assess the ability of antimullerian hormone (AMH) measurements to predictions the time to FMP. DESIGN: Prospective longitudinal cohort study. SETTING: The Study of Women's Health Across the Nation. PARTICIPANTS AND MEASUREMENTS: AMH and FSH were measured in 1537 pre- or early perimenopausal women, mean age 47.5 ±â€…2.6 years at baseline, then serially until 12 months of amenorrhea occurred. AMH was measured using a 2-site ELISA with a detection limit of 1.85 pg/mL. MAIN OUTCOME MEASURE: Areas under the receiver operating curves (AUC) for AMH-based and FSH-based predictions of time to FMP, stratified by age. Probabilities that women would undergo their FMP in the next 12, 24, or 36 months across a range of AMH values were assessed. RESULTS: AUCs for predicting that the FMP will occur within the next 24 months were significantly greater for AMH-based than FSH-based models. The probability that a woman with an AMH <10 pg/mL would undergo her FMP within the next 12 months ranged from 51% at h<48 years of age to 79% at ≥51 years. The probability that a woman with an AMH >100 pg/mL would not undergo her FMP within the next 12 months ranged from 97% in women <48 years old to 90% in women ≥51 years old. CONCLUSIONS: AMH measurement helps estimate when a woman will undergo her FMP, and, in general, does so better than FSH.

Stressors, allostatic load, and health outcomes among women hotel housekeepers: A pilot study.

Hotel housekeepers are exposed to stressors at work and outside of work. A minimal amount is known about these workers' pathophysiological responses to those stressors. Allostatic load is a concept increasingly used to understand pathophysiologic manifestations of individuals' bodily response to stress. The purpose of this study was to examine the associations between work and nonwork stressors, allostatic load, and health outcomes among hotel housekeepers. Work and nonwork stressors (e.g., the number of traumatic events, everyday discrimination, and job strain) and health outcomes (e.g., general health status, physical and mental health, and chronic diseases) were measured. Biometric and anthropometric measures and fasting blood specimens were collected. Blood biomarkers included CRP, HbA1c, HDL, and cortisol. Descriptive analyses, correlations, regressions, and t-tests were conducted. Forty-nine women hotel housekeepers participated, with a mean age of 40 years. One-fifth reported high job strain and more than 40% had at least one traumatic event. Chronic conditions were commonly reported, with about 78%, 55%, and 35% reporting one, two, and three chronic conditions, respectively. Correlation analyses showed that reports of high job strain and everyday discrimination were significantly associated with high ALI quartile score (r = 0.39, p = 0.011; r = 0.41, p = 0.004). Job strain and everyday discrimination had medium to large effect sizes on ALI quartile scores. High ALI quartile score was significantly associated with having at least one chronic disease (r = 0.40, p = 0.005), and it had a large effect size on chronic diseases. To our knowledge, this is the first study to explore allostatic load among hotel housekeepers. Hotel housekeepers have high exposure to stressors within and outside of their work and experience poor chronic conditions. Allostatic load had strong associations with both stressors and health outcomes. Despite this worker group being a hard-to-reach worker group to participate in research studies, this study demonstrates the feasibility of accessing, recruiting and collecting survey data and blood samples among them to determine health risks and guide future targeted interventions.

Association of Vitamin D and Parathyroid Hormone With Barrett's Esophagus.

BACKGROUND: Esophageal adenocarcinoma has been inversely associated with exposure to ultraviolet radiation. This could be because of vitamin D deficiency or hyperparathyroidism promoting gastroesophageal reflux disease (GERD) and Barrett's esophagus. AIM: The aim of this study is to determine the association between parathyroid hormone (PTH) and vitamin D deficiency with GERD symptoms, erosive esophagitis, and Barrett's esophagus. METHODS: We assayed banked serum for PTH and total 25-hydroxy vitamin D from a cross-sectional cohort. Logistic regression was performed to estimate the associations of vitamin D deficiency and hyperparathyroidism with GERD symptoms, erosive esophagitis, and Barrett's esophagus. RESULTS: Sera from 605 men were assayed, including 150 with GERD, 216 with erosive esophagitis, 145 with Barrett's esophagus, and 174 normal subjects. Contrary to our hypothesis, we found a strong inverse association between Barrett's esophagus and hyperparathyroidism (odds ratio=0.516; 95% confidence interval=0.265, 1.01), and a trend toward an inverse association with vitamin D deficiency. We found no association between vitamin D deficiency or hyperparathyroidism with GERD symptoms or erosive esophagitis. CONCLUSIONS: Contrary to our hypothesis, we found an inverse association between serum PTH and Barrett's esophagus. Validation of the finding and the mechanism of that association deserves further study.

Age at Onset of Metabolic Syndrome Among Women With and Without Polycystic Ovary Syndrome-Like Status.

CONTEXT: Women with polycystic ovary syndrome (PCOS) have a higher prevalence of metabolic syndrome (MetS), but whether they develop MetS earlier than women without PCOS is unknown. Understanding the impact of PCOS on the timing of MetS onset is important for screening and clinical care in this population. DESIGN: Women with PCOS-like status (PCOSp) were identified from participants of the Michigan Bone Health and Metabolism Study based upon history of irregular menstrual cycles, high free-androgen index, and high levels of antimüllerian hormone. MetS was defined according to the Adult Treatment Panel III criteria. Age at MetS onset was compared between women with and without PCOSp using an accelerated failure time model adjusted for baseline education, lifestyle factors, and midlife body weight. RESULTS: Among the 496 women in the analysis, 11.7% (n = 58) were determined to have PCOSp. Over a mean follow-up of 11 years, 20 women with PCOSp and 136 women without PCOSp developed MetS. After adjusting for smoking, education, and physical activity, women with PCOSp developed MetS at an age 14.4% (95% CI -22.7, -5.2) younger than women without PCOSp. The magnitude of the association was attenuated to 5.4% in models additionally adjusted for body mass index (95% CI -12.4, 2.1). Because a typical study participant without PCOSp developed MetS at 51.5 years old, 5.4% translates to almost 3 years earlier onset of MetS for a comparable woman with PCOSp. CONCLUSIONS: Women with PCOSp develop MetS at a younger age. Earlier screening for MetS in women with PCOS may be warranted.

Examining associations between action game play and motor control.

The effects of playing action video games have been investigated across a wide range of attentional and cognitive abilities. However, few studies have examined the association between motor control and action gaming experience. We report data from two discrete pointing tasks, manipulating the index of difficulty (ID) by movement distance and target size, respectively. Participants' gaming experience ranged from non-players to individuals who played several hours a night. Our results indicated greater experience playing action games, but not video games in general, was associated with shorter movement times (MT), higher velocities, and shallower ID-MT slopes when difficulty was manipulated across increasingly further distances and smaller target sizes. Additionally casual players, those who only play action games a couple times a week, were able to achieve a similar level of performance as more experienced players.

Cutaneous squamous cell carcinoma: predictors of positive and close margins and outcomes of re-excision in Northland, New Zealand.

BACKGROUND: Non-melanoma skin cancer (NMSC) is the most commonly diagnosed and costly cancer in Australasia. Cutaneous squamous cell carcinoma (cSCC) accounts for approximately 25% of NMSC. A better understanding of predictors of close and positive margins following surgical excision will help guide treatment. METHODS: A retrospective study was carried out of all primary cSCC histologically diagnosed in Northland, New Zealand in 2015. The cohort was identified by searching the regional pathology database. The primary outcome of interest was positive and close (≤1mm) margin rate following surgical excision and factors influencing them. Secondary outcomes of interest were outcomes of re-excisions. RESULTS: A total of 1,040 cSCC were identified in 890 unique patients and 825 lesions were surgically excised. Increased odds of positive margin on surgical excision was found with increased tumour thickness (OR 1.56, 95% CI 1.24-1.96), tumours from the head and neck (OR 2.78, 95% CI 1.33-5.80) and those excised in primary care (OR 2.20, 95% CI 1.07-4.52). Increased odds of close margins was found in females (OR 2.01, 95% CI 1.3-3.2) and excision in primary care (OR 2.44 95% CI 1.5-3.98). Residual tumour was present in 13 (31.7%) patients with positive margins and 0 patients with close margins. CONCLUSIONS: Lesions of the head and neck, those removed in primary care and with increased tumour thickness were more likely to have positive margins following surgical excision. Close margins were associated with excision in primary care and female gender. The value of re-excising tumours with close margins remains uncertain.

Impact of Postmastectomy Radiation Therapy in Prepectoral Versus Subpectoral Implant-Based Breast Reconstruction.

BACKGROUND: This study aimed to compare the impact of postmastectomy radiation therapy (PMRT) on outcomes after prepectoral versus subpectoral implant-based breast reconstruction with local deepithelialized dermal flap and acellular dermal matrix (ADM). METHODS: From 2010 to 2017, 274 patients (426 breasts) underwent prepectoral reconstruction. In this group, 241 patients (370 breasts) were not exposed to PMRT, whereas 45 patients (56 breasts) were exposed to PMRT. Of 100 patients (163 breasts) who underwent partial subpectoral reconstruction, 87 (140 breasts) were not exposed to PMRT, whereas 21 patients (23 breasts) were exposed. The outcomes were assessed by comparing complication rates between the pre- and subpectoral groups. RESULTS: A higher rate of capsular contracture was found for the prepectoral patients with PMRT than for those without PMRT (16.1 vs 3.5%; p = 0.0008) and for the subpectoral patients with PMRT than for those without PMRT (52.2 vs 2.9%; p = 0.0001). The contracture rate was three times higher for the subpectoral patients with PMRT than for the prepectoral patients with PMRT (52.2 vs 16.1%; p = 0.0018). In addition, 10 (83.3%) of 12 cases with capsular contracture in the subpectoral cohort that received PMRT were Baker grades 3 or 4 compared with only 2 (22.2%) of 9 cases of the prepectoral group with PMRT (p = 0.0092). CONCLUSIONS: The patients undergoing subpectoral breast reconstruction who received PMRT had a capsular contracture rate three times greater with more severe contractures (Baker grade 3 or 4) than the patients receiving PMRT who underwent prepectoral breast reconstruction.

The role of individual differences on perceptions of wearable fitness device trust, usability, and motivational impact.

Lack of physical activity is a severe health concern in the United States with fewer than half of all Americans meeting the recommended weekly physical activity guidelines. Although wearable fitness devices can be effective in motivating people to be active, consumers are abandoning this technology soon after purchase. We examined the impact of several user (i.e. personality, age, computer self-efficacy, physical activity level) and device characteristics (trust, usability, and motivational affordances) on the behavioral intentions to use a wearable fitness device. Novice users completed a brief interaction with a fitness device similar to a first purchase experience before completing questionnaires about their interaction. We found computer self-efficacy, physical activity level, as well as personality traits indirectly increased the desire to use a fitness device and influenced the saliency of perceived motivational affordances. Additionally, trust, usability, and perceived motivational affordances were associated with increased intentions to use fitness devices.

Incidence, demographics and surgical outcomes of cutaneous squamous cell carcinoma diagnosed in Northland, New Zealand.

AIM: Non-melanoma skin cancer (NMSC) is the most commonly diagnosed and most costly cancer in Australasia. Cutaneous squamous cell carcinoma (cSCC) accounts for approximately 25% of NMSC. Despite this, reporting of cSCC is not mandatory in Australasia. This creates difficulties in planning, resourcing and improving outcomes in cSCC. Previous studies in New Zealand have lacked data on ethnicity. The aim of this study was to define the incidence and demographics of cSCC diagnosed in Northland, New Zealand, including data on ethnicity. METHODS: A 12-month retrospective study was carried out of all primary cSCC histologically diagnosed in Northland for one year. The cohort was identified by searching the Northland District Health Board pathology database. Data on outcomes and ethnicity were obtained from the hospital results system. Primary outcome of interest was the incidence of cSCC in Northland. Secondary outcomes of interest were lesion characteristics and positive margin rate. RESULTS: 1,040 cSCC were identified in 890 patients. Mean age of patients was 75. Crude incidence of primary cSCC was 668/100,000 patient years. Age standardised incidence was 305/100,000 patient years. An estimate of New Zealand incidence adjusted for age and ethnicity is 580/100,000 patient years. Overall positive margin rate in excised lesions was 9.5%. CONCLUSION: This study has defined the rate of cSCC in a large, well defined New Zealand population, and estimated age and ethnicity adjusted incidence in New Zealand. It has demonstrated the highest incidence of cSCC in the world outside Australia. Overall positive margin rate of excised lesions was acceptable.

Searching for Affective and Cognitive Restoration: Examining the Restorative Effects of Casual Video Game Play.

OBJECTIVE: We investigated the effects of a passive break, relaxation activity, and casual video game on affect, stress, engagement, and cognitive performance. BACKGROUND: Reducing stress and improving cognitive performance is critical across many domains. Previous studies investigated taking a break, relaxation techniques, or playing a game; however, these methods have not been compared within a single experiment. METHOD: Participants completed a baseline affective and cognitive assessment (ACA), which included the Positive and Negative Affect Schedule, shortened version of the Dundee Stress State Questionnaire, and backward digit-span. Next, participants completed a vigilance task, followed by another ACA. Participants were then assigned at random to complete a break or relaxation activity or play a casual video game, followed by a final ACA. RESULTS: Participants who played the casual video game exhibited greater engagement and affective restoration than the relaxation condition. The break condition slightly decreased affect and prevented cognitive restoration. CONCLUSION: Playing a casual video game even briefly can restore individuals' affective abilities, making it a suitable activity to restore mood in response to stress. However, future research is needed to find activities capable of cognitive restoration. APPLICATION: Many activities in life require sustained cognitive demand, which are stressful and decrease performance, especially for workers in performance-critical domains. Our research suggests some leisure activities are better than others for restoring fatigued affective processes.