Multi-ancestry genome-wide gene-sleep interactions identify novel loci for blood pressure.

Long and short sleep duration are associated with elevated blood pressure (BP), possibly through effects on molecular pathways that influence neuroendocrine and vascular systems. To gain new insights into the genetic basis of sleep-related BP variation, we performed genome-wide gene by short or long sleep duration interaction analyses on four BP traits (systolic BP, diastolic BP, mean arterial pressure, and pulse pressure) across five ancestry groups in two stages using 2 degree of freedom (df) joint test followed by 1df test of interaction effects. Primary multi-ancestry analysis in 62,969 individuals in stage 1 identified three novel gene by sleep interactions that were replicated in an additional 59,296 individuals in stage 2 (stage 1 + 2 Pjoint < 5 × 10-8), including rs7955964 (FIGNL2/ANKRD33) that increases BP among long sleepers, and rs73493041 (SNORA26/C9orf170) and rs10406644 (KCTD15/LSM14A) that increase BP among short sleepers (Pint < 5 × 10-8). Secondary ancestry-specific analysis identified another novel gene by long sleep interaction at rs111887471 (TRPC3/KIAA1109) in individuals of African ancestry (Pint = 2 × 10-6). Combined stage 1 and 2 analyses additionally identified significant gene by long sleep interactions at 10 loci including MKLN1 and RGL3/ELAVL3 previously associated with BP, and significant gene by short sleep interactions at 10 loci including C2orf43 previously associated with BP (Pint < 10-3). 2df test also identified novel loci for BP after modeling sleep that has known functions in sleep-wake regulation, nervous and cardiometabolic systems. This study indicates that sleep and primary mechanisms regulating BP may interact to elevate BP level, suggesting novel insights into sleep-related BP regulation.

Mixed-mode versus paper surveys for patient-reported outcomes after critical illness: A randomised controlled trial.

OBJECTIVE: The aim of the study was to determine the response rate to a mixed-mode survey using email compared with that to a paper survey in survivors of critical illness. DESIGN: This is a prospective randomised controlled trial. SETTING: The study was conducted at a single-centre quaternary intensive care unit (ICU) in Adelaide, Australia. PARTICIPANTS: Study participants were patients admitted to the ICU for ≥48 h and discharged from the hospital. INTERVENTIONS: The participants were randomised to receive a survey by paper (via mail) or via online (via email, or if a non-email user, via a letter with a website address). Patients who did not respond to the initial survey received a reminder paper survey after 14 days. The survey included quality of life (EuroQol-5D-5L), anxiety and depression (Hospital Anxiety and Depression Scale), and post-traumatic symptom (Impact of Event Scale-Revised) assessment. MAIN OUTCOME MEASURES: Survey response rate, extent of survey completion, clinical outcomes at different time points after discharge, and survey cost analysis were the main outcome measures. Outcomes were stratified based on follow-up time after ICU discharge (3, 6, and 12 months). RESULTS: A total of 239 patients were randomised. The response rate was similar between the groups (mixed-mode: 78% [92/118 patients] vs. paper: 80% [97/121 patients], p = 0.751) and did not differ between time points of follow-up. Incomplete surveys were more prevalent in the paper group (10% vs 18%). The median EuroQol-5D-5L index value was 0.83 [0.71-0.92]. Depressive symptoms were reported by 25% of patients (46/187), anxiety symptoms were reported by 27% (50/187), and probable post-traumatic stress disorder was reported by 14% (25/184). Patient outcomes did not differ between the groups or time points of follow-up. The cost per reply was AU$ 16.60 (mixed-mode) vs AU$ 19.78 (paper). CONCLUSION: The response rate of a mixed-mode survey is similar to that of a paper survey and may provide modest cost savings.

Impact of Transfer Learning Using Local Data on Performance of a Deep Learning Model for Screening Mammography.

Purpose To investigate the issues of generalizability and replication of deep learning models by assessing performance of a screening mammography deep learning system developed at New York University (NYU) on a local Australian dataset. Materials and Methods In this retrospective study, all individuals with biopsy or surgical pathology-proven lesions and age-matched controls were identified from a South Australian public mammography screening program (January 2010 to December 2016). The primary outcome was deep learning system performance-measured with area under the receiver operating characteristic curve (AUC)-in classifying invasive breast cancer or ductal carcinoma in situ (n = 425) versus no malignancy (n = 490) or benign lesions (n = 44). The NYU system, including models without (NYU1) and with (NYU2) heatmaps, was tested in its original form, after training from scratch (without transfer learning), and after retraining with transfer learning. Results The local test set comprised 959 individuals (mean age, 62.5 years ± 8.5 [SD]; all female). The original AUCs for the NYU1 and NYU2 models were 0.83 (95% CI: 0.82, 0.84) and 0.89 (95% CI: 0.88, 0.89), respectively. When NYU1 and NYU2 were applied in their original form to the local test set, the AUCs were 0.76 (95% CI: 0.73, 0.79) and 0.84 (95% CI: 0.82, 0.87), respectively. After local training without transfer learning, the AUCs were 0.66 (95% CI: 0.62, 0.69) and 0.86 (95% CI: 0.84, 0.88). After retraining with transfer learning, the AUCs were 0.82 (95% CI: 0.80, 0.85) and 0.86 (95% CI: 0.84, 0.88). Conclusion A deep learning system developed using a U.S. dataset showed reduced performance when applied "out of the box" to an Australian dataset. Local retraining with transfer learning using available model weights improved model performance. Keywords: Screening Mammography, Convolutional Neural Network (CNN), Deep Learning Algorithms, Breast Cancer Supplemental material is available for this article. © RSNA, 2024 See also commentary by Cadrin-Chênevert in this issue.

Is the Association between Age and Fertility Problems Modified by Diet Quality? Findings from a National Study of Reproductive Age Women in Australia.

Background: Increasing age is a strong risk factor for infertility, and there is accumulating evidence of the importance of a healthier diet for fertility. Whether a healthier diet modifies the association between increasing age and infertility has not been investigated. This study aimed to (i) examine if better diet quality could help reduce age-related infertility; and (ii) assess whether changes in diet quality over time are associated with fertility problems. Methods: Data were from Surveys 3 and 5 of the 1973−1978 birth cohort of the Australian Longitudinal Study on Women's Health. Cross-sectional analysis with multivariable generalized linear models were used to examine the association between age and fertility status, adjusted for various confounders. Multiplicative and additive effect modification by diet quality was assessed, with additive effect modification evaluated with the relative risk for interaction (RERI). Results: In total, 3387 women were included from Survey 3 (age range 24−31 years) and 5614 women from Survey 5 (age range 30−38 years); 588 (17.4%) and 1321 (23.4%) self-reported to have fertility problems in the respective surveys. In Survey 3, compared to younger women with a good-quality diet, older women with a poor-quality diet had a 43% increased risk for fertility problems, with risk increasing after further adjustment for BMI (RR: 1.59; 95% CI: 1.07, 2.37) and PCOS (RR: 1.74; 95% CI: 1.15, 2.62). In Survey 5 in younger women (<33.9 years), there was no association between diet quality and risk for infertility problems. The RERI (across different adjusted models) was between −0.08 (−0.70, 0.55) to −0.39 (−1.40, 0.62) in survey 3 and 0.07 (−0.17, 0.31) to 0.08 (−0.17, 0.32) in Survey 5. Conclusions: There is little evidence to suggest effect modification on the effect of age and fertility problems with diet quality.

Long-term outcomes of breast reconstruction and the need for revision surgery.

BACKGROUND: Breast reconstruction (BR) often forms part of a patient's breast cancer journey. Revision surgery may be required to maintain the integrity of a BR, although this is not commonly reported in the literature. Different reconstructive methods may have differing requirements for revision. It is important for patients and surgeons to understand the factors leading to the need for revision surgery. METHODS: This retrospective cohort study analyses BRs performed by oncoplastic breast surgeons in public and private settings between 2005 and 2014, with follow-up until December 2018. Surgical and patient factors were examined, including types of BR, complications and reasons for revision surgery. RESULTS: A total of 390 women with 540 reconstructions were included, with a median follow-up of 61 months. Twenty-eight percent (151/540) of reconstructions required at least one revision operation. Overall, implant-based reconstructions (direct-to-implant [DTI] and two-stage expander-implant) had a higher revision rate compared to pedicled flap reconstructions (odds ratio 1.91, 95% confidence interval 1.08, 3.38). DTI reconstructions had the highest odds, and pedicled flap without implants the lowest odds of requiring revision. Post-reconstruction radiotherapy increased the chance of revision surgery, while pre-reconstruction radiotherapy did not. Odds of revision were higher in implant-based reconstructions compared to pedicled flap reconstructions that had radiotherapy. Other factors increasing the rates of revision surgery were being a current smoker and post-operative infection. CONCLUSION: Almost one-third of reconstructive patients require revision surgery. Autologous pedicled flap reconstructions have lower rates of revision compared to implant-based reconstructions. Radiotherapy increases the need for revision surgery, particularly in implant-based reconstructions.

Physical activity is associated with reduced prevalence of self-reported obstructive sleep apnea in a large, general population cohort study.

STUDY OBJECTIVES: Obstructive sleep apnea (OSA) is a common condition with significant symptoms and long-term adverse cognitive, mental health, vascular, and respiratory sequelae. Physical activity has been recognized as a key determinant for good health and has been associated with lower risk of these sequelae. We hypothesized that increased physical activity may be associated with a decreased prevalence of OSA. METHODS: This cross-sectional study used baseline questionnaire data from the Ontario Health Study, a population-based cohort of residents of Ontario, Canada. Participants were adults who provided lifestyle, medical, socio-demographic, and sleep health information. The study sample consisted of 155,448 men (39.8%) and women (60.2%). The prevalence of physician-diagnosed OSA in this cohort was 6.9%. Logistic regression models were used to investigate the association of OSA with physical activity. Missing data were imputed using a multiple imputation by chained equation approach. RESULTS: In multivariable analyses adjusted for potential confounding factors, increased total physical activity (metabolic equivalent [h/wk]) (odds ratio [OR] = .98, 95% confidence interval [CI] = .96 to 1.00), vigorous-intensity activity (OR = .98, 95% CI = .97 to 1.00), and walking (OR = .98, 95% CI = .96 to 1.00) were all associated (all P ≤ .045) with decreased prevalence of OSA. Moderate-intensity activity was not associated with risk of OSA (P = .826). CONCLUSIONS: Independent of known risk factors for OSA, including body mass index, increased levels of physical activity, including walking, were associated with a prevalence of OSA. Our results highlight the importance of physical activity as a preventive measure for sleep apnea.

The Relationship of Sleep Duration with Ethnicity and Chronic Disease in a Canadian General Population Cohort.

STUDY OBJECTIVES: Sleep duration is an important marker of sleep quality and overall sleep health. Both too little and too much sleep are associated with poorer health outcomes. We hypothesized that ethnicity-specific differences in sleep duration exist. METHODS: This cross-sectional study utilized questionnaire data from the Ontario Health Study (OHS), a multi-ethnic population-based cohort of Canadian adult residents aged 18 to 99 years, who provided medical, socio-demographic, and sleep information. Generalised linear models were used to investigate the association of sleep duration with ethnicity. RESULTS: The study sample consisted of 143,307 adults (60.4% women). The sample was multi-ethnic, including self-identified Aboriginal, Arab, Black, Chinese, Filipino, Hispanic, Japanese, Korean, Mixed (>1 ethnicity), South Asian, South-East Asian, West Asian, and White ethnicities. Univariate analyses found that mean sleep duration compared to the White reference group (7.34 hours) was shorter in the Filipino (6.93 hours, 25 min less), Black (6.96 hours, 23 min less), Japanese (7.02 hours, 19 min less), Chinese (7.23 hours, 7 min less), and Mixed (7.27 hours, 4 min less) groups (all P<0.001). Mean sleep duration was shorter in men (7.25 hours) compared to women (7.37 hours) in the cohort as a whole (P<0.001), and in all ethnic groups (P<0.001). Multivariate analyses, adjusted for a wide range of potential risk factors, and analysis of sleep duration as a categorical variable ("short", "average", and "long" sleepers) confirmed these relationships. Both sleep duration and ethnicity were independent significant predictors of a range of physician-diagnosed morbidities including diabetes, stroke, and depression. CONCLUSION: Important differences exist in sleep duration between ethnic groups and may contribute to observed health disparities. Our results highlight the need for ethnicity-specific targeted education on the importance of prioritizing sleep for good health, and the need to account appropriately for ethnicity in future epidemiological, clinical, and translational research into sleep and related conditions.