Flaminia Chiesa

A newly identified group of adolescents at “invisible” risk for psychopathology and suicidal behavior: findings from the SEYLE study

This study explored the prevalence of risk behaviors (excessive alcohol use, illegal drug use, heavy smoking, reduced sleep, overweight, underweight, sedentary behavior, high use of Internet/TV/videogames for reasons not related to school or work, and truancy), and their association with psychopathology and self‐destructive behaviors, in a sample of 12,395 adolescents recruited in randomly selected schools across 11 European countries. Latent class analysis identified three groups of adolescents: a low‐risk group (57.8%) including pupils with low or very low frequency of risk behaviors; a high‐risk group (13.2%) including pupils who scored high on all risk behaviors, and a third group (“invisible” risk, 29%) including pupils who were positive for high use of Internet/TV/videogames for reasons not related to school or work, sedentary behavior and reduced sleep. Pupils in the “invisible” risk group, compared with the high‐risk group, had a similar prevalence of suicidal thoughts (42.2% vs. 44%), anxiety (8% vs. 9.2%), subthreshold depression (33.2% vs. 34%) and depression (13.4% vs. 14.7%). The prevalence of suicide attempts was 5.9% in the “invisible” group, 10.1% in the high‐risk group and 1.7% in the low‐risk group. The prevalence of all risk behaviors increased with age and most of them were significantly more frequent among boys. Girls were significantly more likely to experience internalizing (emotional) psychiatric symptoms. The “invisible” group may represent an important new intervention target group for potentially reducing psychopathology and other untoward outcomes in adolescence, including suicidal behavior.

Early-Life Exposure to Traffic-related Air Pollution and Lung Function in Adolescence

RATIONALE Exposure to air pollution during infancy has been related to lung function decrements in 8-year-old children, but whether the negative effects remain into adolescence is unknown. OBJECTIVES To investigate the relationship between long-term air pollution exposure and lung function up to age 16 years. METHODS A total of 2,278 children from the Swedish birth cohort BAMSE (Children, Allergy, Milieu, Stockholm, Epidemiological Survey) performed spirometry at age 16 years. Levels of outdoor air pollution from local road traffic were estimated (nitrogen oxides [NOx] and particulate matter with an aerodynamic diameter of <10 μm [PM10]) for residential, daycare, and school addresses during the lifetime using dispersion modeling. Associations between exposure in different time windows and spirometry indexes were analyzed by linear regression and mixed effect models. MEASUREMENTS AND MAIN RESULTS Exposure to traffic-related air pollution during the first year of life was associated with FEV1 at age 16 years of -15.8 ml (95% confidence interval [CI], -33.6 to 2.0 for a 10 μg/m(3) difference in NOx), predominately in males (-30.4 ml; 95% CI, -59.1 to -1.7), and in subjects not exposed to maternal smoking during pregnancy or infancy. Later exposures appeared to have had an additional negative effect. High exposure during the first year of life was also associated with odds ratios for FEV1 and FVC less than the lower limit of normal (LLN) (defined as a z-score < -1.64 SD) of 3.8 (95% CI, 1.3-10.9) and of 4.3 (95% CI, 1.2-15.0), respectively. The results for PM10 were similar to those for NOx. CONCLUSIONS Exposure to traffic-related air pollution in infancy is negatively associated with FEV1 at age 16 years, leading to increased risk of clinically important deficits.

We are family—parents, siblings, and eating disorders in a prospective total‐population study of 250,000 Swedish males and females

OBJECTIVE We examined how parental characteristics and other aspects of family background were associated with the development of eating disorders (ED) in males and females. METHOD We used register data and record linkage to create the prospective, total-population study the Stockholm Youth Cohort. This cohort comprises all children and adolescents who were ever residents in Stockholm County between 2001 and 2007, plus their parents and siblings. Individuals born between 1984 and 1995 (N = 249, 884) were followed up for ED from age 12 to end of 2007. We used Cox regression modeling to investigate how ED incidence was associated with family socioeconomic position, parental age, and family composition. RESULTS In total, 3,251 cases of ED (2,971 females; 280 males) were recorded. Higher parental education independently predicted a higher rate of ED in females [e.g., adjusted hazard ratio (HR) 1.69 (95% CI: 1.42, 2.02) for degree-level vs. elementary-level maternal education], but not in males [HR 0.73 (95% CI: 0.42, 1.28), p < 0.001 for gender interaction]. In females, an increasing number of full-siblings was associated with lower rate of ED [e.g., fully adjusted HR 0.92 (95% CI: 0.88, 0.97) per sibling], whereas an increasing number of half-siblings was associated with a higher rate [HR 1.05 (95% CI: 1.01, 1.09) per sibling]. DISCUSSION The effect of parental education on ED rate varies between males and females, whereas the effect of number of siblings varies according to whether they are full or half-siblings. A deeper understanding of these associations and their underlying mechanisms may provide etiological insights and inform the design of preventive interventions.

Epidemiology of Massive Transfusion: A Binational Study From Sweden and Denmark*

Objective:There is an increasing focus on massive transfusion, but there is a paucity of comprehensive descriptions of the massively transfused patients and their outcomes. The objective of this study is to describe the incidence rate of massive transfusion, patient characteristics, and the mortality of massively transfused patients. Design:Descriptive cohort study. Setting:Nationwide study with data from Sweden and Denmark. Patients:The study was based on the Scandinavian Donations and Transfusions database, including all patients receiving 10 or more red cell concentrate transfusions in Sweden from 1987 and in Denmark from 1996. A total of 92,057 patients were included. Patients were followed until the end of 2012. Measurements and Main Results:Descriptive statistics were used to characterize the patients and indications. Post transfusion mortality was expressed as crude 30-day mortality and as long-term mortality using the Kaplan-Meier method and using standardized mortality ratios. The incidence of massive transfusion was higher in Denmark (4.5 per 10,000) than in Sweden (2.5 per 10,000). The most common indication for massive transfusion was major surgery (61.2%) followed by trauma (15.4%). Massive transfusion due to obstetrical bleeding constituted only 1.8%. The overall 5-year mortality was very high (54.6%), however with large differences between indication groups, ranging from 91.1% among those transfused for a malignant disease without surgery to 1.7% among patients transfused for obstetrical bleeding. The early standardized mortality ratios were high and decreased thereafter, but remained elevated throughout the time period. Conclusions:This large-scale study based on nationwide data from Sweden and Denmark describes the complete range of massive transfusion. We report a nonnegligible incidence and both a high absolute mortality and high standardized mortality ratio. The general pattern was similar for Sweden and Denmark, and we believe that similar patterns may be found in other high-resource countries. The study provides a relevant background for clinicians and researchers for designing future studies in this field.

Asthma phenotypes and lung function up to 16 years of age-the BAMSE cohort.

Asthma is a disease affecting many locations throughout the airway. Most studies have used spirometry as the primary assessment of airway obstruction, a method that may be less sensitive in regard to peripheral airway obstruction. The aim of this study was to elucidate the associations between asthma phenotypes based on age of onset and duration of symptoms, and (i) spirometry and (ii) small airway involvement measured by impulse oscillometry (IOS) in adolescence.

Lack of association between blood donor age and survival of transfused patients

To the editor: The possible rejuvenating effects of transfusions from young donors to older patients have generated considerable interest recently, following publication of a study showing improvements in muscle regeneration when older mice were transfused with blood from younger mice.[1][1]

Time-dependent risk of depression, anxiety, and stress-related disorders in patients with invasive and in situ breast cancer

Despite concerns about the mental health of breast cancer patients, little is known regarding the temporal risk pattern and risk factors of common mental disorders among these patients. We estimated standardized incidence ratios (SIRs) of depression, anxiety and stress‐related disorders in a Swedish nationwide cohort of 40,849 women with invasive and 4,402 women with in situ breast cancer (2001–2010, median follow‐up = 4.5 years). The impact of patient, tumor and treatment characteristics was analyzed using flexible parametric survival models in a regional cohort of 7,940 invasive breast cancer patients (2001–2013, median follow‐up = 7.5 years). Women with invasive breast cancer showed increased rates of depression, anxiety and stress‐related disorders [overall SIR (95% CI) = 1.57 (1.46–1.69), 1.55 (1.43–1.68) and 1.77 (1.60‐1.95), respectively]. SIRs were highest shortly after diagnosis, but remained increased up to 5 years. Younger age at diagnosis, comorbidity, higher‐grade disease, lymph node involvement and chemotherapy were independently associated with the risk of depression and anxiety in invasive cancer patients, with chemotherapy and higher‐grade disease conferring short‐term risk only, while comorbidities were mainly associated with late‐onset events. No clinical risk factors were identified for stress‐related disorders except for a greater risk associated with younger age. Patients with in situ cancer only showed an increased incidence of stress‐related disorders during the first 6 months after diagnosis [SIR (95% CI) = 2.76 (1.31‐5.79)]. The time‐dependent risk profile of invasive cancer patients may guide health care professionals for timely and targeted psycho‐oncologic interventions.

Work Disability After Robot-assisted or Open Radical Prostatectomy: A Nationwide, Population-based Study

BACKGROUND Robot-assisted radical prostatectomy (RARP) has been associated with reduced bleeding and shorter hospital stays than open retropubic radical prostatectomy (RRP), but it is unclear whether these differences translate into shorter absence from work. OBJECTIVE To investigate short- and long-term rates of work disability following RARP and RRP. DESIGN, SETTING, AND PARTICIPANTS We conducted a nationwide population-based cohort study of 2571 men of working age treated with RARP or RRP between 2007 and 2009 identified in the National Prostate Cancer Register of Sweden. Information about physician-certified sick leave and disability pension was retrieved from the Swedish Social Insurance Agency through 2012. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS We used Cox regression to calculate time to return to work (RTW, or duration of sick leave) after surgery and used generalised estimating equations to analyse days lost from work (because of sick leave and disability pension) after RTW. RESULTS AND LIMITATIONS Men treated with RARP returned to work after a median of 35 d, whereas the corresponding time for RRP was 48 d (p<0.001). The difference was seen early; within the first month, men treated with RARP returned to work nearly four times faster than men treated with RRP (adjusted relative RTW rate 3.76; 95% confidence interval [CI], 3.04-4.66). During a median of 3.6 yr after return to work, men treated with RARP lost fewer days from work per person-year than men treated with RRP-12 d versus 15 d-but the association was not statistically significant (p=0.10). The adjusted rate ratio was 1.08 (95% CI, 0.82-1.42). One limitation is the nonrandomised design of this study. CONCLUSIONS RARP was associated with a faster RTW compared with RRP, but the surgical method did not influence long-term rates of work disability in terms of days lost from work after RTW. PATIENT SUMMARY We compared disease-related absence from work between two surgical methods for the removal of the prostate. Robot-assisted surgery was associated with a faster return to work compared with open surgery but did not influence absence from work in a long-term perspective.

Amount of stroma is associated with mammographic density and stromal expression of oestrogen receptor in normal breast tissues

Following female sex and age, mammographic density is considered one of the strongest risk factors for breast cancer. Despite the association between mammographic density and breast cancer risk, little is known about the underlying histology and biological basis of breast density. To better understand the mechanisms behind mammographic density we assessed morphology, proliferation and hormone receptor status in relation to mammographic density in breast tissues from healthy women. Tissues were obtained from 2012–2013 by ultrasound-guided core needle biopsy from 160 women as part of the Karma (Karolinska mammography project for risk prediction for breast cancer) project. Mammograms were collected through routine mammography screening and mammographic density was calculated using STRATUS. The histological composition, epithelial and stromal proliferation status and hormone receptor status were assessed through immunohistochemical staining. Higher mammographic density was significantly associated with a greater proportion of stromal and epithelial tissue and a lower proportion of adipose tissue. Epithelial expression levels of Ki-67, oestrogen receptor (ER) and progesterone receptor (PR) were not associated with mammographic density. Epithelial Ki-67 was associated with a greater proportion of epithelial tissue, and epithelial PR was associated with a greater proportion of stromal and a lower proportion of adipose tissue. Epithelial ER was not associated with any tissues. In contrast, expression of ER in the stroma was significantly associated with a greater proportion of stroma, and negatively associated with the amount of adipose tissue. High mammographic density is associated with higher amount of stroma and epithelium and less amount of fat, but is not associated with a change in epithelial proliferation or receptor status. Increased expressions of both epithelial PR and stromal ER are associated with a greater proportion of stroma, suggesting hormonal involvement in regulating breast tissue composition.

Inherited factors contribute to an inverse association between preeclampsia and breast cancer

BackgroundPreeclampsia is frequently linked to reduced breast cancer risk. However, little is known regarding the underlying genetic association and the association between preeclampsia and mammographic density.MethodsThis study estimates the incidence rate ratios (IRRs) of breast cancer in patients with preeclampsia, when compared to women without preeclampsia, using Poisson regression models in two cohorts of pregnant women: a Swedish nationwide cohort (n = 1,337,934, 1973–2011) and the Karolinska Mammography Project for Risk Prediction of Breast Cancer (KARMA, n = 55,044, 1958–2015). To identify the genetic association between preeclampsia and breast cancer, we used logistic regression models to calculate the odds ratios (ORs) of preeclampsia in sisters of breast cancer patients, and in women with different percentiles of breast cancer polygenic risk scores (PRS). Linear regression models were used to estimate the mammographic density by preeclampsia status in the KARMA cohort.ResultsA decreased risk of breast cancer was observed among patients with preeclampsia in both the nationwide (IRR = 0.90, 95% CI = 0.85; 0.96) and KARMA cohorts (IRR = 0.75, 95% CI = 0.61; 0.93). Women with high breast cancer PRS and sisters of breast cancer patients had a lower risk of preeclampsia (OR = 0.89, 95% CI = 0.83; 0.96). Mammographic density was lower in women with preeclampsia compared to women without preeclampsia (-2.04%, 95% CI = -2.65; -1.43). Additionally, among sisters in the KARMA cohort (N = 3500), density was lower in sisters of patients with preeclampsia compared to sisters of women without preeclampsia (-2.76%, 95% CI = -4.96; -0.56).ConclusionPreeclampsia is associated with reduced risk of breast cancer and mammographic density. Inherited factors contribute to this inverse association.