Actigraphic and self-reported characterization of sleep in systemic lupus erythematosus patients.

OBJECTIVES: In a cross-sectional study, we explored possible differences in sleep parameters between SLE patients and age- and gender-matched healthy controls through actigraphic and self-reported measures. Furthermore, we aimed to identify possible predictors of such disturbances in the patient cohort. METHODS: Participants' sociodemographic data and sleep parameters were collected. Sleep parameters were evaluated through the Pittsburgh Sleep Quality Index, the Insomnia Severity Index and 7-day actigraphic monitoring. The 10-item Perceived Stress Scale was used to investigate stress. Disease activity and daily glucocorticoid dose were assessed in SLE patients. Possible predictors of the SLE group were explored through two binomial logistic models. Within the SLE group, possible predictors of sleep parameters were tested estimating multiple linear regression models. RESULTS: A total of 40 SLE patients and 33 controls were included in the study. The SLE group showed worse sleep maintenance actigraphic parameters (i.e. sleep efficiency and wake after sleep onset), higher total sleep time and higher perceived stress. Within the SLE cohort, the daily glucocorticoids dose was associated with an impairment in sleep maintenance despite no reduction in sleep duration, typical of normal sleep duration insomnia, whereas perceived stress was associated with short sleep duration insomnia. CONCLUSION: Compared with healthy controls, SLE patients showed worse sleep quality and greater perceived stress severity. As glucocorticoids and perceived stress are associated with different types of insomnia in these patients, a multidimensional approach to both sleep characterization and therapy might be preferred.

Optimizing the Time and Dose of Melatonin as a Sleep-Promoting Drug: A Systematic Review of Randomized Controlled Trials and Dose-Response Meta-Analysis.

Previous studies have reported inconsistent results about exogenous melatonin's sleep-promoting effects. A possible explanation relies on the heterogeneity in administration schedule and dose, which might be accountable for differences in treatment efficacy. In this paper, we undertook a systematic review and meta-analysis of double-blind, randomized controlled trials performed on patients with insomnia and healthy volunteers, evaluating the effect of melatonin administration on sleep-related parameters. The standardized mean difference between treatment and placebo groups in terms of sleep onset latency and total sleep time were used as outcomes. Dose-response and meta-regression models were estimated to explore how time of administration, dose, and other treatment-related parameters might affect exogenous melatonin's efficacy. We included 26 randomized controlled trials published between 1987 and 2020, for a total of 1689 observations. Dose-response meta-analysis showed that melatonin gradually reduces sleep onset latency and increases total sleep time, peaking at 4 mg/day. Meta-regression models showed that insomnia status (ß = 0.50, p < 0.001) and time between treatment administration and the sleep episode (ß = -0.16, p = 0.023) were significant predictors of sleep onset latency, while the time of day (ß = -0.086, p < 0.01) was the only significant predictor of total sleep time. Our results suggest that advancing the timing of administration (3 h before the desired bedtime) and increasing the administered dose (4 mg/day), as compared to the exogenous melatonin schedule most used in clinical practice (2 mg 30 min before the desired bedtime), might optimize the efficacy of exogenous melatonin in promoting sleep.

Morning naps architecture and mentation recall complexity.

Mentation reports were collected after spontaneous awakenings from morning naps in 18 healthy participants, and associations between sleep stages duration and complexity of recalled mentation were investigated. Participants were continuously recorded with polysomnography and allowed to sleep for a maximum of 2 hr. Mentation reports were classified according to both their complexity (1-6 scale) and their perceived timing of occurrence (Recent or Previous Mentation with respect to the final awakening). The results showed a good level of mentation recall, including different types of mentation with lab-related stimuli. N1 + N2 duration was positively related to the complexity of Previous Mentation recall, while rapid eye movement sleep duration was negatively related. This suggests that the recall of complex mentation, such as dreaming with a plot, occurring far from awakening may depend on the length of N1 + N2. However, the duration of sleep stages did not predict the complexity of Recent Mentation recall. Nevertheless, 80% of participants who recalled Recent Mentation had a rapid eye movement sleep episode. Half of the participants reported incorporating lab-related stimuli in their mentation, which positively correlated with both N1 + N2 and rapid eye movement duration. In conclusion, nap sleep architecture is informative about the complexity of dreams perceived as having occurred early during the sleep episode, but not about those perceived as recent.

Chronotype is differentially associated with lifetime mood and panic-agoraphobic spectrum symptoms in patients with bipolar disorder and healthy controls.

OBJECTIVE: Although the association between chronotype and mood disorders has been consistently reported, conversely, attempts to measure the association between chronotype and anxiety symptoms have generated inconsistent results. We aimed at evaluating whether chronotype (assessed through subjective and objective measures) is associated with lifetime mood and panic-agoraphobic spectrum symptoms in healthy controls (HCs) and in patients with bipolar disorder (BD). METHODS: Overall, 173 subjects, patients with BD in euthymic phase (n = 76) and HC (n = 97), were evaluated through the reduced Morningness-Eveningness Questionnaire (rMEQ), actigraphy monitoring and mood and panic-agoraphobic spectrum self-report (MOODS-SR and PAS-SR). The discrepancy between objective (actigraphic-based) versus subjective (rMEQ-based) circadian typology was estimated through the Circadian Classification Discrepancy Index (CCDI). RESULTS: rMEQ-based evening chronotype (ET) was associated with higher scores in MOODS-SR depressive and rhythmicity and vegetative functions domains in HC and BD.Both ET and morning chronotypes (MT) were associated with higher PAS-SR scores in BD only. Actigraphic-based MT was associated with higher MOODS-SR depressive scores in HC. Likewise, the discrepancy between actigraphic-based and rMEQ-based circadian typology was associated with depressive symptoms in HC only. CONCLUSION: Self-reported ET was consistently associated with mood symptoms, while associations with panic-agoraphobic symptoms only emerged in BD and involved both extreme chronotypes. The discrepancy between the preferred circadian typology (rMEQ-based) and the actual one (actigraphic-based) could contribute to depressive symptoms in HC. These results pave the way for interventional studies targeting circadian typology in an attempt to prevent or treat mental health disorders.

Handling shifts during an overnight sailing regatta: Comparison between sleep management strategies.

The study aims to investigate the association between different sleep management strategies and the final ranking during a one-night sailing race. A large sample of 190 teams participating in the overnight sailing regatta (151 Miglia) were included in the study. The experimental design consisted of two surveys, administered one before the start of the race and the other after the arrival. The questionnaires provided general information on the sailboat, its crew, and the strategy adopted to manage sleep during the race. In this one-night regatta, the self-management of sleep/wake timing emerged as the most successful strategy. Among participants who adopted a shift-based racing strategy, a short night shift duration (i.e., 2 h) significantly predicted a better placement. These findings confirmed the relevance of sleep management in sport performance and provided new insights into the most suitable sleep management strategy during a relatively short offshore regatta. The conclusions might apply also to similar continuous-cycle activities. Further investigations are needed to explore best sleep management strategy in team regattas of longer duration.

Heart rate detection by Fitbit ChargeHR™ : A validation study versus portable polysomnography.

Consumer "Smartbands" can collect physiological parameters, such as heart rate (HR), continuously across the sleep-wake cycle. Nevertheless, the quality of HR data detected by such devices and their place in the research and clinical field is debatable, as they are rarely rigorously validated. The objective of the present study was to investigate the reliability of pulse photoplethysmographic detection by the Fitbit ChargeHR™ (FBCHR, Fitbit Inc.) in a natural setting of continuous recording across vigilance states. To fulfil this aim, concurrent portable polysomnographic (pPSG) and the Fitbit's photoplethysmographic data were collected from a group of 25 healthy young adults, for ≥12 hr. The pPSG-derived HR was automatically computed and visually verified for each 1-min epoch, while the FBCHR HR measurements were downloaded from the application programming interface provided by the manufacturer. The FBCHR was generally accurate in estimating the HR, with a mean (SD) difference of -0.66 (0.04) beats/min (bpm) versus the pPSG-derived HR reference, and an overall Pearson's correlation coefficient (r) of 0.93 (average per participant r = 0.85 ± 0.11), regardless of vigilance state. The correlation coefficients were larger during all sleep phases (rapid eye movement, r = 0.9662; N1, r = 0.9918; N2, r = 0.9793; N3, r = 0.9849) than in wakefulness (r = 0.8432). Moreover, the correlation coefficient was lower for HRs of >100 bpm (r = 0.374) than for HRs of <100 bpm (r = 0.84). Consistently, Bland-Altman analysis supports the overall higher accuracy in the detection of HR during sleep. The relatively high accuracy of FBCHR pulse rate detection during sleep makes this device suitable for sleep-related research applications in healthy participants, under free-living conditions.

Alcohol consumption in relation to carotid subclinical atherosclerosis and its progression: results from a European longitudinal multicentre study.

BACKGROUND/AIM: The association between alcohol consumption and subclinical atherosclerosis is still unclear. Using data from a European multicentre study, we assess subclinical atherosclerosis and its 30-month progression by carotid intima-media thickness (C-IMT) measurements, and correlate this information with self-reported data on alcohol consumption. METHODS: Between 2002-2004, 1772 men and 1931 women aged 54-79 years with at least three risk factors for cardiovascular disease (CVD) were recruited in Italy, France, Netherlands, Sweden, and Finland. Self-reported alcohol consumption, assessed at baseline, was categorized as follows: none (0 g/d), very-low (0 - 5 g/d), low (> 5 to ≤ 10 g/d), moderate (> 10 to ≤ 20 g/d for women, > 10 to ≤ 30 g/d for men) and high (> 20 g/d for women, > 30 g/d for men). C-IMT was measured in millimeters at baseline and after 30 months. Measurements consisted of the mean and maximum values of the common carotids (CC), internal carotid artery (ICA), and bifurcations (Bif) and whole carotid tree. We used quantile regression to describe the associations between C-IMT measures and alcohol consumption categories, adjusting for sex, age, physical activity, education, smoking, diet, and latitude. RESULTS: Adjusted differences between median C-IMT values in different levels of alcohol consumption (vs. very-low) showed that moderate alcohol consumption was associated with lower C-IMTmax[- 0.17(95%CI - 0.32; - 0.02)], and Bif-IMTmean[- 0.07(95%CI - 0.13; - 0.01)] at baseline and decreasing C-IMTmean[- 0.006 (95%CI - 0.011; - 0.000)], Bif-IMTmean[- 0.016(95%CI - 0.027; - 0.005)], ICA-IMTmean[- 0.009(95% - 0.016; - 0.002)] and ICA-IMTmax[- 0.016(95%: - 0.032; - 0.000)] after 30 months. There was no evidence of departure from linearity in the association between alcohol consumption and C-IMT. CONCLUSION: In this European population at high risk of CVD, findings show an inverse relation between moderate alcohol consumption and carotid subclinical atherosclerosis and its 30-month progression, independently of several potential confounders.

Organisational factors and under-reporting of occupational injuries in Sweden: a population-based study using capture-recapture methodology.

OBJECTIVE: To estimate the magnitude of under-reporting of non-fatal occupational injuries (OIs) by different organisational factors in Sweden for the year 2013. METHODS: Capture-recapture methods were applied using two data sources: (1) the national OI register and (2) records from a labour market insurance company. To assure comparability of data sources, the analysis was restricted to the public sector and private companies with at least 50 employees. OIs were matched using personal identification number and reported injury dates (±7 days). Organisational factors were obtained from the national labour market register and injury severity (no healthcare/only outpatient/hospitalised) from the National Patient Register. Total number of OIs and ascertainment by data sources were estimated assuming data source independence. RESULTS: There were an estimated 98 493 OIs in 2013. Completeness of reporting OIs to the national register and to the insurance company was estimated at 73% and 43%, respectively. No report to either source was estimated at 15 000 OIs (~15%). Under-reporting to the national register differed by selected organisational factors, being higher among organisations in the public sector, those with more females, with a younger workforce and with a higher proportion of immigrants. Overall under-reporting was more common in agriculture (19.7%), other services (19.3%), commerce and hospitality (19.1%), health (18.4%) and education (18.4%). Under-reporting decreased as injury severity increased, with little variations across sectors of economic activity. CONCLUSIONS: Results suggest considerable under-reporting of OIs in Sweden and differential under-reporting by organisational factors. Results are relevant for official estimates of burden and for setting priorities for workplace safety and prevention.

Sickness absence and disability pension among women with breast cancer: a population-based cohort study from Sweden.

BACKGROUND: Women's return to work after diagnosis of breast cancer (BC) is becoming more prevalent. However, register-based national investigation on sickness absence (SA) and disability pension (DP) in BC women is lacking. The aim of the study was to explore SA and DP before and after a first BC diagnosis and the possibility to predict new cancer-related SA by using disease-related and sociodemographic factors. METHODS: A longitudinal register study of the 3536 women in Sweden aged 19-64 with a first BC diagnosis in 2010 was conducted by linkage of five nationwide registers. Particularly, detailed information on SA and DP was obtained from the National Social Insurance Agency. Descriptive statistics on SA and DP 2 years before through 3 years after the BC diagnosis were performed. The risk of having a new SA spell due to BC or BC-related diagnoses was modeled using logistic regression. RESULTS: The proportion of women with SA increased during the year following the BC diagnosis date and declined over the next 2 years to proportions before diagnosis. At the time of BC diagnosis, half of the women began a new SA spell > 14 days with cancer, cancer-related, or mental diagnosis. Disease-related and sociodemographic factors including occupational sector, living area, age, cancer stage, educational level, and number of previous SA days showed statistical significance (p < 0.05) in predicting a new SA around BC diagnosis. By using these factors, it was possible to correctly predict 67% of the new SA spell. CONCLUSIONS: SA among women with BC was elevated mainly in the first year after diagnosis. New SA following BC diagnosis can accurately be predicted.

Predicting the duration of sickness absence due to knee osteoarthritis: a prognostic model developed in a population-based cohort in Sweden.

BACKGROUND: Predicting the duration of sickness absence (SA) among sickness absent patients is a task many sickness certifying physicians as well as social insurance officers struggle with. Our aim was to develop a prediction model for prognosticating the duration of SA due to knee osteoarthritis. METHODS: A population-based prospective study of SA spells was conducted using comprehensive microdata linked from five Swedish nationwide registers. All 12,098 new SA spells > 14 days due to knee osteoarthritis in 1/1 2010 through 30/6 2012 were included for individuals 18-64 years. The data was split into a development dataset (70 %, nspells =8468) and a validation data set (nspells =3690) for internal validation. Piecewise-constant hazards regression was performed to prognosticate the duration of SA (overall duration and duration > 90, >180, or > 365 days). Possible predictors were selected based on the log-likelihood loss when excluding them from the model. RESULTS: Of all SA spells, 53 % were > 90 days and 3 % >365 days. Factors included in the final model were age, sex, geographical region, extent of sickness absence, previous sickness absence, history of specialized outpatient healthcare and/or inpatient healthcare, employment status, and educational level. The model was well calibrated. Overall, discrimination was poor (c = 0.53, 95 % confidence interval (CI) 0.52-0.54). For predicting SA > 90 days, discrimination as measured by AUC was 0.63 (95 % CI 0.61-0.65), for > 180 days, 0.69 (95 % CI 0.65-0.71), and for SA > 365 days, AUC was 0.75 (95 % CI 0.72-0.78). CONCLUSION: It was possible to predict patients at risk of long-term SA (> 180 days) with acceptable precision. However, the prediction of duration of SA spells due to knee osteoarthritis has room for improvement.

DNA Methylation Levels in Mononuclear Leukocytes from the Mother and Her Child Are Associated with IgE Sensitization to Allergens in Early Life.

DNA methylation changes may predispose becoming IgE-sensitized to allergens. We analyzed whether DNA methylation in peripheral blood mononuclear cells (PBMC) is associated with IgE sensitization at 5 years of age (5Y). DNA methylation was measured in 288 PBMC samples from 74 mother/child pairs from the birth cohort ALADDIN (Assessment of Lifestyle and Allergic Disease During INfancy) using the HumanMethylation450BeadChip (Illumina). PBMCs were obtained from the mothers during pregnancy and from their children in cord blood, at 2 years and 5Y. DNA methylation levels at each time point were compared between children with and without IgE sensitization to allergens at 5Y. For replication, CpG sites associated with IgE sensitization in ALADDIN were evaluated in whole blood DNA of 256 children, 4 years old, from the BAMSE (Swedish abbreviation for Children, Allergy, Milieu, Stockholm, Epidemiology) cohort. We found 34 differentially methylated regions (DMRs) associated with IgE sensitization to airborne allergens and 38 DMRs associated with sensitization to food allergens in children at 5Y (Sidak p ≤ 0.05). Genes associated with airborne sensitization were enriched in the pathway of endocytosis, while genes associated with food sensitization were enriched in focal adhesion, the bacterial invasion of epithelial cells, and leukocyte migration. Furthermore, 25 DMRs in maternal PBMCs were associated with IgE sensitization to airborne allergens in their children at 5Y, which were functionally annotated to the mTOR (mammalian Target of Rapamycin) signaling pathway. This study supports that DNA methylation is associated with IgE sensitization early in life and revealed new candidate genes for atopy. Moreover, our study provides evidence that maternal DNA methylation levels are associated with IgE sensitization in the child supporting early in utero effects on atopy predisposition.

Increased Sensitivity of Plasmodium falciparum to Artesunate/Amodiaquine Despite 14 Years as First-Line Malaria Treatment, Zanzibar.

Artemisinin-based combination therapies (ACTs) are first-line treatments for uncomplicated Plasmodium falciparum malaria. ACT resistance is spreading in Asia but not yet in Africa. Reduced effects of ACT partner drugs have been reported but with little information regarding widely used artesunate/amodiaquine (ASAQ). We studied its efficacy in Zanzibar after 14 years as first-line treatment directly by an in vivo, single-armed trial and indirectly by prevalences of different genotypes in the P. falciparum chloroquine-resistance transporter, multidrug-resistance 1, and Kelch 13 propeller domain genes. In vivo efficacy was higher during 2017 (100%; 95% CI 97.4%-100%) than during 2002-2005 (94.7%; 95% CI 91.9%-96.7%) (p = 0.003). Molecular findings showed no artemisinin resistance-associated genotypes and major increases in genotypes associated with high sensitivity/efficacy for amodiaquine than before ASAQ was introduced. Thus, the efficacy of ASAQ is maintained and appears to be increased after long-term use in contrast to what is observed for other ACTs used in Africa.

Increased Mortality of Patients With Childhood-Onset Inflammatory Bowel Diseases, Compared With the General Population.

BACKGROUND & AIMS: Childhood-onset inflammatory bowel disease (IBD) is believed to be a more severe disease than adult-onset IBD, but there is little information on all-cause and cause-specific mortality in patients with childhood-onset IBD. We performed a population-based cohort study, with 50 years of follow-up, to estimate absolute and relative risks for overall and cause-specific mortality in patients with childhood-onset IBD, during childhood and adulthood. METHODS: We identified children with a diagnosis of IBD (younger than 18 years) in the Swedish nationwide health registers (1964-2014; n = 9442) and individuals from the general population matched for sex, age, calendar year, and place of residence (reference group; n = 93,180). Hazard ratios (HR) for death were estimated using Cox regression separately in patients with ulcerative colitis (n = 4671), Crohn's disease (n = 3780), and IBD unclassified (n = 991). HRs were compared among calendar periods. RESULTS: During 138,690 person-years of follow-up, 294 deaths (2.1/1000 person-years) occurred among the patients with IBD compared with 940 deaths in the reference group (0.7/1000 person-years; adjusted HR, 3.2; 95% confidence interval [CI] 2.8-3.7). Mean age at end of follow-up was 30 years. HRs were increased for patients with ulcerative colitis 4.0, 95% CI 3.4-4.7; Crohn's disease 2.3, 95% CI 1.8-3.0; and IBD unclassified 2.0, 95% CI 1.2-3.4. Among patients younger than 18 years, there were 27 deaths from IBD 4.9, 95% CI 3.0-7.7. Among young adults with IBD, we found no evidence that HRs for death decreased from 1964 through 2014 (P = .90). CONCLUSIONS: Children with IBD have a 3-fold increase in risk of death when followed through adulthood. The relative risk for death has not decreased with development of new drugs for treatment of IBD.

Predicting the duration of sickness absence spells due to back pain: a population-based study from Sweden.

OBJECTIVES: We aimed to develop and validate a prediction model for the duration of sickness absence (SA) spells due to back pain (International Statistical Classification of Diseases and Related Health Problems 10th Revision: M54), using Swedish nationwide register microdata. METHODS: Information on all new SA spells >14 days from 1 January 2010 to 30 June 2012 and on possible predictors were obtained. The duration of SA was predicted by using piecewise constant hazard models. Nine predictors were selected for the final model based on a priori decision and log-likelihood loss. The final model was estimated in a random sample of 70% of the SA spells and later validated in the remaining 30%. RESULTS: Overall, 64 048 SA spells due to back pain were identified during the 2.5 years; 74% lasted ≤90 days, and 9% >365 days. The predictors included in the final model were age, sex, geographical region, employment status, multimorbidity, SA extent at the start of the spell, initiation of SA spell in primary healthcare and number of SA days and specialised outpatient healthcare visits from the preceding year. The overall c-statistic (0.547, 95% CI 0.542 to 0.552) suggested a low discriminatory capacity at the individual level. The c-statistic was 0.643 (95% CI 0.634 to 0.652) to predict >90 days spells, 0.686 (95% CI 0.676 to 0.697) to predict >180 spells and 0.753 (95% CI 0.740 to 0.766) to predict >365 days spells. CONCLUSIONS: The model discriminates SA spells >365 days from shorter SA spells with good discriminatory accuracy.

NK- and T-cell subsets in malignant mesothelioma patients: Baseline pattern and changes in the context of anti-CTLA-4 therapy.

Malignant mesothelioma (MM) is a highly aggressive form of cancer with limited treatment options. Although the role of NK cells has been studied in many solid tumors, the pattern of NK-cell subsets and their recognition of mesothelioma cells remain to be explored. We used RNA expression data of MM biopsies derived from the cancer genome atlas to evaluate the immune cell infiltrates. We characterized the phenotype of circulating NK and T cells of 27 MM patients before and after treatment with an anti-CTLA-4 antibody (tremelimumab). These immune cell profiles were compared to healthy controls. The RNA expression data of the MM biopsies indicated the presence of NK cells in a subgroup of patients. We demonstrated that NK cells recognize MM cell lines and that IL-15 stimulation improved NK cell-mediated lysis in vitro. Using multivariate projection models, we found that MM patients had a perturbed ratio of CD56bright and CD56dim NK subsets and increased serum concentrations of the cytokines IL-10, IL-8 and TNF-α. After tremelimumab treatment, the ratio between the CD56bright and CD56dim subsets shifted back towards physiological levels. Furthermore, the improved overall survival was correlated with low TIM-3+ CD8+ T-cell frequency, high DNAM-1+ CD56dim NK-cell frequency and high expression levels of NKp46 on the CD56dim NK cells before and after immune checkpoint blockade. Together, our observations suggest that NK cells infiltrate MM and that they can recognize and kill mesothelioma cells. The disease is associated with distinct lymphocytes patterns, some of which correlate with prognosis or are affected by treatment with tremelimumab.

Outcome of kidney function after ischaemic and zero-ischaemic laparoscopic and open nephron-sparing surgery for renal cell cancer.

BACKGROUND: Nephron-sparing surgery (NSS) remains gold standard for the treatment of localised renal cell cancer (RCC), even in case of a normal contralateral kidney. Compared to radical nephrectomy, kidney failure and cardiovascular events are less frequent with NSS. However, the effects of different surgical approaches and of zero ischaemia on the postoperative reduction in renal function remain controversial. We aimed to investigate the relative short- and long-term changes in estimated glomerular filtration rate (eGFR) after ischaemic or zero-ischaemic open (ONSS) and laparoscopic NSS (LNSS) for RCC, and to analyse prognostic factors for postoperative acute kidney injury (AKI) and chronic kidney disease (CKD) stage ≥3. METHODS: Data of 444 patients (211 LNSS, 233 ONSS), including 57 zero-ischaemic cases, were retrospectively analysed. Multiple regression models were used to predict relative changes in renal function. Natural cubic splines were used to demonstrate the association between ischaemia time (IT) and relative changes in renal function. RESULTS: IT was identified as significant risk factor for short-term relative changes in eGFR (ß = - 0.27) and development of AKI (OR, 1.02), but no effect was found on long-term relative changes in eGFR. Natural cubic splines revealed that IT had a greater effect on patients with baseline eGFR categories ≥G3 concerning short-term decrease in renal function and development of AKI. Unlike LNSS, ONSS was significantly associated with short-term decrease in renal function (ß = - 13.48) and development of AKI (OR, 3.87). Tumour diameter was associated with long-term decrease in renal function (ß = - 1.76), whereas baseline eGFR was a prognostic factor for both short- (ß = - 0.20) and long-term (ß = - 0.29) relative changes in eGFR and the development of CKD stage ≥3 (OR, 0.89). CONCLUSIONS: IT is a significant risk factor for AKI. The short-term effect of IT is not always linear, and the impact also depends on baseline eGFR. Unlike LNSS, ONSS is associated with the development of AKI. Our findings are helpful for surgical planning, and suggest either the application of a clampless NSS technique or at least the shortest possible IT to reduce the risk of short-time impairment of the renal function, which might prevent AKI, particularly regarding patients with baseline eGFR category ≥G3.

Correction to: Outcome of kidney function after ischaemic and zero-ischaemic laparoscopic and open nephron-sparing surgery for renal cell cancer.

Following publication.

Histone Acetylation of Immune Regulatory Genes in Human Placenta in Association with Maternal Intake of Olive Oil and Fish Consumption.

Maternal diet modifies epigenetic programming in offspring, a potentially critical factor in the immune dysregulation of modern societies. We previously found that prenatal fish oil supplementation affects neonatal T-cell histone acetylation of genes implicated in adaptive immunity including PRKCZ, IL13, and TBX21. In this study, we measured H3 and H4 histone acetylation levels by chromatin immunoprecipitation in 173 term placentas collected in the prospective birth cohort, ALADDIN, in which information on lifestyle and diet is thoroughly recorded. In anthroposophic families, regular olive oil usage during pregnancy was associated with increased H3 acetylation at FOXP3 (p = 0.004), IL10RA (p = 0.008), and IL7R (p = 0.007) promoters, which remained significant after adjustment by offspring gender. Furthermore, maternal fish consumption was associated with increased H4 acetylation at the CD14 gene in placentas of female offspring (p = 0.009). In conclusion, prenatal olive oil intake can affect placental histone acetylation in immune regulatory genes, confirming previously observed pro-acetylation effects of olive oil polyphenols. The association with fish consumption may implicate ω-3 polyunsaturated fatty acids present in fish oil. Altered histone acetylation in placentas from mothers who regularly include fish or olive oil in their diets could influence immune priming in the newborn.

Postmenopausal hormone therapy and risk of stroke: A pooled analysis of data from population-based cohort studies.

BACKGROUND: Recent research indicates a favourable influence of postmenopausal hormone therapy (HT) if initiated early, but not late, on subclinical atherosclerosis. However, the clinical relevance of timing of HT initiation for hard end points such as stroke remains to be determined. Further, no previous research has considered the timing of initiation of HT in relation to haemorrhagic stroke risk. The importance of the route of administration, type, active ingredient, and duration of HT for stroke risk is also unclear. We aimed to assess the association between HT and risk of stroke, considering the timing of initiation, route of administration, type, active ingredient, and duration of HT. METHODS AND FINDINGS: Data on HT use reported by the participants in 5 population-based Swedish cohort studies, with baseline investigations performed during the period 1987-2002, were combined in this observational study. In total, 88,914 postmenopausal women who reported data on HT use and had no previous cardiovascular disease diagnosis were included. Incident events of stroke (ischaemic, haemorrhagic, or unspecified) and haemorrhagic stroke were identified from national population registers. Laplace regression was employed to assess crude and multivariable-adjusted associations between HT and stroke risk by estimating percentile differences (PDs) with 95% confidence intervals (CIs). The fifth and first PDs were calculated for stroke and haemorrhagic stroke, respectively. Crude models were adjusted for age at baseline only. The final adjusted models included age at baseline, level of education, smoking status, body mass index, level of physical activity, and age at menopause onset. Additional variables evaluated for potential confounding were type of menopause, parity, use of oral contraceptives, alcohol consumption, hypertension, dyslipidaemia, diabetes, family history of cardiovascular disease, and cohort. During a median follow-up of 14.3 years, 6,371 first-time stroke events were recorded; of these, 1,080 were haemorrhagic. Following multivariable adjustment, early initiation (<5 years since menopause onset) of HT was associated with a longer stroke-free period than never use (fifth PD, 1.00 years; 95% CI 0.42 to 1.57), but there was no significant extension to the time period free of haemorrhagic stroke (first PD, 1.52 years; 95% CI -0.32 to 3.37). When considering timing as a continuous variable, the stroke-free and the haemorrhagic stroke-free periods were maximal if HT was initiated approximately 0-5 years from the onset of menopause. If single conjugated equine oestrogen HT was used, late initiation of HT was associated with a shorter stroke-free (fifth PD, -4.41 years; 95% CI -7.14 to -1.68) and haemorrhagic stroke-free (first PD, -9.51 years; 95% CI -12.77 to -6.24) period than never use. Combined HT when initiated late was significantly associated with a shorter haemorrhagic stroke-free period (first PD, -1.97 years; 95% CI -3.81 to -0.13), but not with a shorter stroke-free period (fifth PD, -1.21 years; 95% CI -3.11 to 0.68) than never use. Given the observational nature of this study, the possibility of uncontrolled confounding cannot be excluded. Further, immortal time bias, also related to the observational design, cannot be ruled out. CONCLUSIONS: When initiated early in relation to menopause onset, HT was not associated with increased risk of incident stroke, regardless of the route of administration, type of HT, active ingredient, and duration. Generally, these findings held also for haemorrhagic stroke. Our results suggest that the initiation of HT 0-5 years after menopause onset, as compared to never use, is associated with a decreased risk of stroke and haemorrhagic stroke. Late initiation was associated with elevated risks of stroke and haemorrhagic stroke when conjugated equine oestrogen was used as single therapy. Late initiation of combined HT was associated with haemorrhagic stroke risk.

Parametric modeling of quantile regression coefficient functions with censored and truncated data.

Quantile regression coefficient functions describe how the coefficients of a quantile regression model depend on the order of the quantile. A method for parametric modeling of quantile regression coefficient functions was discussed in a recent article. The aim of the present work is to extend the existing framework to censored and truncated data. We propose an estimator and derive its asymptotic properties. We discuss goodness-of-fit measures, present simulation results, and analyze the data that motivated this article. The described estimator has been implemented in the R package qrcm.